key: cord-304211-5uzqqbr4 authors: tammaro, a.; adebanjo, g.a.r.; parisella, f.r.; pezzuto, a.; rello, j. title: cutaneous manifestations in covid‐19: the experiences of barcelona and rome date: 2020-04-24 journal: j eur acad dermatol venereol doi: 10.1111/jdv.16530 sha: doc_id: 304211 cord_uid: 5uzqqbr4 in december 2019, a new virus called severe acute respiratory syndrome coronavirus 2 (sars‐cov‐2) causing coronavirus disease 2019 (covid‐19) emerged in wuhan, hubei province, china. sars‐cov‐2 is transmitted through respiratory droplets and object infected with droplets containing the virus. the diagnosis is made employing quantitative reverse transcriptase polymerase chain reaction to identify the viral nucleic acid in respiratory specimens or blood samples. as dermatologists we tried to comprehend the cutaneous involvement in covid-19 as there is not much information in this regard in the literature 6,7 . we identified and visited 130 patients affected by covid-19 in sant'andrea hospital in rome and 2 (1.5%) of them presented with isolated herpetiform lesions on their trunk that had appeared during their inpatient stay (fig.1) . such lesions were characterized by vesicles surrounded by erythematous halos and were accompanied by mild pruritus. in one of the patients the vesicles had started to form crusts. furthermore, we visited covid-19 patients in vall d'hebron hospital in barcelona and found one patient who presented with numerous vesicular isolated lesions on her back which appeared 8 days after she had been diagnosed with covid-19 (fig.2) . this article is protected by copyright. all rights reserved the lesions that we found in both hospitals are suggestive and typical of the infections caused by the members of the herpesviridae family. we could speculate that they could be caused by either human herpes virus 1 (hhv-1), human herpes virus 2 (hhv-2) or varicella zoster virus (vzv, to date, there is only one report that investigates the prevalence and nature of dermatological manifestations associated to the disease caused by severe acute respiratory syndrome coronavirus 2 (sars-cov-2) 6 . 148 covid-19 patients were visited lecco hospital, lombardy, italy and 88 were found eligible for data collection: 20.4% of them were found to have remarkable cutaneous manifestations that were mainly localized on the trunk 6 . the manifestations reported were erythematous rash (15.9%), generalized urticaria (3.41%) and chickenpox-like lesions (1.14%) 6 . unfortunately, no pictures of such lesions could be provided 6 . the findings of the report from lecco hospital are in line with the ones that we found. however, more studies should be performed to investigate the nature of the relation between the appearance of skin lesions, in particular chickenpox-like manifestations, and covid-19. hospitalized patients with 2019 novel coronavirus-infected pneumonia in wuhan covid-19: a new challenge for human beings acknowledgments: the patients in this manuscript have given written informed consent to publication of their case details key: cord-327036-0260rrdx authors: dominguez‐santas, m.; diaz‐guimaraens, b.; garcia abellas, p.; moreno‐garcia del real, c.; burgos‐blascoª, p.; suarez‐valle, a. title: cutaneous small‐vessel vasculitis associated with novel 2019 coronavirus sars‐cov‐2 infection (covid‐19) date: 2020-05-26 journal: j eur acad dermatol venereol doi: 10.1111/jdv.16663 sha: doc_id: 327036 cord_uid: 0260rrdx the severe acute respiratory syndrome coronavirus 2 (sars‐cov‐2) has rapidly become a global health issue. although it is known to produce diverse cutaneous manifestations, some of them have yet to be described. this letter reports new dermatologic findings associated with a confirmed covid‐19 case. this article is protected by copyright. all rights reserved the severe acute respiratory syndrome coronavirus 2 (sars-cov-2) has rapidly become a global health issue. although it is known to produce diverse cutaneous manifestations, some of them have yet to be described. this letter reports new dermatologic findings associated with a confirmed covid-19 case. a 71-year-old female presented to our emergency department in april 2020, in the midst of the covid-19 pandemic. she reported the onset of fever, cough and malaise 9 days before admission, and she noticed the appearance of pruritic skin lesions in both legs on the seventh day from the start of symptoms. her husband had also been hospitalized 2 weeks before due to covid-19-induced pneumonia. although the rrt-pcr from skin biopsy was negative, we believe that csvv arising in the context of a covid-19 infected person is no coincidence and should not be categorized as idiopathic. there are numerous reports of viral-induced vasculitis, either associated with cryoglobulin presence (as in hcv infected patients) 4 , or unrelated to them (as in individuals with influenza-vaccine-induced vasculitis) 5 . we believe that this negative rrt-pcr result has two possible explanations, the first and most likely, that immunocomplexes involved in this csvv do not carry viable viruses, and the second being a lack of sensitivity of the test. by sharing this case we hope to improve the scarce knowledge we have on this disease. doctors dealing with csvv in undiagnosed patients during this pandemic may take into consideration testing for sars-cov-2. petechial skin rash associated with severe acute respiratory syndrome coronavirus 2 infection chilblain-like lesions during covid-19 epidemic: a preliminary study on 63 patients morbilliform exanthem associated with covid-19. jaad case rep 2020 vasculitis following influenza vaccination: a review of the literature acknowledgements: the patients in this manuscript have given written informed consent to the publication of their case details.bibliography: key: cord-260218-add4i1c9 authors: bosch‐amate, x; giavedoni, p; podlipnik, s; andreu‐febrer, c; sanz‐beltran, j; garcia‐herrera, a; alós, l; mascaró, jm title: retiform purpura as a dermatological sign of covid‐19 coagulopathy date: 2020-06-03 journal: j eur acad dermatol venereol doi: 10.1111/jdv.16689 sha: doc_id: 260218 cord_uid: add4i1c9 since december 2019, coronavirus disease 2019 (covid‐19) has spread worldwide to become a pandemic. multiple skin manifestations related to the infection have been described progressively. recalcati(1) asserted that 20.4% of infected patients developed cutaneous manifestations and galván‐casas et al(2) have recently proposed 5 clinical patterns (pseudo‐chilblain, vesicular, urticarial, maculopapular and livedo/necrosis). we report a case of covid‐19 with retiform purpura and its histopathological correlation. this article is protected by copyright. all rights reserved patients. 6 purpura, raynaud's phenomenon, chilblain-like and erythema multiforme-like lesions in young asymptomatic patients have also been observed with this infection, although the connection with coagulopathy is unknown. 7, 8 our patient presented with retiform purpura as a cutaneous manifestation of covid-19 coagulopathy. galván-casas et al linked the livedoid/necrotic lesions to older patients and severe disease (10% mortality) but no biopsies were performed. 2 in the present case, histology showed thrombi in small cutaneous vessels, with complement pathway activation as demonstrated by c3 and c9 deposition. heparin was changed to fondaparinux after suspecting heparin-induced thrombocytopenia, but fan et al described mild thrombocytopenia (100-150 x10 9 /l) in 20% of covid-19 patients. 9 our case highlights the concomitant presentation of cutaneous microthrombi presenting as retiform purpura and macrothrombi presenting as pulmonary thromboembolism in the setting of covid-19 coagulopathy. to our knowledge, there have been no histologically proven cases describing this phenomenon. we hope that in the coming months, pathophysiology of skin manifestations secondary to coagulation alterations will be better understood. from now on, we will have to include covid-19 infection in the differential diagnosis of retiform purpura. 10 cutaneous manifestations in covid-19: a first perspective classification of the cutaneous manifestations of covid-19: a rapid prospective nationwide consensus study in spain with 375 cases changes in blood coagulation in patients with severe coronavirus disease 2019 (covid-19): a meta-analysis complement associated microvascular injury and thrombosis in the pathogenesis of severe covid-19 infection: a report of five cases clinical and coagulation characteristics of 7 patients with critical covid-2019 pneumonia and acro-ischemia vascular skin symptoms in covid-19: a french observational study characterization of acute acro-ischemic lesions in non-hospitalized patients: a case series of 132 patients during the covid-19 outbreak hematologic parameters in patients with covid-19 infection the patient in this manuscript has given written informed consent to publication of their case details. this article is protected by copyright. all rights reserved key: cord-282750-d9sb7o63 authors: benhadou, f.; del marmol, v. title: improvement of sars‐cov2 symptoms following guselkumab injection in a psoriatic patient date: 2020-05-07 journal: j eur acad dermatol venereol doi: 10.1111/jdv.16590 sha: doc_id: 282750 cord_uid: d9sb7o63 we read with great interest the publication of messina et al (1) reporting the first case of sars‐cov2 infection in a young patient of 32‐year‐old suffering from psoriasis and psoriatic arthritis treated by guselkumab, a monoclonal antibody that targets specifically the p19 subunit of interleukin (il)‐23(2).the patient contracted the sars‐cov2 infection after a dinner with some friends but fortunately she developed very discrete symptoms including only mild fever and rhinorrhea. these findings support the potential role of il‐23p19 inhibitors to counteract the « cytokine storm » triggered by the sars‐cov2 and which is potentially implicated in the severity of the symptoms (3). arthritis treated by guselkumab, a monoclonal antibody that targets specifically the p19 subunit of interleukin (il)-23 2 .the patient contracted the sars-cov2 infection after a dinner with some friends but fortunately she developed very discrete symptoms including only mild fever and rhinorrhea. these findings support the potential role of il-23p19 inhibitors to counteract the « cytokine storm » triggered by the sars-cov2 and which is potentially implicated in the severity of the symptoms 3 . in some patients, this immune response against sars-cov2 is too this article is protected by copyright. all rights reserved exaggerated which may cause acute respiratory distress syndrome and end organ failure but the precise mechanisms underlying the progression from mild to severe complications are still under investigation 3 . interestingly, the cytokine profile associated with sars-cov2 infection severity is characterised by increased levels of tumor necrosis factor , il-1, il-2, il-6, il-7, granulocyte colony stimulating factor, interferon(ifn)-γ inducible protein 10, monocyte chemoattractant protein 1, and macrophage inflammatory protein 1-α among others 4 by targeting the il-23p19 subunit, guselkumab does not increase the risk for viral, bacterial or fungal infections among psoriasis patients 5 . il-23 does not seem to be essential for controlling virus clearance but may play a role in the deleterious hyperinflammatory state associated to severe symptoms. viral clearance seems to be more depending on other cytokines such as il-15, type i ifn and ifn-γ 6 . in addition to the case reported by messina et al 1 , our present observation strongly supports the need to identify patients who will develop an hyperinflammation during the sars-cov2 infection and to recommend the use of existing and approved biologic therapies to taper down the immune reaction in order to reduce the mortality. further investigations are required to validate accepted article sars-cov-2 infection in a psoriatic patient treated with il-23 inhibitor efficacy and safety of ixekizumab for the treatment of moderate-to-severe plaque psoriasis: results through 108 weeks of a randomized, controlled phase 3 clinical trial (uncover-3) in the eye of the covid-19 cytokine storm covid-19: consider cytokine storm syndromes and immunosuppression efficacy and safety of guselkumab, an anti-interleukin-23 monoclonal antibody, compared with adalimumab for the continuous treatment of patients with moderate to severe psoriasis: results from the phase iii, double-blinded, placebo-and active comparator-controlled voyage 1 trial covid-19: risk for cytokine targeting in chronic inflammatory diseases? reply to "covid-19, syphilis and biologic therapies for psoriasis and psoriatic arthritis: a word of caution key: cord-314422-u2elzgl8 authors: bothra, atul; das, seujee; singh, mehak; pawar, manoj; maheswari, anshu title: retroauricular dermatitis with vehement use of ear loop face masks during covid19 pandemic date: 2020-06-03 journal: j eur acad dermatol venereol doi: 10.1111/jdv.16692 sha: doc_id: 314422 cord_uid: u2elzgl8 the covid‐19 pandemic forged theexponential use of masks of various kinds, not just by health workers but also by general population as a personal protective equipment (ppe). although contact dermatitis due to ppe is well reported, mask induced dermatitis is a relatively unexplored phenomenon. in this article, we report a preliminary data of patients experiencing retroauricaular dermatitis due to ear loop face masks. this article is protected by copyright. all rights reserved to the editor: the covid-19 pandemic forged theexponential use of masks of various kinds, not just by health workers but also by general population as a personal protective equipment (ppe). although contact dermatitis due to ppe is well reported, mask induced dermatitis is a relatively unexplored this article is protected by copyright. all rights reserved phenomenon. in this article, we report a preliminary data of patients experiencing retroauricaular dermatitis due to ear loop face masks. documented. 4 komerickiet.al reported cocopropylenediamin-guanidium-diacetate , used to disinfect medical instruments and apparatus, responsible for acd to non-disposable face masks. 5 similar effects on the face by ppe in healthcare workers managing covid-19 cases has been documented, but no study has elaborated the retroauricular involvement. 6 frequent frictions due to the straps, this article is protected by copyright. all rights reserved trapping of sweat, use of disinfectant to reuse masks, application of dyes to colour homemade masks are frequent causes of dermatitis using ear loop face masks. the strap material including thermoelastic polymer, rubber, latex etc. further leads to contact dermatitis. moreover, the masks can cause exacerbation of pre-existing dermatoses. the authors would like to suggest the use of headband face masks for health care professionals using the mask for prolonged periods. the general population, using homemade face masks should use cotton cloth based masks with gaiters of appropriate elasticityand avoid any disinfectant application. persons with preexisting dermatoses including atopic dermatitis, seborrheic dermatitis and chronic urticaria need to take special precautions and use of disposable surgical masks should be encouraged. donning of masks should be done after proper absorption of the emollient to prevent leeching of strap polymers. adverse skin reactions to personal protective equipment against severe acute respiratory syndrome-a descriptive study in singapore skin reactionsfollowing use of n95 facial masks surgical mask contact dermatitis and epidemiology of contact dermatitis in healthcare workers. current allergy & clinical immunology accepted article this article is protected by copyright. all rights reserved occupational allergic contact dermatitis in an obstetrics and gynecology resident face dermatitis from contaminants on a mask for anaesthesia personal protective equipment induced facial dermatoses in healthcare workers managing covid-19 cases acknowledgement-the patients in this manuscript have given written informed consent to the publication of their case details. key: cord-258581-46p0k9lc authors: bodak, nathalie; chiaverini, christine; barbarot, sebastien title: covid‐19 lockdown induced acral dermatosis in children date: 2020-06-28 journal: j eur acad dermatol venereol doi: 10.1111/jdv.16797 sha: doc_id: 258581 cord_uid: 46p0k9lc recently, several case series of cutaneous acral manifestations in patients with suspected or confirmed coronavirus disease 2019 (covid‐19) have been reported. a majority of these acral manifestations have a pseudo‐chilblain pattern with erythema and oedema and sometimes vesicles. indirect consequences of the ongoing pandemic on skin health have been reported, such as an increased frequency of irritant dermatitis related to repeated hand washing with soap, or occupational dermatoses in health care workers due to wearing gloves or masks (4, 5) . furthermore, there have been some concerns that enforcement of strict social isolation measures may be associated with stress-induced worsening of chronic inflammatory skin diseases such as psoriasis or atopic dermatitis (6). we describe here acral lesions observed in seven children (four girls) by the sixth week of the lockdown period in france. three cases were observed in one family. all were healthy children aged 5 to 8 years (mean age 6 years) referred, by paediatricians or orthopedic surgeons, for this article is protected by copyright. all rights reserved teledermatology consultation, for recently acquired rounded pad-like hyperkeratotic areas on the feet (6/7) (figs. 1a,c,d; 2b,c)and knees (1/7) (fig. 2a) . these asymptomatic lesions were located over the bony prominences of the feet and legs, suggesting a frictional dermatosis (. they were initially erythematous and then slightly hyperpigmented. when specifically asked, the parents reported a recent history of prolonged sessions of playing activities on the floor since the lockdown period had begun. the children had tended to sit cross-legged (fig. 1b) (7), on the feet of professional dancers (8) or in yoga practioners(9). they are sometimes described as "chewing-pads" on the hands in case of chewing, sucking, or manipulating tic-like habits in children and adolescents. these lesions may also be observed in heavy users of video games (10). pachydermatodactyly is a particular form of repeated trauma induced dermatosis of the hands characterized by a cutaneous thickening of the lateral aspects of the fingers with mainly dermal changes and very little epidermal thickening ((11). although a larger case series would strengthen our hypothesis, we suggest that the change of daily habits in young children during the lockdown period may have increased the frequency of acral frictional dermatoses that are not directly due to the virus but rather to prolonged sessions spent playing on the floor. i am grateful to dr jonathan batchelor for his advice. the patients in this manuscript have given written informed consent to publication of their case details. this article is protected by copyright. all rights reserved classification of the cutaneous manifestations of covid-19: a rapid prospective nationwide consensus study in spain with 375 cases vascular skin symptoms in covid-19: a french observational study acral cutaneous lesions in the time of covid-19 skin reactions to non-glove personal protective equipment: an emerging issue in the covid-19 pandemic the role of occupational dermatology in the covid-19 outbreak. contact dermatitis mass quarantine measures in the time of covid-19 pandemic: psycho-social implications for chronic skin conditions and a call for qualitative studies occupational hyperkeratoses in carpet installers metatarsal pain and plantar hyperkeratosis in the forefeet of female key: cord-341999-nosdj7b2 authors: conti, a.; lasagni, c.; bigi, l.; pellacani, g. title: evolution of covid‐19 infection in 4 psoriatic patients treated with biological drugs date: 2020-05-07 journal: j eur acad dermatol venereol doi: 10.1111/jdv.16587 sha: doc_id: 341999 cord_uid: nosdj7b2 since december 2019, the pandemic coronavirus disease (2019‐ncov; covid‐19) has changed the approach to all dermatological diseases; in particular, psoriatic patients undergoing immunosuppressive drugs, such as biologics, can potentially show an increase risk of infection (1). however, few reports are available on the course of covid‐19 infection in psoriatic patients treated with biological drugs (2). we describe a case series of four psoriatic patients treated with biologics who had a risk contact with covid‐19. since december 2019, the pandemic coronavirus disease (2019-ncov; covid-19) has changed the approach to all dermatological diseases; in particular, psoriatic patients undergoing immunosuppressive drugs, such as biologics, can potentially show an increase risk of infection (1) . however, few reports are available on the course of covid-19 infection in psoriatic patients treated with biological drugs (2) . we describe a case series of four psoriatic patients treated with biologics who had a risk contact with covid-19. this article is protected by copyright. all rights reserved in the last two cases, the biologic therapy was interrupted only during the quarantine period, without worsening of psoriasis and no test has be done for covid-19. in sars-cov-2 infection the immune response plays an important role in the development of an excessive inflammatory response, which can evolve towards an acute respiratory distress syndrome (ards), potentially lethal for the patient (3). some key cytokines in the pathogenesis of psoriasis, such as tumor necrosis factor alpha (tnf-α) and interleukin 17 (il17) are increased in inflammatory response to coronavirus and viral pneumonia, while il-23 does not seem to be essential for an effective immune response (4) . the increase in inflammatory cytokines is associated to a worsening of clinical conditions of the patients affected by sars-cov-2 (3, 5) . based on these observations, it has been hypothesized that anti-tnf-α or anti-il17 drugs could play a potential role to improve covid-19's "cytokine storm" and ards (6) . for this reason, the use of ixekizumab and adalimumab associated to antiviral drugs are currently studied in china in the treatment for covid-19 (7, 8) . despite the presence of risk factors for a worse prognosis (hypertension, diabetes, obesity, male gender), only one patient presented a severe form of sars-cov-2, while another one a mild form. despite a prolonged contact with subjects with covid-19 infection, the other two cases did not show any symptoms. this could explain the positive course of covid-19 infection in our four cases, where ongoing treatment with biological drugs could play a protective role against the onset and the evolution of the infection. further studies are needed to investigate this hypothesis. should biologics for psoriasis be interrupted in the era of covid-19? sars-cov-2 infection in a psoriatic patient treated with il-23 inhibitor clinical features of patients infected with 2019 novel coronavirus in wuhan, china inhibition of the inflammatory cytokine tumor necrosis factoralpha with etanercept provides protection against lethal h1n1 influenza infection in mice research progress on the mechanism of cytokine storm induced by new coronavirus pneumonia and related immunotherapy reducing mortality from 2019-ncov: host-directed therapies should be an option a randomized, blinded, controlled, multicenter clinical trial to evaluate the efficacy and safety of ixekizumab combined with conventional antiviral drugs in patients with novel coronavirus pneumonia a clinical study for the efficacy and safety of adalimumab injection in the treatment of patients with severe novel coronavirus pneumonia accepted article key: cord-341118-h5t87vf8 authors: torres‐navarro, ignacio; abril‐pérez, carlos; roca‐ginés, juncal; sánchez‐arráez, javier; botella‐estrada, rafael title: a case of cefditoren‐induced acute generalized exanthematous pustulosis during covid‐19 pandemics. severe cutaneous adverse reactions (scars) are an issue date: 2020-05-26 journal: j eur acad dermatol venereol doi: 10.1111/jdv.16664 sha: doc_id: 341118 cord_uid: h5t87vf8 we read with interest the article by recalcati et al. about the report of cutaneous manifestations in covid‐19 patients. we would like to highlight that some potentially severe manifestations in these patients are not directly related to the coronavirus but to the medications administered. this article is protected by copyright. all rights reserved dear editor, we read with interest the article by recalcati et al. about the report of cutaneous manifestations in covid-19 patients. we would like to highlight that some potentially severe manifestations in these patients are not directly related to the coronavirus but to the medications administered.(1) a 49-year-old-woman with morbid obesity, and no other relevant antecedents, was admitted in the intensive care unit, due to severe respiratory failure. chest x-ray showed bilateral lung diffuse opacities predominantly involving the upper and middle fields. sars-cov-2 rt-pcr rendered a positive result. the patient required invasive ventilatory support in the intensive care unit for 24 days. throughout this period, treatment with interferon beta (250 mg/24h), hydroxychloroquine (200 mg/12h); azithromycin (500 mg/24h), ceftriaxone (2 g/12h), lopinavir-ritonavir (800-200/24h); methylprednisolone (40 mg/12h), and tocilizumab (600 mg single dose) was administered. after successful extubation, the patient was transferred to the pneumology ward remaining asymptomatic. all the drugs where interrupted except for methylprednisolone (tapered to 16 mg daily). seven days later, respiratory worsening was observed with cough and crackles on pulmonary auscultation. empiric treatment with cefditoren (400 mg/12h) was started. the following day, the patient suffered an episode of fever (38.4ºc). blood tests revealed neutrophilia [7.75 x10 3 /μl; normal range (nr), 1.9 -7.3 x10 3 /μl; last measurement, 3.11 x10 3 /μl] and c-reactive protein level of 59 mg/l (nr, 0 -5 mg/l). at that time, a skin rash was noticed. upon physical examination, a confluent reddish macular rash was observed, mainly on the trunk, but also involving the neck, face, arms, and axillary and neck folds. small widespread pustules developed over the macules. no mucosal involvement was seen. clinical diagnosis of acute generalized exanthematous pustulosis (agep) was issued. therefore, cefditoren this article is protected by copyright. all rights reserved was interrupted and methylprednisolone was raised (0.3 mg/kg/day of prednisone). skin lesions improved along with the general condition of the patient. histological analysis showed subcorneal pustules with abundant inflammatory infiltrate, papillary edema, and few eosinophils within superficial dermis. subsequent cultures of pustular content were negative. thus, the diagnosis of agep was confirmed. the euro-scar score was 11 points. cefditoren, a cephalosporin-derived beta-lactam, was the probable culprit drug (naranjo score of 7). this article is protected by copyright. all rights reserved causes of skin lesions arising on the background of sars-cov-2 infection. special effort has to be made to identify drugs as the source of these events, as they may lead to scars. finally, further studies should investigate cross-reactions between cephalosporins, and the role of cefditoren as causative agent of scars. this article is protected by copyright. all rights reserved cutaneous manifestations in covid-19: a first perspective acute generalized exanthematous pustulosis (agep)--a clinical reaction pattern recent advances in the understanding of severe cutaneous adverse reactions acute generalized exanthematous pustulosis: a case series of 13 patients in brazil drug reaction with eosinophilia and systemic symptoms during primary epstein-barr virus infection acknowledgments: the patient in this manuscript has given written informed consent to the publication of her case details. this article is protected by copyright. all rights reserved key: cord-295551-ujnks5ox authors: estébanez, andrea; pérez‐santiago, leticia; silva, esmeralda; guillen‐climent, santiago; garcía‐vázquez, alejandro; ramón, m. dolores title: cutaneous manifestations in covid‐19: a new contribution date: 2020-04-15 journal: j eur acad dermatol venereol doi: 10.1111/jdv.16474 sha: doc_id: 295551 cord_uid: ujnks5ox we have read with great interest dr recalcati’s review about skin manifestations in covid‐19 as it is the first report on this subject(1). in a recent review on clinical characteristics of coronavirus disease 2019 in china, rash was observed in 0,2% of cases(2). however, from the trained eyes of a dermatologist, this percentage may be higher. we have read with great interest dr recalcati's review about skin manifestations in covid-19 as it is the first report on this subject 1 . in a recent review on clinical characteristics of coronavirus disease 2019 in china, rash was observed in 0,2% of cases 2 . however, from the trained eyes of a dermatologist, this percentage may be higher. spain is now the fourth most infected nation in the world with 78.797 confirmed covid-19 cases and 6.528 deaths at the moment. as in italy, there is a lack of medical doctors and dermatologists are involved in triage stations and in the medical wards, especially in madrid. cutaneous manifestations, such as erythematous rash, localized or widespread urticaria, seem to be the most common manifestations in acute severe cases, however, it can be difficult to distinguish the underlying cause (viral infection vs new medication prescribed). a skin rash with petechiae has also been described as a possible initial presentation of covid-19 disease 3 , as well as acute hemorrhagic edema of infancy associated with coronavirus nl63 4 . we want to report one case of covid-19 infection that presented with skin manifestations. a 28-year-old woman with no previous medical history, initially presented with dry cough, nasal congestion, fatigue, myalgias and arthralgias without fever. she tested positive for coronavirus. as she was feeling well, self-isolation at home was recommended. four days later she presented with diarrhea, ageusia and anosmia. during the following days she started feeling better but with persistent dry cough, ageusia and anosmia. she only took paracetamol the first 4 days and did not take any other drugs. thirteen days after being tested (10 days after last dose of paracetamol), the patient started noticing pruritic lesions on both heels and sent us some photos. confluent erythematous-yellowish papules were observed in both heels (fig. 1a-b) , without any lesions on the rest of the skin. she denied wearing tight socks, shoes or any local pressure that could explain the distribution of the lesions. a treatment with local corticosteroids was advised. despite this treatment, three days later, the lesions persisted and became erythematous plaques that were both hardened and pruritic (fig. 2a-b) . at this point, urticaria, urticarial vasculitis, idiopathic plantar hidradenitis and neutrophilic dermatosis were considered within the differential diagnosis. however, a biopsy was not performed. this article is protected by copyright. all rights reserved differing from dr recalcati´s report 1 , the lesions we describe do not look like morbilliform rash, urticaria or chickenpox-like vesicles; they respect the trunk and are intensely pruritic. the case we report is a mild covid-19 disease case with no history of drug intake for the last 10 days. the observed skin manifestations could be related with the covid-19 viral infection or with the immune response. we think it is important to report cutaneous manifestations of this new infection that may help us to pay attention, better diagnose and understand the disease. cutaneous manifestations in covid-19: a first perspective clinical characteristics of coronavirus disease 2019 in china covid-19 can present with a rash and be mistaken for dengue acute hemorrhagic edema of infancy after coronavirus infection with recurrent rash. case rep pediatr the patients in this manuscript have given written informed consent to the publication of their case details key: cord-326737-b6gs9z4h authors: balestri, r.; magnano, m.; rizzoli, l.; infusino, s.d.; urbani, f.; rech, g. title: stis and the covid‐19 pandemic: the lockdown does not stop sexual infections date: 2020-07-27 journal: j eur acad dermatol venereol doi: 10.1111/jdv.16808 sha: doc_id: 326737 cord_uid: b6gs9z4h in december 2019 a novel coronavirus (sars-cov-2) emerged in wuhan, china, responsible for an aggressive interstitial pneumonia. italy was the first western country to be hit by the coronavirus disease 2019 (covid-19) and on 9 march our prime minister announced a nationwide lockdown, strictly forbidding any contacts outside cohabitants, except for urgent or medical reasons. in compliance with the ministerial decree, all scheduled visits were suspended, maintaining hospital access only for emergencies. in december 2019, a novel coronavirus (sars-cov-2) emerged in wuhan, china, responsible for an aggressive interstitial pneumonia. 