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BMJ. 2015 Sep 23;351:h4848. doi: 10.1136/bmj.h4848.

Use of HLA-B*58:01 genotyping to prevent allopurinol induced severe cutaneous adverse reactions in Taiwan: national prospective cohort study.

Author information

1
Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan Graduate Institute of Integrated Medicine, China Medical University, Taichung, Taiwan.
2
Division of Allergy, Immunology, and Rheumatology, Taipei Veterans General Hospital, Taipei Faculty of Medicine, National Yang Ming University, Taipei.
3
Centre of Gout, Country Hospital, Taipei.
4
Tungs' Taichung MetroHarbor Hospital, Taichung.
5
Chang Gung Memorial Hospital, Taoyuan, Taiwan.
6
Kaohsiung Medical University Hospital and Kaohsiung Medical University, Kaohsiung, Taiwan Kaohsiung Municipal Hsiaokang Hospital, Kaohsiung Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung.
7
Graduate Institute of Integrated Medicine, China Medical University, Taichung, Taiwan China Medical University Hospital, Taichung.
8
National Cheng Kung University Hospital, Tainan, Taiwan.
9
National Taiwan University Hospital, Taipei.
10
Far Eastern Polyclinic, Taipei.
11
Division of Allergy, Immunology, and Rheumatology, Taipei Veterans General Hospital, Taipei.
12
Kaohsiung Medical University Hospital and Kaohsiung Medical University, Kaohsiung, Taiwan.
13
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.
14
Tri-Service General Hospital, Taipei.
15
Faculty of Renal Care, Kaohsiung Medical University, Kaohsiung.
16
Division of Nephrology, E-Da Hospital, Kaohsiung School of Medicine, I-Shou University, Kaohsiung.
17
Chang Gung Memorial Hospital, Taoyuan, Taiwan Chang Gung University, Taoyuan.
18
Department of Occupational Safety and Hygiene, Fooyin University, Kaohsiung Department of Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung.
19
Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan.
20
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.
21
Department of Anaesthesiology, Cathay General Hospital, Taipei PharmiGene, Taipei.
22
Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan School of Chinese Medicine, China Medical University, Taichung.
23
Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan Department of Pediatrics, Duke University Medical Center, Durham, NC, USA.
24
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.

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.

DESIGN:

National prospective cohort study.

SETTING:

15 medical centres in different regions of Taiwan, from July 2009 to August 2014.

PARTICIPANTS:

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.

MAIN OUTCOME MEASURES:

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.

PMID:
26399967
PMCID:
PMC4579807
DOI:
10.1136/bmj.h4848
[Indexed for MEDLINE]
Free PMC Article

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