PHENYTOIN-RELATED IMMUNODEFICIENCY ASSOCIATED WITH LOEFFLERS SYNDROME

Background: Phenytoin is one of the most commonly prescribed drugs in the United States. Its use is associated with a myriad of adverse reac tions, including: eosinophilia, selective IgA deficiency and panhypoga mmaglobulinemia, pseudolymphoma, Stevens-Johnson syndrome, and interst itial pneumonia. Objective: To report a case of immunodeficiency manif est by panhypogammaglobulinemia and a low helper-to-suppressor ratio s econdary to phenytoin crossreactivity with phenobarbital and carbamaze pine complicated by hepatotoxicity, eosinophilia, and fleeting pulmona ry infiltrates. Methods: Case report; immunoglobulin levels, T and B c ell studies, and radiologic evaluation of patient. Results: A 37-year- old Oriental female taking phenytoin and phenobarbital for seizure pro phylaxis after resection of a grade IV astrocytoma of the left frontal lobe, developed a rash, elevated liver function tests, and cervical l ymphadenopathy with parotid gland enlargement. The abnormalities resol ved with discontinuation of the drugs and the patient was discharged o n carbamazepine. Eight weeks later the patient was readmitted with fev er, slowed mentation, elevated liver function tests, and panhypogammag lobulinemia. Clonazepam was substituted for carbamazepine and the pati ent subsequently developed a rash and further elevation of her liver f unction tests. The clonazepam was discontinued and the patient was tre ated with methylprednisolone. She subsequently developed Loeffler's sy ndrome and a T cell deficiency with a decreased helper-to-suppressor c ell ratio. She was treated with increased doses of methylprednisolone and granulocyte stimulating factor with complete resolution of her sym ptoms. Conclusions: Phenytoin is associated with a myriad of side effe cts, including, rash, eosinophilia, panhypogammaglobulinemia, pseudoly mphoma, Stevens-Johnson syndrome, immunosuppression in brain tumor pat ients, and rarely, pulmonary complications such as Loeffler's syndrome . Cross-reactivity with other anticonvulsant agents capable of forming arene oxide intermediates occurs in the cytochrome P-450 system.