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Diagnostic utility of HLA‐B*5801 screening in severe allopurinol hypersensitivity syndrome: an updated systematic review and meta‐analysis
Author(s) -
Yu KuangHui,
Yu ChengYen,
Fang YaoFan
Publication year - 2017
Publication title -
international journal of rheumatic diseases
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.795
H-Index - 41
eISSN - 1756-185X
pISSN - 1756-1841
DOI - 10.1111/1756-185x.13143
Subject(s) - medicine , allopurinol , dermatology , meta analysis , immunology
Background Despite many studies suggesting an association between human leukocyte antigen ( HLA )‐B*5801 and allopurinol‐induced toxic epidermal necrolysis ( TEN ) and Stevens‐Johnsons syndrome ( SJS ), the evidence of association in different populations and the degree of association remain uncertain. Methods The primary analysis was based on population‐control studies. Data were pooled by means of a random‐effects model, and sensitivity, specificity, positive likelihood ratios (LR+), negative likelihood ratios (LR−), diagnostic odds ratios ( DOR ), and areas under summary receiver operating characteristic ( SROC ) curves ( AUC ) were calculated. Results In nine population‐control studies, HLA ‐B*5801 was measured in 162 patients with allopurinol‐induced TEN / SJS and 7372 patients without allopurinol‐induced TEN / SJS . The pooled sensitivity, specificity, LR +, LR −, DOR and AUC were 0.78 (95% CI = 0.71–0.85), 0.96 (95% CI = 0.96–0.97), 14.23 (95% CI = 7.89–25.63), 0.29 (95% CI = 0.16–0.54), 83.5 (95% CI = 50.7–137.4), and 0.97 (95% CI = 0.95–0.99), respectively. Subgroup analyses of the DOR s for Chinese, Japanese, and Caucasian populations yielded similar findings for Chinese (196.1; 95% CI = 57.3–672.0), Japanese (78.8; 95% CI = 30.4–203.9), and Caucasian (58.4; 95% CI = 16.9–201.5) populations. Overall, HLA ‐B*5801 was associated with allopurinol‐induced TEN / SJS in European and Japanese populations, but only had a 50–60% sensitivity (pooled sensitivity 56%), compared to the 80–100% sensitivity (pooled sensitivity 97%) observed in Korean, Thai, Sardinia Italian and Han Chinese populations. Conclusions The present study reveals that allopurinol is the leading cause of TEN / SJS in many countries. In contrast to carbamazepine, which is ethnic/population specific, the HLA ‐B*5801 for detecting allopurinol‐induced TEN / SJS is universal. Screening of HLA ‐B*5801 may help patients to prevent the occurrence of allopurinol‐induced TEN / SJS , especially in populations with a higher (≥ 5%) risk allele frequency.