Antiepileptic hypersensitivity syndrome in children.

Objective: To assess clinical features and outcomes of childhood antiepileptic hypersensitivity syndrome (AHS). AHS is an idiosyncratic reaction to aromatic anticonvulsants that can result in severe multiorgan dysfunction and death.

Methods: Children with suspected AHS (fever, rash, lymphadenopathy, liver dysfunction) were identified by an in-house computerized adverse drug event reporting system. The medical charts of children with suspected AHS were reviewed. A MEDLINE search (from 1966 to October 1999) was performed using the term antiepileptic hypersensitivity syndrome.

Results: Fourteen of 36 children who experienced a rash, urticaria, pruritus, fever, or hepatotoxicity associated with aromatic anticonvulsants met the criteria for AHS (mean age 10.4 +/- 6.5 y; males to females 8:6, white to African-American to biracial 10:3:1). Eight patients were receiving phenytoin, six carbamazepine, and four phenobarbital alone or in combination. The mean time from exposure to development of symptoms was 23.0 +/- 14.8 days. In addition to rash and fever (present in all patients by definition), other common features of AHS were lymphocytosis (71.4%), elevated erythrocyte sedimentation rate (64.3%), elevated aminotransferases (64.3%), lymphadenopathy (57.1%), eosinophilia (42.8%, coagulopathy (42.8%), leukocytosis (35.7%), leukopenia (35.7%), hyperbilirubinemia (35.7%), and nephritis (7.1%). All children recovered except one, who died from complications of liver failure. Clinical outcome was simimlar between children who received systemic steroid therapy (n=5) and those who did not. Antiepileptics producing AHS were discontinued in all patients.

Conclusions: AHS can be fatal in children if not promptly recognized. Fever, rash, and hepatotoxicity should serve as presumptive evidence for AHS, which requires immediate discontinuation of an offending anticonvulsant.