Gene Variant Linked to Severe Cutaneous Reactions with Gout Treatment
Findings from a new study published in Seminars in Arthritis and Rheumatism show significant racial disparities in the risk of gout patients developing a serious, sometimes fatal adverse reaction to urate-lowering drugs.
Current treatment for gout includes dietary changes by reducing protein and alcohol intake, as well as anti-inflammatory, analgesic, and urate-lowering agents. Over 95% of the urate-lowering drug prescriptions in the U.S. are for allopurinol. Toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS) are rare but severe cutaneous reactions can be fatal. Prior studies have linked the HLA-B*5801 variant with the risk of these reactions in particular Asian populations—including Korean, Japanese, Thai, and Han Chinese—and in some European populations.
Researchers from Massachusetts General Hospital conducted a study to see whether the frequency of the HLA-B*5801 variant among the races resulted in significant racial disparities in the risk of severe cutaneous reactions to urate-lowering drugs. Using 2009–2013 data from the Nationwide Inpatient Sample of the Agency for Healthcare Research and Quality, the study authors examined 606 hospitalizations with a principal diagnosis of SJS/TEN related to an adverse reaction of urate-lowering drugs.
Among the sample size, there was a greater representation of Asian and black patients vs. whites. Asians represented 2% of U.S. allopurinol users but comprised 27% of hospitalizations for SJS/TEN related to urate-lowering drugs. Similarly, black patients made up 13% of allopurinol users and 26% of hospitalizations. On the other hand, white patients made up 81% of allopurinol users but only 29% of hospitalizations; there was a very small number of Hispanic patients in the hospitalization database with the SJS/TEN diagnosis.
Overall, Asian patients faced a 12-fold higher risk and black patients faced a 5-fold higher risk of these severe cutaneous reactions vs. white patients; these differences were closely correlated with the frequency of HLA-B*5801 variant in these populations. Specifically, there was a 7.4% frequency among Asians, 4% among blacks, and 1% among both whites and Hispanics.
"Right now, we recommend testing for the HLA-B*5801 variant among those patients, and further research may help to identify additional factors that can improve risk management," stated Hyon K. Choi, MD, DrPH, senior author the report.
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