Erythema multiforme (EM) is an acute inflammatory skin disease (Figure 249–1) with a broad range of severity, from a minimal, nuisance-level event to a severe multi-system illness. It is divided into two distinct sub-types, considering the extent of involvement, presence of epidermal detachment, and the development of mucous membranes lesions. Erythema multiforme minor, the less severe form of the illness, is a localized papular eruption of the skin, with an acral distribution and involving target lesions and/or raised, edematous papules. Erythema multiforme major is the more severe form of EM with multi-system involvement and widespread vesiculobullous lesions and erosions of the mucous membranes; specifically, EM major includes involvement of one or more mucous membrane areas and epidermal detachment less than 10% of total body surface area.
Some authorities include Stevens-Johnson syndrome (SJS) as a severe form of EM major while others consider it a less severe form of toxic epidermal necrolysis. Perhaps the most appropriate classification approach for the emergency physician is as follows: Stevens-Johnson syndrome noted with less than 10% of the body surface area with epidermal detachment; the “overlap” presentation of Stevens-Johnson syndrome and toxic epidermal necrolysis noted with 10% to 30% epidermal detachment; and toxic epidermal necrolysis noted with greater than 30% epidermal detachment.1 In either consideration, SJS is a serious dermatologic illness with significant, widespread skin involvement, more extensive epidermal detachment, and mucous membrane lesions. This taxonomic controversy has no meaning for the emergency physician; what is important for the emergency physician is the recognition of a significant, potentially life-threatening, multi-system dermatologic condition.
Morbidity and mortality rise with the amount of epidermal detachment.2 The highest incidence is in young adults (age range, 20 to 40 years), and erythema multiforme occurs commonly in the spring and fall. Common precipitating factors are infection, especially with Mycoplasma and herpes simplex virus; drugs, especially antibiotics and anticonvulsants; and malignancies. However, the cause is often unknown.3 Most likely, erythema multiforme is the result of a hypersensitivity reaction, with immunoglobulin and complement components demonstrated in the cutaneous microvasculature on immunofluorescent studies of skin biopsy specimens, circulating immune complexes found in the serum, and mononuclear cell infiltrate noted on histologic examination.3,4
Symptoms include malaise, fever, myalgias, and arthralgias. Diffuse pruritus or a generalized burning sensation can occur before the skin lesions develop. The morphologic configuration of the lesions is variable, hence the descriptor multiforme. Maculopapular (Figure 249–2) and target, or iris (Figure 249–3), lesions are the most characteristic. Erythematous papules appear symmetrically on the dorsum of the hands and feet and on the extensor surfaces of the extremities. The maculopapule evolves into the classic target lesion during the next 24 to 48 hours. As the maculopapule enlarges, the central area becomes cyanotic, occasionally accompanied by central purpura or a vesicle. Urticarial plaques also may occur with or without the iris lesion in a similar distribution. Vesiculobullous lesions, which may be pruritic and painful, develop within preexisting maculopapules or plaques, usually on the extensor surface of the arms and legs and less frequently on the trunk. Vesiculobullous lesions are found most often on mucosal surfaces, including the mouth, eyes, vagina, urethra, and anus; they may also be seen on the trunk. Ocular involvement rarely occurs in erythema multiforme minor, whereas ophthalmologic lesions are seen in almost 70% of patients with Stevens-Johnson syndrome.5 The various lesions (Table 249–2) develop in successive crops during a 2- to 4-week period and heal over 5 to 7 days. The differential diagnosis of erythema multiforme includes herpetic (herpes simplex virus and varicella-zoster virus) infection, vasculitis, toxic epidermal necrolysis, various primary blistering disorders (pemphigus and pemphigoid), urticaria, Kawasaki's disease, and the toxic and infectious erythemas.
Erythema Multiforme and Toxic Epidermal Necrolysis
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Erythema Multiforme and Toxic Epidermal Necrolysis
|Lesions of Erythema Multiforme ||Lesions of Toxic Epidermal Necrolysis |
|Erythematous maculopapules ||Warm, tender erythroderma |
|Iris or target lesions ||Vesicles and bullae |
|Urticaria ||Exfoliation |
|Mucous membranes involved ||Mucous membranes involved |
Maculopapular erythema multiforme.
Target, or iris, lesions of erythema multiforme. [Photograph used with permission of Kenneth Greer, MD, University of Virginia Dermatology.]
Recurrence may be noted on repeat exposure to the etiologic agent, a special concern in cases associated with herpes simplex virus infection or medication use.6 The rate of erythema multiforme recurrence is very high in children with herpes simplex virus infection. For example, 75% of children with a history of herpes simplex virus–related erythema multiforme developed erythema multiforme recurrence after herpes simplex virus reactivation.6 Fluid and electrolyte disorders and secondary infection from cutaneous sites are the most frequent complications.
Systemic steroids are commonly used for localized disease and provide symptomatic relief but are of unproven benefit in influencing the duration and outcome of erythema multiforme.7 Many authorities recommend a short, intensive steroid course of prednisone, 60 to 80 milligrams PO once a day, particularly in drug-related cases, with abrupt cessation in 3 to 5 days if no favorable response is noted. Systemic analgesic agents and antihistamines provide symptomatic relief. Stomatitis is treated with diphenhydramine and viscous lidocaine mouth rinses. Do not swallow oral viscous lidocaine because it causes neurotoxicity. Treat blisters with cool compresses of Burow solution (5% aluminum acetate). Ocular involvement should be monitored by an ophthalmologist. Unfortunately, burst steroid therapy does not reduce the chance of development or significance of existing ocular lesions.
Disposition is admission to an intensive care or burn unit. Acyclovir may reduce recurrence of herpes simplex virus infection and therefore lessen the potential for another bout of erythema multiforme; prolonged prophylactic acyclovir therapy may reduce the chance of recurrent erythema multiforme related to herpes simplex virus.6