1 italy was the first western country to be hit by the coronavirus disease 2019 (covid-19), and on 9 march, our prime minister announced a nationwide lockdown, strictly forbidding any contacts outside cohabitants, except for urgent or medical reasons. in compliance with the ministerial decree, all scheduled visits were suspended, maintaining hospital access only for emergencies. while the initial guidelines to reorganize medical activities during the pandemic were focused on the management of inflammatory, autoimmune and neoplastic disorders, scarce attention was paid to sexually transmitted infections (stis) and sti clinics. we report here data of our sti clinic, one of the 12 italian clinical sentinel sites for the surveillance of stis, which is located in the provincia autonoma di trento, the italian district most affected by covid-19 (cumulative incidence: 1007.77 cases/100 000 inhabitants). 2 during the lockdown (9 march -4 may), we diagnosed, by naats, 9 chlamydia trachomatis infections and 2 neisseria gonorrhoeae infections (one of these patients experienced a reinfection during the lockdown despite a negative-tested partner), and 4 cases of syphilis (table 1) . concerning the urethritis and cervicitis, symptoms were reported by 10 of 11 patients, while the last patient was asymptomatic but underwent testing because her partner had recently received a diagnosis of c. trachomatis infections. regarding the cases of syphilis, 3 were latent, and 1 was primary. of these 15 stis, 9 patients referred risky sexual behaviour during lockdown. in the same period in 2019, we had diagnosed 17 stis: 6 c. trachomatis infections, 7 n. gonorrhoeae infections, 1 concomitant infection of c. trachomatis and n. gonorrhoeae, and 3 latent syphilis. therefore, the incidence was comparable, despite the unlimited number of daily accesses possible in 2019. common sense suggests that social isolation and the closure of leisure venues may significantly reduce the opportunity for casual sexual encounters, and some authors suggested that quarantine and social distancing measures might reduce the incidence of stis in the future. 3 however, our recent experience strengthened the lesson learned from the aids epidemic: 'not having sex is not an option'. even though resources from health systems are often redirected in response to an outbreak, crucial healthcare services table 1 age, sex, disease, onset of symptoms and history of exposure in the described population during the italian lockdown (9 march-4 may) 4 3 should remain accessible during public health emergencies. 4 therefore, we suggest that visits of sti patients should not be cancelled, making use of teledermatology where possible and visiting any doubtful cases. moreover, patients should not be discouraged to seek sti screening, because risky behaviours do not seem to decrease during the pandemic and, not least, a delay in diagnosis could result in sequelae and complications. finally, our key message is a reiteration, referred to stis, of the who director-general's words during the pandemic: 'we have a simple message for all countries: test, test, test'. 5 all authors have agreed to the contents of the manuscript in its submitted form. clinical features of patients infected with 2019 novel coronavirus in wuhan, china the impacts of isolation measures against sars-cov-2 infection on sexual health not a luxury: a call to maintain sexual and reproductive health in humanitarian and fragile settings during the covid-19 pandemic the authors thank alessandra iadicicco, who made it possible to perform the study. the patients in this manuscript have given written informed consent to publication of their case details. none. key: cord-282653-9n5sjn23 authors: rodríguez‐jiménez, pedro; chicharro, pablo; de argila, diego; muñoz‐hernández, patricia; llamas‐velasco, mar title: reply to “acute urticaria with pyrexia as the first manifestations of a covid‐19 infection”: urticaria‐like lesions in covid‐19 patients are not really urticaria. a case with clinicopathologic correlation date: 2020-05-09 journal: j eur acad dermatol venereol doi: 10.1111/jdv.16618 sha: doc_id: 282653 cord_uid: 9n5sjn23 we have read with great attention the article by van damme et al. considering urticarial lesions as a coronavirus disease 2019 (covid‐19) associated skin manifestation(1). they observed two patients with erythemato‐edematous lesions surrounded by whitish halo, thus similar to hives but without additional data on their evolution(1). a previous report of covid19‐related urticarial lesions had also been first published by recalcati(2). however, none of these two published articles detailed if the lesions where evanescent, as it is mandatory for urticaria, nor did a pathological study. tables: 0 funding sources: none to be declared. disclosure statment: dr. rodriguez-jimenez has nothing to disclose, dr. chicharro has nothing to disclose, dr. de argila has nothing to disclose, dr. muñoz-hernandez has nothing to disclose and dr. llamas-velasco has nothing to disclose, this article is protected by copyright. all rights reserved dear editor, we have read with great attention the article by van damme et al. considering urticarial lesions as a coronavirus disease 2019 (covid-19) associated skin manifestation 1 . they observed two patients with erythemato-edematous lesions surrounded by whitish halo, thus similar to hives but without additional data on their evolution 1 . a previous report of covid19-related urticarial lesions had also been first published by recalcati 2 . however, none of these two published articles detailed if the lesions where evanescent, as it is mandatory for urticaria, nor did a pathological study. madrid, spain, has been considered by the world health organization as an area of sars-cov-2 of community transmission 3 . since then, we began to observe different skin manifestations in patients with covid-19 infection. we present the case of a patient with non-evanescent urticarial lesions and its clinicopathologic correlation. a 60-year-old woman was admitted to the hospital for dry cough and pyrexia in the previous three weeks. in the last 5 days she developed an urticarial eruption (fig. 1) . the patient had no relevant past medical history and had only suffered one episode of pompholyx three years ago. when the cutaneous rash appeared, she was not under any medication. she presented a bilateral interstitial pneumonia on x-ray and blood test revealed a mild lymphopenia (370/mm³) and increased liver enzymes (got, gpt, ldh, ggt three times normal). a cutaneous punch biopsy was performed showing slight vacuolar-type interface dermatitis with occasional necrotic keratinocytes. no eosinophils were encountered. these histological alterations were compatible with an erythema multiforme like pattern (fig.2) . on follow up, the lesions were persistent on the same locations without evolving to blistering. surprisingly, in the work by marzano et al 4 , reporting varicella-like lesions on covid-19 patients, the histological image included in their report resembles our case. this article is protected by copyright. all rights reserved in conclusion, we want to highlight that histopathological studies are important to characterize covid-19 related skin lesions. in our experience, these urticaria-like lesions may also appear in late phases and not only as early manifestations of covid. thus, this type of skin lesions should be further studied to clarify its relation with covid-19 and if it may be useful to identify earlier covid-19 patients. but we must remember, that even today, when it seems that all of our patients are affected of covid-19 and all the skin diseases may be related to it, we have to ground on clinicopathological correlation and to maintain the same quality standards that we used to have before sars-cov-2 appeared. this will be the key to unravel our enemy in this battle. acute urticaria with pyrexia as the first manifestations of a covid-19 infection cutaneous manifestations in covid-19: a first perspective world health organization. novel coronavirus situation reports varicella-like exanthem as a specific covid-19-associated skin manifestation: multicenter case series of 22 patients key: cord-346017-wforwxes authors: kasperkiewicz, m.; schmidt, e.; fairley, j.a.; joly, p.; payne, a.s.; yale, m.l.; zillikens, d.; woodley, d.t. title: expert recommendations for the management of autoimmune bullous diseases during the covid‐19 pandemic date: 2020-04-25 journal: j eur acad dermatol venereol doi: 10.1111/jdv.16525 sha: doc_id: 346017 cord_uid: wforwxes autoimmune bullous diseases (aibds) are potentially life‐threatening disorders comprising intra‐epidermal/epithelial (pemphigus) and sub‐epidermal/epithelial blistering diseases (pemphigoid and dermatitis herpetiformis). corticosteroids and non‐steroid immunomodulatory agents are the mainstays of treatment. treatment can be challenging particularly in pemphigus, mucous membrane pemphigoid, and epidermolysis bullosa acquisita which may require more intense immunosuppressive approaches this article is protected by copyright. all rights reserved dermatitis herpetiformis). corticosteroids and non-steroid immunomodulatory agents are the mainstays of treatment. treatment can be challenging particularly in pemphigus, mucous membrane pemphigoid, and epidermolysis bullosa acquisita which may require more intense immunosuppressive approaches. 1, 2 a novel coronavirus named severe acute respiratory syndrome coronavirus-2 (sars-cov-2) is responsible for the recent worldwide coronavirus disease 2019 (covid-19) pandemic. since immunosuppressive therapy can generally inhibit antiviral immunity, aibd patients undergoing immunomodulatory treatment, especially elderly patients with co-morbidities, may be at higher risk of worse outcomes should they develop covid-19. on the other hand, it has been postulated that immune system over-activation is responsible for the lung injury caused by sars-cov-2 and that a subgroup of patients might actually benefit from immunosuppressive drugs. 3 similar to a recent publication concerning atopic dermatitis, 4 -maintain immunomodulatory therapy when needed since unjustified withdrawal could lead to uncontrolled aibd activity associated with high morbidity and mortality. 1,2 -adhere to the advice from local health authorities in each country. -follow standard precautions including social distancing and hygienic procedures. -patients with confirmed covid-19 should initially undergo risk evaluation. -azathioprine, mycophenolate mofetil/sodium, cyclophosphamide, methotrexate, and cyclosporine may be stopped for the duration of covid-19 symptoms, whereas topical corticosteroids, prednis(ol)one ≤10 mg/d, dapsone/sulfapyridine, doxycycline/tetracycline, colchicine, and ivig can be continued. age, co-morbidities, and severity of covid-19 in collaboration between the dermatologist and physician in charge of covid-19. -abrupt termination or considerable dose reduction of systemic corticosteroids should be avoided, particularly in patients with severe forms of aibds. of note, there is some evidence that prednisolone may potentially have beneficial impacts on covid-19. 3 -patients with aibds on immunosuppressive therapies are generally prone to develop opportunistic infections including viral infections, and microbial pathogens may potentially in turn trigger the bullous disease. of note, both pemphigus and pemphigoid are associated with increased risk of death due to pneumonia and, in the case of paraneoplastic pemphigus, bronchiolitis obliterans. 1,2 however, there is currently little information specifically pertaining to sars-cov-2 and aibds. -dapsone/sulfapyridine, doxycycline/tetracycline, or ivig are usually not considered to increase the risk for infections and may even decrease the risk of some infections, thus may be preferred in the covid-19 pandemic where applicable. -aibd patients treated with rituximab were reported to have no additional risks for infections over high-dose corticosteroids without rituximab in general. 5 however, since long-lived sars-cov-2-specific plasma cells are not expected to be present in most individuals, aibd patients treated with rituximab within the last one year may have a more severe/prolonged covid-19 infection compared to healthy persons. -initiation of rituximab or immunoadsorption/plasmapheresis in aibd patients must be weighed against the risks of conventional immunomodulatory regimens. finally, it is advised to remain updated through the who/cdc homepage (www.who.int, www.cdc.gov). pemphigoid diseases associations between immune-suppressive and stimulating drugs and novel covid-19-a systematic review of current evidence european task force on atopic dermatitis (etfad) statement on severe acute respiratory syndrome coronavirus 2 (sars-cov-2)-infection and atopic dermatitis first-line rituximab combined with short-term prednisone versus prednisone alone for the treatment of pemphigus (ritux 3): a prospective, multicentre, parallel-group, open-label randomised trial accepted article key: cord-342254-vdovpfu1 authors: mugheddu, c.; pizzatti, l.; sanna, s.; atzori, l.; rongioletti, f. title: cid‐19 pulmonary infection in erythrodermic psoriatic patient with oligodendroglioma: safety and compatibility of apremilast with critical intensive care management date: 2020-06-04 journal: j eur acad dermatol venereol doi: 10.1111/jdv.16625 sha: doc_id: 342254 cord_uid: vdovpfu1 novel coronavirus 2019 (sars-cov2) pandemic has particularly affected italy, with a profound impact on the therapeutic strategy for complex disorder such as psoriasis, whose extensive skin damage might expose to an increased infective risk compared to the general population. psoriasis treatment relies on immunosuppression, and although most experts agree that the benefit-to risk-ratio is in favor of maintaining selective biologic therapies, and small molecules such as apremilast, they recommend dismission if severe covid-19 symptoms occur. apremilast 30 mg orally twice a day was started. the patient gradually improved, allowing prednisone tapering to a minimal dose of 12.5 mg daily. on february 19, 2020, he was enough stabilized to travel to milan, northern italy, to be evaluated for brain radiotherapy. on february 26, he developed a severe cough with high fever (tc 40°c) and a chest x-ray revealed bilateral interstitial pneumonia with positive swab to sars cov2. after referral to the infective disease unit, the patient started treatment with lopinavir/ritonavir400/100 mg twice a day and intravenous ceftriaxone 2 g/day. he was discharged on march 3, clinically healed after two consecutive negative sars-cov-2 swabs. apremilast had never been stopped during the covid-19 hospitalization, with acceptable control of the psoriasis, limited to mild scaling and erythema, especially on the trunk (fig. 2) . the fact that patient with a severe form of psoriasis contracted the covid-19 pneumonia, while on treatment with apremilast is worth of some considerations. first of all, the information of apremilast safety, not interfering with the infection, as the drug was not interrupted during the whole course of the infection. our patient had several risk factors for a worst outcome: obesity, recent chemotherapy, persistence of brain oligodendroglioma and viral contagion in a nosocomial setting. by converse, the infection recovered rapidly and the patient was discharged 6 days after the onset of symptoms. apremilast has previously demonstrated a long-term safety profile in the setting of serious infections such as hiv, hbv and hcv. 7, 8 however, therapeutic strategy during severe covid-19 pneumonia are still in the process of definition, and it was quite surprising apremilast was maintained. we cannot rule out that apremilast anti-inflammatory activity might have played a role in the rapid recovery. the selective inhibition of the enzyme phosphodiesterase 4 (pde4) allows higher levels of cyclic amp, which decreases the production of inflammatory cytokines such as tumour necrosis factor-alpha (tnf-a). 7 interestingly, the efficacy of apremilast has been reported in acute lung injury caused by the anticancer proteasome inhibitor carfilzomib, characterized by an exaggerated inflammatory response. 9 another experiment in mouse has documented an inhibitory effect of apremilast on the release of profibrotic cytokine from macrophages, including interleukin-6. 10 during covid19, pneumonia has been documented a 'cytokines storm', with markedly higher levels of il-6, and tnf-a, suggesting the use of interleukin-6 receptor blocker tocilizumab in severe cases. 11 recently, another italian psoriasis patient contracting covid-19 under il-23 inhibitor treatment (guselkumab) has been reported, and completely recovered from the infection. 12 from our experience, apremilast confirms its safety in very critical patients with severe infections, including covid-19. its efficacy in our sub-erythrodermic psoriasis was not completely satisfactory, but other treatments were contraindicated for the recurrent brain oligodendroglioma. further studies are warrant to explore the intriguing immune modulating activities of this very manageable drug. dermatologists and sars-cov-2: the impact of the pandemic on daily practice changes in emergency service access after spread of covid19 across italy global coronavirus pandemic (2019-ncov): implication for an italian medium size dermatological clinic of a ii level hospital psoriasis health care in the time of the coronavirus pandemic: insights from dedicated centers in sardinia (italy) should sars-cov-2 influence immunosuppressive therapy for autoimmune blistering diseases? covid-19 and immunomodulator/ immunosuppressant use in dermatology apremilast (otezla): a new oral treatment for adults with psoriasis and psoriatic arthritis apremilast for a psoriasis patient with hiv and hepatitis c apremilast ameliorates carfilzomib-induced pulmonary inflammation and vascular injuries inhibition of phosphodiesterase 4 (pde4) reduces dermal fibrosis by interfering with the release of interleukin-6 from m2 macrophages the cytokine release syndrome (crs) of severe covid-19 and interleukin-6 receptor (il-6r) antagonist tocilizumab may be the key to reduce the mortality sars-cov-2 infection in a psoriatic patient treated with il-23 inhibitor key: cord-253552-qreg4emx authors: bouaziz, jd; duong, t; jachiet, m; velter, c; lestang, p; cassius, c; arsouze, a; domergue than trong, e; bagot, m; begon, e; sulimovic, l; rybojad, m title: vascular skin symptoms in covid‐19: a french observational study date: 2020-04-27 journal: j eur acad dermatol venereol doi: 10.1111/jdv.16544 sha: doc_id: 253552 cord_uid: qreg4emx coronavirus 19 (covid‐19) was declared as a pandemic viral infection by the world health organization on march 11(th) 2020. usual clinical manifestations of covid‐19 infection include fever, fatigue, myalgia, headache, diarrhea, dry cough, dyspnea that may lead to acute respiratory distress syndrome and death (1). skin symptoms of covid‐19 have been poorly described but may include erythematous rash, urticaria and chicken pox like lesions (2‐7). angiotensin‐converting enzyme 2 (ace2) is a cellular receptor for covid‐19. this article is protected by copyright. all rights reserved coronavirus 19 was declared as a pandemic viral infection by the world health organization on march 11 th 2020. usual clinical manifestations of covid-19 infection include fever, fatigue, myalgia, headache, diarrhea, dry cough, dyspnea that may lead to acute respiratory distress syndrome and death (1). skin symptoms of covid-19 have been poorly described but may include erythematous rash, urticaria and chicken pox like lesions (2-7). angiotensinconverting enzyme 2 (ace2) is a cellular receptor for covid-19. this peculiar mode of entry of covid-19 in human cells induces angiotensin ii accumulation. angiotensin ii excess may contribute to acute lung injury and vessel dysfunction such as vasoconstriction, vascular permeability and abnormal myocardial remodeling (8). vascular skin lesions during covid-19 infection have never been described to date. we performed a retrospective observational nationwide study of skin lesions encountered during covid-19 epidemy in france from march (2-7). vascular lesions were reported in 7 patients: violaceous macules with "porcelain-like" appearance (n=1, figure 1a ), livedo (n= 1, figure 1b ), nonnecrotic purpura (n=1, figure 1 c), necrotic purpura (n=1, figure 1d ), chilblain appearance with raynaud's phenomenon (n=1, figure 1e ), chilblain (n=1, figure 1f ), eruptive cherry angioma (n=1, figure 1g ). forty other patients with chilblain lesions were reported by the sndv but their pcr for covid-19 detection was either negative (n=6) or not performed (n=34). the pathophysiology of these lesions is unclear but may include immune dysregulation, vasculitis, vessel thrombosis or neoangiogenesis. infected covid-19 patients with severe respiratory distress have an increased risk of pulmonary embolism (9) suggesting a hypercoagulable state of these patients. seven patients with acro-ischemia (toe cyanosis, skin bulla and gangrene) and this article is protected by copyright. all rights reserved frequent disseminated intravascular coagulation (4 patients) have been reported during covid-19 epidemy in wuhan (china)(10). a well-described case of antiphospholipid syndrome has been recently published (11). chilblain "like lesions" in our study had clinical similarities with digital changes observed in type 1 interferonopathies such as aicardi-goutières syndrome and stingassociated vasculopathy with onset in infancy that includes skin and pulmonary manifestations.importantly, french dermatologists belonging to the sndv reported numerous chilblain lesions in persons in close contact with covid-19+ patients without covid-19 pcr confirmation and without general symptoms of covid-19 infections which raises 3 hypotheses: these chilblain lesions may: i/ be due to another confounding factor than covid-19, ii/ be due to a post viral immunological reaction in asymptomatic forms of covid-19, iii/ represent a skin presentation of covid-19 infection in a subgroup of patients with peculiar immune anti-viral response. as isolated sudden onset anosmia was recently described as a symptom highly suggesting covid-19 infection (12) , eruptive chilblain lesions during spring and containment may be a new symptom revealing a pauci-symptomatic covid 19 infection. the inclusion of our patients was declarative which did not allow us to analyze the frequency of vascular skin lesions in covid-19 affected patients. nonetheless, clinicians should be aware of these skin symptoms to optimize covid-19 detection and quarantine procedures. prospective study with skin biopsies, serological and pcr analysis of covid-19 suspected patients with vascular skin symptoms are warranted in order to understand the pathophysiology and the prognosis of such vascular skin lesions. clinical features of patients infected with 2019 novel coronavirus in wuhan, china. lancet a distinctive skin rash associated with coronavirus disease cutaneous manifestations in covid-19: a new contribution viral exanthem in covid-19, a clinical enigma with biological significance eur acad dermatol venereol urticarial eruption in covid-19 infection renin-angiotensin-aldosterone system inhibitors in patients with covid-19 findings of acute pulmonary embolism in covid-19 patients e006. 11: zhang y et al. coagulopathy and antiphospholipid antibodies in patients with covid-19 isolated sudden onset anosmia in covid-19 infection. a novel syndrome? key: cord-303514-2ljmkabk authors: recalcati, s.; barbagallo, t.; frasin, l.a.; prestinari, f.; cogliardi, a.; provero, m.c.; dainese, e.; vanzati, a.; fantini, f. title: acral cutaneous lesions in the time of covid‐19 date: 2020-05-27 journal: j eur acad dermatol venereol doi: 10.1111/jdv.16533 sha: doc_id: 303514 cord_uid: 2ljmkabk coronavirus disease 2019 (covid-19) has become a pandemic condition, yet little is known about its dermatologic manifestations. we report here on peculiar (perniosis-like) skin lesions, unreported in the previous years, observed in young outpatients visited in our dermatologic unit in the last 4 weeks of covid-19 pandemic (march-april 2020). similar cases were referred to us in the same period by pediatricians and dermatologists from italy and european countries. dear editor, coronavirus disease 2019 (covid-19) has become a pandemic condition, yet little is known about its dermatologic manifestations. 