Drug-Induced Adverse Reactions

Some people who take otherwise effective medications develop severe immune reactions that range from skin rashes to life-threatening conditions like Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis, in which the skin blisters and peels away across large portions of the body. Researchers in this area work to understand why certain drugs — including the HIV medication abacavir, the anticonvulsant carbamazepine, and the gout treatment allopurinol — trigger these reactions in a small fraction of patients, and have found that inherited variations in HLA genes, which govern how the immune system recognizes foreign molecules, are strong predictors of risk. Screening for HLA-B\*5701 before prescribing abacavir has already reduced hypersensitivity reactions substantially, and similar logic is now being applied to other drug-HLA pairings. Active questions include why the same HLA variant raises risk for one drug but not another, how to extend reliable pharmacogenomic screening to lower-resource settings, and what cellular mechanisms convert an innocuous drug molecule into a trigger for a catastrophic immune response.

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Keywords

HLA-B*5701Stevens-Johnson SyndromeToxic Epidermal NecrolysisDrug HypersensitivityAbacavirCarbamazepine