Ethnicity may be a risk factor for allopurinol hypersensitivity
medwireNews: People of Black, Asian, or Native Hawaiian/Pacific Islander ethnicity have a substantially higher risk for allopurinol-associated severe cutaneous adverse reactions (AASCARs) than White and Hispanic individuals, US researchers report.
These findings call for “heightened vigilance when initiating allopurinol in these racial/ ethnic groups,” say Hyon Choi (Massachusetts General Hospital, Boston, USA) and study co-authors.
They explain that allopurinol, the predominant first-line urate-lowering therapy for gout, is well tolerated overall, but “an uncommon yet feared adverse reaction is severe allopurinol hypersensitivity syndrome, manifesting as severe cutaneous adverse reactions.”
Choi and team used the Medicaid database to analyze the occurrence of AASCARs requiring hospitalization among 400,401 patients who initiated allopurinol treatment over a 13-year period.
In all, 0.08% of 111,619 Black patients, 0.07% of 21,442 Asian patients, and 0.18% of 18,839 Native Hawaiian/Pacific Islanders experienced AASCARs, compared with just 0.03% of 248,501 White/Hispanic patients, indicating “substantial variations in the incidence of hospitalized AASCARs according to race/ethnicity,” report the researchers in the Annals of the Rheumatic Diseases.
After adjustment for age, sex, chronic kidney disease, and initial allopurinol dose, patients of Black or Asian ethnicity were three times more likely to experience AASCARs than White/Hispanic patients, while Native Hawaiian/Pacific Islanders had an almost sevenfold increased risk.
“To our knowledge, this study provides the first evidence that this [Native Hawaiian/Pacific Islander] group has a high risk of AASCARs,” say the study authors, who hypothesize that this finding may be explained by a higher incidence of the HLA-B*5801 allele – previously shown to be associated with an increased risk for severe cutaneous adverse reactions – among US Pacific Islanders.
The team also identified female sex, age of 60 years or older, chronic kidney disease (CKD), and initial allopurinol dose of more than 100 mg/day as significant predictors of AASCARs, with adjusted relative risk values of 2.49, 1.66, 2.33, and 1.85, respectively.
“These findings support the use of extra caution among Native Hawaiians/Pacific Islanders, Asians and blacks when considering allopurinol (including screening for HLA-B*5801), particularly among elderly women with CKD,” write Choi and colleagues.
And they stress that initial allopurinol dose was “the only modifiable risk factor,” noting that starting with a low dose “is readily implementable and is also recommended by the latest rheumatology guidelines.”
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