key: cord-0703145-kogsj18m
authors: Sugai, T.; Fujita, Y.; Inamura, E.; Maya, Y.; Shimizu, S.
title: Prevalence and patterns of cutaneous manifestations in 1245 COVID‐19 patients in Japan: a single‐centre study
date: 2022-03-18
journal: J Eur Acad Dermatol Venereol
DOI: 10.1111/jdv.18062
sha: 9791b87d3cb246e839422647388e36905e060d64
doc_id: 703145
cord_uid: kogsj18m

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erythematous papules on the body and livedo reticularis-like lesions on the legs (Fig. 1a and 1b) . The skin rashes had mostly disappeared spontaneously by day 22. A drug-induced lymphocyte stimulation test (DLST) was negative for favipiravir.

Case 2: A 60-year-old Japanese man was admitted for severe COVID-19. A generalized skin rash developed on day 3 of favipiravir treatment (Fig. 1c) . Histopathology showed vacuolar degeneration and scattered dyskeratosis (Fig. 1d) . Drug eruptions were ruled out by DLST and oral challenge test.

We conducted a retrospective observational single-centre study to investigate the prevalence of cutaneous manifestations associated with COVID-19. Overall 1245 inpatients at Sapporo City General Hospital from January 2020 to June 2021 were extracted. This study was approved by the institutional ethics committee of our institute (R3-060-869).

The median age was 68 years (range: 0-105) and 53.7% of cases were male. All but two patients were Japanese (one Han Chinese and one Canadian). The average hospital stay was 14.0 AE 8.8 days. The distribution of COVID-19 severity was as The prevalence of cutaneous manifestations was 0.56% (7/ 1245 cases three females and four males). The cutaneous manifestations were maculopapules in five cases erythema multiforme in two cases and livedo in one case. The average time from COVID-19 onset to cutaneous lesion appearance was 16.7 days and the average duration of lesions was 9.3 days.

Next we performed a literature search of the PubMed database for articles in English about cases of COVID-19 with cutaneous manifestations between December 2019 and September 2021 (accessed on 30 September 2021) and we added nine Japanese cases. The most frequent cutaneous manifestations were maculopapules (12/16 75.0%) followed by erythema multiforme (2/16 12.5%); there was only one case each of pseudo-chilblain and livedo.

Our study highlights that cutaneous manifestations in COVID-19 cases are rarely observed in Japan. A meta-analysis reported a 6.6% prevalence of skin manifestations in Europe and a 0.2% prevalence in Asia (China and Thailand). 2 In Japan one small study reported a 4.3% (3/69) prevalence in mild-to-moderate COVID-19 patients. 3 Since our study included 1245 inpatients for 17 months the prevalence of 0.56% is thought to accurately reflect the clinical situation.

We also reveal that maculopapular lesions are common (75.0%) in Japan. The most common COVID-19-related skin rash was reported to be pseudo-chilblain lesions (40.9%) and 97% of these cases were from Europe or the USA. 4 The differences in cutaneous patterns may owe to a genetic/racial predisposition. The minor allele frequency of the IFIH1 gene which is common in Caucasians increases the production of type-1 interferons that can induce microangiopathy. 5 The patient age and the observation period might also explain the low frequency of pseudo-chilblains. The median age of pseudo-chilblains is reported to be 16.6-27.2 years and approximately 80% of cases were noticed at more than 2 weeks after onset whereas the figures for our study are median age of pseudo-chilblains of 68 years and mean duration of hospitalization of 14.0 days. 4, 6, 7 

Classification of the cutaneous manifestations of COVID-19: a rapid prospective nationwide consensus study in Spain with 375 cases

COVID-19 and skin manifestations: an overview of case reports/case series and meta-analysis of prevalence studies

Three cases of COVID-19 patients presenting with erythema

Skin manifestations of COVID-19: a worldwide review

The African-American population with a low allele frequency of SNP rs1990760 (T allele) in IFIH1 predicts less IFN-beta expression and potential vulnerability to COVID-19 infection

Time of onset of selected skin lesions associated with COVID-19: a systematic review

COVID toes": A meta-analysis of case and observational studies on clinical, histopathological, and laboratory findings

We would like to express our gratitude to Drs. A. Nagasaka and F. Kodama for their great contributions to COVID-19 treatment and for their support. The patients in this manuscript have given written informed consent to publication of their case details.