Clinical Reference / Therapeutic Strategies / Erythema Multiforme

Erythema Multiforme

Key Points

  • Erythema multiforme (EM) is a clinical syndrome marked by either target lesions and/or mucosal erosions. It may be idiopathic or seen in association with infections or medications.
  • EM has been reported in association with herpes simplex infection, mycoplasma pneumonial infection, contact dermatitis, medications, and radiation.
  • There is considerable controversy in the literature regarding the proper classification and terminology of erythema multiforme. EM may be subdivided into EM minor and major, connoting distinct associations, although many investigators and consensus groups no longer distinguish between the two entities. In general, EM minor is associated with infections (classically, herpes simplex virus) and is typically a self-limited process. EM major, according to some authors, may be synonymous with Stevens-Johnson syndrome (SJS) and entails a more severe clinical syndrome with more atypical target lesions and pronounced mucosal involvement at two anatomic sites. EM major occurs in association with many different infections or as an adverse reaction to medications, and requires hospitalization.


The presence of annular lesions, often acrally distributed, with a central target or bulla, is characteristic of erythema multiforme (EM). True target lesions are tri-partite and consist of sharply marginated circular or polycyclic lesions with central dusky erythema, concentric edematous blanching, rimmed by a macular erythematous border. The central portion may be bullous. Mucosal lesions are seen in 25% of cases and typically affect the oral mucosa. EM may be seen in association with herpes simplex infection, mycoplasma pneumonial infection, contact dermatitis, medications, radiation, or be idiopathic.

The classification and terminology of EM in the literature is controversial, and at times, confusing. EM may be clinically subdivided into EM minor and EM major, connoting distinct disease associations. EM minor is typified by minimal skin and/or mucosal disease, with minimal systemic symptoms, in association with either herpes simplex virus (HSV) or mycoplasma pneumonial infection. Therapy is generally not required or helpful for EM minor (limited to skin and/or one mucosal surface without systemic symptoms), which is a self-limited process. Because this form of erythema multiforme invariably follows infection and is self-limited, usually lasting only days to weeks, in the majority of cases the therapeutic strategy is symptom control or no treatment at all. EM major (sometimes alternatively termed infection or drug-related EM or Stevens-Johnson syndrome), however, requires in-patient management because of significant systemic symptoms and involvement of one and usually more mucosal surfaces. Unfortunately, specific therapy does not exist, and administration of systemic steroids may cause complications. Fortunately, like EM minor, the disease is self-limited regardless of severity and supportive care is the mainstay of treatment.

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