Development of a pulmonary phenytoin-associated hypersensitivity reaction despite concomitant dexamethasone and prednisolone administration.

Objective: This is the report about a very early onset of phenytoin hypersensitivity reaction showing respiratory insufficiency, fever, hepatic and skin reactions in a 68-year-old male patient who was concomitantly treated with high dose dexamethasone/prednisolone because of brain edema. Case report: The patient developed a hypersensitivity reaction one week after starting a phenytoin treatment, 250 mg daily intravenously, because of a focal epileptic seizure after a transsphenoidal resection of a pituitary tumor. The drug hypersensitivity was diagnosed first clinically and was confirmed by an in vitro rechallenge using the lymphocyte transformation test three months later. Phenytoin itselfdid not stimulate the lymphocytes' proliferation. The test was performed successfully using human reference sera. Conclusions: The results suggest that protein-bound reactive drug metabolites which are assumed to occur in the sera may be responsible for the reaction. Corticosteroids did not prevent the reaction and even seem to mask laboratory and clinical findings. Dexamethasone might accelerate the accumulation of potential allergotoxic epoxide metabolites. Both phenytoin and dexamethasone should be withdrawn urgently in the case of suspected hypersensitivity syndrome.