Allopurinol is a highly effective, cheap and simple therapy for gout if dosing is adequate and patients adhere to the therapy
Serious allopurinol-related adverse events (for example, allopurinol hypersensitivity syndrome [AHS]) are rare, but are associated with high morbidity and mortality
Risk factors for allopurinol-related serious adverse events include recent introduction of allopurinol, the presence of the HLA-B*58:01 allele, a higher starting dose, renal impairment and the concomitant use of diuretics
Allopurinol hypersensitivity is primarily mediated by an oxypurinol-specific T-cell response
Allopurinol is the most commonly prescribed urate-lowering therapy for the management of gout. Serious adverse reactions associated with allopurinol, while rare, are feared owing to the high mortality. Such reactions can manifest as a rash combined with eosinophilia, leukocytosis, fever, hepatitis and progressive kidney failure. Risk factors for allopurinol-related severe adverse reactions include the recent introduction of allopurinol, the presence of the HLA-B*58:01 allele, and factors that influence the drug concentration. The interactions between allopurinol, its metabolite, oxypurinol, and T cells have been studied, and evidence exists that the presence of the HLA-B*58:01 allele and a high concentration of oxypurinol function synergistically to increase the number of potentially immunogenic-peptide–oxypurinol–HLA-B*58:01 complexes on the cell surface, thereby increasing the risk of T-cell sensitization and a subsequent adverse reaction. This Review will discuss the above issues and place this in the clinical context of reducing the risk of serious adverse reactions.
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L.K.S. declares she has received consulting and speaker fees from Astra Zeneca. The other authors declare no competing interests.
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