key: cord-0992399-npa3vtso authors: Herrero‐Moyano, M; Capusan, TM; Andreu‐Barasoain, M; Alcántara‐González, J; Ruano‐Del Salado, M; Sánchez‐Largo Uceda, ME; Calzado‐Villarreal, L; Pérez‐González, Y title: A clinicopathological study of 8 patients with COVID‐19 pneumonia and a late‐onset exanthema date: 2020-05-19 journal: J Eur Acad Dermatol Venereol DOI: 10.1111/jdv.16631 sha: 8f872ad3b0c5d8eba993c5cca7994cf744c3385e doc_id: 992399 cord_uid: npa3vtso Our hospital diagnosed the two first non‐imported COVID‐19 cases in Spain on 26(th) February. Up to date, a total of 1177 COVID‐19 patients have been hospitalized. Eight of them were referred for dermatological examination. Due to the overwhelming situation, the incidence of cutaneous manifestations in our hospitalized COVID‐19 patients is probably greater than this 0.7%(1, 2). Most frequent drugs during hospitalization were hydroxychloroquine (HCQ), lopinavir/ritonavir and ceftriaxone. These treatments had finished at least one week before the onset of the cutaneous rash in all cases, except patient 2. Three patients had no new medications in the previous 15 days. Only two patients received new drugs in the previous 48 hours. Mean latency time from systemic symptoms to exanthema was 27.6 days. Exanthema varied from illdefined erythematous patches to coalescent maculopapules, some of them with violaceous centre (Fig. 1 ) .The trunk was invariably involved with predilection for the back and folds. Patient 7 developed pustules and desquamation ( Fig. 1: f) . Mean duration of the exanthema is 11.6 days so far. Histologically, patients showed in a variable degree: spongiosis dermatitis, non-follicular subcorneal pustules, neutrophilic exocytosis, an interstitial neutrophilic infiltrate and scarce eosinophils ( Table 1 , Our patients presented maculopapular eruptions that shared a late onset. This fact leads us to hypothesize that the rash could be caused by the cytokine storm of the hyperinflammatory phase 4 rather than by the virus itself. A common histological pattern was found and it was more striking in patients whose biopsies were performed later, therefore, it might be the same process in different stage of evolution. Three patients showed microthrombi in dermal capillaries as the ones described by Gianotti et al in 2 cases 5 . Recent publications have found evidence of direct viral infection of the endothelial cell in different organs that could explain the impaired microcirculatory function of this disease 6 . In our cases, microthrombi could be a clue for severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection. They could also be an epiphenomenon of a possible acute generalized exanthematous pustulosis (AGEP), but this has not been described before 7 . A further in situ hybridization or SARS-CoV2 immunohistochemistry would help to clarify this question. We found difficulty to distinguish the viral or drug origin of the rashes. However, only 2 patients started new medications during the few days before, as usually occurs in AGEP 8 . Furthermore, clinically no This article is protected by copyright. All rights reserved patient except one resembled a classical AGEP. Patch tests need to be performed to determine a possible drug responsibility. An atypical form of AGEP, generalized pustular figurate erythema, has been described as a delayed reaction to HCQ 9 . Nevertheless, the incidence of this adverse effect to HCQ is infrequent 10 . Thus, if the type of exanthema we are describing here is related to HCQ, there may be another factors (as SARS-CoV2 virus itself) playing a role. To conclude, we present a series of 8 patients with COVID-19 pneumonia who developed a late-onset maculopapular exanthema with a distinct histological pattern. Microthrombi may be a clue for SARS-CoV2 endothelial infection. This article is protected by copyright. All rights reserved Clinical Characteristics of Coronavirus Disease 2019 in China 1056/NEJMoa2002032 2-Recalcati S. 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 COVID-19 Illness in Native and Immunosuppressed States: A Clinical-Therapeutic Staging Proposal Cutaneous Clinico-Pathological Findings in three COVID-19-Positive Patients Observed in the Metropolitan Area of Endothelial cell infection and endotheliitis in COVID-19 EuroSCAR and RegiSCAR study group. The spectrum of histopathological features in acute generalized exanthematous pustulosis: a study of 102 cases Generalized pustular figurate erythema: A newly delineated severe cutaneous drug reaction linked with hydroxychloroquine Characterizing the adverse dermatologic effects of hydroxychloroquine: a systematic review We thank all the health workers of Hospital Universitario de Torrejón for their extraordinary work during this pandemic. All patients in this manuscript have given written informed consent to the publication of their case details and pictures.