Dermatology: Practical and Conceptual Research Letter | Dermatol Pract Concept. 2023;13(3):e2023180 1 Folliculitis-Decalvans Like Alopecia During Treatment with EGFR Inhibitors for Lung Cancer: A Case Series of 6 Patients Michela Starace1,2, Bianca Maria Piraccini1,2, Miriam Anna Carpanese1,2, Matilde Iorizzo3, Zoe Apalla4 1 Dermatology Unit - IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy 2 Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy 3 Private Dermatology Practice, Bellinzona/Lugano, Switzerland 4 Second Dermatology Department, Aristotle University of Thessaloniki, Papageorgiou General Hospital, Greece Key words: folliculitis decalvans; EGFR inhibitors; drug-induced alopecia; cancer patients; antibiotic therapy Citation: Starace M, Piraccini BM, Carpanese MA, Iorizzo M, Apalla Z. Folliculitis-Decalvans Like Alopecia During Treatment With EGFR Inhibitors for Lung Cancer: A Case Series of 6 Patients. Dermatol Pract Concept. 2023;13(3):e2023180. DOI: https://doi.org/10.5826/dpc.1303a180 Accepted: March 15, 2023; Published: July 2023 Copyright: ©2023 Starace et al. This is an open-access article distributed under the terms of the Creative Commons Attribution- NonCommercial License (BY-NC-4.0), https://creativecommons.org/licenses/by-nc/4.0/, which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original authors and source are credited. Funding: None. Competing interests: None. Authorship: All authors have contributed significantly to this publication. Corresponding author: Michela Starace, MD PhD, Dermatology Unit - IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy; Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy Via Massarenti 1, 40100 Bologna, Italy. E-mail: michela.starace2@unibo.it Introduction Epidermal growth factor receptor inhibitors (EGFRi) repre- sent a valid therapeutic option for the treatment of cancers caused by EGFR dysregulation. Skin toxicity is the most common adverse event related to EGFRi, and even though rarely life-threatening, it can seriously affect patients quality of life and their compliance to treatment, often leading to treatment modification or discontinuation [1]. Case Presentation We report 5 patients developing alopecia during treat- ment with EGFRi for non-small-cell lung carcinoma (NS- CLC) (Table 1). The clinical and trichoscopic presentations mimicked Folliculitis Decalvans (FD) in all patients, with 4 of them presenting a more severe, diffuse and debilitating picture showing erythema, pustules, crusts and patches of scarring alopecia (Figure 1A). The other patients had a milder, less defined areas of alopecia not yet scarring, but with a prominent erythema, telangectasia, casts and scales. Trichoscopy confirmed the clinical picture, highlighting findings as erythema, telangiectasia, scales, haemorrhagic and serum crusts, perifollicular hyperkeratosis and pili torti (Figure 1B). Histology showed keratin aggregation and a dilatation of the infundibulum in combination with nu- merous intraluminal neutrophils. Sebaceous glands are de- stroyed early in the process. Additionally, an intrafollicular and perifollicular predominately neutrophilic infiltrate could be found (Figure 2) Based on the clinical, trichoscopic, and 2 Research Letter | Dermatol Pract Concept. 2023;13(3):e2023180 Ta b le 1 . D at a of p at ie nt s di ag no se d w it h fo lli cu lit is d ec al va ns -l ik e al op ec ia d ur in g tr ea tm en t w it h E G FR in hi bi to rs . Se x A g e (y ea rs ) N eo p la si a Pe rs o n al o r fa m ily h is to ry O n co lo g ic t re at m en t (d ru g a n d d o sa g es ) N u m b er o f EG FR i cy cl es B o d y ar ea s in vo lv ed Tr ic h o sc o p y Tr ea tm en t O u tc o m e Im p ac t o n o n co lo g ic tr ea tm en t R el ap se s M /5 7 L un g (N SC L C ) N o E rl ot in ib a t 15 0 m g on ce da ily + b ev ac iz um ab (1 5m g/ K g ev er y 3 w ee ks ) 1 Fa ce A bs en ce o f fo lli cu la r os ti a, p us tu le s, c ru st s, se ve re e ry th em a, pe ri fo lli cu la r hy pe rk er at os is , d if fu se de sq ua m at io n, p ili t or ti D ox yc yc lin e 10 0 m gx 2 an d cl ob et as ol 1 /d ay fo r 1 m on th PR N o Y es M /6 2 L un g (N SC L C ) N o E rl ot in ib a t 15 0 m g on ce da ily + r am uc ir um ab (1 0  m g/ kg e ve ry 2 w ee ks ) 2 Fa ce a nd tr un k A bs en ce o f fo lli cu la r os ti a, p us tu le s, c ru st s, m ild e ry th em a, pe ri fo lli cu la r hy pe rk er at os is , d if fu se de sq ua m at io n D ox yc yc lin e 10 0 m gx 2 an d cl ob et as ol 1 7d ay fo r 1 m on th PR N o Y es M /5 8 L un g (N SC L C ) N o E rl ot in ib a t 15 0 m g on ce da ily + b ev ac iz um ab (1 5m g/ K g ev er y 3 w ee ks ) 2 Fa ce A bs en ce o f fo lli cu la r os ti a, p us tu le s, c ru st s, se ve re e ry th em a, pe ri fo lli cu la r hy pe rk er at os is , d if fu se de sq ua m at io n, h ai r tu ft ed D ox yc yc lin e 10 0 m g/ da y an d cl ob et as ol 1 /d ay fo r 2 m on th s PR D R Y es M /6 3 L un g (N SC L C ) N o G efi ti ni b 25 0 m g on ce da ily 2 Sc al p A bs en ce o f fo lli cu la r os ti a, p us tu le s, m od er at e er yt he m a, pe ri fo lli cu la r hy pe rk er at os is , d if fu se de sq ua m at io n D ox yc yc lin e 10 0 m g/ da y an d cl ob et as ol 1 /d ay fo r 2 m on th s PR N o Y es F/ 76 L un g (N SC L C ) N o G efi ti ni b 25 0 m g on ce  d ai ly 2 Sc al p V as cu la r ec ta si a, h ai r ca st s, m ild k er at ot ic pl ug s K et oc on az ol e sh am po o 2- 3/ w ee k; d ox ic ic lin e 10 0 m g/ da y fo r 2  m on th s PR N o Y es C R = c om pl et e re sp on se ; D R = d os e re du ct io n; D W = d os e w it hh ol di ng ; E G FR i = ep id er m al g ro w th f ac to r re ce pt or i nh ib it or ; N SC L C = n on -s m al l- ce ll lu ng c ar ci no m a; P D = p er m an en t di sc on ti nu at io n; PR = p ar ti al r es po ns e. Research Letter | Dermatol Pract Concept. 