Clinical Description

Erythema multiforme (EM) is an inflammatory eruption characterized by symmetric erythematous, macular, bullous, papular, nodular, or vesicular lesions of the skin or mucous membranes. The characteristic lesion is an iris (or bull's eye or target) lesion that consists of a central papule with two or more concentric rings. Stevens-Johnson syndrome is a severe form of EM with involvement of at least two mucosal surfaces in addition to the skin eruption. A hypersensitivity reaction to a number of substances, including infectious agents, is a proposed mechanism, but the pathophysiology has not been defined. No population-based incidence rates were identified.

History of Suspected Association

There is no particular history of suspected association between EM and either diphtheria or tetanus toxoid. Two cases of EM following DPT immunization were identified by Leung (1984b). Leung and Szabo (1987) reported two additional cases following administration of DPT in 1987.

Evidence for Association

Biologic Plausibility

In 1980, Shelley produced the classic iris lesions of EM by intradermal injection of a variety of heat-killed bacteria or their common endotoxin, lipopolysaccharide W, into a patient who was recovering from erythema multiforme bullosum of unknown etiology. Biopsy of the lesions induced by injection of bacterial products showed immunoglobulin A (IgA), IgM, fibrin, and complement deposition that duplicated the findings in the patient's spontaneous lesions. In addition, the patient's peripheral leukocytes produced fibrin thrombi in vitro when exposed to gram-negative bacterial antigens and endotoxin. It is biologically plausible that similar bacterial antigens in diphtheria or tetanus toxoid could induce EM.

Case Reports, Case Series, and Uncontrolled Observational Studies

In 1988, Griffith and Miller reported a case of EM following administration of diphtheria and tetanus toxoids. Eight hours after his third immunization with DT and OPV, a 9-month-old infant developed a generalized maculopapular dermatitis that progressed to vesicular lesions after 4 days.

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