• Tai-Ming Ko, Chang-Youh Tsai, Shih-Yang Chen, Kuo-Shu Chen, Kuang-Hui Yu, Chih-Sheng Chu, Chung-Ming Huang, Chrong-Reen Wang, Chia-Tse Weng, Chia-Li Yu, Song-Chou Hsieh, Jer-Chia Tsai, Wen-Ter Lai, Wen-Chan Tsai, Guang-Dar Yin, Tsan-Teng Ou, Kai-Hung Cheng, Jeng-Hsien Yen, Teh-Ling Liou, Tsung-Hsien Lin, Der-Yuan Chen, Pi-Jung Hsiao, Meng-Yu Weng, Yi-Ming Chen, Chen-Hung Chen, Ming-Fei Liu, Hsueh-Wei Yen, Jia-Jung Lee, Mei-Chuan Kuo, Chen-Ching Wu, Shih-Yuan Hung, Shue-Fen Luo, Ya-Hui Yang, Hui-Ping Chuang, Yi-Chun Chou, Hung-Ting Liao, Chia-Wen Wang, Chun-Lin Huang, Chia-Shuo Chang, Ming-Ta Michael Lee, Pei Chen, Chih-Shung Wong, Chien-Hsiun Chen, Jer-Yuarn Wu, Yuan-Tsong Chen, Chen-Yang Shen, and Taiwan Allopurinol-SCAR Consortium.
• Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan Graduate Institute of Integrated Medicine, China Medical University, Taichung, Taiwan.
• BMJ. 2015 Jan 1;351:h4848.

ObjectiveTo evaluate the use of prospective screening for the HLA-B*58:01 allele to identify Taiwanese individuals at risk of severe cutaneous adverse reactions (SCARs) induced by allopurinol treatment.DesignNational prospective cohort study.Setting15 medical centres in different regions of Taiwan, from July 2009 to August 2014.Participants2926 people who had an indication for allopurinol treatment but had not taken allopurinol previously. Participants were excluded if they had undergone a bone marrow transplant, were not of Han Chinese descent, and had a history of allopurinol induced hypersensitivity. DNA purified from 2910 participants' peripheral blood was used to assess the presence of HLA-B*58:01.Main Outcome MeasuresIncidence of allopurinol induced SCARs with and without screening.ResultsParticipants who tested positive for HLA-B*58:01 (19.6%, n=571) were advised to avoid allopurinol, and were referred to an alternate drug treatment or advised to continue with their prestudy treatment. Participants who tested negative (80.4%, n=2339) were given allopurinol. Participants were interviewed once a week for two months to monitor symptoms. The historical incidence of allopurinol induced SCARs, estimated by the National Health Insurance research database of Taiwan, was used for comparison. Mild, transient rash without blisters developed in 97 (3%) participants during follow-up. None of the participants was admitted to hospital owing to adverse drug reactions. SCARs did not develop in any of the participants receiving allopurinol who screened negative for HLA-B*58:01. By contrast, seven cases of SCARs were expected, based on the estimated historical incidence of allopurinol induced SCARs nationwide (0.30% per year, 95% confidence interval 0.28% to 0.31%; P=0.0026; two side one sample binomial test).ConclusionsProspective screening of the HLA-B*58:01 allele, coupled with an alternative drug treatment for carriers, significantly decreased the incidence of allopurinol induced SCARs in Taiwanese medical centres.© Ko et al 2015.

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