title: Use of HLA-B*58:01 genotyping to prevent allopurinol induced severe cutaneous adverse reactions in Taiwan: national prospective cohort study.
abstract: OBJECTIVE
  To 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.
  
  
  METHODS
  National prospective cohort study.
  
  
  METHODS
  15 medical centres in different regions of Taiwan, from July 2009 to August 2014.
  
  
  METHODS
  2926 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.
  
  
  METHODS
  Incidence of allopurinol induced SCARs with and without screening.
  
  
  RESULTS
  Participants 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).
  
  
  CONCLUSIONS
  Prospective 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.
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan Graduate Institute of Integrated Medicine, China Medical University, Taichung, Taiwan.
authors.forename: Tai-Ming
authors.initials: TM
authors.lastname: Ko
authors.affiliation: Division of Allergy, Immunology, and Rheumatology, Taipei Veterans General Hospital, Taipei Faculty of Medicine, National Yang Ming University, Taipei.
authors.forename: Chang-Youh
authors.initials: CY
authors.lastname: Tsai
authors.affiliation: Centre of Gout, Country Hospital, Taipei.
authors.forename: Shih-Yang
authors.initials: SY
authors.lastname: Chen
authors.affiliation: Tungs' Taichung MetroHarbor Hospital, Taichung.
authors.forename: Kuo-Shu
authors.initials: KS
authors.lastname: Chen
authors.affiliation: Chang Gung Memorial Hospital, Taoyuan, Taiwan.
authors.forename: Kuang-Hui
authors.initials: KH
authors.lastname: Yu
authors.affiliation: Kaohsiung Medical University Hospital and Kaohsiung Medical University, Kaohsiung, Taiwan Kaohsiung Municipal Hsiaokang Hospital, Kaohsiung Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung.
authors.forename: Chih-Sheng
authors.initials: CS
authors.lastname: Chu
authors.affiliation: Graduate Institute of Integrated Medicine, China Medical University, Taichung, Taiwan China Medical University Hospital, Taichung.
authors.forename: Chung-Ming
authors.initials: CM
authors.lastname: Huang
authors.affiliation: National Cheng Kung University Hospital, Tainan, Taiwan.
authors.forename: Chrong-Reen
authors.initials: CR
authors.lastname: Wang
authors.affiliation: National Cheng Kung University Hospital, Tainan, Taiwan.
authors.forename: Chia-Tse
authors.initials: CT
authors.lastname: Weng
authors.affiliation: National Taiwan University Hospital, Taipei.
authors.forename: Chia-Li
authors.initials: CL
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authors.affiliation: National Taiwan University Hospital, Taipei.
authors.forename: Song-Chou
authors.initials: SC
authors.lastname: Hsieh
authors.affiliation: Kaohsiung Medical University Hospital and Kaohsiung Medical University, Kaohsiung, Taiwan Kaohsiung Municipal Hsiaokang Hospital, Kaohsiung Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung.
authors.forename: Jer-Chia
authors.initials: JC
authors.lastname: Tsai
authors.affiliation: Kaohsiung Medical University Hospital and Kaohsiung Medical University, Kaohsiung, Taiwan Kaohsiung Municipal Hsiaokang Hospital, Kaohsiung Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung.
authors.forename: Wen-Ter
authors.initials: WT
authors.lastname: Lai
authors.affiliation: Kaohsiung Medical University Hospital and Kaohsiung Medical University, Kaohsiung, Taiwan Kaohsiung Municipal Hsiaokang Hospital, Kaohsiung Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung.
authors.forename: Wen-Chan
authors.initials: WC
authors.lastname: Tsai
authors.affiliation: Far Eastern Polyclinic, Taipei.
authors.forename: Guang-Dar
authors.initials: GD
authors.lastname: Yin
authors.affiliation: Kaohsiung Medical University Hospital and Kaohsiung Medical University, Kaohsiung, Taiwan Kaohsiung Municipal Hsiaokang Hospital, Kaohsiung Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung.
authors.forename: Tsan-Teng
authors.initials: TT
authors.lastname: Ou
authors.affiliation: Kaohsiung Medical University Hospital and Kaohsiung Medical University, Kaohsiung, Taiwan Kaohsiung Municipal Hsiaokang Hospital, Kaohsiung Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung.
authors.forename: Kai-Hung
authors.initials: KH
authors.lastname: Cheng
authors.affiliation: Kaohsiung Medical University Hospital and Kaohsiung Medical University, Kaohsiung, Taiwan Kaohsiung Municipal Hsiaokang Hospital, Kaohsiung Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung.
authors.forename: Jeng-Hsien
authors.initials: JH
authors.lastname: Yen
authors.affiliation: Division of Allergy, Immunology, and Rheumatology, Taipei Veterans General Hospital, Taipei.
authors.forename: Teh-Ling
authors.initials: TL
authors.lastname: Liou
authors.affiliation: Kaohsiung Medical University Hospital and Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Tsung-Hsien
authors.initials: TH
authors.lastname: Lin
authors.affiliation: Faculty of Medicine, National Yang Ming University, Taipei Department of Medical Education and Research, and Division of Allergy, Immunology and Rheumatology, Taichung Veterans General Hospital, Taichung Institute of Biomedical Science and Rong Hsing Research Centre for Translational Medicine, National Chung Hsing University, Taichung.
authors.forename: Der-Yuan
authors.initials: DY
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authors.affiliation: Kaohsiung Medical University Hospital and Kaohsiung Medical University, Kaohsiung, Taiwan Kaohsiung Municipal Hsiaokang Hospital, Kaohsiung Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung.