1, 2 we report here on peculiar (perniosis-like) skin lesions, unreported in the previous years, observed in young outpatients visited in our dermatologic unit in the last 4 weeks of covid-19 pandemic (march-april 2020). similar cases were referred to us in the same period by paediatricians and dermatologists from italy and european countries. we directly observed 14 cases including 11 children (average age 14.4 years, range 13-18) and three young adults (average age 29 years, range 23-39). in this series, three couples were siblings and the ratio female-male was 8 : 6. the cutaneous manifestations consisted of an acral eruption of erythemato-violaceous papules and macules, with possible bullous evolution, or digital swelling (fig. 1a-c) . lesions were localized on the feet in eight cases, on the hands in four cases and on both sites in 2. two children developed erythemato-papular targetoid lesions on the hands and elbows after few days (fig. 1c,d) . no systemic symptoms were reported, except mild itch in three cases. in three cases, cough and fever preceded the onset of the lesions 3 weeks before. lesions resolved after 2-4 weeks without treatment. no association with cold exposure, comorbidities or drug intake was recorded. no familial history of covid-19-related symptoms was elicited. routine laboratory findings were normal, including complete blood count, c-reactive protein, lactic dehydrogenase and ddimer; serology ruled out epstein-barr virus, cytomegalovirus, coxsackie and parvovirus b19 infection. skin biopsies were performed from lesions on the fingers (n = 2) and from targetoid lesions on the elbows (n = 2). histology of the acral lesions showed a diffuse dense lymphoid infiltrate of the superficial and deep dermis, as well as hypodermis, with a prevalent perivascular pattern, and signs of endothelial activation (fig. 2) . histology of the targetoid lesions of the elbows showed a mild superficial perivascular dermatitis. both nasopharyngeal (three patients) and rectal swabs (two patients) for covid-19 yielded negative results. rectal swabs were performed considering that gastrointestinal tract involvement induces a prolonged virus rna shedding in feces. 3, 4 nevertheless, in the hypothesis that these skin lesions were linked to covid-19 infection, we checked accurately for acral perniotic signs 107 covid-19-positive patients (average age 72.2 years, 58 males, 49 females) hospitalized in our hospital for acute respiratory illness. we found only two patients with acrocyanosis due to respiratory failure and one patient with left foot thrombosis. none showed perniotic lesions. we suspect that these cutaneous manifestations could be covid-19 related. the temporal relationship with the covid-19 pandemia, the rapid outbreak and clustering of unusual skin lesions, the occurrence of familial cases in a situation of home restriction and the multiple reporting of similar cases from other affected areas in parallel with pandemic diffusion strongly support this hypothesis. young age, swab negativity and the absence of other symptoms appear to be common features of these subjects. the swab negativity could be explained with the disappearance of detectable viral presence after a brief asymptomatic course: according to this hypothesis, the observed skin lesions would represent late manifestations of the covid-19 infection in young healthy subjects, possibly due to an immunologic response targeting the cutaneous vessels. the absence of similar signs in acute covid-19-positive patients of older age would corroborate this assumption. thus, children could be facilitators of viral transmission in the early stage, before skin involvement. 5 only serology, showing antibody response to covid-19 virus, could validate this hypothesis, and we are waiting for such an answer from reliable serological tests. sars-cov-2 infection among travelers returning from wuhan, china cutaneous manifestations in covid-19: a first perspective a case series of children with 2019 novel coronavirus infection: clinical and epidemiological features covid-19 in the pediatric population covid-19 in children: the link in the transmission chain the patients in this manuscript have given written informed consent to publication of their case details. key: cord-266475-t04pukea authors: balestri, r.; termine, s.; rech, g.; girardelli, c.r. title: late onset of acral necrosis after sars‐cov‐2 infection resolution date: 2020-05-26 journal: j eur acad dermatol venereol doi: 10.1111/jdv.16668 sha: doc_id: 266475 cord_uid: t04pukea sars‐cov‐2 has been hypothesized as the aetiologic agent of cll, on the basis of the temporal correlation between the “burst” of skin manifestations and the viral pandemic, even though we have scarce evidence of swab‐confirmed infections. authors have therefore suggested some pathogenetic mechanisms such as a delayed immune‐mediated reaction to the virus in genetically‐predisposed patients(1) or an early ifn‐i response in young patients, muting early viral replication but also inducing microangiopathic changes. the presence of a worldwide outbreak of chilblain-like lesions (cll) contemporarily to covid-19 pandemic has been largely reported, not only on social media, but also in the literature. [1] [2] [3] [4] sars-cov-2 has been hypothesized as the aetiologic agent of cll, on the basis of the temporal correlation between the "burst" of skin manifestations and the viral pandemic, even though we have scarce evidence of swab-confirmed infections. authors have therefore suggested some pathogenetic mechanisms such as a delayed immunemediated reaction to the virus in genetically-predisposed patients 1 or an early ifn-i response in young patients, muting early viral replication but also inducing microangiopathic changes. 2 the dermatologic community is currently focusing on the pediatric population, 1 having observed acute acral areas of erythema-oedema in asymptomatic or mildly symptomatic young patients 4 and is speculating on clinical implications. on the contrary acral, true ischemic lesions have been described in covid-19 as a consequence of clotting disorders, but only in severely affected patients, hospitalized in intensive care units. [4] [5] [6] we would like to report a case of sars-cov-2-related acro-ischemia, peculiar for several reasons: i) the patient presented real acral ischemia that progressed toward necrosis; ii) she was otherwise completely asymptomatic; iii) she was on regular medication with warfarin for atrial fibrillation. a 74-year-old female was referred to our emergency service because of the presence of livedoid macules that had initially appeared on her hands 6 days before. she reported only pain, while she had no complaint referable to currently known covid-19 symptomatology. her medical history included chronic venous leg ulcers, atrial fibrillation on regular medication with warfarin, and a recent hospitalization due to congestive heart failure one month before. during this hospitalization, in accordance with the directives of the regional health service, she was tested for sars-cov-2 even though she was completely asymptomatic, and resulted positive. she was later discharged and was tested twice at home, resulting negative both times; the last test was 20 days before our evaluation. this article is protected by copyright. all rights reserved on examination we observed blanching of fingers, dusky red macules, digital infarcts and an ischemic necrosis of the left third fingertip (fig.1) . we requested power doppler ultrasound examination and vascular surgery assessment, but the patient opted for discharge against medical advice. we contacted her by phone 6 days later, but she refused any further visits, claiming improvement. the present case, to the best of our knowledge, is the first case of true acral necrosis in an asymptomatic sars-cov-2 infected. this observation raises several questions and considerations. firstly, it would be important to determine the pathogenesis of vascular damage to understand why the patient developed acral necrosis 20 days after her second test had resulted negative (i.e. the patient could be considered healed). our case seems to support the theory of a delayed immune-mediated reaction to the virus. 1 moreover, until now we have been used to observing benign acral lesions that progress toward complete recovery, therefore it is important to determine whether the necrotic outcome is related to any risk factor such as the advanced age of the patient, a genetic predisposition or whether it could be related to her well-established venous impairment, the latter being less likely as we did not observe a worsening of the leg ulcers. we would like to draw clinicians' attention to the possibility that acral lesions may also be observed in the elderly and that these could have a necrotic outcome. finally, we underline that, whilst necrosis is considered a primary lesion of covid-19, 4, 5 it can also present with a late onset, suggesting that a longer period of follow-up is needed also in the healed population to detect late complications. chilblain-like lesions during covid-19 epidemic: a preliminary study on 63 patients covid-19) infection-induced chilblains: a case report with histopathologic findings. jaad case rep characterization of acute acro-ischemic lesions in non-hospitalized patients: a case series of 132 patients during the covid-19 outbreak classification of the cutaneous manifestations of covid-19: a rapid prospective nationwide consensus study in spain with 375 cases coagulopathy and antiphospholipid antibodies in patients with covid-19 the authors have no conflict of interest to disclose all authors have agreed to the contents of the manuscript in its submitted form acknowledgment: "the patient in this manuscript has given written informed consent to publication of her case details." this article is protected by copyright. all rights reserved key: cord-252123-z8c14q5d authors: negrini, s.; guadagno, a.; greco, m.; parodi, a.; burlando, m. title: an unusual case of bullous hemorrhagic vasculitis in a covid‐19 patient date: 2020-06-19 journal: j eur acad dermatol venereol doi: 10.1111/jdv.16760 sha: doc_id: 252123 cord_uid: z8c14q5d a novel coronavirus strain, named “severe acute respiratory syndrome coronavirus 2” (sars‐cov‐2) was recently identified as the etiological agent of the coronavirus disease 2019 (covid‐19). interestingly, a consistent number of covid‐19‐associated skin manifestations seem to share a certain degree of vascular damage as common pathogenetic mechanism(1). vascular injury may be due to the direct damage of endothelial cells by the virus or may represents an epiphenomenon of a dysregulated host inflammatory responses triggered by the infection(2). here, we describe an unprecedented case of leukocytoclastic vasculitis presenting with a hemorrhagic bullous eruption in a patient affected by covid‐19. interestingly, a consistent number of covid-19-associated skin manifestations seem to share a certain degree of vascular damage as common pathogenetic mechanism 1 . vascular injury may be due to the direct damage of endothelial cells by the virus or may represents an epiphenomenon of a dysregulated host inflammatory responses triggered by the infection 2 . here, we describe an unprecedented case of leukocytoclastic vasculitis presenting with a hemorrhagic bullous eruption in a patient affected by covid-19. a 79-year-old man with a history of hypertension, myocardial infarction and chronic obstructive pulmonary disease has been hospitalized for acute heart failure. the patient was tested for covid-19 (rt-pcr on nasopharyngeal swab sample) and resulted negative. medical treatment for heart failure was started and patient's conditions progressively improved. on day 15 of the hospitalization, he rapidly developed fever and dyspnea. chest radiograph and ct scan revealed a radiologic pattern suggestive for covid-19 pneumonia and nasopharyngeal swab rt-pcr confirmed sars-cov-2 infection. treatment with hydroxychloroquine (400 mg bid), prophylactic anticoagulation (enoxaparin 4000 iu qd), empiric antibiotics (ceftaroline 600 mg bid) and intravenous corticosteroids (methylprednisolone 80 mg qd) was started. concomitantly, oxygen therapy was initiated at 8 liters/minute (approximately 40% fio2) via a non-rebreathe mask. after ten days, the patient this article is protected by copyright. all rights reserved developed multiple non-itching vesiculobullous lesions on neck and dorsal areas of hands (fig 1a,b) . laboratory tests including whole blood count, biochemical and coagulation parameters were within normal limits. antinuclear antibody, antineutrophil cytoplasmic antibody and cryoglobulins resulted negative and serum protein electrophoresis as well as complement levels were normal. moreover, the patient tested negative for enzyme-linked immunosorbent assay (elisa) for detecting bp180 and bp230 antibodies. a punch skin biopsy was performed. histopathologic examination demonstrated irregular hyperplasia of the epidermis and abundant erythrocytes extravasation with formation of intraepithelial hemorrhagic bullae. the epidermis was partly necrotic with keratinocytes focally showing nuclear hyperchromasia and cytoplasmic eosinophilia (fig 1c) . within the superficial dermis, there were marked erythrocytes extravasation and severe neutrophilic infiltrate within the wall of small vessels and in their proximity with scant leukocytoclasia (acute vasculitis). endothelial cells were activated showing nuclear enlargement and hyperchromasia (fig 1d) . eosinophils and lymphocytic infiltration were not observed. fibrinoid vascular changes and thrombi were absent as well as no viral cytopathic changes were observed. the histopathologic findings demonstrated a typical picture of leukocytoclastic vasculitis. unfortunately, in the following days patient's respiratory conditions deteriorated and, despite intensive care support, he died of respiratory insufficiency. the case described is an unusual case of bullous hemorrhagic vasculitis in a covid-19 patient. the macroscopic characteristics of the lesions were compatible with a localized bullous pemphigoid (bp) or a heparin induced bullous hemorrhagic dermatosis (bhd) 3, 4 . in our patient, absence of eosinophilic infiltrate as well as negativity of elisa for bp180/bp230 autoantibodies reasonably rule out the hypothesis of localized bp. the second diagnostic diagnosis was bhd. nevertheless, focally necrotic epidermis and vasculitis observed in our case, have never been reported in bhd and thus we excluded this diagnosis. histopathologic features observed in our patient are characteristic of an evolving leukocytoclastic vasculitis (lcv) 5 . interestingly, capillary injury and/or neutrophilic infiltrates have been described in lung tissues from covid-19 and, in one recent report, also in the skin 6, 7 . nonetheless, we can expect that the number of reports concerning covid-19-related vasculitis is likely to increase since inflammatory vascular damage is emerging as one of the main pathogenic mechanisms of sars-cov-2 infection, including its cutaneous manifestations. however, only further studies, novel reports including clinical images and detailed histology as well as data from international dermatology registries will be able to confirm this hypothesis. vascular skin symptoms in covid-19: a french observational study complement associated microvascular injury and thrombosis in the pathogenesis of severe covid-19 infection: a report of five cases atypical presentations of bullous pemphigoid: clinical and immunopathological aspects bullous hemorrhagic dermatosis is an under-recognized side effect of full dose low-molecular weight heparin: a case report and review of the literature leukocytoclastic vasculitis (hypersensitivity vasculitis) endothelial cell infection and endotheliitis in covid-19 key: cord-339195-aq3hb68r authors: falkenhain‐lópez, d.; agud‐dios, m.; ortiz‐romero, p.l.; sánchez‐velázquez, a. title: covid‐19‐related acute genital ulcers date: 2020-06-26 journal: j eur acad dermatol venereol doi: 10.1111/jdv.16740 sha: doc_id: 339195 cord_uid: aq3hb68r a wide variety of cutaneous manifestations has recently been reported as covid-19-related skin lesions, such as erythematous rash, acro-ischemia or chilblain-like lesions 1, 2 , which can be useful for the clinical diagnosis of covid-19. case reports of other less frequent covid-19-related skin disorders such as pytiriasis rosea 3 or livedo reticularis 4 have been also described. in order to report a new clinical manifestation of sars-coronavirus-2, we present a case of acute reactive genital ulcers in a covid-19 patient. dear editor, a wide variety of cutaneous manifestations has recently been reported as covid-19-related skin lesions, such as erythematous rash, acro-ischaemia or chilblain-like lesions, 1,2 which can be useful for the clinical diagnosis of covid-19. case reports of other less frequent covid-19-related skin disorders such as pityriasis rosea 3 or livedo reticularis 4 have been also described. in order to report a new clinical manifestation of sars coronavirus 2, we present a case of acute reactive genital ulcers in a covid-19 patient. a 41-year-old otherwise healthy woman arrived at the emergency department with a 5-day history of painful genital ulcers. she presented also dry cough and rhinorrhoea for the last 10 days. review of systems was negative except as noted above. the patient did not take any medication before the development of the lesions and denied any recent sexual risk behaviour. she had never presented genital ulcers before. there was no personal or familiar history of inflammatory bowel and/or autoimmune diseases. physical examination revealed two necrotic ulcers with raised, sharply demarcated borders in the inferior medial aspect of the right minor labia, with no evidence of 'kissing' lesions. a single oral aphtha was also observed ( fig. 1 ). there was no cutaneous involvement. ulcer exudate bacterial culture and herpes simplex virus pcr were negative. blood test showed no abnormalities in blood cell count, coagulation and biochemical parameters. serologic testing for hiv, epstein-barr virus, cytomegalovirus and syphilis was negative. ana and complement c3 and c4 levels were normal. the patient tested also negative for hla-b51. treatment with prednisone 30 mg daily was initiated. one week later, the patient returned to our department referring improvement of the genital ulcers with pain reduction and complete resolution of the oral aphtha. physical examination showed less severe erythema and disappearance of the necrotic eschar with a central fibrinous area (fig. 2) . however, she presented worsening of the cough and a 3-day history of chest pain, lowgrade dyspnoea and dysthermia. chest radiography was performed with no evidence of pneumonia. sars coronavirus 2 pcr was tested on nasopharyngeal swab with positive result, and a covid-19 diagnosis with reactive acute genial ulcers (agu) was made. 5 genital ulcers evolved to resolution after one more week of corticosteroid treatment. chest pain and dysthermia resolved with acetaminophen; cough and dyspnoea also showed improvement. no antibiotic or antiviral agents were required. acute genital vulvar ulcerations are non-sexually acquired lesions characterized by sudden onset of a few genital ulcers, presented typically in girls and young women. the terms agu or lipsch€ utz ulceration are used to describe ulcers associated with an immunologic reaction to a distant source of infection or inflammation. 6 the most common triggering factors are infectious diseases, specially flu-like and mononucleosis syndrome infections. 5, 7 in many cases, the patients present also other symptoms, mainly oral aphthae, malaise, lymphadenopathy or fever, 8 and concomitant cutaneous manifestations such as erythema nodosum can also be observed. 6 therapies for agu include anti-inflammatory drugs, topical anaesthetics and corticosteroids. when a triggering infection is documented, antimicrobial agents are also useful for the management of the ulcerations. the lesions commonly resolve within 3 weeks. some virus species have been well defined as triggering agents of lipsch€ utz ulcers, specially epstein-barr virus. although sars figure 1 oral aphtha on the upper lip mucosa. coronavirus 2 has been associated with oral ulcers, 9 we did not find previous reports of coronavirus-related agu in the english literature. we report this case in order to describe a potential reactive dermatologic manifestation of the covid-19. moreover, we propose that lipsch€ utz ulcers could be triggered by sars coronavirus 2, comparably to other respiratory virus infections. classification of the cutaneous manifestations of covid-19: a rapid prospective nationwide consensus study in spain with 375 cases cutaneous manifestations in covid-19: a first perspective pityriasis rosea as a cutaneous manifestation of covid-19 infection a dermatologic manifestation of covid-19: transient livedo reticularis ulcus vulvae acutum lipsch€ utz: a systematic literature review and a diagnostic and therapeutic algorithm lipschutz ulcers: evaluation and management of acute genital ulcers in women lipsch€ utz's acute vulvar ulcer: a systematic review non-sexually related acute genital ulcers in 13 pubertal girls: a clinical and microbiological study oral vesiculobullous lesions associated with sars-cov-2 infection the patients in this manuscript have given written informed consent to the publication of their case details. key: cord-283716-tleh9323 authors: amatore, f.; macagno, n.; mailhe, m.; demarez, b.; gaudy‐marqueste, c.; grob, j.j.; raoult, d.; brouqui, p.; richard, m.a. title: sars‐cov‐2 infection presenting as a febrile rash date: 2020-05-27 journal: j eur acad dermatol venereol doi: 10.1111/jdv.16528 sha: doc_id: 283716 cord_uid: tleh9323 the world health organization (who) has declared that coronavirus disease 2019 (covid-19) is a public health emergency of international concern as it continues to spread worldwide.1 after a median incubation period of 4 days, fever and cough are the two most common manifestations of severe acute respiratory syndrome coronavirus 2 (sars-cov-2) infection. the world health organization (who) has declared that coronavirus disease 2019 (covid-19) is a public health emergency of international concern as it continues to spread worldwide. 1 after a median incubation period of 4 days, fever and cough are the two most common manifestations of severe acute respiratory syndrome coronavirus 2 (sars-cov-2) infection. 2 physicians worldwide are facing this new disease for which little is known about the full spectrum of its clinical features. for instance, some patients with covid-19 associated cutaneous manifestation have been reported, but there is a lack of iconographic and histological documentation. [3] [4] [5] [6] [7] [8] [9] herein, we describe a febrile rash as the only clinical manifestation of sars-cov-2 infection in a patient free from pulmonary symptoms. on march the 7th this year, a 39-year-old caucasian male with no relevant medical history presented to the emergency department with a fever of 39°c, along with a concomitant skin rash that had appeared the same day. this rash was characterized by erythematous and oedematous non-pruritic annular fixed plaques involving the upper limbs, chest, neck, abdomen and palms, sparing the face and mucous membranes ( fig. 1a-e) . importantly, the patient declared having taken no medication in the days and weeks before the onset of symptoms. his vitals were normal, and he had no signs of upper respiratory tract or pulmonary infection. the patient promptly reported to the physician that he had been in contact 5 days earlier with a family member, who was afterwards tested positive for sars-cov-2. quantitative reverse-transcriptase-polymerase-chain-reaction (qrt-pcr) assay performed on both nasopharyngeal swab and sputum sample revealed the presence of sars-cov-2 rna. the search for other respiratory viruses, such as influenza a and b viruses, rhinovirus, and common coronaviruses was negative, as was the blood culture. blood count, electrolytes, c-reactive protein and anti-dna antibodies were normal too. the histological examination of the skin showed non-specific changes, compatible with viral exanthemata: predominantly superficial perivascular infiltrate of lymphocytes without eosinophils, papillary dermal oedema, subtle epidermal spongiosis, mild lymphocyte exocytosis, lichenoid and vacuolar interface dermatitis with occasional dyskeratotic keratinocytes in the basal layer (fig. 1f) . no virally-induced cytopathic alterations or intranuclear inclusions were present. direct immunofluorescence was negative. despite normal chest radiograph on admission, a chest ct scan showed bilateral and peripheral ground-glass and consolidative pulmonary opacities, highly suggestive of sars-cov-2 infection. 10 on march the 8th, the patient started oral hydroxychloroquine sulfate 200 mg three times per day for 10 days with a daily monitoring of sars-cov-2 qrt-pcr on nasopharyngeal swab. no pulmonary symptoms developed. on march the 14th, the rash fully recovered and laboratory tests for sars-cov-2 qrt-pcr became negative on march the 20th. our case report provides two important facts that need highlighting. firstly, covid-19 disease can present with a distinctive rash, which is histologically similar but clinically different to classic viral exanthemata. indeed, the annular, polycyclic and circinate appearance of the skin lesions differed from classic paraviral rashes in adults, as did the papules on the palms. in addition, unlike viral infection-associated urticaria, the plaques were both fixed and non-pruritic. secondly, a febrile rash may be the only clinical manifestation of covid-19. as the outbreak spreads around the world, including in medically underdeveloped countries, choices will have to be made regarding which patients need to be tested or not for sars-cov-2. we suggest that patients presenting with a febrile rash during the current pandemic should be tested. histological findings were unspecific but consistent with viral exanthemata: superficial perivascular lymphocytic infiltrate, papillary dermal edema, mild spongiosis, lichenoid and vacuolar interface dermatitis, dyskeratotic basilar eratinocytes, occasional neutrophils but no eosinophils within the dermal infiltrate. clinical features of patients infected with 2019 novel coronavirus in wuhan, china cutaneous manifestations in covid-19: a first perspective covid-19 can present with a rash and be mistaken for dengue a distinctive skin rash associated with coronavirus disease cutaneous manifestations in covid-19: a new contribution viral exanthem in covid-19, a clinical enigma with biological significance urticarial eruption in covid-19 infection covid-19 and cutaneous manifestations correlation of chest ct and rt-pcr testing in coronavirus disease 2019 (covid-19) in china: a report of 1014 cases the patient in this manuscript has given written informed consent to the publication of his case details. key: cord-323334-ie7iklr4 authors: tartari, f; guglielmo, a; fuligni, f; pileri, a title: changes in emergency service access after spread of covid19 across italy date: 2020-04-27 journal: j eur acad dermatol venereol doi: 10.1111/jdv.16553 sha: doc_id: 323334 cord_uid: ie7iklr4 the italian national health system is currently living through some catastrophic days, owing to the rapid spread of covid‐19 across the country. at the time of writing, our government has passed emergency laws (march 11, 2020), with a view to preventing widespread viral infection among the population, which may well lead to an increase in the number of people requiring intensive care unit (icu) hospital treatment. currently, most of the northern italian regions are close to saturation point in terms of the number of available icu inpatient beds. this article is protected by copyright. all rights reserved the italian national health system is currently living through some catastrophic days, owing to the rapid spread of covid-19 across the country. at the time of writing, our government has passed emergency laws (march 11, 2020) , with a view to preventing widespread viral infection among the population, which may well lead to an increase in the number of people requiring intensive care unit (icu) hospital treatment. currently, most of the northern italian regions are close to saturation point in terms of the number of available icu inpatient beds. albeit dermatologic "true" emergencies are a small number, many patients access our emergency services (es) for routine diseases in order to avoid having to wait any length of time for a scheduled dermatological examination. the aim of our study is to analyse any possible changes in access to our es by examining two different weeks before and after covid-19 emergency in italy. the first week in the pre-covid-19 era was randomly selected, while the second was chosen during the actual covid-19 emergency. we analysed a six-day workload because our unit does not operate an es on sundays. diseases such as burns, drug eruption, acute urticaria-angioedema, skin rash (including psoriasis and bullous autoimmune dermatitis) involving more than 10% of the body surface area, along with acute infection (bacterial or viral) were identified as real emergencies. the remaining pathologies were considered to be unjustified consultations. the week between october 21 and 26, 2019 was identified as the pre-covid-19 (no closure of the outpatients' surgeries available in our unit for holidays or meetings). the days between march 12 and 18, 2020 characterised the weekly activity of our emergency service during the covid-19 era (days in the run-up to the government decree law). in the pre-covid-19 era, 106 patients accessed our emergency outpatients' room, whereas just 20 cases were examined after the emergency decree law. the number of unjustified accesses was 60 in pre-covid era, 46 patients showed "true" emergencies. acute bacterial/viral infections on a par with diffuse skin rashes (19 cases each) were the most common problems, while 8 patients accessed the es for burns. after march 11, 2020, 19 patients referred to the es. five patients turned up for an unjustified consultation, while 14 showed a "true" problem (4 diffuse rashes, 7 acute