Genetic markers of severe cutaneous adverse reactions

ABSTRACT

Adverse drug reactions can cause considerable discomfort. They can be life-threatening in severe cases, requiring or prolonging hospitalization, impeding proper treatment, and increasing treatment costs considerably. Although the incidence of severe cutaneous adverse reactions (SCARs) is low, they can be serious, have permanent sequelae, or lead to death. A recent pharmacogenomic study confirmed that genetic factors can predispose an individual to SCARs. Genetic markers enable not only elucidation of the pathogenesis of SCARs, but also screening of susceptible subjects. The human leukocyte antigen (HLA) genotypes associated with SCARs include HLA-B*5701 for abacavir (Caucasians), HLA-B*5801 for allopurinol (Asians), HLA-B*1502 (Han Chinese) and HLA-A*3101 (Europeans and Koreans) for carbamazepine, HLA-B*5901 for methazolamide (Koreans and Japanese), and HLA-B*1301 for dapsone (Asians). Therefore, prescreening genetic testing could prevent severe drug hypersensitivity reactions. Large-scale epidemiologic studies are required to demonstrate the usefulness and cost-effectiveness of screening tests because their efficacy is affected by the genetic differences among ethnicities.