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  • Erythema multiforme is a rare cutaneous or mucocutaneous eruption characterized by “target” lesions, predominantly on the face and extremities.

  • The highest incidence was found in male children and young adults.

  • It has a benign course but frequent recurrences, possible ocular complications.

  • Most cases are related to infections (herpes simplex virus [HSV] and Mycoplasma pneumoniae). Medications are not a common cause, in contrast to the spectrum of drug-induced epidermal necrolysis (see Chap. 44) that are different diseases.

  • Herpes-induced recurrences can be prevented by long-term use of anti-HSV medications. Thalidomide, mycophenolate mofetil, or both may be considered in recalcitrant, recurrent cases.



Erythema multiforme (EM) is an acute mucocutaneous syndrome originally described by von Hebra in 1860 as erythema exudativum multiforme. It is defined by a distinctive clinical pattern (with consistent histopathology when done). The course is usually mild and self-limited but carries a risk of relapse. Based on the degree of mucous membrane involvement, EM is separated into EM minus (EMm, also called EM minor) if only the skin and lips are involved and EM majus (EMM, also called EM major) when mucous membranes are affected. Subtypes of EM are described in Table 43-1.

Table 43-1Erythema Multiforme (EM) Subtypes

Historically, a variety of factors have contributed to a confusing nosology, especially with the concept of a so-called “EM spectrum” from EMm to Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). The definition of EM in this chapter is based on the classification proposed 25 years ago by Bastuji-Garin and colleagues.1 The principle of the classification was to consider SJS and TEN as severity variants of a process termed epithelial necrolysis (EN; see Chap. 44) and to separate them from EM. The validity of that classification has been established by several studies, especially the prospective international Severe Cutaneous Adverse Reactions study2 and by recent series3,4 showing that compared with SJS and TEN, EM cases have different demographic features, clinical presentation, severity, and causes.

The consensus classification was improved by German investigators by separation of EMM into typical EMM (typical targets on the extremities) and atypical EMM with more extensive distribution of atypical, larger targets, occasionally involving the skin around the mouth and the eyes, ...

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