Background: Thus far, human leukocyte antigen (HLA)-B∗58:01 has been recognized as the most important risk factor for allopurinol induced severe cutaneous adverse reactions (SCARs).
Objective: To determine the usefulness of prospective screening for the HLA-B∗58:01 allele to identify Korean individuals at risk for SCARs induced by allopurinol treatment.
Methods: We prospectively enrolled 542 patients with chronic renal insufficiency (CRI) from 10 hospitals nationwide and performed DNA genotyping to determine whether they carried the HLA-B∗58:01 allele. Of these, 503 HLA-B∗58:01-negative patients (92.8% of total) were treated with allopurinol, and 39 HLA-B∗58:01-positive patients (7.2%) were treated with febuxostat, an alternative drug. The patients then were followed up biweekly for 90 days using a telephone survey to monitor symptoms of adverse drug reactions, including SCARs. As a control, we used the historical incidence rate of allopurinol-induced SCARs in 4002 patients with CRI from the same hospitals who were enrolled retrospectively.
Results: Nineteen patients in the prospective cohort developed mild and transient adverse reactions but none showed allopurinol-induced SCARs. By contrast, we identified 38 patients with allopurinol-induced SCARs (0.95%) in the historical control. The difference in the incidence of allopurinol-induced SCARs between the prospective cohort and historical control was statistically significant (0% vs 0.95%, respectively; P = .029).
Conclusions: The present study demonstrated the clinical usefulness of the HLA-B∗58:01 screening test before allopurinol administration to prevent allopurinol-induced SCARs in patients with CRI.
Keywords: Allopurinol; Chronic; Drug hypersensitivity; HLA-B(∗)58:01 allele; Renal insufficiency.
Copyright © 2018 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.