Impact of the HLA-B(*)58:01 Allele and Renal Impairment on Allopurinol-Induced Cutaneous Adverse Reactions.

Abstract

Allopurinol, a common drug for treating hyperuricemia, is associated with cutaneous adverse drug reactions ranging from mild maculopapular exanthema to life-threatening severe cutaneous adverse reactions, including drug reaction with eosinophilia and systemic symptoms, Stevens-Johnson syndrome, and toxic epidermal necrolysis. We have previously reported that HLA-B*58:01 is strongly associated with allopurinol-induced severe cutaneous adverse reactions in Han Chinese, but the associations of the HLA-B*58:01 genotype in an allopurinol-induced hypersensitivity phenotype remain unclear. To investigate the comprehensive associations of HLA-B*58:01, we enrolled 146 patients with allopurinol-induced cutaneous adverse drug reactions (severe cutaneous adverse reactions, n = 106; maculopapular exanthema, n = 40) and 285 allopurinol-tolerant control subjects. Among these allopurinol-induced cutaneous adverse drug reactions, HLA-B*58:01 was strongly associated with severe cutaneous adverse reactions (odds ratio [OR] = 44.0; 95% confidence interval = 21.5-90.3; P = 2.6 × 10(-41)), and the association was correlated with disease severity (OR = 44.0 for severe cutaneous adverse reactions, OR = 8.5 for maculopapular exanthema). The gene dosage effect of HLA-B*58:01 also influenced the development of allopurinol-induced cutaneous adverse drug reactions (OR = 15.25 for HLA-B*58:01 heterozygotes and OR = 72.45 for homozygotes). Furthermore, coexistence of HLA-B*58:01 and renal impairment increased the risk and predictive accuracy of allopurinol-induced cutaneous adverse drug reactions (heterozygous HLA-B*58:01 and normal renal function: OR = 15.25, specificity = 82%; homozygous HLA-B*58:01 and severe renal impairment: OR = 1269.45, specificity = 100%). This HLA-B*58:01 correlation study suggests that patients with coexisting HLA-B*58:01 and renal impairment (especially estimated glomerular filtration rate < 30ml/minute/1.73 m(2)) should be cautious and avoid using allopurinol.

• Authors: Chau Yee Ng, Yu-Ting Yeh, Chuang-Wei Wang, Shuen-Iu Hung, Chih-Hsun Yang, Ya-Ching Chang, Wan-Chun Chang, Yu-Jr Lin, Chee-Jen Chang, Shih-Chi Su, Wen-Lang Fan, Der-Yuan Chen, Yeong-Jian Jan Wu, Ya-Chung Tian, Rosaline Chung-Yee Hui, Wen-Hung Chung, Taiwan Severe Cutaneous Adverse Reaction Consortium
• Journal: The Journal of investigative dermatology (J Invest Dermatol) Vol. 136 Issue 7 Pg. 1373-1381 (07 2016) ISSN: 1523-1747 [Electronic] United States
• PMID: 26996548 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Chemical References

• HLA-B Antigens
• HLA-B*58:01 antigen
• Allopurinol

Topics

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Alleles
• Allopurinol (adverse effects)
• Child
• China
• Drug Eruptions (pathology)
• Eosinophilia
• Exanthema (chemically induced, pathology)
• Female
• Genotype
• Glomerular Filtration Rate
• HLA-B Antigens (genetics)
• Homozygote
• Humans
• Hyperuricemia (etiology)
• Kidney (drug effects, physiopathology)
• Male
• Middle Aged
• Odds Ratio
• ROC Curve
• Risk
• Sensitivity and Specificity
• Skin (drug effects, pathology)
• Stevens-Johnson Syndrome (pathology)
• Young Adult