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Pathogenesis, clinical features, and diagnosis of erythema multiforme

David A Wetter, MD
Section Editor
Jeffrey Callen, MD, FACP, FAAD
Deputy Editor
Abena O Ofori, MD


Erythema multiforme (EM) is an acute, immune-mediated condition characterized by the appearance of distinctive target-like lesions on the skin. These lesions are often accompanied by erosions or bullae involving the oral, genital, and/or ocular mucosae. Erythema multiforme major is the term used to describe EM with mucosal involvement; erythema multiforme minor refers to EM without mucosal disease.

A variety of factors have been implicated in the pathogenesis of EM. The disorder is most commonly induced by infection, with herpes simplex virus being the most frequent precipitator. The clinical course of EM is usually self-limited, resolving within weeks without significant sequelae. However, in a minority of cases, the disease recurs frequently over the course of years.

Similarities in clinical and histopathologic findings have led to controversy over the distinction between EM and Stevens-Johnson syndrome (SJS), an often drug-induced disorder that may present with cutaneous targetoid lesions and mucosal erosions. However, there is suggestive evidence that EM with mucous membrane involvement and SJS are different diseases with distinct causes [1]. The term erythema multiforme major should not be used to refer to SJS.  

The epidemiology, pathogenesis, clinical features, evaluation, and diagnosis of acute and recurrent EM will be reviewed here. The treatment of EM and similar issues related to SJS are discussed separately. (See "Treatment of erythema multiforme" and "Stevens-Johnson syndrome and toxic epidermal necrolysis: Pathogenesis, clinical manifestations, and diagnosis".)


The annual incidence of erythema multiforme (EM) is unknown, although it is estimated to be far less than 1 percent [2]. EM most frequently occurs in young adults between the ages of 20 and 40 and exhibits a slight male predominance. Children and older adults can also be affected [2,3].

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Literature review current through: Nov 2017. | This topic last updated: Nov 15, 2016.
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