ANTIEPILEPTIC DRUG HYPERSENSITIVITY SYNDROME

The antiepileptic drug hypersensitivity syndrome (AHS) is an adverse d rug reaction associated with the aromatic antiepileptic drugs (AEDs) p henytoin (PHT), carbamazepine (CBZ), phenobarbital (PB), and primidone . The syndrome is defined by the triad of fever, skin rash, and intern al organ involvement. It can also be caused by other drugs, such as su lfonamides, dapsone, minocycline, terbinafine, azathioprine, and allop urinol. Diagnosis of AHS may be difficult because of the variety of cl inical and laboratory abnormalities and manifestations and because the syndrome may mimic infectious, neoplastic, or collagen vascular disor ders. The incidence is approximately 1 in 3,000 exposures. AHS starts with fever, rash, and lymphadenopathy, within the first 2-8 weeks afte r initiation of therapy. Internal manifestations include, among others , agranulocytosis, hepatitis, nephritis, and myostitis. AHS is associa ted with a relative excess of reactive oxidative metabolites of the AE D. Insufficient detoxification may lead to cell death or contribute to the formation of antigen that triggers an immune reaction. Crossreact ivity among PHT, CBZ, and PB is as high as 70-80%.