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 m2) should be cautious and avoid using allopurinol.
Original language | English |
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Pages (from-to) | 1373-1381 |
Number of pages | 9 |
Journal | Journal of Investigative Dermatology |
Volume | 136 |
Issue number | 7 |
DOIs | |
State | Published - 01 07 2016 |
Bibliographical note
Publisher Copyright:© 2016 The Authors