key: cord-0789194-qdbunnk8 authors: Burlando, Martina; Russo, Roberto; Cozzani, Emanuele; Parodi, Aurora title: Six months into the pandemic. A review of skin manifestations in SARS‐CoV‐2 infection date: 2020-12-14 journal: Dermatol Ther DOI: 10.1111/dth.14641 sha: bb257e2273c2bf72b8cd82897372527bb3b854a7 doc_id: 789194 cord_uid: qdbunnk8 During the COVID‐19 pandemic, various cutaneous manifestations have been described as associated with SARS‐CoV2 infection. It is debated if skin lesions could represent a diagnostic or prognostic indicator. Specifically, it is unclear whether skin lesions may be used to perform an early diagnosis and/or to predict worse outcomes. In this review, we described the cutaneous signs so far reported as COVID‐19‐related and discussed their incidence, clinico‐pathological features, and diagnostic and prognostic value. In December 2019, the coronavirus disease of 2019 (COVID- 19) , caused by the severe acute respiratory syndrome coronavirus (SARS-CoV-2), was identified in Wuhan, China. In the ensuing months, the COVID-19 pandemic has spread across the world. Emergency departments have adopted screening and triage procedures to identify potential cases and isolate them during evaluation. 1 Suspect of COVID-19 is mainly made on clinical signs (fever, fatigue, dry cough, anorexia, dyspnea, rhinorrhea, ageusia, anosmia), vital parameters (temperature, pulse oximetry saturation), and radiological settings (X-ray, Chest CT scan). Laboratory findings often demonstrate lymphopenia and elevated LDH. Nasopharyngeal and oropharyngeal swabs, allowing the virus isolation, confirms the diagnosis. 2 Recently, the suspect that skin manifestations could be a sign of infection is increasing day by day, due to growing publication of case reports and case series. The exact incidence of skin reactions due to COVID-19 is still unknown. Also, it is unclear whether COVID-19 affects skin and whether a possible link between skin reactions and infection severity exists. For these reasons, the aim of this paper is to review the available evidence on the cutaneous reactions related to COVID-19. Up to 10 September 2020, a literature search was conducted in the PubMed/MEDLINE database, using the terms ''COVID-19'' and ''SARS-CoV-2'' in combination with the terms ''skin'', ''cutaneous'', ''rash''. Language was restricted to English. To limit interference from isolated reports or chance associations, as we aimed to provide an overview on the most frequently observed skin manifestations in the setting of Sars-CoV-2 infection, only the original articles and case series reporting at least 10 patients were comprised. Two blinded reviewers independently screened articles for fulfillment of inclusion criteria. Articles from the references cited in the retrieved papers were considered as well. Initial and updated searches found 1736 titles, with 1107 titles once duplicates were removed. A total of 629 full-text papers were reviewed and checked for inclusion criteria. The final analysis included 36 papers, with a total of 1340 patients with SARS-Cov-2 skin manifestations. The characteristics of the cutaneous symptoms were clustered together into categories, following a method elsewhere described, 3 and included: vesicular eruption (88 cases), urticarial eruptions Martina Burlando and Roberto Russo contributed equally to this study. (86 cases), erythematous and maculopapular exanthemas (451 cases), and vascular skin lesions (715). The latter category was subdivided as follows: livedo, purpuric lesions (23) , and chilblain-like and erythema multiforme-like lesions (692). It was not possible to separate the cases confirmed by swab test or biopsy from patients whose diagnosis was not confirmed, as this datum was not always reported. higher incidence of herpes zoster has also been reported. 6 Also, a Grover-like picture has been described by Matar et al. 11 Except for one patient presenting with clinical and histological features of an acantholytic, Grover-like disease, 12 there is no certain report about vesicular rash in outpatients. Urticarial eruptions among COVID-19 patients have been reported. 8, 13 A prospective Italian study on 103 PCR-confirmed COVID-19 patients identified 2 patients with urticarial rash. 12 In an Italian study, 3 out of 88 COVID-19 inpatients showed urticarial eruptions. 2 A Spanish multicentric study on 375 patients with COVID-19-compatible symptoms and cutaneous lesions reported 73 patients with urticarial rash, of which 49 were PCR-confirmed cases. 6 Among 153 patients diagnosed with SARS-CoV-2 infection in Bangkok, Thailand, who were retrospectively interviewed to collect data on skin manifestations, urticarial rash was the most commonly reported dermatological sign. 9 Wheals were also the most frequent skin manifestations (3 out of 10 patients with cutaneous lesions, among 138 COVID-19 inpatients) in a hospital in India. 14 Erythematous, macular, and papular exanthemas have been widely reported. 8, 12, 15 Erythematous rash was the most common cutaneous manifestation (14 out of 88 COVID-19 inpatients) described by Recalcati et al. 2 According to Galvàn-Casas et al., 5 half of the cutaneous manifestations in COVID-19 patients were maculopapular rashes. Maculopapular exanthema was the most common skin manifestation among 759 COVID-19 patients in a hospital in Paris, France; still, it was very rarely recognized. 11 Erythematous scaly rash and maculopapular rash accounted respectively for 32.7% and 23% of skin manifestations among 210 COVID-19 patients in a hospital in Turkey, 52 of whom developed skin lesions during infection. 16 According to a Spanish study, mucosal enanthems were found in 6 out of 21 PCRpositive patients showing a skin rash. 17 Four out of 153 COVID-19 patients showed a maculopapular eruption in a study conducted in Thailand. 9 Pangti et al. reported only one case of macular erythematous rash among 138 SARS-CoV-2-positive inpatients. 14 Another Indian study reported 13 patients with cutaneous manifestations out of 102 COVID-19 patients; however, itching with no skin lesions was the most common sign, followed by maculopapular rash, which was described in 3 patients only. 18 A case of eruptive pseudoangiomatosis, a skin condition related to viral infections, was reported. 8 Livedo, necrotic purpura, and dry gangrene were rarely found in studies with large samples 6, 8, 9, 14 ; and numerous series reported no case of vascular lesions. 2, 12 More commonly, chilblain-like lesions were found on the extremities. They are described in both inpatients and outpatients. Histology of these skin lesions were described by Kanitakis et al., although in PCR-negative patients. 19 Most reports involve young outpatients. 20, 21 Analyzing the results of a large study, 6 In several studies, erythematous and maculopapular exanthemas were the most common cutaneous findings associated with COVID-19. Their incidence was variable among studies. However, exanthemas, as well as urticarial eruptions, do not represent a specific finding. Their association with viral infection in general is well known. COVID-19-associated vascular cutaneous lesions could be divided into two groups: severe, necrotic manifestations and mild, acral signs. The former tend to be recognized in hospitalized, critical patients, often in the setting of IT; the latter are generally found in patients with moderate disease, mostly outpatients, often young. Although many of the outpatients were negative or not tested for SARS-CoV-2 (maybe because many of them lacked testing access due to testing criteria), 27 all over the world an increased incidence of acral chilblain-like lesions was noticed in spring 2020. Moreover, patients developing this kind of lesions were often in familial clusters, for example, were relatives of COVID-19 patients. Thus, we could reasonably suppose that mild acral manifestations could reveal previous infection with a sufficient control of it (probably IgA-mediated, according to serologic findings), 29 Although many reports are available about cutaneous findings associated with SARS-CoV-2 infection, no specific skin manifestation, which could be useful for COVID-19 diagnosis, has been found yet. Although repeatedly described, vesicular and urticarial rashes, as well as exanthemas, should be considered uncommon and not specific. This work did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. The authors declare no potential conflict of interest. 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