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Anticonvulsant Hypersensitivity Syndrome: Lymphocyte Toxicity Assay for the Confirmation of Diagnosis and Risk Assessment

Professor of Pediatrics, Seth GS Medical College and KEM Hospital, Mumbai, India

Mamta N Muranjan, MD DCH

Associate Professor of Pediatrics, Seth GS Medical College and KEM Hospital

Nithya J Gogtay, MD DNB

Associate Professor of Clinical Pharmacology, Seth GS Medical College and KEM Hospital

Vishakha Kantharia, MD DCH

Registrar, Department of Pediatrics, Seth GS Medical College and KEM Hospital

Nilima A Kshirsagar, MD PhD

Professor and Head, Department of Clinical Pharmacology; Dean, Seth GS Medical College and KEM Hospital

Reprints: Mamta N Muranjan MD DCH, Suman Apartments, 16B, Naushir Bharucha Rd., Tardeo, Mumbai 400007 India, fax 91-22-24143435, drsuji{at}vsnl.com

OBJECTIVE: To report a case of anticonvulsant hypersensitivity syndrome (AHS) precipitated by exposure to phenobarbital.

CASE SUMMARY: An 11-year-old girl receiving phenobarbital developed fever, exfoliative skin rash, mucous membrane lesions, alopecia, and hepatic inflammation. Investigations ruled out an infectious etiology; an adverse event following phenobarbital administration was considered. Applying the Naranjo probability scale for objective causality assessment showed the adverse reaction was probably due to phenobarbital. The diagnosis was confirmed by in vitro lymphocyte toxicity assay, which demonstrated increased cell death following exposure to phenobarbital, as well as other aromatic anticonvulsants and lamotrigine.

DISCUSSION: AHS is a rare, potentially fatal event with multisystem manifestations. It is reported following exposure to aromatic antiepileptics. The mechanism proposed for AHS is accumulation of toxic arene oxide metabolites due to a defect in epoxide hydrolase–mediated detoxification. Despite the difference in chemical structure of lamotrigine, in vitro susceptibility to AHS was demonstrated in our patient.

CONCLUSIONS: Although AHS is a rare event, it should be suspected in patients who develop unexplained systemic manifestations following exposure to aromatic antiepileptics. The potential of lamotrigine to cause AHS should be remembered when this drug is used in subjects who have developed AHS on exposure to phenobarbital and other first-line antiepileptic agents.

Key Words: antiepileptic drugs, lymphocyte toxicity assay

Published Online, August 10, 2004. www.theannals.com, DOI 10.1345/aph.1E042