Systematic review on the association of HLA-B*5801 and allopurinol-induced severe cutaneous adverse reactions

Abstract

Background: Studies have suggested a possible association between HLA-B*5801 and allopurinol induced Severe Cutaneous Adverse Reactions such as Stevens-Johnston Syndrome and Toxic Epidermal Necrolysis, which is fatal. Objectives: This systematic review aims to investigate the correlation between HLA-B*5801 and allopurinol-induced Severe Cutaneous Adverse Reactions, and whether gene-testing prior to allopurinol prescription might be a possible alternative. Methods: A comprehensive literature search was performed in MEDLINE and EMBASE from 2010 January to 2015 December. Only studies using allopurinol as the de novo drug and those investigating the association between HLA-B*5801 and allopurinol-induced Severe Cutaneous Adverse Reactions were included. Comparison were done between allopurinol induced Severe Cutaneous Adverse Reactions Case group with allopurinol tolerant control group and/or population control group. Systematic analysis was performed to examine the intervention and outcome. Newcastle-Ottawa Scale was used to evaluate the quality of individual studies. Results: A total of 4 published studies were identified. Comparison of association between case and allopurinol tolerant control group were found in Han Chinese and Hong Kong, while comparison of association between case and control population were found in Portuguese and Japanese. The presence of HLA-B*5801 with allopurinol induced SCAR was statistically significant p<0.05 in all the four individual studies. Conclusion: This systematic review concludes that association of HLA-B*5801 and allopurinol induced Severe Cutaneous Adverse Reactions is statistically significant among different ethnic groups in all the four studies, prior gene test before allopurinol administration is recommended.