Allopurinol hypersensitivity: Pathogenesis and prevention

Allopurinol, a first line urate-lowering therapy, has been associated with serious cutaneous reactions that have a high mortality. A number of risk factors for these serious adverse reactions have been identified including ethnicity, HLA-B∗5801 genotype, kidney impairment, allopurinol starting dose, and concomitant diuretic use. There is a complex interplay between these risk factors, which may (albeit rarely) lead to allopurinol-related serious adverse events. Although oxypurinol, the active metabolite of allopurinol, has been implicated, there is no defined drug concentration at which the reaction will occur. There is no specific treatment other than the cessation of allopurinol and supportive care. Whether hemodialysis, which rapidly removes oxypurinol, improves outcomes remains to be determined. Strategies to help reduce this risk are therefore important, which includes screening for HLA-B∗5801 in high-risk individuals, commencing allopurinol at low dose, and educating patients about the signs and symptoms of severe cutaneous adverse reactions, and what to do if they occur.