Phenytoin-related immunodeficiency associated with Loeffler's syndrome

Phenytoin is one of the most commonly prescribed drugs in the United States. Its use is associated with a myriad of adverse reactions, including: eosinophilia, selective IgA deficiency and panhypogammaglobulinemia, pseudolymphoma, Stevens-Johnson syndrome, and interstitial pneumonia.

To report a case of immunodeficiency manifest by panhypogammaglobulinemia and a low helper-to-suppressor ratio secondary to phenytoin crossreactivity with phenobarbital and carbamazepine complicated by hepatotoxicity, eosinophilia, and fleeting pulmonary infiltrates.

Case report; immunoglobulin levels, T and B cell studies, and radiologic evaluation of patient.

A 37-year-old Oriental female taking phenytoin and phenobarbital for seizure prophylaxis after resection of a grade IV astrocytoma of the left frontal lobe, developed a rash, elevated liver function tests, and cervical lymphadenopathy with parotid gland enlargement. The abnormalities resolved with discontinuation of the drugs and the patient was discharged on carbamazepine. Eight weeks later the patient was readmitted with fever, slowed mentation, elevated liver function tests, and panhypogammaglobulinemia. Clonazepam was substituted for carbamazepine and the patient subsequently developed a rash and further elevation of her liver function tests. The clonazepam was discontinued and the patient was treated with methylprednisolone. She subsequently developed Loeffler's syndrome and a T cell deficiency with a decreased helper-to-suppressor cell ratio. She was treated with increased doses of methylprednisolone and granulocyte stimulating factor with complete resolution of her symptoms.

Phenytoin is associated with a myriad of side effects, including, rash, eosinophilia, panhypogammaglobulinemia, pseudolymphoma, Stevens-Johnson syndrome, immunosuppression in brain tumor patients, 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.