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Title: Risk factors of allopurinol-induced severe cutaneous adverse reactions in a Thai population
Authors: Niwat Saksit
Wichittra Tassaneeyakul
Nontaya Nakkam
Parinya Konyoung
Usanee Khunarkornsiri
Pansu Chumworathayi
Chonlaphat Sukasem
Sumitra Suttisai
Napacha Piriyachananusorn
Pawinee Tiwong
Nathorn Chaiyakunapruk
Kittisak Sawanyawisuth
Ticha Rerkpattanapipat
Wongwiwat Tassaneeyakul
Khon Kaen University
Pharmacy Unit
Faculty of Medicine
Research and Diagnostic Center for Emerging Infectious Diseases
Research Center in Back
Sleep Apnea Research Group
University of Phayao
Udon Thani Center Hospital
Division of Pharmacogenomics and Personalized Medicine
Somdech Phra Debaratana Medical Center
Mahidol University
Phrae Hospital
Naresuan University
School of Pharmacy
Monash University Malaysia
University of Wisconsin Madison
Keywords: Biochemistry, Genetics and Molecular Biology
Issue Date: 1-Jan-2017
Citation: Pharmacogenetics and Genomics. Vol.27, No.7 (2017), 255-263
Abstract: Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved. 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.
ISSN: 17446880
Appears in Collections:Scopus 2016-2017

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