Niwat Saksit1, 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. 1. aDepartment of Pharmacology bPharmacy Unit cDepartment of Medicine, Faculty of Medicine dResearch and Diagnostic Center for Emerging Infectious Diseases eResearch Center in Back, Neck Other Joint Pain and Human Performance fSleep Apnea Research Group gFaculty of Pharmaceutical Sciences, Khon Kaen University, Khon Kaen hSchool of Pharmaceutical Sciences, University of Phayao, Phayao iPharmacy Unit, Udon Thani Hospital, Udon Thani jDepartment of Pathology, Division of Pharmacogenomics and Personalized Medicine kLaboratory for Pharmacogenomics, Somdech Phra Debaratana Medical Center lDivision of Allergy Immunology and Rheumatology, Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok mDepartment of Pharmacy, Phrae Hospital, Phrae nCenter of Pharmaceutical Outcomes Research, Department of Pharmacy Practice, Faculty of Pharmaceutical Sciences, Naresuan University, Phitsanulok, Thailand oSchool of Pharmacy pHealth and Well-being Cluster, Global Asia in the 21st Century (GA21) Platform, Monash University Malaysia, Malaysia qSchool of Pharmacy, University of Wisconsin, Madison, Wisconsin, USA.
Abstract
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<1.00×10]. Similar results were observed in allopurinol-induced SJS/TEN (OR=175.0, 95% CI=44.3-690.9, P=1.69×10). The risk of allopurinol-induced SCARs in women was higher than that in men (OR=4.6, 95% CI=1.4-15.6, P=1.44×10). 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 HLA-B*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 life-threatening SCARs.
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<1.00×10]. Similar results were observed in allopurinol-induced SJS/TEN (OR=175.0, 95% CI=44.3-690.9, P=1.69×10). The risk of allopurinol-induced SCARs in women was higher than that in men (OR=4.6, 95% CI=1.4-15.6, P=1.44×10). 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 HLA-B*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 life-threatening SCARs.