Immunopathogenesis and risk factors for allopurinol severe cutaneous adverse reactions

Purpose of review The article reviews the immunopathogenesis and risk factors related to allopurinol-induced severe cutaneous adverse reactions (SCARs). Recent findings For years, allopurinol remains one of the leading cause for SCARs worldwide. The pathogenesis of allopurinol-induced SCARs have been discovered in recent years. HLA-B ∗ 58 : 01 has been found to be strongly associated with allopurinol-SCARs with functional interactions between allopurinol/its metabolite-oxypurinol and the T-cell receptor (TCR). However, the genetic strength of HLA-B ∗ 58 : 01 may vary among different ethnic populations. In addition to HLA-B ∗ 58 : 01, specific T cells with preferential TCR clonotypes, which have no cross-reactivity with new xanthine oxidase inhibitors structurally different from allopurinol, are found to play a crucial role for allopurinol-induced SCARs. Furthermore, other nongenetic factors such as renal impairment are also found to be an important factor resulting in allopurinol-induced SCARs of greater severity and poorer prognosis. Summary There are multiple risk factors for allopurinol-induced SCARs, including genetic and nongenetic factors. Activation of specific T cells with preferential TCR and its functional interaction of HLA-B ∗ 58 : 01 molecule and allopurinol/oxypurinol are involved in the immune mechanism of allopurinol-induced SCAR. Patients with allopurinol-induced SCARs with renal impairment have significantly higher risk of mortality. A structurally different new generation xanthine oxidase inhibitor can provide a safer alternative for patients intolerant to allopurinol.