COMBINATION CHEMOTHERAPY WITH 5-FLUOROURACIL, FOLINIC ACID, AND ALPHA-INTERFERON PRODUCING HISTOLOGIC FEATURES OF GRAFT-VERSUS-HOST DISEASE

Fluorouracil is a common cause of acral erythema and a variety of pigmentary anomalies. These conditions are believed to be the result of a direct toxic effect or a graft-versus-host-like reaction. We describe two cases in which an erythematous eruption that evolved into hyperpigmented, hyperkeratotic lesions developed in two patients who were receiving combination chemotherapy (5-fluorouracil, folinic acid, and alpha-interferon). The histologic features included apoptotic keratinocytes with exocytosis of mononuclear cells, some showing satellitosis, and hydropic change of the basal cell layer with an interface dermatitis that was most marked within the distal eccrine duct and acrosyringium. Clinicopathologic correlation suggests that the eruption was primarily caused by involvement of the sweat glands and hair follicles. Although a direct toxic effect may play some role, the histologic features suggest that the dominant mechanism is a graft-versus-host-like or host-versus-altered-host-type reaction.