Erythema Multiforme

Erythema multiforme (EM) was initially described by Ferdinand von Hebra in the late 19th century as a “a self-limited eruption characterized by symmetrically distributed erythematous papules, which develop into characteristic target-like lesions consisting of concentric color changes with a dusky central zone that may become bullous” (Fig. 27.9).
This classic description still holds true for the typical lesions of EM.
EM minor, by definition, occurs when only typical skin lesions are present.
EM major, traditionally referred to as Stevens-Johnson syndrome (SJS), occurs when the target lesions are accompanied by extensive mucosal involvement and systemic symptoms. SJS is currently considered to be part of the spectrum of toxic epidermal necrolysis (TEN) and distinct from EM major (see Chapters 26 and 33). Sometimes clinical distinction between the two is difficult to make.
Both types of EM are most often seen in young adults.
EM is most often triggered by an infection (most often HSV).
Affected people are generally in good health.

Pathogenesis ⬆ ⬇

It is currently thought that EM represents a mucocutaneous immune reaction pattern in response to an infection.
About 90% of cases are triggered by a preceding infection.
HSV1, and less often HSV2, are the most commonly associated infectious agents.
The most common precipitating cause of recurrent EM is recurrent herpes labialis (Fig. 27.10) and usually the herpes outbreak precedes the skin eruption by 3 to 14 days.
Other infectious triggers include Epstein-Barr virus (EBV), Mycoplasma pneumonia, histoplasmosis, Streptococcus infection, hepatitis A and B, and coccidioidomycosis.
Rarely, EM is precipitated by a drug or a systemic disease. Reported associated drugs include sulfonamides, penicillin, hydantoins, barbiturates, allopurinol, and NSAIDs.

Clinical Manifestations ⬆ ⬇

EM presents with the acute onset of characteristic erythematous lesions with dusky centers in a symmetric distribution, with most lesions appearing within 24 hours.
The skin lesions seen in EM can vary from erythematous patches with slightly dusky centers to the typical target, “bull's eye” lesions.
Lesions begin as round, well-demarcated, erythematous macules or patches (<3 cm).
Some lesions evolve to form typical target lesions consisting of three distinct zones, a central dusky zone, a surrounding pale zone, and a peripheral red zone.
Some lesions are atypical targets with dusky centers and a surrounding zone of erythema.
The dusky center may become vesicobullous or crusted.
Lesions persist (are “fixed”) for at least 1 week.
The eruption is bilateral and symmetric and typically occur on the palms and soles, dorsa of hands and feet, extensor forearms and legs, face, and genitalia.
Erythema multiforme minor presents with the skin lesions with little to no mucosal involvement and no systemic symptoms.
Erythema multiforme major presents with the typical skin lesions plus severe mucosal involvement and systemic features.
Extensive, severe, mucous membrane lesions in EM major may be located in multiple sites, including the mouth, pharynx, eyes, and genitalia (see Fig. 26.6).
Possible complications include keratitis, corneal ulcers, upper airway damage, and pneumonia.

Diagnosis ⬆

Differential Diagnosis

Urticaria

Primary Herpes Gingivostomatitis and Primary Bullous Diseases of the Oral Cavity

Clinically lesions may be indistinguishable from those of mucous membrane EM.
Mucous membrane biopsy may be necessary to distinguish oral bullous EM from primary bullous diseases such as pemphigus vulgaris or bullous pemphigoid.

Management

EM is generally an acute self-limited disorder but may be recurrent in some cases.
If known, the precipitating infectious cause should be treated.
Suspected etiologic drugs should be discontinued.
Wet dressings (e.g., Burow solution) and topical steroids may be applied to oozing lesions.
Oral antihistamines may help alleviate associated skin symptoms.
For recurrent EM minor due to HSV, prophylactic daily treatment with oral acyclovir, famciclovir (Famvir), or valacyclovir (Valtrex) may prevent or mitigate recurrences (see Chapter 17: Mucocutaneous Manifestations of Viral Infections for dosages).
In cases of severe mucosal involvement, as may occur in EM major, hospitalization may be required.
The use of systemic steroids in such severe cases is controversial, and their effectiveness has not been established.
For severe recurrent EM azathioprine, cyclosporine and prednisone have all been used.

Helpful Hint

Points to Remember

Solid evidence supports the current concept that EM is a condition distinct from SJS and TEN.
Both EM minor and major are a reaction pattern to underlying stimuli and can present with varying degrees of severity.
Even in the clinical absence of herpes simplex virus infection, recurrent EM minor may be suppressed with oral acyclovir, famciclovir, or valacyclovir.