Drug Allergy Pharmacogenetics: A Clinical Perspective

Purpose of review Genetic variation contributes both to dose-related adverse drug effects and to immune-mediated drug reactions, but these two forms of risk sit in different parts of the genome. We summarize what the practicing allergist and immunologist needs to know about pharmacogenetics, with emphasis on human leukocyte antigen (HLA)-associated delayed reactions, and propose a framework for combining genotype with phenotype, drug chronology and established allergy testing. Recent findings A small number of drug–HLA pairs are clinically actionable, and pre-prescription screening has reduced abacavir hypersensitivity, carbamazepine-induced Stevens-Johnson syndrome and toxic epidermal necrolysis, and allopurinol-induced severe cutaneous adverse reactions in targeted populations. Newer associations show that single-allele screening leaves at-risk patients unidentified and that the dominant risk allele is itself population-dependent. Summary Genotype is best used as a risk modifier and diagnostic adjunct rather than a stand-alone test. Incomplete positive predictive value, residual risk after a negative result, and underrepresentation of geographically heterogeneous populations in discovery cohorts remain the principal barriers to wider implementation.