Somdech Phra Debaratana Medical Center

Sathing Phra, Thailand

Somdech Phra Debaratana Medical Center

Sathing Phra, Thailand
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Saksit N.,Khon Kaen University | Saksit N.,University of Phayao | Tassaneeyakul W.,Khon Kaen University | Tassaneeyakul W.,Research and Diagnostic Center for Emerging Infectious Diseases | And 15 more authors.
Pharmacogenetics and Genomics | Year: 2017

Background Allopurinol is one of the most common causes of severe cutaneous adverse drug reactions (SCARs) including drug reactions with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN). This study identified the risk factors associated with the development of allopurinol-induced SCARs in a Thai population. Patients and methods Eighty-six allopurinol-induced SCARs (i.e. 19 DRESS and 67 SJS/TEN) and 182 allopurinol-tolerant patients were enrolled in the study. The HLA-B∗58:01 allele was determined. Clinical and medicinal data were collected. Results Results from multivariate analysis showed that only the HLA-B∗58:01 and female sex were identified as risk factors of allopurinol-induced SCARs in this Thai population. Patients who carried the HLA-B∗58:01 allele were at a higher risk of allopurinol-induced DRESS [odds ratio (OR)=149.2, 95% confidence interval (CI)=24.0-∞, P<1.00X10-4]. Similar results were observed in allopurinol-induced SJS/TEN (OR=175.0, 95% CI=44.3-690.9, P=1.69X10-13). The risk of allopurinolinduced SCARs in women was higher than that in men (OR=4.6, 95% CI=1.4-15.6, P=1.44×10-2). The overall mortality rate of allopurinol-induced SCARs was 11.39% and a higher mortality rate was observed in elderly women. Conclusion Among the risk factors identified, the HLAB∗58:01 allele had the greatest impact on the development of both phenotypes of allopurinol-induced SCARs in this studied Thai population. In case HLA-B∗58:01 genotyping cannot be accessed, close monitoring of allopurinol usage, especially in elderly women with impaired renal function, is necessary to reduce the mortality rate of these lifethreatening SCARs. Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.

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