Erythema Multiforme

Erythema multiforme can appear as a variety (multiforme) of lesions including plaques, vesicles and the classic "target" lesion. A target lesion has three distinct zones of color: a central dark or blistered area surrounded by a pale edematous ring, surrounded by a band of erythema. Target lesions are typically seen on the palms and soles but may occur anywhere. The lesions of erythema multiform are usually symmetrically distributed and favor the extremities. Patients are not normally febrile or systemically ill.

The disease has traditionally been thought of as being on a continuum with Stevens-Johnson syndrome (Erythema multiforme (major), a more severe reaction with systemic symptoms, blistering, and mucous membrane involvement (blistering and erosions), commonly of the conjunctivae, oral mucosa and lips. The view of Stevens-Johnson syndrome as being a "major" form erythema multiforme has more recently come into question. Toxic epidermal necrolysis, in which large areas of skin are involved, is also viewed as being in the same disease spectrum.

Erythema multiforme is believed to be caused by an reaction to circulating immune complexes that get deposited in the skin. It can be caused by drugs, infection, especially recurrent herpes simplex virus or mycoplasma pneumoniae, and, it is posited, by many other factors. HLA-B15 is associated with the development of erythema multiforme following herpes simplex virus. Often, a cause is not identified. In some cases, fever and upper respiratory symptoms precedes the rash by several days (up to 2 weeks).

With what can it be confused?

Erythema multiforme can be confused with urticaria (hives) and viral exanthems. Hives only have two distinct zones, central pallor and peripheral erythema. Also, individual hives last for less than 24 hours. For viral exanthems, a history of other viral symptoms can usually be elicited. The lesions of a viral exanthem are usually monomorphous, tend toward confluence, and are more centrally distributed.

Stevens-Johnson syndrome (classically considered erythema multiforme (major)) must be differentiated from other blistering disorders including bullous pemphigoid, pemphigus vulgaris, and staphylococcal scalded skin syndrome. In bullous pemphigoid the blister is subepidermal, as is the case for Stevens-Johnson syndrome, but IgG is detectable by immunofluorescence at the dermal-epidermal junction. In pemphigus vulgaris, the blister forms intraepidermally and can be distinguished from Stevens-Johnson syndrome by histology. In staphylococcal scalded skin the skin is diffusely erythematous and the epidermis sloughs off easily in strips and sheets.

How is it diagnosed?

The diagnosis is usually made by the detection of the distinctive "target' lesions; biopsy is usually not required. It is important to take a complete drug history (also see: drug eruptions). A knowledge of common causative drugs is helpful. These include sulfonamides, penicillins, barbituates, and hydantoin. A history of fever and cough should be sought (mycoplasma pneumoniae); a chest radiograph may be warranted. Mycoplasma infection can be confirmed after-the-fact with acute and convalescent titers. Recurrent erythema multiforme should prompt a search for signs, or history of recurrent herpes simplex virus, which usually precedes the eruption by several days. A Tzanck smear or viral culture can confirm the diagnosis of herpes simplex virus.

How is it treated?

Any precipitating factor should be treated or eliminated. Other intervention for the skin lesions of erythema multiforme (minor) is not required or helpful. Stevens Johnson syndrome can be life threatening. It is usually treated in a burn unit when one is available. Supportive measures such as wound care, prevention of infection, and maintenance of fluid and electrolyte balance are the mainstay of care. Systemic analgesics are used for pain control. Local anesthetics (e.g. viscous lidocaine) can be used for oral lesions. Systemic steroids (prednisone) is often used, but its role in treatment is not entirely clear. An ophthalmologist should be consulted for conjunctival involvement.

What is the prognosis?

Erythema multiforme (minor) usually resolves within 2 to 3 weeks. Stevens-Johnson syndrome may be fatal, with death intervening from infection, shock, and occasionally pneumonia or renal failure. Conjunctival involvement may result in corneal scarring.

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