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Erythema multiforme (EM) is a self-limited acute hypersensitivity reaction to a variety of inciting agents including medications, viruses, bacteria, and fungi. The cutaneous lesions of EM have been described for centuries, the current name having been adopted in 1866 by von Hebra.1 EM is characterized by an abrupt onset of red papules that progress to form target lesions.2

Erythema multiforme is often separated into two forms: EM minor and EM major.4,5 EM minor is primarily the term used to describe the classic form described by von Hebra in 1866 and is most often associated with herpes simplex virus. EM major describes the more severe form with mucosal involvement, that is more often related to medications and Mycoplasma pneumoniae.2,3 About 20% of cases of EM minor occur in children and adolescents,4 with a small male preponderance.2 EM major is less common than its EM minor counterpart, but it has a higher predilection for the pediatric population, especially adolescents. There are a multitude of infections that are reported in association with erythema multiforme including Epstein Barr virus, herpes simplex virus (HSV), vaccinia, and certain bacterial and fungal infections. Many consider EM major a less severe form of Stevens–Johnson syndrome (SJS).3 SJS and toxic epidermal necrolysis are discussed in Chapter 161. In EM, a local cell-mediated response to an inciting antigen occurs at the site of lesion eruption and leads to local tissue damage.2,4 Skin cells demonstrate a change in the histocompatibility antigens displayed that is thought to be induced by infiltration of T cells into dermal tissues.2,4


Many patients with EM minor do not have prodromal symptoms; however, in those suffering from recurrent EM, a relationship with previous HSV eruption is well established.1,2,4,5 Those with EM major often have a prodrome of symptoms such as headache, fever, and malaise that may occur from a few days to 2 weeks before onset of the eruption. The EM spectrum can be seen any time throughout the year; however, there is an increase in incidence during the spring and fall.

The classic skin finding in EM is a fixed target or iris lesion. This is usually preceded by a red papule or plaque. The target lesion is manifested as an area of central duskiness surrounded by a circular plaque of pallor and a peripheral rim of erythema yielding a ring-like shape.2-5 The rash is symmetrical and may develop anywhere on the body, but often presents on the extensor surfaces of the extremities, gradually progressing proximally (Figure 64-1). Once lesions appear, they remain fixed in the affected areas for at least a week or longer.

FIGURE 64-1.

Classic appearance of erythema multiforme minor with target (iris) lesions on the palm. (Image used ...

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