Efficacy of the HLA-B 58:01 Screening Test in Preventing Allopurinol-Induced Severe Cutaneous Adverse Reactions in Patients with Chronic Renal Insufficiency—A Prospective Study

Heung Woo Park, Dong Ki Kim, Sae Hoon Kim, Sejoong Kim, Dong Wan Chae, Min Suk Yang, Yun Kyu Oh, Jung Pyo Lee, Jae Woo Jung, Jungho Shin, Jin Ho Hwang, Min Gyu Kang, Sun Moon Kim, Soon Kil Kwon, Hye Young Kim, Min Hye Kim, Seung Jung Kim, Dong Ryeol Ryu, Young Joo Cho, Young Koo JeeSo Mi Kim, Eun Kyoung Lee, Ju Young Kim, Hyun Seop Cho, Yi Yeong Jeong, Sang Heon Kim, Jae Bum Jun, Joon Sung Park, Gheun Ho Kim, Sujeong Kim, Hee Yeon Jung, Jong Myung Lee

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17 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)1271-1276
Number of pages6
JournalJournal of Allergy and Clinical Immunology: In Practice
Volume7
Issue number4
DOIs
StatePublished - Apr 2019

Keywords

  • Allopurinol
  • Chronic
  • Drug hypersensitivity
  • HLA-B 58:01 allele
  • Renal insufficiency

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