infections and 3 burns). see table 1 for all the patient details. this article is protected by copyright. all rights reserved the misuse of the emergency consultation facility is a bad habit and it has been estimated that at least half of the patients do not have a "true" emergency (range 49-82%) 1-6 , which is confirmed by our study (60 vs 5 unjustified accesses, before/after the covid19 pandemic). however, emergencies still exist, even in the presence of a potentially life-threatening virus. patients suffering from acute myocardial infarction will refer to the es even in the covid19 era and the same will occur in the case of dermatological emergencies. drago et al 7 appropriately defined a "true emergency" in dermatology as a severe dermatosis that requires immediate medical attention and an observation period lasting at least 24 hours. a possible bias in our research may be due to the panic related to the covid19 disease, which can explain the drop in the number of consultations (106 vs 19, for an 81% reduction). our data clearly show a decrease in unjustified referrals (60 vs 4, for a 93% reduction, p-value for fisher exact test 0.0032) highlighting the misuse of the es at our unit. to conclude, a solution for select patient access to es could be to: 1) implement the number of scheduled examinations by recruiting more dermatologists; 2) have more outpatients accessing during the daytime, especially in afternoon (an infrequent event in italy); 3) train general practitioners to recognize and diagnose the most commonly occurring dermatosis. dermatologic emergencies: descriptive analysis of 861 patients in a tertiary care teaching hospital cutaneous conditions leading to dermatology consultations in the emergency department primary care and pattern of skin diseases in a mediterranean island evaluation of emergency dermatological consultations in a tertiary care centre in north india global coronavirus pandemic (2019-ncov): implication for an italian medium size dermatological clinic of a ii level hospital medical education and care in dermatology during the sars-cov2 pandemia: challenges and chances dermatological consultations in an observation unit of an emergency department in italy this article is protected by copyright. all rights reserved this article is protected by copyright. all rights reserved accepted article key: cord-309507-oe4i6v5x authors: sacchelli, l.; viviani, f.; orioni, g.; rucci, p.; rosa, s.; lanzoni, a.; patrizi, a.; gaspari, v. title: sexually transmitted infections during the covid‐19 outbreak: comparison of patients referring to the service of sexually transmitted diseases during the sanitary emergency with those referring during the common practice date: 2020-06-03 journal: j eur acad dermatol venereol doi: 10.1111/jdv.16694 sha: doc_id: 309507 cord_uid: oe4i6v5x sexually transmitted infections (stis) and diseases (stds) affect millions of people every year worldwide(1). in italy, data are provided by the italian national institute of health (inih) and reported to the european centre for disease prevention and control (ecdc)(2,3). in 1991 and 2009 the italian sentinel surveillance system was established, consisting in 25 public centers (12 clinical, 13 laboratories) on the national field for diagnosis, treatment and data transmission to the inih(4). the stds service of dermatology, bologna belongs to it and is a free‐access service (7.30‐11 am) from monday to friday, with a patient flow of 50 patients/day. this article is protected by copyright. all rights reserved to the editor, sexually transmitted infections (stis) and diseases (stds) affect millions of people every year worldwide 1 . in italy, data are provided by the italian national institute of health (inih) and reported to the european centre for disease prevention and control (ecdc) 2, 3 . in 1991 and 2009 the italian sentinel surveillance system was established, consisting in 25 public centers (12 clinical, 13 laboratories) on the national field for diagnosis, treatment and data transmission to the inih 4 . the stds service of dermatology, bologna belongs to it and is a free-access service (7.30-11 am) from monday to friday, with a patient flow of 50 patients/day. as consequence of the covid-19 emergency, the ministerial decree limited the circulation in italy from 9 march 2020 to 3 april 2020 5 . thus, after the lockdown, the number of accesses was reduced to a maximum of 30 accesses/day. we conducted a prospective observational study collecting age, sex, type of sexual relationship and diagnostic question for each patient referring to the service. then, we compared data with those of the 4 weeks before the lockdown (20 february to 6 march 2020). we used the χ² test for categorical variables (gender, diagnostic question and sexual orientation) and the t-test for continuous variables (age). after the lockdown, 200 patients attended the service, with an average flow of 10 patients/day. patients' age ranged from 18 to 77 years. concerning sexual orientation, 122 (61%) were heterosexual, 75 (37.5%) homosexual and 3 (1.5%) bisexual. compared with the patients before the lockdown, they were more likely to be male (75.5% vs. 64.6, χ²=14.8, p<0.001), msm (37.5% vs. 28.8%, χ²=22.6, p<0.001) and significantly older (35.4 vs. 33.1 years, t-test=2.47, p=0.018) ( table 1) . before and after the lockdown patients from 15 to 49 years accounted for 88.6% and 85% but, among them, those from 15 to 24 years declined from 27.3% to 15.5% (χ²=12.3, p<0.001) and, after the lockdown, the youngest patient was 18-year-old, while before he/she was 15-year-old. a total of 214 medical provisions were recorded after the lockdown: 13 patients required more than one healthcare service. the most common were prophylaxis (n=28) and medical reports withdrawal (n=52), accounting for 37.4%. furthermore, consultations were for genital warts this article is protected by copyright. all rights reserved contagiosum (n=3, 1.4%), candida vulvo-vaginitis (n=2, 0.9%) ( table 1 ). the remaining 33 medical provisions (15.4%) not included in the former categories, and defined as other, encompass stis-related and non-stis-related issues, as therapeutic counseling and pathologies involving genital area (inflammatory diseases, or diagnostic workup). before the lockdown, a total of 1081 medical provisions were delivered. the percentage of visits for prophylaxis declined after the lockdown, while visits for syphilis, gonococcal pharyngitis and inflammatory genital diseases increased significantly (figure 1) . the percentage of patients requiring more than one provision increased from 2.1% to 6.5%, after the lockdown. patients characteristics and medical provisions before and after the lockdown were consistent with the literature 3,6,7 . however, the percentage of msm recorded remained higher than the national trends, (28.8% vs less than 20%) 2, 4 . moreover, the profile of patients and the type of medical provisions required changed. whether this is due to a real decline of sex-related risk or if it is only a consequence of the fear of referring to hospitals, is unknown. some italian cardiologists, indeed, showed that during the lockdown the diagnostic delay of myocardial infarctions and cardiovascular emergencies increased, leading to higher mortality/morbidity, especially when a timely intervention would have led to better outcomes 8 . this is an open scenario and further information is required. sexually transmitted diseases treatment guidelines rete sentinella dei centri clinici, laboratori di microbiologia clinica per le infezioni sessualmente trasmesse european centre for disease prevention and control. long-term surveillance strategy european centre for disease prevention and control. long-term surveillance strategy world health organization. global prevalence and incidence of selected curable sexually transmitted infections: overview and estimates global estimates of the prevalence and incidence of four curable sexually transmitted infections in 2012 based on systematic review and global reporting being a cardiologist at the time of sars-covid-19: is it time to reconsider our way of working? this article is protected by copyright. all rights reserved key: cord-344273-uztk6pc0 authors: tejera‐vaquerizo, antonio; nagore, eduardo title: estimated effect of covid‐19 lockdown on melanoma thickness and prognosis: a rate of growth model date: 2020-05-02 journal: j eur acad dermatol venereol doi: 10.1111/jdv.16555 sha: doc_id: 344273 cord_uid: uztk6pc0 the coronavirus covid‐19 pandemic, which emerged in wuhan, china several months ago,(1) has led to large‐scale lockdown in many countries around the world, including spain. uncertainty about the duration of these measures led us to consider the potential impact of diagnostic delays due to the paralyzation of certain health procedures and services on the prognosis of patients with melanoma. to de editor, the coronavirus covid-19 pandemic, which emerged in wuhan, china several months ago, 1 has led to large-scale lockdown in many countries around the world, including spain. uncertainty about the duration of these measures led us to consider the potential impact of diagnostic delays due to the paralyzation of certain health procedures and services on the prognosis of patients with melanoma. to estimate this impact, we built a model based on melanoma rate of growth (rog). 2 rog is the rate of increase in breslow thickness, as a surrogate measure for tumor volume, from the time a patient first notices a lesion or observes changes in an existing lesion, to excision of the tumor. it is measured as millimeters per month (fig. 1) . although rog in our model was based on subjective information provided by the patient, it has been found to match rog values calculated using biopsy specimens taken from the same lesions at different moments of time. 3 melanoma rog has been associated with prognosis 4,5 and a higher probability of lymph node involvement. 6 we randomly selected 1000 melanomas with a known rog from the database of instituto valenciano de oncología in valencia, spain. the tumors were classified according to thickness (t1, t2, t3, or t4) based on the melanoma staging criteria of the american joint committee on cancer (ajcc). 7 for each case, we used rog to estimate tumor thickness after a diagnostic delay of 1, 2, and 3 months. we calculated, for example, that a melanoma with a breslow thickness of 2 mm at diagnosis and a rog of 0.5 mm a month would measure 2.5 mm after 1 month, 3 mm after 2 months, and 3.5 mm after 3 months. using ajcc survival data for the different t stages, 7 we then calculated 5-and 10-year survival rates for the patients divided into diagnostic groups (initial sample and the same group at the three time points analyzed). over half of the melanomas in the initial sample (n=403; 40.3%) were t1. of the remaining tumors, 24.2% were t2, 19.2% were t3, and 16.3% were t4. for patients in the 1-month diagnostic delay group, the model predicted an upstaging rate of 21% (i.e., progression to the next tumor stage in 21% of cases). the proportion of tumors that would be upstaged in the other two groups was 29% in the 2-month-delay group and 45% in the 3-month-delay group ( estimated 5-year survival for the group as a whole was 94.2% in the initial sample and 92.3% in the group of patients whose diagnosis was delayed by 3 months. the respective 10-year survival rates were 90% and 87.6%. one limitation of our study is that the random sample included 1000 cases, although the distribution of tumor thickness measurements was very similar to that in the spanish national melanoma registry. 8 we did not estimate clinical progression rates, as it was impossible to estimate the proportion of nonulcerated tumors that would become ulcerated in the time periods considered. the actual differences in survival rates could thus be even greater. our rog model shows that in the absence of adequate care for cancer patients in the current lockdown situation in spain, our healthcare system could see a considerable rise in melanoma upstaging cases, and, of course, healthcare costs. 9 approximately 300 patients are diagnosed of cutaneous melanoma every month in spain, 10 and if we extrapolate this figure to countries with similar lockdown measures, many of which have a higher incidence of melanoma, it would not be unrealistic to predict a situation with potentially serious consequences. in conclusion, considering the current situation, efforts should be made to promote self-accepted article examination and facilitate controlled access to dermatologists (through teledermatology, for example), as this will prevent delays resulting in worse prognosis. this article is protected by copyright. all rights reserved the novel coronavirus originating in wuhan, china: challenges for global health governance the kinetics of the visible growth of a primary melanoma reflects the tumor aggressiveness and is an independent prognostic marker: a prospective study an objective measure of growth rate using partial biopsy specimens of melanomas that were initially misdiagnosed growth rate as a prognostic factor in localized invasive cutaneous melanoma growth rate as an independent prognostic factor in localized invasive cutaneous melanoma. j eur acad dermatology venereol melanoma staging: evidence-based changes in the american joint committee on cancer eighth edition cancer staging manual registro nacional de melanoma cutaneo. caracteristicas del tumor en el momento del diagnostico: 15 anos de experiencia estudio descriptivo de costes en melanoma cut??neo de diferentes estadios key: cord-301483-dsaltzdd authors: hashizume, h.; sano, y.; furukawa, s.; imokawa, s. title: eosinophilic granulomatosis with polyangiitis mimicking covid‐19: a case report date: 2020-06-04 journal: j eur acad dermatol venereol doi: 10.1111/jdv.16705 sha: doc_id: 301483 cord_uid: dsaltzdd coronavirus disease 2019 (covid‐19), caused by severe acute respiratory syndrome coronavirus 2 (sars‐cov‐2) infection, is currently spreading worldwide, causing the worst pandemic experienced this century. during the present outbreak, reports have been accumulating that various types of cutaneous manifestations were observed in covid‐19 patients. we read with interest the recent article by amatore et al. describing a covid‐19 case who presented with a febrile rash consisting of annular, polycyclic, and circinate erythema, presumably specific to covid‐19. coronavirus disease 2019 (covid-19), caused by severe acute respiratory syndrome coronavirus 2 (sars-cov-2) infection, is currently spreading worldwide, causing the worst pandemic experienced this century [1] . during the present outbreak, reports have been accumulating that various types of cutaneous manifestations were observed in covid-19 patients [2] [3] [4] [5] [6] [7] . we read with interest the recent article by amatore et al. describing a covid-19 case who presented with a febrile rash consisting of annular, polycyclic, and circinate erythema, presumably specific to covid-19 [3] . recently, we experienced a case of polycyclic erythema, which was very similar to theirs, in a patient with respiratory distress whose eosinophilic granulomatosis with polyangiitis (eagp) was later confirmed by skin biopsy. a 30-year-old chinese male had a high fever (>38 °c) with respiratory distress on a flight to japan, where he worked, and was referred to us. laboratory examination revealed elevated white (9.2-10.5×10 4 cells/µl, normal range 3.3-8.6×10 4 cells/µl) and red (615-692×10 4 cells/µl, normal range 435-555×10 4 cells/µl) blood cell counts, eosinophilia (15%-28%, normal range <5%), a decreased platelet count (2-7×10 4 cells/µl, normal range 15-42×10 4 cells/µl), and high levels of d-dimers (10-22 µg/ml, normal range <0.1 µg/ml), fibrin-fibrinogen degradation products (6.3-35.3 µg/ml, normal range <5.0 µg/ml), and c-reactive protein (3.05-4.59 µg/dl, normal range <0.14 µg/dl). his high red blood cell count had been clinically observed previously, without treatment. neither anti-neutrophil cytoplasmic antibody nor anti-nuclear antibody was detected. the chest this article is protected by copyright. all rights reserved computed tomogram revealed bilateral interstitial shadows (fig. 1) , like those frequently seen in covid-19 cases, so a pulmonologist segregated him on suspicion of covid-19. during treatment with 6 g/day of intravenous ceftriaxone, erythema suddenly developed. multiple circinate and annular erythema with slight pruritus were observed on his body, arms (fig. 2a) , palms (fig. 2b) , and legs (fig. 2c) . ecchymosis after bruising was found in his right leg (fig. 2c) . a skin biopsy specimen taken from the skin lesion on his right thigh revealed mild perivascular infiltrates with lymphocytes and eosinophils. some vessels had markedly infiltrated eosinophils with erythrocyte extravasation (fig. 2d and inset) . afterwards, rt-pcr tests on the patient's sputum and nasopharyngeal swabs were negative for sars-cov-2 rna detection. based on these laboratory and histological findings, we diagnosed the patient with egpa. steroid pulse therapy for three successive days promptly relieved all his symptoms, in parallel with the normalization of his chest radiogram and laboratory data. his treatment was then changed to oral administration of 50 mg/day prednisolone for 2 weeks, after which the prednisolone dose was gradually tapered to 25 mg/day. although the eruption reappeared transiently, it was successfully treated with olopatadine hydrochloride. no relapse occurred. various clinical signs, laboratory parameters, and imaging modalities are suggestive of covid-19. additionally, recent reports have implicated distinctive skin manifestations, such chilblain-like erythema, livedoid eruptions [2, 8] , morbilliform rash [9] , urticarial rash [4] , and varicella-like rash [6] , in covid-19. here, we found bilateral interstitial pneumonia accompanied with a hypercoagulation state, which is a typical pulmonary this article is protected by copyright. all rights reserved manifestation of covid-19. in addition, we also observed polycyclic erythema, manifesting very similarly to the covid-19 case described by amatore et al. [3] . these findings might have supported a diagnosis of covid-19. however, because eosinophilia and eosinophilic infiltrates in skin lesions are an exceptional feature of covid-19 [10] , egpa was the more appropriate diagnosis for our case. the patient's complete response to steroid therapy, which usually causes deterioration in covid-19 cases, supports our diagnosis. it is important to be aware of the similar clinical manifestations between egpa and covid-19. infection among travelers returning from wuhan, china a case of covid-19 presenting in clinical picture resembling chilblains disease. first report from the middle east sars-cov-2 infection presenting as a febrile rash accepted article this article is protected by copyright. all rights reserved urticarial eruption in covid-19 infection complement associated microvascular injury and thrombosis in the pathogenesis of severe covid-19 infection: a report of five cases varicella-like exanthem as a specific covid-19-associated skin manifestation: multicenter case series of 22 patients cutaneous manifestations in covid-19: the experiences of barcelona and rome characterization of acute acro-ischemic lesions in non-hospitalized patients: a case series of 132 patients during the covid-19 outbreak viral exanthem in covid-19, a clinical enigma with biological significance eosinophil responses during covid-19 infections and coronavirus vaccination this patient in this manuscript has given written informed consent to the publication of his case details. key: cord-270500-5pkx94zu authors: duong, t.a.; velter, c.; rybojad, m.; comte, c.; bagot, m.; sulimovic, l.; bouaziz, j.d. title: did whatsapp(®) reveal a new cutaneous covid‐19 manifestation? date: 2020-05-19 journal: j eur acad dermatol venereol doi: 10.1111/jdv.16534 sha: doc_id: 270500 cord_uid: 5pkx94zu in march 2020, europe became the epicenter of covid-19 pandemic. several countries organized nationwide population containment, starting on march 9th in italy and march 17th in france1 . for the continuity of care and to avoid in person consultation and disease propagation, the french ministry of health released incentives to facilitate live interactive consultation for covid and non-covid patients. in march 2020, europe became the epicentre of covid-19 pandemic. several countries organized nationwide population containment, starting on march 9th in italy and march 17th in france. 1 for the continuity of care and to avoid in person consultation and disease propagation, the french ministry of health released incentives to facilitate live interactive consultation for covid and non-covid patients. 1 the french union of dermatologists created a text messaging group on whatsapp â to share administrative information about teledermatology, as well as scientific reviews about the pandemic. in the dermatology field, publications related to covid-19 mostly focused on skin damages of healthcare workers, unspecific viral skin manifestation, and strategies to avoid virus transmission in dermatologists' practices, favouring teledermatology implementation. [2] [3] [4] [5] on the whatsapp â group, which included four hundred dermatologists, atypical skin eruptions or lesions of suspected or confirmed covid-19 patients were posted. while some dermatologists were academics, most had private practices. we performed an analysis of all 295 cases submitted in this group from its creation date on march 14th till april 10th 2020. the first post was an atypical eruption of vesicles in a suspected covid-19 patient (fig. 1) . then, after the first atypical hands eruption reported on march 23rd, an outbreak of chilblain-like lesion was reported during the third week of containment in pauci-symptomatic covid-19 patients (fig. 1 ). on this whatsapp â group, 74% (n = 219) of cases were shared for the first time by the members, 4% (n = 11) were re-posted from a dermatologist facebook â network, and 22% (n = 65) from the group administrator network. chilblains or chilblain-like lesions represented 146 posts, and 149 posts included other suspected covid19-related skin eruption, for example, urticaria, rash, chickenpox-like or pytiriasis rosea. a signal was also detected in other european physicians' networks, and 36 patients submitted their testimonials through the sndv website (fig. 2) . the number of observed chilblain or chilblain-like lesions during this pandemic is very unusual, especially in spring time and in patients confined at home. a previous case was reported in a child in italy. further studies are needed to establish the role of covid-19 in these lesions, but altered coagulation status, and micro-thrombi observed in severe covid-19 patients are consistent with the observed lesions. this alert was pointed out through the sndv messaging group. since most of their practices were on hold, french dermatologists replaced in-person consultation by liveand-interactive consultation or store-and-forward teledermatology. this helped detect pauci-symptomatic skin lesions in patients with pauci-covid symptoms managed by general physicians. this clinical presentation was not reported among skin manifestations in inhospital cases series. 3 similar to anosmia, chilblain may be a symptom mainly reported in covid-19 outpatients, which supports the important role that dermatologists play in this outbreak control. 6 covid-19 outbreak was first described by dr li wenliang using wechat â . our observation highlights the strength of social networks or instant text messaging in healthcare providers' activity and the necessity of telemedicine implementation. this crisis urges countries to widespread telehealth adoption. 7 finally, in the interest of time-saving, social networks can be a platform for novel findings or unusual case reports sharing. 8 in the era of open access science, an expert moderator as well as an express reviewing of published cases are needed to avoid spreading of false or untrustworthy information. we strongly encourage learned societies and healthcare institutions to develop appropriate tools in the field for extraction or release of scientific information. this is a major challenge to limit physician isolation, provide continuous learning, and benefit from collective intelligence. it is time for interactive device-mediated technologies that facilitate sharing of information to contribute to the increasing knowledge and expansion of skill-sets in a new disease. adaptation of the national plan for the prevention and fight against pandemic influenza to the 2020 covid-19 epidemic in france skin damage among healthcare workers managing coronavirus disease-2019 cutaneous manifestations in covid-19: a first perspective global coronavirus pandemic (2019-ncov): implication for an italian medium size dermatological clinic of a ii level hospital what are we doing in the dermatology outpatient department amidst the raging of the 2019 novel coronavirus? sudden and complete olfactory loss function as a possible symptom of covid-19 global telemedicine implementation and integration within health systems to fight the covid-19 pandemic: a call to action social media and outbreaks of emerging infectious diseases: a systematic review of literature the authors thank all the dermatologists of the french union of dermatologists and venereologists sndv, general practitioners, paediatricians, who provided data and pictures, and the patients involved in this study. dr charbel skayem for his proof reading. key: cord-272321-znnipzym authors: verheyden, m.; grosber, m.; gutermuth, j.; velkeniers, b. title: relapsing symmetric livedo reticularis in a patient with covid‐19 infection date: 2020-06-25 journal: j eur acad dermatol venereol doi: 10.1111/jdv.16773 sha: doc_id: 272321 cord_uid: znnipzym during the coronavirus 2019 (covid‐19) pandemic, several associated skin conditions were reported in infected patients, including; urticaria [1], exanthema [1], erythema multiforme [2], chickenpox‐like vesicles [1], pityriasis rosea [3], herpes simplex reactivation [4], erythema nodosum like sweet’s syndrome [5], symmetrical drug‐related intertriginous and flexural exanthema [6], petechial rash [7], vasculitic purpura [7], acro‐ischemia/necrosis [8], kawasaki disease [2] and chilblain lesions [9]. the patient in this manuscript has given written informed consent to the publication of his case details including the clinical pictures. during the coronavirus 2019 (covid-19) pandemic, several associated skin conditions were reported in infected patients, including; urticaria [1] , exanthema [1] , erythema multiforme [2] , chickenpox-like vesicles [1] , pityriasis rosea [3] , herpes simplex reactivation [4] , erythema nodosum like sweet's syndrome [5] , symmetrical drug-related intertriginous and flexural exanthema [6] , petechial rash [7] , vasculitic purpura [7] , acro-ischemia/necrosis [8] , kawasaki disease [2] and chilblain lesions [9] . this article is protected by copyright. all rights reserved we present a 57-year old man with cough, dyspnea, headache, myalgia arthralgia, fever up to 38.7°c and abdominal pain worsening over 8 days. extensive, symmetric livedo reticularis (lr) was present on trunk and thighs. lab testing showed elevated c-reactive protein, ferritin, d-dimers and lymphopenia. nasopharyngeal pcr detected sars-cov-2 and chest ct showed multifocal ground glass opacities, suggestive for covid-19. because of the unusual sudden onset of symmetric lr in a middle-aged man, an additional work-up for underlying conditions was performed. while antineutrophilic cytoplasmic antibodies, platelets, inr/aptt, rheumatoid factor, cryoglobulins and antiphospholipid antibodies were negative, antinuclear factor (ana) was positive with nuclear pattern (titer 1/320, but without enablot specificity). the patient's previous ana titer was unknown and so far, it has not been investigated whether covid-19 can induce such antibodies (as described in other viral disease [10] ). infectious causes of livedo including hiv, mycoplasma pneumonia, syphilis, legionella pneumophila, influenza a/b, rsv, hepatitis b/c were negative. during 8 days, oxygen, acetaminophen, hydroxychloroquine and low-molecular-weight-heparin in preventive dosing were administered. after discharge, livedo fluctuated, but progressively weaned. at three-weeks follow-up, inflammatory parameters were normal (besides insignificantly elevated ferritin), while the patient still experienced slight dyspnea on exertion. lr describes a regular, lace-like network of non-fixed, dusky patches forming complete rings surrounding a pale centre [11] . this clinical picture is caused by constriction of central arterioles and subsequent peripheral venodilation [11] . lr is rarely associated with underlying diseases. it is mostly seen in healthy young woman as a physiological reaction triggered by cold-induced vasospasms and is then named cutis marmorata [11] . when lr is not influenced by cold exposure it is called primary lr [11] . a congenital form is referred to as cutis marmorata telangiectatica congenita [11] . when livedo presents as a nonsymmetric, localized, mostly unilateral and irregular network with broken rings it is named livedo racemosa (lrc) [11] lrc is associated with more significant reduction of blood flow caused by protracted arteriolar vasospasm, thrombosis, and/or hyperviscosity. lrc is always a red flag for an underlying pathology, such as vasculitis, auto-immune disease, infection, systemic disorders, neoplasia) [11] . this article is protected by copyright. all rights reserved our patient had a first occurrence of a symmetric, fluctuating, unsuspicious-looking lr in the context of covid-19, without other causes. livedo was not blanching on pressure and typical clinical signs of vasculitis, like purpura, (asymmetric) lrc or skin necrosis were absent. covid-19 can cause a procoagulant state [12] , with small blood vessel occlusion. however, the absence of purpura and skin necrosis together with normal coagulation parameters make thrombi unlikely as cause of the observed lr. this suggests the presence of low-grade vascular inflammation and vasodilation caused by direct sars-cov-2-infection of endothelial-cells or vessel-associated smooth muscle-cells. both cell types express angiotensin-converting enzyme 2-receptor on their surface, the target of sars-cov-2-spike protein [13] . in addition to previously reported two cases of asymmetric/unilateral and transient livedo [14] , our case identifies a symmetric, fluctuating, relapsing, non-blanching lr as a warning sign for covid-19. if symmetric lr occurs for the first time in patients without any risk factors, it warrants the search for underlying pathology, including covid-19. bibliography cutaneous manifestations in covid-19: a first perspective erythema multiforme and kawasaki disease associated with covid-19 infection in children pityriasis rosea as a cutaneous manifestation of covid-19 infection diversity of clinical appearance of cutaneous manifestations in the course of covid-19 covid-19 presenting with atypical sweet's syndrome a distinctive skin rash associated symmetric cutaneous vasculitis in covid-19 pneumonia late onset of acral necrosis after sars-cov-2 infection resolution vascular skin symptoms in covid-19: a french observational study antinuclear antibodies in infectious diseases braun-falco's dermatologie, venerologie und allergologie the procoagulant pattern of patients with covid-19 acute respiratory distress syndrome fact sheet: covid-19 disease (sars-cov-2 virus), version 2 key: cord-281703-6xwcxe8l authors: di altobrando, ambra; patrizi, annalisa; bardazzi, federico title: should sars‐cov‐2 influence immunosuppressive therapy for autoimmune blistering diseases? date: 2020-04-17 journal: j eur acad dermatol venereol doi: 10.1111/jdv.16491 sha: doc_id: 281703 cord_uid: 6xwcxe8l in this dramatic period where the whole world is affected by the outbreak of coronavirus disease 19 (covid‐19), scientific data relating to the causative virus sars‐cov‐2 as well as the subsequent therapeutic repercussions on the management of other diseases should be divulged in order to share as much information as possible among experts in a timely manner. subsequent therapeutic repercussions on the management of other diseases should be divulged in order to share as much information as possible among experts in a timely manner. regarding autoimmune blistering diseases, it is already widely acknowledged that physicians should search for triggers in all newly identified patients before starting any therapy, including infectious agents. but what about patients already in immunosuppressive therapy for these potentially life-threatening disorders? given the current lack of scientific evidence on the basis of which official recommendations with a high degree of reliability are possible, some indications have been proposed by the international pemphigus and pemphigoid foundation, as the result of expertise and clinical common sense, inspired by a principle of prudence. 