Volume 4 Supplement 3

6th Drug Hypersensitivity Meeting (DHM 6)

Open Access

A prospective study of HLA*B-5801 genotyping in preventing allopurinol- induced severe cutaneous adverse reactions

  • Tai-Ming Ko1,
  • Jer-Yuarn Wu2,
  • Yuan-Tsong Chen2 and
  • Chen-Yang Shen2
Clinical and Translational Allergy20144(Suppl 3):O4

DOI: 10.1186/2045-7022-4-S3-O4

Published: 18 July 2014

Background

Allopurinol, a commonly prescribed medication for gout and hyperuricemia, is a frequent cause of severe cutaneous adverse reactions (SCAR), which include the hypersensitivity syndrome, Stevens-Johnson syndrome, and toxic epidermal necrolysis. Allopurinol-induced SCAR is strongly associated with the HLA-B*58:01 allele. We sought to prevent allopurinol-induced SCAR by using HLA-B*58:01 screening to prospectively identify subjects at risk for this condition.

Methods

From 14 hospitals in Taiwan, we recruited 2037 candidate subjects who had indication for allopurinol treatment but had not taken allopurinol previously. We genotyped DNA purified from the subjects' PBMC to determine whether they carried the HLA-B*58:01 allele. Those testing positive for HLA-B*58:01 (20.57% of the total) were advised not to take allopurinol and were given an alternative medication or advised to continue taking their pre-study medication; those testing negative (79.43%) were given allopurinol. We interviewed the subjects by telephone once a week for 3 months to monitor them for symptoms. We used the estimated historical incidence of SCAR for comparison.

Results

Mild, transient rash developed in 4.63% of subjects during follow-up; more widespread rash was observed in 0.13% of subjects, who were hospitalized. SCAR did not develop in any of the HLA-B*58:01-negative subjects receiving allopurinol; this is in contrast to the 4 expected cases of SCAR based on the estimated historical incidence of allopurinol-induced SCAR (0.29%) (p value=0.0266; Fisher's two-tailed exact tests).

Conclusions

The identification of subjects carrying the HLA-B*58:01 allele and the avoidance of allopurinol therapy in these subjects were strongly associated with a decreased incidence of allopurinol-induced SCAR.

Funding

Funded by the Academia Sinica Genomic Medicine Multicenter Study and National Science Council of Taiwan.

Authors’ Affiliations

(1)
Institute of Biomedical Sciences, Academia Sinica
(2)
Academia Sinica, Institute of Biomedical Sciences

Copyright

© Ko et al; licensee BioMed Central Ltd. 2014

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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