Abstract
Background: Erythema multiforme (EM) is an acute cutaneous eruption often associated with infections and more rarely with drugs. This review aimed to evaluate the association between erythema multiforme and coronavirus disease 2019 (COVID-19). Methods: A systematic search of PubMed/MEDLINE, Scimago Scopus, and ISI/Web of Science was performed. Original articles, case series, or case reports were evaluated and selected. Results: Fourteen articles were selected, describing a total of 70 patients. EM is a cutaneous eruption rarely occurring in COVID-19 and is, in most cases, associated with a hypersensitivity reaction to the virus. In these cases, EM seems to affect patients younger than 30 years or older than 55 years. Infrequently, some drugs used in the management of COVID-19 may induce EM, especially hydroxychloroquine. The three groups of patients seem to have different clinical characteristics and courses. Conclusions: From these data, it is possible to preliminarily propose that EM or EM-like eruptions linked to COVID-19 might be divided into three types: the virus-related juvenile type (affecting patients <30-year-old), the virus-related older type (affecting patients >55 years), and the drug-induced type. The occurrence of a skin rash does not seem to be related to the severity and clinical course of COVID-19.
Highlights
Erythema multiforme (EM) is a skin disease characterized by the appearance, usually on the extremities but often occurring in other skin areas, of reddish, annular macules, which later become papules, sometimes coalescing to plaques
A study analyzing 132 patients infected by SARS-CoV-2 and with various types of acute palmoplantar skin lesions found that 37 (28.03%) of them had EM-like lesions [7]
SARS-CoV-2 infection or, much more rarely, induced by the disease’s treatment. These skin eruptions’ pathophysiological mechanism could be a hypersensitivity reaction mediated by lymphocytes targeting SARS-CoV-2 antigens in the skin, similar to what was reported for EM associated with other infections
Summary
Erythema multiforme (EM) is a skin disease characterized by the appearance, usually on the extremities but often occurring in other skin areas, of reddish, annular macules, which later become papules, sometimes coalescing to plaques. The earliest EM lesions have a target appearance, with a central portion that can appear as a dusky area, surrounded by a dark red inflammatory zone and another lighter ring on the extreme periphery [1]. EM lesions usually evolve, leading to geographic, polycyclic, and annular configurations. The clinical pattern of EM may be atypical, i.e., an unusual distribution or a lack of the target appearance, and is sometimes called an EM-like eruption. The histological aspect can be variable, consisting of inflammatory perivascular and interface infiltration, hyperkeratosis, granulation tissue, mucinosis, and acanthosis [2]
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