2 however, no clear and comprehensive data have been provided on the management of ongoing immunosuppressive therapies in these patients. regarding other inflammatory diseases, the indications of the major scientific societies of dermatologists, rheumatologists and gastroenterologists in italy 3-5 , but also the american academy of dermatology association, 6 suggest that if the patient is stable or in good health, the stop of the ongoing biologic therapy is not reasonable/indicated, as the risk of reactivation of the underlying pathology could add an additional risk factor to infections, including covid-19. this article is protected by copyright. all rights reserved here we report our experience of around 380 patients suffering from autoimmune bullous diseases and in treatment with immunosuppressive drugs currently referring to our bullous diseases outpatient service, sant'orsola-malpighi university hospital, bologna, italy. about 20 patients are visited per week in the space of one day. since 9 th march 2020, in accordance with the sant'orsola-malpighi hospital directives made following the last decree of the president of the council of ministers (dpcm) of march 9, 2020 (gu serie generale n.62 del 09-03-2020), all the outpatient services, of any priority, first visits or control visits, have been temporary suspended and in place telephone calls have been made to all patients who were scheduled to be visited in our outpatient service in the following weeks to prevent them from leaving their home and crowding the hospital, given that social distancing is one of the most effective safeguards in order to limit the spread of the virus. we therefore held a telephone consultation, checking the health of patients over the last month. in particular, we asked whether patients in immunosuppressive therapy among possible trigger factors of autoimmune blistering diseases, immunization and viral infections are mentioned in the literature, although the underlying immunological mechanism is still unclear. [7] [8] [9] the most acceptable hypothesis involves the possible molecular mimicry existing between viral and epidermal proteins, and over activation of the immune system as a consequence of the viral attack. 9 indeed, in autoimmune blistering disorders, once the autoantibodies bind to this article is protected by copyright. all rights reserved their targets, namely self-structural proteins, several pathways are activated, including complement activation and deposition, and neutrophilic chemotaxis, with the release of proteases and elastases that lead to blister formation and of cytokines such as il-6 and il-8, which recruit additional immune cells. 1 to the best of our knowledge, no studies regarding previous viral outbreaks and the effects of these viruses on autoimmune blistering disease patients have been reported in the literature so far. moreover, the pathogenesis of sars-cov-2 infection in humans is still unclear, although massive and prolonged chemokine response known as 'cytokine storm' correlating with high morbidity and mortality has been observed in these patients. 10 we hypothesize that the interruption of immunosuppressive therapy in autoimmune blistering disease patients may determine a dysregulation of inflammatory cytokines that not only exacerbates the bullous disease itself but may also be involved in the pathogenesis of the viral infection. therefore, it is likely that the management of the inflammatory processes guaranteed by immunosuppressive therapies not only controls blistering, but also contributes to a less aggressive organic response to sars-cov-2. in conclusion, to date there is a lack of direct scientific evidence to support the continuation of immunosuppressive therapies in patients infected with sars-cov-2. therefore, it will be crucial for our community to learn of more cases of autoimmune bullous disease patients under immunosuppressive treatment who have developed covid-19, in order to better quantify the risk of infection under immunosuppressive therapy. moreover, now more than ever, research into autoimmune blistering diseases should focus attention on emerging safer therapeutic options that decrease the rate of mortality and morbidity as well as the risks connected to the therapy itself. what is novel in the clinical management of pemphigus information for pemphigus and pemphigoid patients related to coronavirus disease 2° comunicazione del presidente sir: infezione da covid-19 accepted article this article is protected by copyright. all rights reserved infezione da coronavirus: vademecum per i pazienti affetti da psoriasi cutanea e/o artropatia psoriasica italian group for the study of inflammatory bowel disease, avviso per i pazienti con mici guidance on the use of biologic agents during covid-19 outbreak three case reports of post immunization and post viral bullous pemphigoid: looking for the right trigger bullous pemphigoid viruses and pemphigus: an intriguing never-ending story hypothesis for potential pathogenesis of sars-cov-2 infection--a review of immune changes in patients with viral pneumonia acknowledgments: the patients in this manuscript have given written informed consent to publication of their case details. this article is protected by copyright. all rights reserved key: cord-299143-vcfu79ij authors: mccoy, john; wambier, carlos gustavo; herrera, sabina; vaño‐galván, sergio; gioia, francesca; comeche, belen; ron, raquel; serrano‐villar, sergio; iwasiow, rafal m; tayeb, michael a; cadegiani, flávio adsuara; mesinkovska, natasha atanaskova; shapiro, jerry; sinclair, rodney; goren, andy title: androgen receptor genetic variant predicts covid‐19 disease severity: a prospective longitudinal study of hospitalized covid‐19 male patients date: 2020-09-25 journal: j eur acad dermatol venereol doi: 10.1111/jdv.16956 sha: doc_id: 299143 cord_uid: vcfu79ij men infected with sars‐cov‐2 are more likely to be admitted to the intensive care unit (icu) compared to women.(1) previously, we have reported that among hospitalized men with covid‐19, 79% presented with androgenetic alopecia (aa) compared to 31‐53% that would be expected in a similar aged match population.(2) aa is known to be mediated by variations in the androgen receptor (ar) gene.(3) in addition, the only known promoter of the enzyme implicated in sars‐cov‐2 infectivity, tmprss2, is regulated by an androgen response element.(4) the polyglutamine repeat (cag repeat) located in the ar gene is associated with androgen sensitivity and aa.(3) these observations led us to hypothesize that variations in the ar gene may predispose male covid‐19 patients to increased disease severity. this article is protected by copyright. all rights reserved to the editor, men infected with sars-cov-2 are more likely to be admitted to the intensive care unit (icu) compared to women. 1 previously, we have reported that among hospitalized men with covid-19, 79% presented with androgenetic alopecia (aa) compared to 31-53% that would be expected in a similar aged match population. 2 aa is known to be mediated by variations in the androgen receptor (ar) gene. 3 in addition, the only known promoter of the enzyme implicated in sars-cov-2 infectivity, tmprss2, is regulated by an androgen response element. 4 the polyglutamine repeat (cag repeat) located in the ar gene is associated with androgen sensitivity and aa. 3 these observations led us to hypothesize that variations in the ar gene may predispose male covid-19 patients to increased disease severity. we conducted a prospective longitudinal study of hospitalized covid-19 males. the subjects were categorized into two cohorts: subjects with a cag>=22 and subjects with a cag<22. subjects taking androgen modifying drugs, e.g., 5aris, were excluded. dna was collected using oracollect•dx: (dnagenotek, ottawa, canada). ar cag repeat region was pcr-amplified and 300bp paired-end sequencing was performed using a miseq (illumina, san diego, california). reads were mapped to reference ar sequences containing 1 to 50 cag repeats, the reference with the greatest number of mapped reads was reported as the cag repeat count. subjects were followed for a period of 60 days from the date of hospitalization. primary and secondary outcomes were the rate of icu admissions and length of hospitalization, respectively. 77 covid-19 positive men were recruited to the study; 12 were excluded due to their use of androgen modifying drugs, leaving 65 patients enrolled in the study. 31 (48%) subjects had a cag<22, with average age of 67.9 (+/-12.3). the median duration of hospitalization among subjects with a cag<22 was 25 days (95% ci: 9.000-41.6512), and 14 (45.2%) were admitted to the icu. 34 (52%) subjects had a cag>=22, their average age was 65.0 (+/-12.15). among the 34 subjects with a cag>=22, the median duration of hospitalization was 47.5 days (95% ci: 22.9533-49.0935), and 24 (70.6%) were admitted to the icu. the proportion of subjects admitted to the icu with cag<22 was significantly lower than the proportion of subjects with cag>=22 (fisher's exact test p= 0.046791. subjects with a cag>=22 had a higher risk for icu admissions compared to subjects with a cag<22: or 2.9143(95% ci: 1.0487this article is protected by copyright. all rights reserved 8.0985) and likelihood ratio 1.705(95% ci: 0.985-2.951). further, estimating 40% of hospitalized covid-19 male patients are likely admitted to the icu, 5 the bayes' adjusted positive predictive value of the ar cag score in predicting icu admissions was 53.202% (95%ci: 39.646%-66.301%) and the negative predictive value was 71.938% (95%ci: 60.693%-80.974%). our data suggest that longer ar cag score is associated with more severe covid-19 disease. in some androgen mediated disease, short cag has been associate with worse prognosis, e.g., in prostate cancer. 6 however, in skeletal muscle, a long cag repeat length produces higher androgen mediated activity. 7 we believe this discrepancy can be explained by the tissue dependent expression of co-factors important for activation of the androgen response element (are). 8 for example, protein arginine methyltransferase 6 has been shown to be highly expressed in lung and has been shown to be a specific co-activator of the androgen receptor. 9 the results of this study suggest that the ar cag repeat length could potentially be used as a biomarker to identify male coviid-19 patients at risk for icu admissions. more importantly, identification of a biomarker associated with the androgen receptor is yet another piece of evidence supporting the important role of androgens in sars-cov-2 disease severity. we recognize the limitations of this small study; however, our findings, combined with previous reports implicating androgens in covid-19 disease severity, [3] [4] [5] should encourage other groups to explore interventional studies of anti-androgens in covid-19 patients. currently, we are conducting a double-blinded interventional study with dutasteride (nct04446429). sex hormones signal why virus hits men harder impact of sex and gender on covid-19 outcomes in europe androgen sensitivity gateway to covid-19 disease severity androgenetic alopecia present in the majority of hospitalized covid-19 patients -the "gabrin sign androgen-deprivation therapies for prostate cancer and risk of infection by sars-cov-2: a population-based study (n = 4532) influence of cag repeat polymorphism on the targets of testosterone action androgen receptor polyglutamine repeat length affects receptor activity and c2c12 cell development androgen receptor (ar) coregulators: a diversity of functions converging on and regulating the ar transcriptional complex protein arginine methyltransferase 6 enhances polyglutamine-expanded androgen receptor function and toxicity in spinal and bulbar muscular atrophy accepted article this article is protected by copyright. all rights reserved key: cord-304946-fs02dxg5 authors: brochez, l.; baurain, j.f.; del marmol, v.; nikkels, a.; kruse, v.; sales, f.; stas, m.; van laethem, a.; garmyn, m. title: recommendations for skin cancer consultation and surgery during covid‐19 pandemic date: 2020-08-12 journal: j eur acad dermatol venereol doi: 10.1111/jdv.16772 sha: doc_id: 304946 cord_uid: fs02dxg5 nan as a result of the outbreak of the severe acute respiratory syndrome coronavirus 2 (sars-cov-2) and government lockdown measures, healthcare systems were challenged worldwide. medical doctors were faced with prioritization of non-covid19 medical problems in order to reduce potential exposures and to mobilize staff and resources for covid-19 care. on the other hand, decreases in some non-covid19 health problems have been observed, e.g. myocardial infarction, newly diagnosed cancers among which esp. skin cancer, . . . and there is concern that delay in these may negatively affect patient outcome. [1] [2] [3] in this respect, it is important to define and communicate recommendations on prioritization of non-covid19 related health care. in this position paper, we describe recommendations developed by the belgian association of dermato-oncology (bado) for prioritization of patients in the field of dermato-oncology during covid19 pandemic without compromising quality of care and safety. bado was founded in 2012, and the board consists of a mix of derrmatologists, oncologists and surgeons. its main goals are to promote multidisciplinary approach of dermato-oncology, to exchange scientific knowledge about dermato-oncology and to work on treatment recommendations for different skin cancer types. these (covid-19) recommendations are based on estimated potentially harmful effects by delaying a specific consultation type as also discussed in the letter of tejera-vaquerizo. 1 we categorized dermato-oncology care into urgent (no delay), semi-urgent (delay for max 8-12 weeks) and low priority (more than 12 weeks delay acceptable) (tables 1-3 ). in addition, measures for limiting viral transmission during consultation and surgery are described (tables 4-6 ). in conclusion, the covid-19 outbreak posed significant challenges to medical staff to offer optimal and timely care in non-covid19 health problems at the same time keeping the risk of covid19 spread as low as possible. in the last months, proposals for triage in several health conditions have been published especially in oncology including skin cancer. 4-9 bado developed recommendations to prioritize dermato-oncological care on a national level in belgium. in the circumstances of the covid19 pandemic, the approval and refunding of tele/videoconsultations by the government was accelerated but for skin cancer treatment and follow-up teleconsultations are often suboptimal. 10, 11 these recommendations were needed to take on a nationwide similar approach for the different indications in dermato-oncology; it was also a way to monitor replanning of postponed consultations since acceptable delay period was defined for different indications in dermato-oncology. because of the fast changing situation, the introduction of the guidelines mentions that 'these recommendations could serve as a guidance and are based on a general weighing of pros/cons. they need to be tuned according to the evolving situation and advices for covid19 by the government and the weighing of the pros/cons for the individual patient'. for the moment, the lockdown measures in belgium have been gradually decreased and care has returned to (nearly) normal levels taking into account basic preventive measures • follow-up actinic keratosis table 4 practical planning of the consultation • consider teleconsultation whenever possible. • this is especially important in patients at risk for serious covid19 infection (e.g. old ageimmunosuppressive r/other comorbidities) • prior to consultation, ask the patient: a if he/she has has (had) any fever-or cough-or flu-like symptoms b to bring a face mask if he/she has one table 5 general precautions during the consultation • patients should be spaced at least 1.5 m apart while waiting. • patient should clean their hands with soap and water for at least 20 s. alternatively they can be asked to use alcohol 70% desinfectant • if patients have a face mask (or the dermatology practice can provide one) they should be asked to wear it. • patients with fever-or cough-or flu-like symptoms in the past 4 weeks or patients who tested covid19 positive should wear a face mask up to 30 days after the start of their first symptoms/ positive covid-19 pcr testing. • the dermatologist who performs a total body examination with dermoscopy should wear a face mask and wash/desinfect hands. the dermatologist can consider to wear gloves during examination. • the dermatoscope should be desinfected with an 70% alcohol solution. the use of a protective cap or polyvinyl chloride (pvc) food wrap on the dermatoscope should be considered. an alcohol solution or gel can be used as interface medium for dermoscopy 12 • dermoscopy at certain sites like the area under the face mask should be avoided as much as possible 12 table 6 precautions during surgery patient wears face mask doctor wears face mask and gloves and normal surgical clothing when in the face outside the face mask area sterile field protects as much as possible mask area; normal protective clothing (mask, gloves, surgical clothing) 2. outpatient intervention in mask area of the face covid testing (swab screening day before) negative if testing is not available, treat the patients as potentially positive and increase doctor's protection: (ffp2) mask and extra protection (e.g. shield and extra surgical apron over surgical clothing) consider covid testing in all patients prior to hospitalization the covid-19 pandemic and the incidence of acute myocardial infarction fewer cancer diagnoses during the covid-19 epidemic in the netherlands estimated effect of covid-19 lockdown on melanoma thickness and prognosis: a rate of growth model skin cancer triage and management during covid-19 pandemic managing urology consultations during covid-19 pandemic: application of a structured care pathway anti-cancer therapy and clinical trial considerations for gynecologic oncology patients during the covid-19 pandemic crisis esmo management and treatment adapted recommendations in the covid-19 era: breast cancer australian and new zealand consensus statement on the management of lymphoma, chronic lymphocytic leukaemia and myeloma during the covid-19 pandemic recommendations on management of the sars-cov-2 coronavirus pandemic (covid-19) in kidney transplant patients the role of telemedicine in the delivery of healthcare in the covid-19 pandemic will teledermatology be the silver lining during and after covid-19? art of performing dermoscopy during the times of coronavirus disease (covid-19): simple change in approach can save the day! key: cord-310841-scg0h40b authors: atzori, l.; mugheddu, c.; addis, g.; sanna, s.; satta, r.; ferreli, c.; atzori, m.g.; montesu, m.a.; rongioletti, f. title: psoriasis health care in the time of the coronavirus pandemic: insights from dedicated centers in sardinia (italy) date: 2020-04-15 journal: j eur acad dermatol venereol doi: 10.1111/jdv.16473 sha: doc_id: 310841 cord_uid: scg0h40b psoriasis is a major chronic inflammatory skin disease, affecting about 3% of the population in italy, whose management require experienced specialists in order to guarantee high‐quality standards of care. the pandemic coronavirus (2019‐ncov; covid‐19) has changed the approach to all patients requiring close contact during a visit, including dermatologic consultations. in italy, true outbreak begun in lombardy, by february 21, 2020 with exponential contagion, surpassing china in the number of deaths. this article is protected by copyright. all rights reserved copyright: the authors certify that the manuscript is original, never submitted to other journal for publication before. all authors contributed equally to the manuscript and had the opportunity to revise and approve the final text. dr. l atzori has nothing to disclose dr. mugheddu has nothing to disclose. dr. addis has nothing to disclose. dr. sanna has nothing to disclose. dr. satta has nothing to disclose. dr. ferreli has nothing to disclose. dr. mg atzori has nothing to disclose. dr. montesu has nothing to disclose. dr. rongioletti has nothing to disclose. dear editor, psoriasis is a major chronic inflammatory skin disease, affecting about 3% of the population in italy, whose management require experienced specialists in order to guarantee high-quality standards of care. 1 the pandemic coronavirus (2019-ncov; covid-19) has changed the approach to all patients requiring close contact during a visit, including dermatologic consultations. in italy, true outbreak begun in lombardy, by february 21, 2020 with exponential contagion, surpassing china in the number of deaths. 2 the health care system was overwhelmed, best hospitals in northern italy unable to cope with the huge number of desperately ill patients. concern about the impact on the south was great due to the chronic shortage of facilities and limited intensive care equipment. in sardinia, with a population of 1 640 000 inhabitants, 3 the institutional recognition found only 20 intensive care beds available to welcome covid-19 cases. a strategic plan will increase the number to 224 beds, but full implementation would require time (resolution of the regional council 11/17 of the 11/03/2020). as isolation is the main weapon to control the spread, 4 and on march 9, 2020 a decree of the president of the council of ministers ordered the suspension of all outpatients' services, including clinics for psoriasis patients. unfortunately, thousands of patients were suddenly deprived of dermatologic care. the dedicated psoriasis clinics in the major hospital of cagliari, nuoro, and sassari account approximately 6890 patients. about 23% of them afflicted with severe psoriasis and psoriatic arthritis, requiring systemic treatments or phototherapy (table 1) . this article is protected by copyright. all rights reserved we began calling all patients with scheduled visits and programmable procedures to remain at home, providing telephone consultation and counselling. patients were completely unprepared, upset, and disoriented by the lock down. some patients could not understand the crisis and demanded full attention, quite aggressively. other patients were more understanding. only patients requiring dose adjustment and/or blood chemistry controls were admitted, as well as patients requiring infusions, such as infliximab. the access to the phototherapy service was also maintained for selected cases. on march 13, 2020 the italian medicines agency (aifa) allowed the automatic renewal of all expiring therapeutic plan, required for biotechnological drugs, preventing patients from referral only to have their prescription renewed. as awareness of the severity of the covid-19 increased some patients were concerned about continuing their biologics. we followed the sidemast recommendations, 5 and advised patients not to dismiss their drugs without consultation, especially biologics. clinical trials were continued for patients already enrolled; but new screening was discontinued, and prudently, not new treatment was started. patients were admitted only after a strict triage: body temperature was registered, and was required the compilation of a questionnaire, on recent symptoms (fever, cough, breathing difficulties) or travels outside sardinia. a quarantine of two weeks had become mandatory from march 8, 202. thankfully, sardinia covid-19 cases are small in magnitude, but we hold an unpleasant record. on march 26, 2020 the number of infections among health personnel was higher (40%) than the national average of 7-8%. 