Antiepileptic hypersensitivity syndrome in children

Ann Pharmacother. 2001 May;35(5):533-8. doi: 10.1345/aph.10284.


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.

MeSH terms

  • Adolescent
  • Adult
  • Adverse Drug Reaction Reporting Systems
  • Anticonvulsants / adverse effects*
  • Child
  • Diethylcarbamazine / adverse effects
  • Drug Hypersensitivity / drug therapy
  • Drug Hypersensitivity / physiopathology*
  • Female
  • Histamine H1 Antagonists / therapeutic use
  • Humans
  • Infant
  • Liver / drug effects
  • Liver / enzymology
  • Male
  • Medical Records Systems, Computerized
  • Phenobarbital / adverse effects
  • Phenytoin / adverse effects
  • Syndrome


  • Anticonvulsants
  • Histamine H1 Antagonists
  • Phenytoin
  • Diethylcarbamazine
  • Phenobarbital