The genetic basis of carbamazepine hypersensitivity was investigated in 60 affected patients (37 with mild rashes and 23 severe reactions) and 63 control non-sensitive subjects taking carbamazepine and treated at the University of Liverpool, UK. Using PCR and focusing on the major histocompatibility complex (MHC) on chromosome 6, a region linked to diseases of immune etiology, the association of hypersensitivity with polymorphisms in the TNFa promotor region gene and with HLA-DR3 and -DQ2 was determined. The TNF2 allele acted as a predisposing factor for CBZ sensitivity, but only in severe reactions, including exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis. Also, HLA-DR3 and -DQ2 were associated with severe reactions. None of the alleles were independently associated with CBZ sensitivity. Hypersecretion of TNFa (tumor necrosis factor a) may determine the severity of the tissue reaction to CBZ. 
COMMENT. CBZ hypersensitivity reaction, an immune mediated side effect of anticonvulsant treatment, is found to have a genetic basis involving polymorphisms and hypersecretion of tumor necrosis factor a (TNFa) contained within the major histocompatibility complex on chromosome 6. Further studies may help to identify susceptible patients and lessen the risk of these serious skin reactions.