authors.forename: Pi-Jung
authors.initials: PJ
authors.lastname: Hsiao
authors.affiliation: National Cheng Kung University Hospital, Tainan, Taiwan.
authors.forename: Meng-Yu
authors.initials: MY
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authors.affiliation: Faculty of Medicine, National Yang Ming University, Taipei Department of Medical Education and Research, and Division of Allergy, Immunology and Rheumatology, Taichung Veterans General Hospital, Taichung Institute of Biomedical Science and Rong Hsing Research Centre for Translational Medicine, National Chung Hsing University, Taichung.
authors.forename: Yi-Ming
authors.initials: YM
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authors.affiliation: Tri-Service General Hospital, Taipei.
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authors.initials: CH
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authors.affiliation: National Cheng Kung University Hospital, Tainan, Taiwan.
authors.forename: Ming-Fei
authors.initials: MF
authors.lastname: Liu
authors.affiliation: Kaohsiung Medical University Hospital and Kaohsiung Medical University, Kaohsiung, Taiwan Kaohsiung Municipal Hsiaokang Hospital, Kaohsiung Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung.
authors.forename: Hsueh-Wei
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authors.affiliation: Kaohsiung Medical University Hospital and Kaohsiung Medical University, Kaohsiung, Taiwan.
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authors.initials: JJ
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authors.affiliation: Faculty of Renal Care, Kaohsiung Medical University, Kaohsiung.
authors.forename: Mei-Chuan
authors.initials: MC
authors.lastname: Kuo
authors.affiliation: Kaohsiung Medical University Hospital and Kaohsiung Medical University, Kaohsiung, Taiwan Kaohsiung Municipal Hsiaokang Hospital, Kaohsiung Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung.
authors.forename: Chen-Ching
authors.initials: CC
authors.lastname: Wu
authors.affiliation: Division of Nephrology, E-Da Hospital, Kaohsiung School of Medicine, I-Shou University, Kaohsiung.
authors.forename: Shih-Yuan
authors.initials: SY
authors.lastname: Hung
authors.affiliation: Chang Gung Memorial Hospital, Taoyuan, Taiwan Chang Gung University, Taoyuan.
authors.forename: Shue-Fen
authors.initials: SF
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authors.affiliation: Department of Occupational Safety and Hygiene, Fooyin University, Kaohsiung Department of Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung.
authors.forename: Ya-Hui
authors.initials: YH
authors.lastname: Yang
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan.
authors.forename: Hui-Ping
authors.initials: HP
authors.lastname: Chuang
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan.
authors.forename: Yi-Chun
authors.initials: YC
authors.lastname: Chou
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan.
authors.forename: Hung-Ting
authors.initials: HT
authors.lastname: Liao
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan.
authors.forename: Chia-Wen
authors.initials: CW
authors.lastname: Wang
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan.
authors.forename: Chun-Lin
authors.initials: CL
authors.lastname: Huang
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan.
authors.forename: Chia-Shuo
authors.initials: CS
authors.lastname: Chang
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan Laboratory for International Alliance on Genomic Research, Core for Genomic Medicine, RIKEN Centre for Integrative Medical Sciences, Yokohama, Kanagawa, Japan.
authors.forename: Ming-Ta Michael
authors.initials: MT
authors.lastname: Lee
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan.
authors.forename: Pei
authors.initials: P
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authors.affiliation: Department of Anaesthesiology, Cathay General Hospital, Taipei PharmiGene, Taipei.
authors.forename: Chih-Shung
authors.initials: CS
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authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan School of Chinese Medicine, China Medical University, Taichung.
authors.forename: Chien-Hsiun
authors.initials: CH
authors.lastname: Chen
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan School of Chinese Medicine, China Medical University, Taichung.
authors.forename: Jer-Yuarn
authors.initials: JY
authors.lastname: Wu
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan Department of Pediatrics, Duke University Medical Center, Durham, NC, USA.
authors.forename: Yuan-Tsong
authors.initials: YT
authors.lastname: Chen
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan College of Public Health, China Medical University Hospital, Taichung Taiwan Biobank, Academia Sinica, Taipei bmcys@ibms.sinica.edu.tw.
authors.forename: Chen-Yang
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mesh_terms: D000493:Allopurinol / Q000009:adverse effects*; D002908:Chronic Disease; D003875:Drug Eruptions / Q000235:genetics / Q000517:prevention & control*; D005076:Exanthema / Q000139:chemically induced; D005260:Female; D005820:Genetic Testing; D005838:Genotype; D006074:Gout Suppressants / Q000009:adverse effects*; D015235:HLA-B Antigens / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011537:Pruritus / Q000139:chemically induced; D013624:Taiwan
chemical_list: D006074:Gout Suppressants; D015235:HLA-B Antigens; C041533:HLA-B58 antigen; D000493:Allopurinol