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Epidermal apoptotic cell death in erythema multiforme and Stevens-Johnson syndrome. Contribution of perforin-positive cell infiltration.

OBJECTIVE: To clarify the mechanism of epidermal cell death in erythema multiforme.

DESIGN: Retrospective study.

SETTING: Academic referral center.

PARTICIPANTS: Nine patients with Stevens-Johnson syndrome (SJS), 9 patients with Hebra disease (EMH), and 5 healthy volunteers.

INTERVENTIONS: Biopsy specimens were obtained from the border of the fresh lesions before treatment. Control specimens were obtained from normal skin.

MAIN OUTCOME MEASURES: Histopathological epidermal apoptosis detected with nuclear DNA fragmentation and counts of dermal immunoreactive perforin-positive infiltrates were compared between SJS and EMH.

RESULTS: Eight patients (89%) with SJS showed clear apoptosis with keratinocyte DNA fragmentation. All SJS samples had intensive perforin-positive dermal infiltrates. Only 3 patients (33%) with EMH showed apoptotic change, and it was to a far less extent with far less dermal perforin-positive infiltrates. Control specimens showed no apoptotic cells in the epidermis or expression of perforin in the dermis.

CONCLUSIONS: Perforin mediates apoptosis in the pathogenesis of the epidermal cell changes in SJS but not in EMH. In addition to the differences in clinical severity and histopathological conditions, our findings indicate a pathogenic difference between SJS and EMH.

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