The article discusses the immunopathogenesis and risk factors for allopurinol-induced severe cutaneous adverse reactions (SCARs). For many years, allopurinol has been identified as a primary cause of SCARs globally. In recent years, the pathophysiology of allopurinol-induced SCARs has been identified. HLA-B58:01 was discovered to be highly linked with allopurinol-SCARs, with functional connections between allopurinol/its metabolite-oxypurinol and the T-cell receptor (TCR). However, the genetic strength of HLA-B58 : 01 may differ amongst ethnic groups. Specific T cells with preferred TCR clonotypes that have no cross-reactivity with novel xanthine oxidase inhibitors structurally distinct from allopurinol are known to have a critical role in allopurinol-induced SCARs in addition to HLA-B58 : 01 Furthermore, other non genetic variables, such as renal impairment, have been discovered to have a role in allopurinol-induced SCARs with higher severity and a worse prognosis.
There are several risk factors for allopurinol-induced SCARs, both hereditary and nongenetic. The immunological mechanism of allopurinol-induced SCAR involves the activation of particular T cells with selective TCR and its functional interaction with the HLA-B58 : 01 molecule and allopurinol/oxypurinol. Patients with allopurinol-induced SCARs who have renal impairment have a substantially increased risk of death. For people who are intolerant to allopurinol, a structurally distinct next generation xanthine oxidase inhibitor may provide a safer option.
