Severe cutaneous adverse reactions (SCARs) constitute a set of life threatening conditions that include drug rash with eosinophilia and systemic symptoms, Stevens-Johnson syndrome, and toxic epidermal necrolysis. Allopurinol is one of the most common causes of SCARs in Asia and Europe and has been correlated strongly with the allele human leukocyte antigen (HLA)-B*58:01 in Han Chinese populations. This study assessed whether prospective screening via HLA-B*58:01 genotyping before allopurinol treatment could reduce the incidence of allopurinol induced SCARs.
According to an accompanying editorial, the findings of this study are not generalisable enough to prompt routine genetic testing for patients needing allopurinol, as participants were all Han Chinese from Taiwan, a population with a high prevalence of the HLA-B*58:01 allele (~10%). It notes that the risk allele frequency is low in white populations (<1%) and even in other Asian populations, the strength of association between allele and reaction is weaker. It adds that almost all carriers of HLA-B*58:01 (~98%) do not develop SCARs, and in some ethnic groups (including white populations), many patients with the adverse effect do not carry the risk allele. The commentator adds that even when genetic prediction of risk is robust, the alternative drug treatments to allopurinol, a drug with a well-defined efficacy and safety profile, may be potentially more toxic (e.g. hepatotoxicity with benzbromarone) or more expensive with a poorly defined, long term safety profile (i.e. febuxostat) that includes reports of potentially lethal liver failure and cardiovascular events. He warns that “if genotyping is not available, prescribers could be tempted to substitute allopurinol for less safe or effective alternatives, to the detriment of most patients.”