6 . in this uncomfortable setting, a covid-19 patient indicated the skin consultation at the dermatology clinic of sassari as the possible source of contagion. all the health personnel resulted negative for the infection, but we clearly felt the risk of being considered "spreaders" for the community, instead of essential care providers. we were more exposed to involuntary contagion from asymptomatic patients, and not provided with the necessary personal protective equipment. as dermatologists are specialists not directly involved in the management of critical patients, the supply of specific protective equipment against bio-hazards, as well as of environmental sanitizers, was very limited, and the massive consumption from critical care wards depleted all stocks. thus, all not essential sanitary personnel were placed on vacation, but with the possibility of being called back into service to support other critical specialties. educational programs for medical students, graduate and resident have been interrupted. effects of pandemic coronavirus infection are without precedents. restrictive measures were mandatory, and dermatologists had to adapt: more counselling to support patients, detect unmet needs, and find ways to reassure patients about their disease, to keep them safely home. italian guidelines on the systemic treatments of moderate-to-severe plaque psoriasis covid-19 in italy: momentous decisions and many uncertainties emergency management for preventing and controlling nosocomial infection of 2019 novel coronavirus: implications for the dermatology department istituto superiore sanità), epidemia covid-19 this article is protected by copyright. all rights reserved key: cord-300995-tqz2bkdo authors: tagliaferri, luca; di stefani, alessandro; schinzari, giovanni; fionda, bruno; rossi, ernesto; del regno, laura; gentileschi, stefano; federico, francesco; valentini, vincenzo; tortora, giampaolo; peris, ketty title: skin cancer triage and management during covid‐19 pandemic date: 2020-04-25 journal: j eur acad dermatol venereol doi: 10.1111/jdv.16529 sha: doc_id: 300995 cord_uid: tqz2bkdo the worldwide medical community is striving to pursue the most appropriate clinical choices in the worst event of pandemic of the modern times [1], with over 1 million patients affected by covid‐19 (i.e., swab positive patients with or without symptoms) reported so far [1]. in this context, the aim of the ideal management of cancer patients is to achieve the best possible balance between the two different issues to be considered, which include the risk of cancer progression and the risk of infectious disease. this article is protected by copyright. all rights reserved the worldwide medical community is striving to pursue the most appropriate clinical choices in the worst event of pandemic of the modern times [1] , with over 1 million patients affected by covid-19 (i.e., swab positive patients with or without symptoms) reported so far [2] . in this context, the aim of the ideal management of cancer patients is to achieve the best possible balance between the two different issues to be considered, which include the risk of cancer progression and the risk of infectious disease. in detail, the risk to develop covid-19 disease in the setting of oncological patients can be stratified into three scenarios: a) to prevent a patient with advanced skin cancer who is covid-19 negative to be exposed to viral infection; b) to prevent a patient with advanced skin cancer who is covid-19 positive to infect the health professionals; c) to prevent a patient with advanced skin cancer covid-19 positive to infect other patients. in italy as well as in europe, since the beginning of march 2020, we are in the front line of the pandemic and therefore we felt that it might be useful and ethical to share how we faced these issues [3, 4] . we suggest practical recommendations about follow-up and treatment of skin cancer patients during the covid-19 pandemic. our university hospital is one of the largest covid-19 referral this article is protected by copyright. all rights reserved regarding the literature search, no specific papers about the topic were identified. therefore, the proposal was to meet twice monthly instead of once weekly, with the following rules: 1) only one specialist for each discipline can be physically present at the tumour board meeting (no residents allowed); 2) the room identified to hold the meeting allows to have at least 1.5 meters of distance among the participants; 3) all other participants can take part to the meeting through a dedicated teleconference platform that guarantees the audio-video participation of doctors and sharing of radiological images, photographic documentation and medical records; 4) the possibility to gather the s-mdtb for urgent cases before the scheduled meetings through teleconference. as for the management of the clinical workload, the s-mdtb decided to identify three major classes of skin tumours according to their biological aggressiveness, i.e. advanced melanoma and advanced squamous cell carcinoma (scc) and basal cell carcinoma (bcc). the main recommendations for patients' management are reported in table 1, 2 and 3 respectively. a major limiting factor in our daily practice is the reduced number of available anaesthetists and operating rooms, with the consequent need to elaborate a patients' priority list according to individual oncological prognosis, health condition and comorbidities. in case of symptomatic patient or suspected sars-cov-2 infection, the recommendation is to wait until swab result is ready (12-24 hours) and act according to the result. we use a "triage" colour system to better identify the different situations: -red: the covid-19 risk might be higher than the oncological risk. in this case, we postpone the patient's visit or treatment. -yellow: the covid-19 risk might be high for patients and health care professionals, and the final decision takes into account the feasibility of required procedures, the oncological risk and patient's age and comorbidities on a patient-by-patient basis. the s-mdtb may decide to postpone the visit or therapy or switch to other type of treatments. -green: the covid-19 risk is less than the oncological risk (i.e. a patient with a clear-cut melanoma or a patient with advanced skin cancer under systemic treatment or radiotherapy): the patient must be treated or continue his/her treatment. -white: the covid-19 risk is low, and the delay of treatment does not considerably affect the prognosis -the team discusses with the patient the alternative therapeutic approaches, which may represent the best option during the pandemic and possible schedule time. this article is protected by copyright. all rights reserved we therefore propose that the oncological risk and the risk of sars-cov-2 infection need to be considered and balanced in order to provide a weighted and controlled strategy to advanced skin cancer patients. a useful approach, as already suggested by other authors, is to identify the different classes of priorities, both for the patients and for health professionals [5, 6] .only a few national and international societies have released specific recommendations for skin cancer patients [7] . it is important to underline that in order to consider patients to be covid-19 negative they have to be asymptomatic and with no history of previous exposure, while in case of symptoms or history of previous exposure it is necessary to confirm the negativity with a swab [8] based on the internal hospital and national recommendation [9] . the clinical activities should be managed in a different way for patients covid-19 positive. specific clinical conditions must be evaluated on an individual basis (e.g. young patient with invasive melanoma requiring sentinel node biopsy) discussing the priority list of operating rooms in case of limited access or limited availability of anaesthetists. when surgical treatment for advanced scc or bcc is unfeasible, radiotherapy should be considered as an alternative option, mainly for elderly patients. as far as follow-up visits are concerned, they could be managed by implementing a dedicated system of telemedicine unless the patient reports side effects, relapse or worsening of disease, which might instead require access to the hospital. notably, the italian medicines agency (aifa) has facilitated the bureaucratic procedures allowing cancer patients under treatment with oral anti-tumour drugs to directly collect the medications by the pharmacy hospital without medical prescription for the next 3 months. in addition, due to the lockdown, the italian civil protection offers a home drug delivery service available throughout the entire country. for patient who need to come to the hospital for the cure, some rules must be abided: a) only patients and no caregivers are allowed to enter the hospital, b) patient's body temperature is checked at the main entrance of the hospital or at the department, c) each individual in the hospital must wear a mask and gloves, and must keep at least 1.5 m inter-personal distance [10] . for patients under treatment with radiotherapy or systemic therapy who become covid-19 positive, the treatment should be discontinued or discussed on an individual basis involving the infectivologists. a unique pathway for covid-19 positive patients who still need to be treated is under investigation at the radiology and radiotherapy departments of our university. this article is protected by copyright. all rights reserved characteristics of and important lessons from the coronavirus disease 2019 (covid-19) outbreak in china: summary of a report of 72 314 cases from the chinese centre for disease control and prevention european centre for disease prevention and control. situation update worldwide the response of milan's emergency medical system to the covid-19 outbreak in italy european task force on atopic dermatitis (etfad) statement on severe acute respiratory syndrome coronavirus 2 (sars-cov-2)-infection and atopic dermatitis covid-19 outbreak in northern italy: first practical indications for radiotherapy departments global coronavirus pandemic (2019-ncov): implication for an italian medium size dermatological clinic of a ii level hospital società italiana di dermatologia medica, chirurgica, estetica e delle malattie sessualmente trasmesse (sidemast) the royal college of radiologists. coronavirus (covid-19): cancer treatment documents pandemic planning clinical guideline for patients with cancer guidance document for risk assessment and management of patients and healthcare professionals in radiation oncology departments during ongoing covid-19 spread the authors would like to thank the s-mdtb: roberta albanese, mario balducci, maria this article is protected by copyright. all rights reserved key: cord-311523-erntrh3p authors: gisondi, p; piaserico, s; conti, a; naldi, l title: dermatologists and sars‐cov‐2: the impact of the pandemic on daily practice date: 2020-04-22 journal: j eur acad dermatol venereol doi: 10.1111/jdv.16515 sha: doc_id: 311523 cord_uid: erntrh3p since the first case of “pneumonia of unknown aetiology” was diagnosed at the wuhan jinyintan hospital in china on 30 december 2019, what was recognised thereafter as “severe acute respiratory syndrome coronavirus 2” (sars‐cov‐2) has spread over the four continents, causing the respiratory manifestations of coronavirus disease‐19 (covid‐ 19) and satisfying the epidemiological criteria for a label of “pandemic.” the ongoing sars‐cov‐2 pandemic is having a huge impact on dermatological practice including the marked reduction of face‐to‐face consultations in favour of teledermatology, the uncertainties concerning the outcome of covid‐19 infection in patients with common inflammatory disorders such as psoriasis or atopic dermatitis receiving immunosuppressive/immunomodulating systemic therapies; the direct involvement of dermatologists in covid‐19 care for patients assistance and new research needs to be addressed. it is not known yet, if skin lesions and derangement of the skin barrier could make it easier for sars‐cov‐2 to transmit via indirect contact; it remains to be defined if specific mucosal or skin lesions are associated with sars‐cov‐2 infection, although some unpublished observations indicate the occurrence of a transient varicelliform exanthema during the early phase of the infection. sars‐cov‐2 is a new pathogen for humans that is highly contagious, can spread quickly, and is capable of causing enormous health, economic and societal impacts in any setting. the consequences may continue long after the pandemic resolves, and new management modalities for dermatology may originate from the covid‐19 disaster. learning from experience may help to cope with future major societal changes. since the first case of "pneumonia of unknown aetiology" was diagnosed at the wuhan jinyintan hospital in china on 30 december 2019, what was recognised thereafter as "severe acute respiratory syndrome coronavirus 2" (sars-cov-2) has spread over the four continents, causing the respiratory manifestations of coronavirus disease-19 and satisfying the epidemiological criteria for a label of "pandemic," broadly defined as the uncontained spread of an infection in multiple regions [1] . as of 24 march 2020, more than 420,000 cases has been identified worldwide, and almost 19,000 deaths have occurred. after china, the area more severely affected nowadays is europe, with italy having the dubious record of the number of deaths [2] . sars-cov-2 is a zoonotic single-stranded rna virus of the coronaviridae family, which has crossed species to infect humans, as previously occurred for the virus of the "severe airborne spread, per se, is not a major route of transmission. faecal shedding has been demonstrated in some patients, but oro-fecal transmission is not recognised as a relevant driver of infection [4] . transmission of sars-cov-2 mainly occurs in households and other close settings. nosocomial outbreaks have been reported [5] . disease presentation can range from no symptoms to severe pneumonia and death ( table 1 ). the mean incubation period is 5-6 days (range 1-14 days) and the virus can be isolated from the nasopharynx 1-2 days prior to symptom onset. about 90% of people have mild disease and recover [6] . a small proportion has a severe or critical condition. the proportion of truly asymptomatic people remains to be determined. transmission during an asymptomatic stage does not seem to play a relevant role in spreading the virus. individuals at higher risk for severe disease include people aged over 60 years and those with underlying conditions such as hypertension, diabetes, cardiovascular disease, chronic respiratory disease and cancer [3, 6] . the disease in children is unapparent or mild. to date, the management of infection has been largely supportive [3, 5, 7] . case this article is protected by copyright. all rights reserved fatality rates, i.e., the proportion of deaths from the disease compared to the total number of people diagnosed during a certain period of time, varies, among the others, with location, intensity of transmission, demography of the population, health service organization, and modalities adopted to identify cases. the estimates range from 0.3% in germany to about 10% in italy [2]. sars-cov-2 is a new virus to humans, and no immunization exists in the population at large. hence, the virus spreads with astonishing speed. the basic reproduction number (i.e., the number of cases one infected individual generates), r0, has been estimated to range between 1.4 to 3.9 according to the mitigating measures adopted, and the epidemic in the early phase in china was doubling every 6.4 days [3, 7, 8] . some model predictions indicate that millions of people may be infected by the end of 2020. there is evidence that public health interventions can reduce and even interrupt transmission. these measures must fully incorporate immediate case detection and isolation, rigorous close contacts tracing with quarantine, and direct population engagement (table 2) [9] [10] [11] . contents of educational interventions should include social distancing measures and personal protection strategies such as hand hygiene. the on going pandemic is having a huge impact on dermatological practice. we are making specific reference to italy, but the situation is similar to what is happening in other countries (personal communications and [12]). a significant reduction of outpatient dermatological visits both in public hospitals and in private practice offices is registered in most countries. in italy, the reduction of dermatological consultations is approximately 80-90%. such a marked reduction also applies to medical specialities other than dermatology. most hospitals have postponed appointments for elective surgery and non-urgent visits to avoid people moving form home and to focus on covid-19 management. in italy, the reduction is also one of the consequences of the legislative decree of the italian prime minister #iorestoacasa (translated: i stay at home) recommending the closure of any commercial activities all over italy, except for pharmacies, groceries and other essential services [13] . citizens are not allowed to leave their homes unless there is the need of going to work (such as in the case of health workers), for urgent health reasons or the purchase of necessary goods. triage is made before any patient attends a health consultation looking for any respiratory symptom or fever. in case of symptoms the patient is put in a separate area. this article is protected by copyright. all rights reserved in this situation, remote working is boosted, and telemedicine -that is defined as ''the remote diagnosis and treatment of patients by means of telecommunications technology'' -could be very appropriate [14] . by practicing teletriage, which prioritizes in-person clinic visits for patients with conditions associated with greater morbidity or mortality and uses telemedicine for the rest, the delivery of dermatologic care can be pursued during the pandemic [15] [16] [17] [18] . dermatology forum and the american academy of dermatology guidelines [21] ). the safety of initiating immunosuppressant medications during the pandemic is questionable [22] . the benefit-to-risk ratio of any immunosuppressive therapeutic intervention should be carefully weighted in dermatological patients on a case-to-case basis. individuals over the age of 60 years and/or patients with comorbid conditions including cardiovascular diseases, diabetes, metabolic syndrome, chronic obstructive pulmonary disease, chronic kidney diseases, and cancer have a higher risk of developing more serious infections [20, 23] . as of now, there is insufficient evidence to determine how sars-cov-2 infection will impact the clinical course of chronic inflammatory conditions such as psoriasis and to estimate potential risks associated with systemic treatment [24] . in covid-19 patients, but also in sars and mers patients, inflammatory cytokines assume a double role: in the first place they stimulate the activation of an effective immune response, while at a later time, in case of failure of the adaptive immunity (mainly th1-polarized), they mediate the development of an exaggerated systemic inflammation [25] [26] [27] . this "cytokine storm" is this article is protected by copyright. all rights reserved both ineffective toward the pathogen and detrimental for the body, eventually leading to acute respiratory distress syndrome (ards) and potentially to death [28] . (tnf)-alpha elevation plays a key role in the development of the detrimental inflammatory response correlated to both coronavirus and non coronavirus viral pneumonia [29] . in a model of immunosuppressed macaques infected with mers-cov, significantly higher levels of mers-cov replication in respiratory tissues and viral shedding, was found. however, despite increased viral replication, pathologic changes in the lungs were significantly lower in immunosuppressed animals [30] . mers-cov virus itself caused little damage to the cells that it infected and the tissue damage might be attributed to the overactive inflammatory response. therefore, it has been hypothesized that treatment for patients with symptomatic covid-19 would benefit from additional therapy that lessens the inflammatory response, and not be based solely on therapies that are aimed at controlling virus replication. in this context, agents blocking tnf or il17 pathways could have the potential to improve covid-19's aberrant immune response and ards-related mortality [31] . the exaggerated inflammatory responses (cytokine storm) and increased damage of tissues seen in sars, mers and covid-19 might also be enhanced by patient's comorbidities, namely diabetes, or even by ageing per se. older adults have elevated levels of pro-inflammatory cytokines, and the term 'inflamm-ageing' was coined to describe this phenomenon. this could partially explain the association between patient's older age and some comorbidities with a worse outcome [34] . intriguingly, during sars outbreak in 2002 and mers and covid-19 (so far), no death was reported in transplanted patients or under immunosuppressive treatments, (e.g. cyclosporine, methotrexate, azathioprine) at any age. in a recent letter, d'antiga reported 3 immunosuppressed children in bergamo, italy, who were tested positive for sars-cov-2 but only had a mild disease without any pulmonary involvement [35] . published data on sars, mers and sars-cov-2 seem to suggest this article is protected by copyright. all rights reserved that patients with drug-induced immunosuppression are not at particularly increased risk of severe pulmonary disease compared to the general population. the role of dermatologists during the pandemic may not be limited to their dermatology clinics. in the areas of italy severely affected by the coronavirus outbreak, extra beds have been created in internal medicine wards for covid-19 patients; dermatologists, along with doctors from other medical subspecialties, have therefore been asked to provide assistance to covid-19 patients in these departments due to the shortage of doctors. for those dermatologists who are now fighting in the front line against covid-19, a number of challenges need to be faced on a daily basis, the most crucial one being personal protection. as of 20 th march, 3.654 health workers were infected with covid-19 in italy, representing about 10% of the total number of positive patients [36] , and 17 physicians died due to sars-cov-2 infection [37] . such appalling data underscore the importance of the availability of protective equipment like medical masks, gloves, eye protection and gowns for medical personnel dealing with infected patients. shortage of medical masks for health workers due to "panic shopping" from the population may jeopardize the safety of physicians dealing with covid-19 patients. a further area where dermatologists are involved is with damages to the skin from personal protective equipment of healthcare professionals and with procedures such as frequent hand washing. clinical manifestations include acute and chronic irritant dermatitis, secondary infections and possible aggravation of pre-existing cutaneous disorders. recommendations for preventing these adverse effects have been published [38] . recommendations for preventing irritant hand dermatitis include avoiding harsh soaps because while these will clear any infectious agent from the skin, at the same time, they destroy the protective barrier that protects us from other pathogens. we need to compensate for the damage we're inflicting on our skin with frequent hand washing or alcohol-based hand sanitizers by putting moisturizer on damp skin [38] . this article is protected by copyright. all rights reserved there are several unaddressed issues of sars-cov-2 infection for dermatologists. first, dermatologists from wuhan suggested that skin lesions and derangement of the skin barrier could make it easier for sars-cov-2 to transmit via indirect contact [39] . however, no clear evidence is currently available pointing to any modes of transmission other than inhaling droplets and aerosols, or contact with a contaminated surfaces followed by touching mouth, nose, or eyes [40] . secondly, it remains to be defined if specific mucosal or skin lesions are associated with sars-cov-2 infection. recalcati s. disease's severity [41] . from thailand, joob b et al. reported a case presenting with a skin rash with petechiae associated with low platelet count, initially diagnosed as dengue, suggesting that also vascular lesions may be early signs of the infection [42] . we observed a diffuse papular eruption in a woman with covid-19 febrile infection, as reported in figure 1 . finally, data are currently lacking, as already discussed, concerning the outcome of covid-19 infection in patients with inflammatory and malignant skin conditions. the course of covid-19 in patients with immune-mediated diseases like psoriasis receiving different systemic therapies, is completely unknown and may be of special interest to guide the future management of these patients and, more in general, to understand the role of immune response in covid-19 outcome [43] . covid-19 is a new pathogen for humans that is highly contagious, can spread quickly, and is capable of causing enormous health, economic and societal impacts in any setting. dermatological care is already deeply impacted by the pandemic. the consequences may continue long after the pandemic resolves, and new management modalities for dermatology may originate from the covid-19 disaster. learning from experience may help to cope with future major societal changes [44] . time to use the p-word? coronavirus enter dangerous new phase detection of sars-cov-2 in different types of clinical specimens novel coronavirus-important information for clinicians clinical course and risk factors for mortality of adult inpatients with covid-19 in wuhan, china: a retrospective cohort study covid-19 and italy: what next? lancet potential impact of seasonal forcing on a sars-cov-2 pandemic feasibility of controlling covid-19 outbreaks by isolation of cases and contacts covid-19 cacophony: is there any orchestra conductor? accepted article this article is protected by copyright. all rights reserved new coronavirus outbreak: framing questions for pandemic prevention on the front lines of coronavirus: the italian response to covid-19 virtually perfect? telemedicine for covid-19 the growth of teledermatology: expanding to reach the underserved teledermatology as a tool to improve access to care for medically underserved populations: a retrospective descriptive study implementation of a dermatology teletriage system to improve access in an underserved clinic: a retrospective study impact of store-and-forward (saf) teledermatology on outpatient dermatologic care: a prospective study in an underserved urban primary care setting storeand-forward teledermatology versus in-person visits: a comparison in pediatric teledermatology clinic accepted article this article is protected by copyright. all rights reserved 20 guidance on the use of biologic agents during covid-19 outbreak covid-19 and psoriasis: is it time to limit treatment with immunosuppressants? a call for action prevalence of comorbidities in the novel wuhan coronavirus (covid-19) infection: a systematic review and meta-analysis should patients stop their biologic treatment during the covid-19 pandemic cell host response to infection with novel human coronavirus emc predicts potential antivirals and important differences with sars coronavirus il-17 boosts proinflammatory outcome of antiviral response in human cells inhibition of tumor necrosis factor reduces the severity of virus-specific lung immunopathology covid-19: a recommendation to examine the effect of hydroxychloroquine in preventing infection and progression accepted article this article is protected by copyright. all rights reserved inhibition of the inflammatory cytokine tumor necrosis factor-alpha with etanercept provides protection against lethal h1n1 influenza infection in mice pathogenicity and viral shedding of mers-cov in immunocompromised rhesus macaques. front immunol reducing mortality from 2019-ncov: host-directed therapies should be an option age-dependent dysregulation of innate immunity coronaviruses and immunosuppressed patients. the facts during the third epidemic integrated surveillance of covid-19 in italy elenco dei medici caduti nel corso dell'epidemia di covid-19 consensus of chinese experts on protection of skin and mucous membrane barrier for healthcare workers fighting against coronavirus disease 2019 emergency management for preventing and controlling nosocomial infection of 2019 novel coronavirus: implications for the dermatology department epidemiology, causes, clinical manifestation and diagnosis, prevention and control of coronavirus disease (covid-19) during the early outbreak period: a scoping review cutaneous manifestations in covid-19: a first perspective covid-19 can present with a rash and be mistaken for hypothesis for potential pathogenesis of sars-cov-2 infection--a review of immune changes in patients with viral pneumonia this article is protected by copyright. all rights reserved key: cord-277110-e27lm7rr authors: iria, neri; annalucia, virdi; ilaria, corsini; alba, guglielmo; tiziana, lazzarotto; liliana, gabrielli; cosimo, misciali; annalisa, patrizi; marcello, lanari title: major cluster of pediatric “ true ” primary chilblains during the covid‐19 pandemic: a consequence of lifestyle changes due to lockdown date: 2020-06-13 journal: j eur acad dermatol venereol doi: 10.1111/jdv.16751 sha: doc_id: 277110 cord_uid: e27lm7rr background: over the last months, during the covid‐19 pandemic, a growing number of chilblain‐like lesions was reported mainly in children, rarely in young adults. the relationship with sars‐cov‐2 infection was postulated, often without any laboratory, instrumental or clinical confirmation. the disclosure of information about chilblain‐like lesions as a covid‐19 manifestation in social media has created concern in children’s families and pediatricians objectives: to verify whether the chilblain‐like lesions were caused by sars‐cov‐2 infection. methods: prospective study on a case series including children who presented with acral lesions at the pediatric dermatology outpatient and pediatric emergency unit of the university of bologna, from april 1 to april 30, 2020. we reported demographical, laboratory and clinical features, history of close contact with covid‐19 patients, presence of similar skin lesions in other family members, precipitating and risk factors for chilblain onset. results: we evaluated 8 patients (5 females, 3 males) aged between 11 and 15 years. we excluded acute or previous sars‐cov‐2 infection with rt‐pcr nasopharyngeal swab, serum antibody levels using chemiluminescent immunoassays. other acute infections causing purpuric lesions at the extremities were negative in all patients. skin lesion biopsy for histological and immunohistochemical evaluation was made in two cases and was consistent with chilblain. pcr‐assay on skin lesion biopsy for parvovirus b19, mycoplasma pneumoniae and sars‐cov‐2 was performed in a patient and resulted negative. we identified common precipitating and risk factors: physical (cold and wet extremities, low bmi), cold and wet indoor and outdoor environment, behaviors, habits, lifestyle. we therefore reached a diagnosis of primary chilblains. conclusions: during the covid‐19 pandemic, a “cluster” of primary chilblains developed in predisposed subjects, mainly teenagers, due to to cold exposure in the lockdown period. laboratory findings support our hypothesis, although it is also possible that an unknown infectious trigger may have contributed to the pathogenesis. global public health is still challenged by the severe acute respiratory syndrome coronavirus 2 (sars-cov-2) pandemic, the causative agent of coronavirus disease 2019 (covid-19). the emilia romagna region, as well as lombardy, is one of the largest and most serious clusters of covid-19 in italy. the transmission of sars-cov-2 occurs through airborne spread, droplets, aerosol, hand contact and fecal shedding. the main paths of transmission in pediatric age are through close contact with other infected family members (89%), exposure to epidemic areas (33%) or both. 1 clinical manifestations in the pediatric age range from mild to critical; however, most patients are asymptomatic or present a mild disease with fever, fatigue, dry cough, myalgia and diarrhea. severe and critical forms are rarer if compared with adults or the elderly, although bilateral interstitial pneumonia and late-onset neonatal sepsis have been reported. 