Drug-Induced Adverse Reactions

Some patients who take otherwise effective drugs develop severe immune-mediated reactions that range from widespread skin blistering to life-threatening organ failure, and understanding why requires tracing the intersection of pharmacology, immunology, and human genetics. A central discovery driving current research is that certain HLA alleles — genetic variants that shape how immune cells recognize molecules — can make individuals dramatically more susceptible to reactions like Stevens-Johnson Syndrome, Toxic Epidermal Necrolysis, and DRESS Syndrome when exposed to drugs such as abacavir, carbamazepine, or allopurinol. Prospective genetic screening has already proven it can prevent some of these reactions before they occur, as demonstrated by HLA-B*5701 testing prior to abacavir prescription, but most implicated drug-allele pairs lack the clinical evidence needed to translate similar screenings into routine care. Open questions center on the precise immunological mechanisms by which drug-HLA complexes trigger T-cell responses, and on how to build pharmacovigilance systems sensitive enough to detect rare but catastrophic reactions across diverse populations.

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Keywords

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