Increased risk of erythema multiforme major with combination anticonvulsant and radiation therapies

Erythema multiforme major (EMM; Stevens-Johnson syndrome) is a cutaneous di sorder associated with a wide variety of factors including ingestion of dru gs such as phenytoin and exposure to intracranial radiation therapy. Based on observations of a 47-year-old black man with brain metastases who develo ped EMM after combined phenytoin and radiation therapy, we conducted a MEDL INE literature search for articles on similar cases from 1966 to the presen t. Twenty cases were identified that support the hypothesis that EMM is ass ociated with combined phenytoin and radiation therapy. The reaction, or its severity, has no relationship to the phenytoin or radiation therapy dosage , or to the histologic type of brain tumor. Also, EMM has no apparent age o r gender predisposition in association with phenytoin-radiation therapy. Th us this is a clinical phenomenon that occurs with unusual frequency in pati ents with brain tumor who undergo radiation therapy while taking phenytoin. Phenytoin and other anticonvulsants such as phenobarbital and carbamazepin e induce cytochrome P450 3A and produce oxidative reactive intermediates th at may be implicated in hypersensitivity reactions such as EMM. Both carbam azepine and barbiturates have shown cross-sensitivity with phenytoin; furth ermore, a case of EMM in a patient receiving carbamazepine and whole brain radiation therapy has been reported. As carbamazepine, valproate, and barbi turates have been associated with EMM, gabapentin may be considered as alte rnative anticonvulsant therapy when appropriate.