Excerpt from Erythema Multiforme

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Background

Erythema multiforme (EM) was initially described in 1866 by Ferdinand von Hebra as an acute self-limited skin disease, symmetrically distributed on the extremities with typical and often recurrent concentric "target" lesions. The term EM minor was proposed later to differentiate the mild cutaneous syndrome from the more severe form, EM major, which involves several mucous membranes.

Stevens-Johnson syndrome (SJS) was considered an extreme variant of EM for many years, while toxic epidermal necrolysis (TEN) was considered a different entity. However, in 1993, a group of medical experts proposed a consensus definition and classification of EM, SJS, and TEN based on a photographic atlas and extent of body surface area involvement. According to the consensus definition, SJS was separated from the EM spectrum and added to TEN. Essentially SJS and TEN are considered severity variants of a single entity. The two spectra are now divided into (1) EM consisting of erythema minor and major (EMM) and (2) SJS/TEN. The clinical descriptions are as follows:

• EM minor - Typical targets or raised, edematous papules distributed acrally
• EM major - Typical targets or raised, edematous papules distributed acrally with involvement of one or more mucous membranes; epidermal detachment involves less than 10% of total body surface area (TBSA).
• SJS/TEN - Widespread blisters predominant on the trunk and face, presenting with erythematous or pruritic macules and one or more mucous membrane erosions; epidermal detachment is less than 10% TBSA for SJS and 30% or more for TEN.

Pathophysiology

Pathophysiology of EM is not completely understood but appears to involve a hypersensitivity reaction that can be triggered by a variety of stimuli, particularly bacterial, viral, or chemical products.

A recent international prospective study showed that the major cause of EM is herpes virus. It appeared to play a smaller role in SJS/TEN. In fact, recent or recurrent herpes was the principle risk factor for EMM. Drugs were found to be a more common trigger for SJS/TEN.

Histopathologic characteristics include a lymphocytic infiltrate at the dermal-epidermal junction and around dermal blood vessels, dermal edema, epidermal keratinocyte necrosis, and subepidermal bullae formation. Histology and immunochemistry studies have shown that inflammatory infiltrates of EM and SJS/TEN are strikingly different in density and nature. EM has a high density of cell infiltrate rich in T-lymphocytes. By contrast, SJS/TEN is characterized by a cell-poor infiltrate of macrophages and dendrocytes with strong TNF-alpha immunoreactivity. Immune complex deposition is variable and nonspecific. In severe cases, fibrinoid necrosis can occur in the stomach, spleen, trachea, and bronchi.

Frequency

United States

The true incidence of EM is unknown, but it has been estimated to be between 0.01 and 1%. Incidence of SJS and TEN are better characterized and estimated at 0.4-1.2 and 1.2-6 per million person-years, respectively.

International

Similar to US incidence

Mortality/Morbidity

• EM not usually associated with any mortality. Most cases are self-limited and resolve without sequelae in 2-4 weeks.
• SJS has a mortality around 5%.
• TEN has a mortality approximately 30%.

Sex

EM affects males more often than females, with a male-to-female ratio ranging from 3:2 to 2:1. Incidence of SJS and TEN are equal in males and females.

Age

All ages are affected, with a peak incidence in the second through fourth decades of life, 20% occur in children and adolescents. This condition is rare in persons younger than 3 years and older than 50 years. EM occurs more in younger patients, while SJS and TEN occur more in older persons.

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