Phenytoin-induced agranulocytosis: a nonimmunologic idiosyncratic reaction?

Agranulocytosis is a rare side effect of phenytoin treatment. We describe the case of an elderly man who developed agranulocytosis 2 weeks following initiation of phenytoin treatment, on no cytotoxic drugs or any other medications except decadron. The white blood cell count was 300/mm3 with absent granulocytes. The liver enzymes were also noted to be newly elevated. Complete workup showed no evidence of infection. The patient was managed as a case of neutropenic fever and phenytoin was discontinued. A bone marrow biopsy showed absent granulocyte precursors after myelocytes, and an antigranulocyte antibody titer was negative, which suggests a direct toxic effect rather than an immunologic phenomenon. Both agranulocytosis and hepatitis were readily reversible on phenytoin cessation.