Antiepileptic Drug Hypersensitivity Syndrome

Authors

  • Raymond G. Schlienger,

    1. Divisions of Clinical Pharmacology, Sunnybrook Health Science Centre, University of Toronto, Toronto, Ontario, Canada
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  • Neil H. Shear

    Corresponding author
    1. Divisions of Clinical Pharmacology, Sunnybrook Health Science Centre, University of Toronto, Toronto, Ontario, Canada
    2. Divisions of Dermatology, Departments of Medicine, Pharmacology, and Pharmacy, and the Glaxo Wellcome-Sunnybrook Drug Safety Clinic, Sunnybrook Health Science Centre, University of Toronto, Toronto, Ontario, Canada
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  • Raymond G. Schlienger was supported by a grant from the Swiss National Science Foundation.

Address correspondence and reprint requests to Dr. N. H. Shear at Division of Clinical Pharmacology, Room E-240, Sunnybrook Health Science Centre, 2075 Bayview Avenue, Toronto, ON, Canada M4N 3M5.

Abstract

Summary: : The antiepileptic drug hypersensitivity syndrome (AHS) is an adverse drug reaction associated with the aromatic antiepileptic drugs (AEDs) phenytoin (PHT), carbamazepine (CBZ), phenobarbital (PB), and primidone. The syndrome is defined by the triad of fever, skin rash, and internal organ involvement. It can also be caused by other drugs, such as sulfonamides, dapsone, minocycline, terbinafine, azathioprine, and allopurinol. Diagnosis of AHS may be difficult because of the variety of clinical and laboratory abnormalities and manifestations and because the syndrome may mimic infectious, neoplastic, or collagen vascular disorders. The incidence is approximately 1 in 3,000 exposures. AHS starts with fever, rash, and lymphadenopathy, within the fist 2–8 weeks after initiation of therapy. Internal manifestations include, among others, agranulocytosis, hepatitis, nephritis, and myostitis. AHS is associated with a relative excess of reactive oxidative metabolites of the AED. Insufficient detoxification may lead to cell death or contribute to the formation of antigen that triggers an immune reaction. Crossreactivity among PHT, CBZ, and PB is as high as 70–80%.

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