2023;13(3):e2023180 3 A B C D Figure 1. (A) Scarring alopecia with erythema, pustules, crusts, and pili torti in a 57-years-old patient. A similar dermatitis was present also on the face, especially in the beard area. (B) Trichoscopy of the same patient, showing lack of follicular ostia, yellowish serum crusts and reddish hemorrhagic crusts. (C) Clinical picture of the same patient after one month of treatment showing a good improvement of the inflammation. (D) Trichoscopy of the same patient, showing absence of inflammatory signs. Figure 2. H&E stain showed  destructive suppurative folliculitis, with dense neutrophilic infiltrate and tufted hairs,  confirming the diagnosis of folliculitis decalvans. histopathological features we established the diagnosis of folliculitis decalvans-like, scarring alopecia. In collaboration with the oncologists, the anticancer treatment was continued without modification in all indi- viduals, except for a patient who required a dose reduction. Management included systemic doxycycline in combination with topical clobetasol in 4 individuals, doxycycline alone and clobetasol shampoo alone in the patient with milder in- volvement. Follow-up period of patients included three vis- its, respectively after one month, six months and one year. We observed that all patients showed satisfactory response after one month (Figure 1, C and D), except of one who showed only mild improvement and experienced frequent re- lapses, too, but with remission at the one year follow up visit. 4 Research Letter | Dermatol Pract Concept. 2023;13(3):e2023180 recognize it and promptly start the treatment in order to pre- vent the scarring evolution. Unless no response to treatment is evident, we discourage the discontinuation of the antican- cer treatment. Multidisciplinary management, dermatologic and oncologic in this case, is always advisable in presence of skin toxicities from anticancer drugs. References 1. Kozuki T. Skin problems and EGFR-tyrosine kinase inhibitor. Jpn J Clin Oncol. 2016;46(4):291-298. DOI: 10.1093/jjco/hyv207. PMID: 26826719. PMCID: PMC4886131. 2. Vañó-Galván S, Molina-Ruiz AM, Fernández-Crehuet P, et al. Folliculitis decalvans: a multicentre review of 82 patients. J Eur Acad Dermatol Venereol. 2015;29(9):1750-1757. DOI: 10.1111 /jdv.12993. PMID: 25682915. 3. Uchiyama M, Harada K, Tobita R, Irisawa R, Tsuboi R. Histopathologic and dermoscopic features of 42 cases of follic- ulitis decalvans: A case series. J Am Acad Dermatol. 2021;85(5): 1185-1193. DOI: 10.1016/j.jaad.2020.03.092. PMID: 32272176. 4. Dervout C, Chiappa AM, Fleuret C, Plantin P, Acquitter M. Alopécie cicatricielle à type de folliculite décalvante induite par l’erlotinib [Erlotinib-induced scarring alopecia with a fol- liculitis decalvans-like presentation]. Ann Dermatol Venereol. 2020;147(12):848-852. DOI: 10.1016/j.annder.2020.08.043. PMID: 33097309. 5. Hoekzema R, Drillenburg P. Folliculitis decalvans associated with erlotinib. Clin Exp Dermatol. 2010;35(8):916-918. DOI: 10.1111/j.1365-2230.2010.03852.x. PMID: 20456379. Conclusions FD is a primary form of cicatricial alopecia, clinically start- ing as a painful purulent folliculitis with tufts of hairs and perifollicular crusts that eventually evolve in an irreversible scarring process, initially boggy and then atrophic [2]. The main dermoscopic findings are characterized by lack of fol- licular ostia, erythema, pustules, tuft of hairs emerging from the same ostium, yellowish serum crusts, reddish hemor- rhagic crusts [3]. In the 4 cases of FD induced by anti-EGFR reported in literature, the management was similar to our cases, with the prescription of oral antibiotic therapy in combination with topical steroids, and with a marked improvement reported after 3-4 weeks [4]. The most important adverse events caused by the EGFRi are represented by cutaneous toxicity that can sometimes se- verely impact the quality of life and the compliance to treat- ment. The most frequent adverse effects include acneiform rash, xerosis, erythema, photosensitivity, paronychia and can be correlated with efficacy of the therapy [1]. Among them, follicular acneiform rash occur in 60%-80% of case, result- ing from abnormal keratinization, follicular retention and subsequent rupturing of affected hair follicles [5]. FD-like scalp reaction is a rare, but possible, adverse event induced by EGFRi. Therefore, it is important to early