2, 3 skin findings associated with sars-cov-2 infection represent a new hot topic. the dermatological manifestations range from viral exanthema-like rashes to vasculopathy-related lesions. 4 although this debate is very lively in adults, little is known about the dermatological manifestations of the virus in the pediatric age. genovese and morey-olivé reported different types of rash, such as varicella-like, maculopapular and urticaria-like eruptions, in children with confirmed or highly suspected covid-19. 5, 6 in the last month an "outbreak" of chilblain-like lesions was reported, mainly in the pediatric population. 7, 8 the relationship with sars-cov-2 infection was postulated by several authors. the chilblain-like lesions were variably associated with the presence of respiratory and systemic symptoms or with the history of close contact with positive cases, though lacking the criteria for testing for sars-cov2 in the majority of cases. 8 this article is protected by copyright. all rights reserved in april 2020, we observed a growing number of chilblain-like manifestations similar to coldinduced lesions during the pandemic, with the opportunity to study 8 cases, 2 children and 6 adolescents, and report here our results. the aim of this study is to verify whether the chilblain-like lesions were a cutaneous clue for sars-cov-2 infection or due to other causes. this article is protected by copyright. all rights reserved -pcr-assay on blood samples for parvovirus b19 dna and enterovirus rna -pcr-assay on skin biopsy for parvovirus b19, mycoplasma pneumoniae and sars-cov-2 was performed in a single patient (12.5%). a second evaluation (time 1 = t1) was performed on all patients 8 to 20 days after t0, repeating routine analysis and serological tests for parvovirus b19, cmv, ebv, mycoplasma pneumonia. skin biopsy for histological and immunohistochemical evaluation was made in two cases on finger and toe lesions respectively. qualitative detection of covid-19 was performed through rna extraction from throat swab and biopsy using qiasymphony sp/as instruments with qiasymphony dsp virus/pathogen midi kit (qiagen, hilden, germany). real-time reverse-transcription was carried out according to corman vm et al. 9 using rna-dependent rna polymerase gene (rdrp) as amplicon target. the limit of detection for the rdrp assay is 3.6 copies per reaction (95%: 2.7-11.2). 9 the patients evaluated were 8, 5 females and 3 males. the age ranged from 11 to 15 years. the mean time from the lesions onset to the visit was 19.6 days (9-30). all patients were asymptomatic and their medical history was unremarkable. none of them, including all family members, referred history of close contact with covid-19 patients. moreover, neither parents or siblings presented any cutaneous or systemic and respiratory symptoms. clinical aspect was the same in all cases, presenting multiple red-purple macules and/or patches patches or nodular type and 2) blistering type ( figure 1 ). also pcr-assay skin biopsy for sars-cov-2 rna of the chilblain lesion in one case was negative. regarding laboratory findings, all patients had normal blood count and biochemical profile; 3/8 (37.5%) showed only slight lymphocytosis (t0), then returning to normal value (t1). furthermore, the immune inflammatory parameters and cytokines considered to be related to this article is protected by copyright. all rights reserved sars-cov-2 (il6, ldh and ferritin) were unaltered. the ana reflex titer was normal in all patients. the values of homocysteine, lymphocyte subset, lac, anti-cardiolipin and anti-beta2 glycoprotein i antibodies (igm and igg) were within range in all patients. concerning the serological tests, four patients (50%) showed an increased level of igg for mycoplasma pneumoniae (nr <12 u/ml) at t0; at t1, igg level was slightly decreased in two patients (25%), unchanged in one patient (12.5%), and slightly increased in one patient (12.5%). elevated igm levels were not observed in any patients at any time. seven patients (87.5%) were immune (igg positive, igm negative) to ebv; igm were observed in only one patient (12.5%) in association with igg and ebna, both at t0 and t1: these values are relatable to a previous infection. three patients (37.5%) were immune to cmv, none showed active infection. regarding viral pcr examinations on blood, two patients (25%) showed a low viral load of parvovirus b19 dna (<250 copies/ml), which corresponds to residual copies from a past infection. finally, enterovirus rna was not found in any of the cases. since laboratory tests excluded infectious or autoimmune etiology and considering the habits and behavior of the patients during the lockdown, a diagnosis of idiopathic or primary chilblains (pc) was made. we recommended protection from the cold. topical steroids were prescribed in all patients. after a 4-5 week follow-up, the patients denied any symptoms and the lesions healed. our primary aim was to investigate a potential link between sars-cov-2 infection and the occurrence of chilblain-like lesions in children. various cutaneous findings were observed in adults infected with covid-19 and, simultaneously, a marked increase of chilblain-like lesions occurred worldwide among children during the covid-19 pandemic 10, 11 in our cases we exclude sars-cov-2 infection. the serology was performed in all cases three weeks after the appearance of the chilblains and both igm and igg were negative, and this led us this article is protected by copyright. all rights reserved infected patients. 13 even in large study the virus was detected in less than half of patients with pseudo-chilblains. 7 covid-19-related pseudo-chilblains has been supposed associated with younger age, less severe disease, and late appearance compared to covid-19 onset. 7 pseudo-chilblain late onset led to hypothesize a late manifestation of vascular damage secondary to antigen-antibody mechanism 7, 14 and according to some authors this might explain the frequently negative pcr results on nasopharingeal swab. 7, 8 few pediatric cases with clinical, instrumental or virologic confirmation were included in these studies. 14, 15 the disclosure of chilblain information as a covid-19 cutaneous sign in social media has created concern in children's families and paediatricians. however many of the recently reported chilblains occurred in children without general symptoms of sars-cov-2 and coming from asymptomatic families. 16 as chilblains are not frequent in pediatric age and uncommon in 'mediterranean' climate, the recent increasing number of cases could suggest an infectious aetiology. so after sars-cov-2, we ruled out other pathogens causing purpuric lesions at the extremities, such as in papular purpuric gloves and socks syndrome and/or atypical hand-foot-mouth disease, and viral infections which are rarely reported as precipitating factors of chilblains. 17 we tested for mycoplasma pneumoniae, epstain-barr-virus, parvovirus b19, enterovirus and citomegalovirus. none of the 8 children involved in our study was found to be in the acute phase of any of these infections. in all cases a complete blood count and c-reactive protein were within normal limits. lockdown involving the main gathering places for children (kindergartens, schools, gyms, parks) from the end of february resulted in a reduction in the spread of typical childhood infectious diseases and a lower number of admissions to the pediatric health care facilities. in 2 cases biopsy was performed to evaluate the histological characteristics of skin lesions and to exclude the presence of vasculitis or thrombi (reported by colonna et al. 18 ), whose appearance in the late phase of covid-19 has been discussed. 14 this article is protected by copyright. all rights reserved consistent with a diagnosis of chilblain. 15, 16, 18, 21 clinical examination, microbiological investigations, laboratory data (including ana, lac, fibrinogen, d-dimer) did not reveal any other underlying diseases (viral infection, lupus, hypercoagulation status). it is also possible that an unknown infectious trigger may have contributed to our cluster. we therefore reached a diagnosis of idiopathic or primary chilblains. the primary chilblain (pc), also called pernio, is a self-limiting inflammatory disorder, caused by prolonged exposure to cold temperatures and wet weather, especially during late winter or early spring. cold may cause persistent or prolonged vasoconstriction in vulnerable people, with subsequent hypoxemia and secondary inflammatory reaction. 22 the pathogenesis of pc has been attributed to a defective vasodilatory reflex. we observed typical pc lesions in bilateral acral areas of the hands and feet, especially on the dorsal aspect of toes and in 3/8 cases also on the heel and plantar surface. pc affects susceptible individuals, mainly young females between the ages of 15 and 30 years, and less frequently children and the old people. 23 at this point why a "cluster" of chilblains was taking place in children not only in italy but also in other countries 14 remains to be clarified. many other published cases were evaluated through teledermatology, 10 often without tests and the evaluation of other possible etiologies common to various countries, such as the drastic lifestyle changes due to lockdown. we therefore investigated predisposing factors, including age, common characteristics in affected subjects (such as cold and wet extremities and familiarity for chilblains) and trigger factors in environmental conditions (indoor and outdoor). in the pediatric age, girls going through puberty seem to be more at risk, especially teenagers with thin body habitus. 19 our cases were all adolescent, f:m=5:3 with a mean age of 12.8 years. bmi was <25th percentile in 4/8 patients and within 25-50 th percentile in 4/8. non-freezing weather and humidity represented triggering factors to be considered. in the late winter-early spring the climate is generally not rigid at our latitude, whereas pronounced temperature variations were registered in bologna this march (figure 3) . a marked humidity characterized the climate in bologna and in one case also the home environment. around this time also many apartments are cooler because the heating has been turned off. new behaviors, habits and/or lifestyles arising from the lockdown were evaluated. toddlers and school-age children were forced to stay at home all day and changed their habits. we evaluated the this article is protected by copyright. all rights reserved clothing, the new behaviors and the characteristics of the home. some "domestic behaviors" already frequent among adolescents increased during the lockdown period, such as the tendency to isolation in their room with computers due to school needs and entertainment on social network with friends. an accurate personal history showed inadequate clothing in most cases and in fact many of them walked barefoot on cold marble or ceramic floors, or had prolonged incorrect postural habits such as staying with their legs bent or crossed on the floor or on a chair for many hours. incorrect postural habits may have contributed to a reduction of blood flow and to lowering skin temperature. these data led us to assume that although the outside temperature was not rigid, these new behaviors, poor clothing, unheated apartments, and the characteristics of the indoor environments may have caused the cooling of extremities and feet. this explains the unusual plantar localization of chilblains in 3 of our cases who walked barefoot, similar to 3 other reported cases who wore shoe boots. 24 in the literature recreational chilblains are reported with involvement of unusual areas. unusual localization appears on the hips due to prolonged cold exposure, provoked by tight low-cut jeans. 25 we have assumed that in predisposed subjects, mainly teenagers, the changes in life style due to the covid-19 lockdown, the weather conditions in march and april 2020 and the cold and wet indoor climate may justify the 'cluster' of pc. the longer course of the lesions in our patients compared to typically acute pc 23 might be explained by the persistence of the lockdown. it would be interesting to verify whether in covid-19 positive young adults the presence of chilblains is caused by exposure to cold in predisposed subjects and not linked to sars-cov-2 infection, as already suspected. 7 the major limitation of our study was the small sample size. we were not able to test other patients due to the difficulties to access the hospital. the observation of other cases, with a careful clinical examination and an accurate history will provide further diagnostic clues and will be necessary to verify our hypothesis. in the literature, the reasons for the chilblain "cluster" during the covid-19 pandemic have so far been not well identified, also on account of the difficulties to perform clinical and diagnostic evaluation. negative results of rt-pcr nasopharyngeal swab, serological tests and pcr-assay skin biopsy accepted article ruled out a sars-cov-2 infection in all of our cases. it is also possible that an unknown infectious trigger may have contributed to our cluster of cases. nevertheless, the exclusion of other more frequent infectious agents, the normality of laboratory tests, and the histologic findings led us to the diagnosis of chilblain, a benign acral inflammatory disorder. we conclude that the chilblains observed in our cases are primary and affect predisposed subjects due to cold exposure in the lockdown period (march-april 2020), during a worldwide emergency. clinical and epidemiological features of 36 children with coronavirus disease 2019 (covid-19) in zhejiang, china: an observational cohort study detection of covid-19 in children in early late-onset neonatal sepsis in a patient with covid-19 cutaneous manifestations in covid-19: lessons learned from current evidence varicella-like exanthem associated with covid-19 in an 8-year-old girl: a diagnostic clue? pediatr dermatol cutaneous manifestations in the current pandemic of coronavirus infection disease (covid 2019). an pediatr (engl ed classification of the cutaneous manifestations of covid-19: a rapid prospective nationwide consensus study in spain with 375 cases characterization of acute acroischemic lesions in non-hospitalized patients: a case series of 132 patients during the covid-19 outbreak detection of 2019 novel coronavirus (2019-ncov) by real-time rt-pcr did whatsapp® reveal a new cutaneous covid-19 manifestation? j eur acad dermatol venereol chilblain-like lesions during covid-19 epidemic: a preliminary study on 63 patients clinical and coagulation characteristics of 7 patients with critical covid-2019 pneumonia and acro-ischemia vascular skin symptoms in covid-19: a french observational study chilblain-like lesions on feet and hands during the covid-19 pandemic chilblain and acral purpuric lesions in spain during covid confinement: retrospective analysis of 12 cases acral cutaneous lesions in the time of covid-19 major cluster of chilblain cases in a cold dry western australian winter chilblains-like lesions in children following suspected covid-19 infection the patients in this manuscript have given written informed consent to the publication of their this article is protected by copyright. all rights reserved key: cord-290146-7fz9bj0b authors: ring, j. title: covid‐19 and its implications for dermatology and venereology date: 2020-05-22 journal: j eur acad dermatol venereol doi: 10.1111/jdv.16414 sha: doc_id: 290146 cord_uid: 7fz9bj0b nan in a time where the novel coronavirus disease (covid-19) is dominating the news in all media around the world, it may be good to reflect briefly on the implications of this new pandemics on dermatology and venereology. to do so, not only the aspects affecting the patients but also those affecting the healthcare workers and the teachers must be considered. there is excellent information on epidemiology, general health prevention measures, and especially on the affected airways as major target organ with severe complications of pneumonia and septic shock that are giving rise to a high number of fatalities (cdc website). 1 surprisingly, little is known for the skin and skin diseases. although this seems trivial, the implications for dermatology give rise to a number of critical questions that are only partly answered. the question as to whether skin symptoms belong to the disease symptomatology is not often communicated, but even when they are reported, about 10 % of skin manifestations are described rather unspecifically as 'rash' (recalcati, in this issue). 2 more importantly, the aspect of prevention for healthcare workers who must apply disinfectants and wash their hands many times a day needs to be taken into account. this may lead in persons with sensitive skin, which accounts for as many as 20-40% of the population, to the risk of irritant or allergic contact dermatitis; also skin damage caused by prolonged use of equipment such as gloves and masks must be mentioned. therefore, adequate skin protection by using the right type and amount of emollients is crucial in healthcare workers with a long-term exposure to the protective equipment (long et al., this issue). 3 for patients, the most important prevention measures are continuously given in media and by government recommendations and rules with the aim to minimize social contacts. the question as to whether and which of our patients with skin disease are at risk for developing severe covid-19 symptoms touches our daily clinical practice and treatment, for example the use of immunosuppressants, topical or systemic drugs such as cyclosporine, methotrexate or the new biologics. patients with hiv infection are perceived to have similar risks as immunosuppressed patients and should take special care in the general prevention measures. at the moment, there is no scientific evidence guiding our therapeutic decisions in systemic immunosuppression; there are only theoretical considerations. for many diseases and therapeutic regimens, some position statements or recommendations are currently being developed by expert groups, for example those for atopic dermatitis or allergic conditions. 4, 5 most individual recommendations support continuing necessary anti-allergic, anti-inflammatory or antineoplastic treatment. with regard to biologics, caution may be advised for anti-tnf, while th2 cytokine antagonists or il-17, il-23 and il-12 may be continued. systemic steroids could possibly aggravate the virus infection, but they may also be considered as a therapeutic modality in severe cases for fighting septic shock. furthermore, we should also contemplate implications of this new pandemic on educational efforts that usually take place in university settings, often involving practical bedside teaching in small groups (reinholz et al., this issue). 6 should dermatologists and venereologists reduce their service in this time of pandemics in order to contribute to general prevention by decreasing social contacts? probably yes. this is the time to take full advantage of teledermatology and telemedicine in order to avoid unnecessary face-to-face contacts while still cultivating a good patient-doctor interactions with shared decision-making. contributions in this or future issues of our journal will explore all of these aspects. we will keep you updated about the coronavirus-related news relevant to our specialty. cutaneous manifestations in covid-19: a first perspective protecting medical staff from skin injury/ disease caused by personal protective equipment during epidemic period of covid-19: experience from china special article: covid-19: pandemic contingency planning for the allergy and immunology clinic european task force on atopic dermatitis (etfad) statement on severe acute respiratory syndrome coronavirus 2 (sars-cov-2)-infection and atopic dermatitis medical education and care in dermatology during the sars-cov2 2 pandemia: challenges and chances key: cord-345514-71qgingu authors: najafzadeh, mojgan; shahzad, fanila; ghaderi, nader; ansari, kaveh; jacob, badie; wright, andrew title: urticaria (angioedema) and covid‐ 19 infection date: 2020-06-11 journal: j eur acad dermatol venereol doi: 10.1111/jdv.16721 sha: doc_id: 345514 cord_uid: 71qgingu the novel coronavirus, otherwise known as covid‐19 has fast become a major health concern.(1 2) it has been reported that in addition to the conventional respiratory symptoms, patients also display skin manifestations such as urticaria and angioedema.(3) here we present a case study of an elderly man who first presented with generalised pruritic hives ranging from 1.5 to 8.0 cm in diameter on the 5(th) of march 2020. the patient was investigated for another differential diagnosis of urticaria such as parasitic and bacterial infection, for which negative results were found. on the 5th of march 2020 the patient‐reported these symptoms plus general malaise, fatigue, 37.9⁰c temperature and sore throat. initial biochemical tests showed that the patient presented with low numbers of white blood cells (wbc) (wbc=2.75x10(3)). the novel coronavirus, otherwise known as covid-19 has fast become a major health concern. 1 2 it has been reported that in addition to the conventional respiratory symptoms, patients also display skin manifestations such as urticaria and angioedema. 3 here we present a case study of an elderly man who first presented with generalised pruritic hives ranging from 1.5 to 8.0 cm in diameter on the 5 th of march 2020. the patient was investigated for another differential diagnosis of urticaria such as parasitic and bacterial infection, for which negative results were found. on the 5th of march 2020 the patient-reported these symptoms plus general malaise, fatigue, 37.9⁰c temperature and sore throat. initial biochemical tests showed that the patient presented with low numbers of white blood cells (wbc) (wbc=2.75x10 3 ). the most hallmark issue, which is lymphopenia, was detected in this case (lymphocytes= 852). 4 the other blood tests results were found to be normal. real-time polymerase chain reaction (rt-pcr) for covid-19 was not performed due to the time lapse between starting the symptoms and hospital admission. therefore, the ct chest was carried out, which showed pneumonia with bilateral and subpleural areas of ground-glass opacification, consolidation affecting the lower lobes, confirming the diagnosis of covid-19. the relationship between urticaria and infection has rarely been reported; this is probably due to the difficulty in establishing a cause and effect relationship. 5 literature suggests that urticaria and angioedema can be induced by viral and bacterial infection. 6 7 urticaria has previously been this article is protected by copyright. all rights reserved associated with cytomegalovirus, herpesvirus, and epstein-barr virus. a systematic review undertaken in 2016, found that viral infections could also act as potential triggers and sometimes even as the main etiologic agent in causing both acute and chronic urticaria. additionally, they found that in adults, hepatitis viral infections appeared to be the most frequent cause of urticaria, whereas, in children, herpesviral infections were more frequent. to further support this data, it was also found that urticarial manifestations cleared up after the viral infections was treated or controlled. 5 another study found that acute urticaria is a common manifestation of viral infections for both children and adults but more so for children. infections were also identified as the primary cause of urticaria in approximately 37% of cases. 8 currently, there is no significant data regarding the association between skin manifestations such as urticaria and covid-19. 9 one study, in which a group of dermatologists analysed the cutaneous involvement in covid-19 found that from 88 patients, 20.4% portrayed cutaneous manifestation. of these, 8 patients developed the manifestations at disease onset whereas 10 developed the manifestations after hospitalisation. these cutaneous manifestations presented themselves as erythematous rash, widespread urticaria and chickenpox like vesicles. from this data, it can be speculated that the skin manifestations observed with covid-19, may be similar to the cutaneous involvement that is often seen during common viral infections. 