Immunological studies on delayed hypersensitivity to phenytoin--II. The delayed skin reaction induced by BSA-phenytoin conjugate

Remarkable swelling of the foot pad was induced in guinea pigs sensitized with BSA-phenytoin by challenging with BSA-phenytoin or EA-phenytoin. Forty-eight hours after local injection of a mixture of exudate cells obtained from the abdominal cavity of sensitized guinea pigs. and BSA (EA)-phenytoin, both erythema and induration developed at the injection sites in normal guinea pigs. At the sites exhibiting these skin reactions, an exudation of mononuclear leukocytes was noted. In addition, macrophages obtained from the abdominal cavity of phenytoin-sensitized animals showed a low migration index in the presence of phenytoin. When phenytoin was administered to rats (p.o.), large amounts of the compound were detected in the gingiva and there was a good correlation between the tissue and serum phenytoin concentrations. These findings indicate that the etiology of gingival hyperplasia produced by chronic administration of phenytoin may be related in some way to a delayed-type hypersensitivity induced by the drug.