9 another case was recently seen in bangkok, a patient presented with only a skin rash, petechia and a low platelet count and was thus diagnosed with dengue fever, however after the patient was admitted with respiratory problems, the correct diagnosis for covid-19 was made. 10 this further highlights a possible association between skin manifestations and the novel coronavirus. this report presents evidence regarding a possible association between urticarial skin manifestations in the early stages of covid-19 and thus its use as a possible early diagnostic indicator. the patient may initially present with a skin rash such as urticaria, which can cloud the diagnosis, resulting in misdiagnosis for another common disease. clinicians should take this report into considerations in order to prevent misdiagnosis as well to allow early diagnosis and better patient outcomes. clinical features of patients infected with 2019 novel coronavirus in wuhan cutaneous manifestations of covid-19: report of three cases and a review of literature lymphopenia predicts disease severity of covid-19: a descriptive and predictive study association between urticaria and virus infections: a systematic review impact of mycoplasma pneumonia infection on urticaria: a nationwide, population-based retrospective cohort study in taiwan urticaria and infections accepted article this article is protected by copyright. all rights reserved first and foremost, we express our deepest gratitude to the doctors and nurses who work on the front line, battling each day against this covid 19 pandemic. we thank the medical teams who, with each shift, risk their own lives to save those of their patients. also, we acknowledge that the patients in this manuscript have given written informed consent to the publication of their case details. key: cord-322069-ys9s7l6e authors: gaspari, valeria; neri, iria; misciali, cosimo; patrizi, annalisa title: covid‐19: how it can look on the skin. clinical and pathological features in twenty covid‐19 patients observed in bologna, northeastern italy date: 2020-06-03 journal: j eur acad dermatol venereol doi: 10.1111/jdv.16693 sha: doc_id: 322069 cord_uid: ys9s7l6e global public health is currently dealing with the explosive spread of the novel coronavirus disease 2019 (covid‐19) [1]. this new type of viral pneumonia, spread from its first focus in wuhan (hubei, china) to across all the world, until a pandemic condition was declared. clinically. the most common symptoms of the disease are cough and fever. more than 80% of patients have asymptomatic to moderate disease, but about 15% get severe pneumonia and 5% develope a multi‐organ failure [2]. global public health is currently dealing with the explosive spread of the novel coronavirus disease 2019 (covid-19) [1] . this new type of viral pneumonia, spread from its first focus in wuhan (hubei, china) to across all the world, until a pandemic condition was declared. clinically. the most common symptoms of the disease are cough and fever. more than 80% of patients have asymptomatic to moderate disease, but about 15% get severe pneumonia and 5% develope a multi-organ failure [2] . the diagnosis of covid 19 is based on a multifactorial approach including clinical symptoms, vital parameters, radiological and laboratory findings the virus isolation, necessary to confirm the diagnosis, is obtained through nasopharyngeal and oropharyngeal swab. italy is one of the most involved countries in this pandemia with 207.428 total cases till now [3] . there are only a few reports concerning the skin manifestations in covid 19 patients. until now twenty skin manifestations in covid 19 patients came to the attention of the dermatology unit of the city of bologna, in emilia romagna, the third italian most affected region. of the twenty patients observed, eighteen of the cases were related to the disease, and two to the devices used for the ventilation assistance, one developing a severe sebopsoriasis of the face, and one a facial herpes. among the eighteen cases related to the disease nine presented exanthematic rashes ( figure 1a-b) , six presented acral vasculitic eruptions (figure 1c-d), two a polymorpholike urticaria (figure 1e) and one a varicelliform eruption. the median age of the patients was 51 years; seventeen were male, three were female. with regards the cases related to the disease, in two the signs were present at the onset, while in the other sixteen they appeared later. we excluded a iatrogenic origin, as these patients had not this article is protected by copyright. all rights reserved assumed any drugs potentially involved in skin reactions over the previous 15 days. other viral etiologies were excluded by performing serology for the viral infections associated with cutaneous manifestations, for example parvovirus b19 and enterovirus. most of them reported itching and burning sensation. only two of them referred pain. they were variably symptomatic for the respiratory tract, but none of them had such a severe lung involvement as to require intubation. one of them was completely asymptomatic, and only the acral vascular manifestation led us the suspicion of coronavirus infection. in six of the patients showing exanthematic rashes a punch biopsy for histological examination was obtained ( figure 1f) , showing features of perivascular dermatitis and vasculitis, which are compatible with that of a viral exanthem. it is known that exanthematic rashes can occur during viral infection [4] . we can say that erythematous rashes during coronavirus infections may have the same origin as the other viral rashes [5] . instead, the vasculitic eruptions could be due to the vascular changes observed in these patients. degeneration of the endothelium, and vascular damages including both formation of thrombus and congestion in small vessels, were observed in organs other than the lung in autopsies from skin. indeed, while the 2019-ncov is mainly distributed in the lung, the damage caused by the infection also involvesthe vessels, with the possibility of ischemic and embolic damages [6] . the clinical patterns of the rashes described in covid-19 patients till now include urticaria, acral ischemia, morbilliform, livedo reticularis, vesicular, and petechial [5;7-9] . as regards the histological patterns, perivascular dermatitis, and transient acantholytic dermatosis are those described till now [10]. we are presenting this paper to share our cases of skin involvement during the coronavirus disease. undoubtedly no certain association can be established between covid-19 and skin eruptions, and further studies are needed. coronavirus disease 2019 (covid-19) situation report -29 clinical characteristics of coronavirus disease 2019 in china ministero della salute. coronavirus disease 2019 (covid-19) parvovirus b19: a dna virus associated with multiple cutaneous manifestations cutaneous manifestations in covid-19: a first perspective a pathological report of three covid-19 cases by minimally invasive autopsies a case of covid-19 pneumonia in a young male with full body rash as a presenting symptom. clin pract cases emerg med covid-19 can present with a rash and be mistaken for dengue a dermatologic manifestation of covid-19: transient livedo reticularis key: cord-300546-s29ycc8i authors: balestri, r.; rech, g.; girardelli, c.r. title: occurrence of sars‐cov‐2 during mycophenolate mofetil treatment for pemphigus date: 2020-05-02 journal: j eur acad dermatol venereol doi: 10.1111/jdv.16578 sha: doc_id: 300546 cord_uid: s29ycc8i we read with great interest the article entitled “should sars‐cov‐2 influence immunosuppressive therapy for autoimmune blistering diseases?” published by di altobrando a. et al. in the jeadv. this is the first report of coronavirus disease 2019 (covid‐19) in a patient affected by autoimmune blistering disease (abd) during immunosuppressive treatment (i.e. azathioprine). the authors conclude that it is crucial to learn of more cases of abd patients under immunosuppressive treatment who have developed covid‐19, in order to better quantify the risk of infection under immunosuppressive therapy. we read with great interest the article entitled "should sars-cov-2 influence immunosuppressive therapy for autoimmune blistering diseases?" published by di altobrando a. et al. in the jeadv. 1 this is the first report of coronavirus disease 2019 in a patient affected by autoimmune blistering disease (abd) during immunosuppressive treatment (i.e. azathioprine). the authors conclude that it is crucial to learn of more cases of abd patients under immunosuppressive treatment who have developed covid-19, in order to better quantify the risk of infection under immunosuppressive therapy. also in our clinical practice we suspended all follow-up visits and, in accordance with the directives of the regional health service, we contacted all scheduled patients by phone. we called a total of 43 patients: 30 affected by bullous pemphigoid, 9 by pemphigus and 4 by mucous membrane pemphigoid. even though our region is the second most affected by covid-19 in italy (cumulative incidence: 718,72 cases/100.000 inhabitants) 2 , only one of these patients tested positive for sars-cov-2, a 65-year old female, affected by pemphigus for 40 months and in therapy with mycophenolate mofetil (mpm) for 38 months. on march 24 her husband was discovered to be affected by covid-19 and was isolated at home, while on march 27 our patient presented severe nausea, fever (37.1° c), anorexia and asthenia; the next day she tested positive for sars-cov-2. however, she did not inform us immediately, and did not suspend therapy until we contacted her on march 29, when we advised her to interrupt mpm. we then called her daily for the next days: on april 2 her fever rose to 39°c, but lowered with paracetamol, and continued this pattern over the following 2 days. starting from april 5 the fever ceased and she progressively improved; on april 8 she referred a total absence of any symptom. the patient did not experience any pemphigus recurrence, but reported only some posterior tongue "discomfort". moreover, she never developed cough, dyspnea, anosmia, ageusia, myalgia or other symptoms of the infection. at present we are waiting for 2 weeks after the end of symptoms to repeat a swab and restart the immunosuppressive treatment. this article is protected by copyright. all rights reserved mpm is an immune suppressant, antineoplastic and antiviral mediation, used in pemphigus as a corticosteroid-sparing agent. due to its anti-viral properties some studies have investigated mpm as a potential therapy for mers-cov. 3 the drug has also been demonstrated to inhibit mrna expression of pro-inflammatory cytokines tnf-α, il-6 and il-1β 4 , which are known to be associated with the progression of covid-19 toward the worsening of clinical conditions. 5,6 even though the in vitro studies showed promising results for mpm against mers, the in vivo studies suggest that its use is likely to cause more harm than benefit and hence is not likely to be useful against coronavirus infections. 3 however, our patient experienced a very mild form of the disease, without pulmonary complications, suggesting that the immunosuppressant therapy with mpm was not detrimental in the setting of covid-19 infection. unfortunately abds are rare conditions and it is difficult to collect large cohorts to confirm our observation. this would require much time, which is scarcely compatible with the urgency related to the covid-19 sanitary emergency. therefore our present knowledge can only be based on anecdotal reports, and it is important to share also the single experience of any center involved in the management of rare diseases. should sars-cov-2 influence immunosuppressive therapy for autoimmune blistering diseases? associations between immune-suppressive and stimulating drugs and novel covid-19-a systematic review of current accepted article this article is protected by copyright. all rights reserved evidence mycophenolate mofetil modulates differentiation of th1/th2 and the secretion of cytokines in an active crohn's disease mouse model research progress on the mechanism of cytokine storm induced by new coronavirus pneumonia and related immunotherapy clinical features of patients infected with 2019 novel coronavirus in wuhan, china acknowledgment: "the patients in this manuscript have given written informed consent to publication of their case details." key: cord-340842-s00465sy authors: cabrera‐hernández, r.; solano‐solares, e.; chica‐guzmán, v.; fernández‐guarino, m.; fernández‐nieto, d.; ortega‐quijano, d.; de‐andrés‐martín, a.; moreno, c.; carretero‐barrio, i.; garcía‐abellás, p.; gonzález‐de‐olano, d.; de‐la‐hoz‐caballer, b. title: sars‐cov‐2, skin lesions and the need of a multidisciplinary approach date: 2020-06-13 journal: j eur acad dermatol venereol doi: 10.1111/jdv.16745 sha: doc_id: 340842 cord_uid: s00465sy covid‐19 is a disease caused by severe acute respiratory syndrome coronavirus 2 of the genus betacoronavirus (sars‐cov‐2). it was first described in wuhan (china) on december 2019 and has spread to become a pandemic. its clinical presentation is mainly characterized by cough, fever and dyspnea, although many other symptoms have been described within its presentation pattern. in some cases, it causes an acute respiratory distress that has lead to the death of thousands of people around the world. furthermore, different types of skin lesions have been described during the infection period of illness.1 in this exceptional situation of global health emergency, physicians are undertaking research work in order to achieve notions on the etiopathogenesis of these skin lesions. the first report of cutaneous manifestations described different forms of skin lesions such as erythematous rash, urticaria and chicken‐pox‐like vesicles.2 further studies have classified 5 different type of skin lesions, and associated them with patient demographics, timing in relation to symptoms of the disease, severity and prognosis. this article is protected by copyright. all rights reserved covid-19 is a disease caused by severe acute respiratory syndrome coronavirus 2 of the genus betacoronavirus (sars-cov-2). it was first described in wuhan (china) on december 2019 and has spread to become a pandemic. its clinical presentation is mainly characterized by cough, fever and dyspnea, although many other symptoms have been described within its presentation pattern. in some cases, it causes an acute respiratory distress that has lead to the death of thousands of people around the world. furthermore, different types of skin lesions have been we present 4 patients with covid-19, confirmed by positive polymerase chain reaction, who were referred to our service due to the appearance of skin lesions ( figure 1 ). two of them developed skin lesions during hospitalization whilst presenting respiratory symptoms and the other two developed skin lesions many days after hospital discharge. demographic data, description and histology of skin lesions, blood parameters, clinical symptoms and drugs administered are shown in table 1 . the algorithm of the spanish pharmacovigilance system (asps), which evaluates the possible implication of a drug reaction as a cause of the skin lesions,6 was also applied. the asps analizes: i) the interval between drug administration and the aparition of skin lesions, ii) the degree of knowledge of the relationship between the drug and the effect described in literature, iii) the evaluation of drug withdrawal, iv) the rechallenge effect, and v) alternative causes. each item receives and individual subscore, and a total sum ≥ 6 indicates a probable causality.6 this article is protected by copyright. all rights reserved as mentioned above, skin lesions appear to be a sign within patients suffering from covid-19. to date, no hypothesis has been proposed to explain if the lesions (including the different types) are attributable to the virus, to drug adverse reactions or to any other clinical condition. histopathological study alone cannot conclude an etiology, as it does not distinguish between a posible viral exanthema and a toxicoderma (figure 1 ). in our series, small enough to draw conclusions, we have found no differences between the multiple types of skin lesions and analytical or clinical features. even in lesions with apparent vascular involvement, which have been associated with alterations in coagulation,3-5 the analitycal parameters did not differ from those with other types of skin lesions. regarding drug involvement, since all the patients were exposed to multiple drugs at the same time, the asps was not able to differentiate the possibility of drug implication nor the immune mechanisms involved. thus, further assays with selective (in vitro or in vivo) tests for each drug seem necessary in order to completely rule out drug involvement. in addition, since many patients worldwide are being infected with sars-cov-2, and many of them present similar medical history and receive the same treatments, it seems necessary to investigate the existence of an individual predisposition that facilitates the developement of skin lesions. for all these reasons, in order to correctly study the etiology of the skin lesions, a multidisciplinary approach should be carried out. this article is protected by copyright. all rights reserved classification of the cutaneous manifestations of covid-19: a rapid prospective nationwide consensus study in spain with 375 cases cutaneous manifestations in covid-19: a first perspective clinical and coagulation characteristics of 7 patients with critical covid-2019 pneumonia and acro-ischemia a new vasculitis at the time of covid-19 lesiones pernióticas y acrales en españa durante el confinamiento por covid: análisis retrospectivo de 12 casos causality assessment in reports on adverse drug reactions. algorithm of spanish pharmacovigilance system the patients in this manuscript have given written informed consent to publication of their case details. this article is protected by copyright. all rights reserved this article is protected by copyright. all rights reserved key: cord-267748-uzt8a5nx authors: shiohara, tetsuo; mizukawa, yoshiko title: comment on “drug reaction with eosinophilia and systemic symptoms syndrome in a patient with covid‐19”: involvement of herpesvirus reactivations and adverse drug reactions in diverse cutaneous manifestations and overall disease severity of covid‐19 date: 2020-09-24 journal: j eur acad dermatol venereol doi: 10.1111/jdv.16959 sha: doc_id: 267748 cord_uid: uzt8a5nx we have read with great interest the publication by herman, et al., which reported occurrence of drug reaction with eosinophilia and systemic symptoms (dress), also known as drug‐induced hypersensitivity syndrome (dihs), in a covid‐19 patient:(1) the patient developed dihs/dress 17~18 days after starting azithromycin and hydroxychloroquine. we have read with great interest the publication by herman, et al., which reported occurrence of drug reaction with eosinophilia and systemic symptoms (dress), also known as drug-induced hypersensitivity syndrome (dihs), in a covid-19 patient: 1 the patient developed dihs/dress 17~18 days after starting azithromycin and hydroxychloroquine. the benefits shortly after starting these drugs appeared to be minor, whereas the long-term immune dysregulation was significant. dihs/dress is a life-threatening multi-organ system reaction induced by a limited number of the causative drugs with the immunosuppressive potential and are characterized by sequential occurrence of herpesvirus reactivations. 2, 3 here, we provide a brief insight into the similarities and differences in the clinical manifestations of covid-19 and dihs/dress. cytomegalovirus-induced infectious mononucleosis, parvovirus b19 infection, dengue virus infection and kawasaki disease. 2 in dihs/dress, even after drug withdrawal, resolution of symptoms in one organ is often followed by a stepwise development of other organ failures, such as gastroenteritis, interstitial pneumonia, limbic encephalitis and myocarditis. 2 such clinical variability in the presentation and course could be mediated by sequential occurrence of herpesvirus reactivations. initial expansions of regulatory t cells (tregs) and their subsequent exhaustion provide a mechanism for why herpesviruses can be sequentially reactivated at the acute~subacute phases (3~40 days after onset) and why the patients have severe complications/sequelae: ４ a gradual loss of treg function could increase the risk of developing widespread collateral tissue damage. [2] [3] [4] in dihs/dress, the pathogenic cascade triggered by drug damages many organs from the skin to the brain, as shown in covid-19 patients. during this article is protected by copyright. all rights reserved the disease process in covid-19 as well as dihs/dress, a variety of clinical symptoms may develop later depending on the herpesvirus reactivated. indeed, diverse clinical symptoms in dihs/dress have been also reported as covid-19-related cutaneous manifestations without confirming viral or drug etiologies: they include erythema multiforme, varicella, herpes zoster, pityriasis rosea, kawasaki disease and urticaria, 5~7 in which herpesviruses, such as varicella-zoster virus (vzv) and human herpesvirus 6 (hhv-6), have been suggested to play a role. a recent report also describes co-reactivation of herpes simplex virus-1 and vzv in a critically ill covid-19 patient. 8 because hhv-6 has been shown to be associated with chronic spontaneous urticaria, herpesvirus reactivations including hhv-6 could be involved in diverse cutaneous manifestations previously attributed to sars-cov-2. if so, anti-viral agents may ameliorate severe covid-19 symptoms when used as adjuncts to putative anti-covid-19 agents. in addition, adverse drug reactions (adrs) could have contributed to the diverse cutaneous manifestations. in support of this, a recent report describe 5.84-fold higher incidence rate of severe adrs in covid-19 patients; 9 and we have recently reported a covid-19 patient who developed typical covid-19-associated cutaneous manifestations, 10 symmetrical drug-related intertriginous and flexural exanthema, in which "multiple drug hypersensitivity" not only to the causative drug but also to other drugs used for covid-19 was demonstrated by lymphocyte transformation tests. 10 such "multiple drug hypersensitivity" was typically observed in the acute~subacute phases of dihs/dress, at which time treg function becomes impaired. 4 most reports, however, demonstrated cutaneous manifestations of covid-19 without performing screening tests for herpesvirus reactivation and adrs. thus, severe covid-19 symptoms appear to be driven by a complex interplay involving reactivations of latent herpesviruses, this article is protected by copyright. all rights reserved anti-viral immune responses, and dug-driven immune responses, as demonstrated in dihs/dress. patients who experienced herpesvirus reactivations and adrs are more likely than those without them to have a more severe disease course: the combination of these factors could result in covid-19-associated multiorgan failures. accurate assessment of the patient's viral infection status and a possibility of adrs is highly required. the etiology of severe covid-19 symptoms may be multifactorial. drug reaction with eosinophilia and systemic symptoms syndrome in a patient with covid-19 drug-induced hypersensitivity syndrome(dihs)/drug reaction with eosinophilia and systemic symptoms (dress):an update in 2019 drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms severity and predicting fatal cytomegalovirus disease accepted article this article is protected by copyright. all rights reserved defective regulatory t cells in patients with severe drug eruptions: timing of the dysfunction is associated with the pathological phenotype and outcome erythema multiforme and kawasaki disease associated with covid-19 infection in children pityriasis rosea as a cutaneous manifestation of covid-19 infection urticaria-like lesions in covid-19 patients are not really urticaria -a case with clinicopathological correlation co-reactivation of human herpesvirus alpha subfamily (hsv 1 and vzv) in critically iii patient with covid-19 suspected serious adverse reactions in hospitalized covid-19 patients. preprints covid-19-related cutaneous manifestations associated with multiple drug sensitization as shown by lymphocyte transformation test all authors have agreed to the contents of the manuscript in its submitted form. no funding sources. key: cord-346763-xdfl659q authors: herman, a.; matthews, m.; mairlot, m.; nobile, l.; fameree, l.; jacquet, l.‐m.; baeck, m. title: drug reaction with eosinophilia and systemic symptoms syndrome in a patient with covid‐19 date: 2020-08-13 journal: j eur acad dermatol venereol doi: 10.1111/jdv.16838 sha: doc_id: 346763 cord_uid: xdfl659q skin rashes associated with covid-19 include eruptions induced by drugs prescribed for management of this infection. we report a case of drug reaction with eosinophilia and systemic symptoms (dress) syndrome in a patient with covid-19. a 50-year-old man was admitted to the intensive care unit for pneumonia with acute respiratory distress syndrome. covid-19 was confirmed by positive rt-pcr sars-cov-2 on nasopharyngeal swabs and later by positive igm and igg antibodies against sars-cov-2 (114,5 au/ml). in the context of fever >38,5°c, nine days after admission, the patient developed a generalized maculopapular rash on more than 70% of his body surface area with oedema of hands and face (fig.1). azithromycin and hydroxychloroquine had been initiated 18 and 17 days respectively prior to the skin eruption. skin rashes associated with covid-19 include eruptions induced by drugs prescribed for management of this infection. we report a case of drug reaction with eosinophilia and systemic symptoms (dress) syndrome in a patient with covid-19. a 50-year-old man was admitted to the intensive care unit for pneumonia with acute respiratory distress syndrome. covid-19 was confirmed by positive rt-pcr sars-cov-2 on nasopharyngeal swabs and later by positive igm and igg antibodies against sars-cov-2 (114.5 au/ml). in the context of fever >38.5°c, nine days after admission, the patient developed a generalized maculopapular rash on more than 70% of his body surface area with oedema of hands and face (fig. 1 ). azithromycin and hydroxychloroquine had been initiated 18 and 17 days, respectively, prior to the skin eruption. the patient had also received the following drugs: heparin, propofol, clonidine, norepinephrine, sufentanil and rocuronium (at admission); pantoprazole (9 days before); sevoflurane (8 days before); cefuroxime (6 days before); and flucloxacillin (4 days before). laboratory tests revealed a new elevation of c-reactive protein (crp) level (349 mg/l; nl. <5 mg/l), high absolute blood eosinophilia (950/ µl; nl. <600/µl), atypical lymphocytes (120/µl) and elevated ddimer (7343 ng/ml; nl. <500 ng/ml). moreover, patient presented abnormal renal function (blood urea nitrogen 93 mg/ml, serum creatinine 1.37 mg/dl) and altered liver tests [elevated serum aspartate amino transferase (asat): 59 u/l; nl. <35, and gamma glutamyl transferase (ggt): 579 u/l; nl. <60]. serologic investigations carried out 8 days after the beginning of the eruption for epstein-barr virus (ebv) and cytomegalovirus (cmv), and after 11 days for human immunodeficiency virus (hiv), and hepatitis b and c were negative. histopathological analysis of skin biopsy specimens showed oedema of the dermis associated with moderate perivascular infiltrate including lymphohistiocytic cells and eosinophils, suggestive of a dress. according to the scoring system for classifying dress cases (regiscar) reported by kardaun et al., 1 a drug reaction with eosinophilia and systemic symptoms (dress) syndrome was diagnosed as follows: fever ≥38.5°c (0), enlarged lymph nodes (0), eosinophilia (1), atypical lymphocytes (1), skin rash extent >50% body surface area (1), skin rash suggesting dress (1), biopsy suggesting dress (0), organ involvement (liver, kidney, lung) (2), resolution ≥15 days (0), viral titers (hbv/hcv) negative (1) . the prognosis of dress in our patient was considered severe according to the severity and prognosis scoring system proposed by mizukawa et al. 2 with a total score in the early phase (calculated during the first 3 days of the eruption) of 8 (>4) as follows: age (0), duration of drug exposure after onset (1), erythema >70% bsa (1), erosion, <10% bsa (0), fever >38.5°c during >7 days (2), appetite loss (<70% of regular food intake) (1), renal dysfunction (creatinine) (1), liver dysfunction (alt) (0), c-reactive protein (2) . all suspected drugs (in particular azithromycin and hydroxychloroquine) had already been stopped and intravenous corticosteroids were administered (methylprednisolone 1 mg/kg/day). progressive resolution (over more than 15 days) of the exanthema and systemic involvement (inflammatory, haematological, hepatic, renal) was observed with gradual tapering of corticosteroid therapy (80 mg/day for 9 days; 40 mg/day for 11 days; 20 mg/day for 11 days; 8 mg/day for 5 days), and the patient was discharged from icu 3 weeks later. rt-pcr sars-cov-2 rna performed on skin samples as well as sequential rt-pcr sars-cov-2 rna performed on nasopharyngeal swabs after the resolution of the symptoms was negative. dress syndrome is a severe cutaneous adverse drug reaction. usually, the rash appears 3-8 weeks after the initial administration of the drug. in the present case, many drugs were administered. however, from a chronological point of view, hydroxychloroquine and azithromycin, used for their probable antiviral activity against sars-cov-2, were most likely responsible for the syndrome. in this case, the latency period between therapy and onset of the adverse reaction might seem quite short (17-18 days). this could result from repeated use of the same drug; however, it was not the case for this patient. a few cases of dress have already been reported with hydroxychloroquine, 3, 4 including one case with ebv reactivation. 5 rare cases of dress linked to azithromycin have also been described, 6, 7 including one case in a child also associated with primary ebv infection. 8 the pathophysiology of dress syndrome is complex and not completely defined. on the one hand, a delayed hypersensitivity to drugs suggests a t-cell-mediated reaction, but viral reactivations or antiviral immunity also seem to be implicated. however, the interaction and role of viral infections on the drug metabolism as well as onset and amplification of the culprit drug-specific t lymphocyte response remain incompletely defined. the most frequently associated viruses are human herpes virus (hhv) 6 and 7, ebv and cmv. one case of dress has been reported associated with the influenza a and b virus. 9 due to negative rt-pcr sars-cov-2 on nasopharyngeal swabs after the eruption in our patient, viral reactivation seems unlikely. lymphocyte transformation tests will be performed 4-6 weeks after onset of the eruption and patch tests will only be performed within 3-6 months to confirm the imputability of either drug, however, it is important to make clinicians aware of such reactions with severe inflammatory effects and end organ involvement could become more frequent during the current pandemic and could complicate the management of covid-19 patients. 4 however, it remains plausible that that the high dose of systemic corticosteroid administrated for the dress syndrome could have had a positive impact on the clinical course of the critical covid-19 of this patient. to conclude, we report a case of dress syndrome possibly due to hydroxychloroquine or azithromycin in a patient with covid-19. variability in the clinical pattern of cutaneous side-effects of drugs with systemic symptoms: does a dress syndrome really exist? drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms severity score: a useful tool for assessing disease severity and predicting fatal cytomegalovirus disease hydroxychloroquine-induced dress syndrome drug reaction with eosinophilia and systemic symptoms syndrome to hydroxychloroquine, an old drug in the spotlight in the covid-19 era pustular dress syndrome secondary to hydroxychloroquine with ebv reactivation dress associated with azithromycin in a child drug reaction with eosinophilia and systemic symptoms syndrome (dress) syndrome associated with azithromycin presenting like septic shock: a case report drug reaction with eosinophilia and systemic symptoms (dress) associated with azithromycin in acute epstein-barr virus infection dress syndrome associated with influenza virus the patient in this manuscript has given written informed consent to the publication of their case details. the authors disclosed any financial association or other conflicts of interest. 