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J Allergy Clin Immunol Pract. 2018 Dec 21. pii: S2213-2198(18)30834-1. doi: 10.1016/j.jaip.2018.12.012. [Epub ahead of print]

Efficacy of the HLA-B58:01 Screening Test in Preventing Allopurinol-Induced Severe Cutaneous Adverse Reactions in Patients with Chronic Renal Insufficiency-A Prospective Study.

Author information

1
Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea. Electronic address: guinea71@snu.ac.kr.
2
Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
3
Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.
4
Department of Internal Medicine, Seoul National University Boramae Medical Center, Seoul, Korea.
5
Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea; Department of Internal Medicine, Seoul National University Boramae Medical Center, Seoul, Korea.
6
Department of Internal Medicine, Chug-Ang University College of Medicine, Seoul, Korea.
7
Department of Internal Medicine, Chungbuk National University College of Medicine, Cheongju, Korea.
8
Department of Internal Medicine, College of Medicine, Ewha Womans University, Seoul, Korea.
9
Department of Internal Medicine, Dankook University College of Medicine, Cheonan, Korea.
10
Department of Internal Medicine, Gyeongsang National University Hospital, Jinju, Korea.
11
Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Korea.
12
Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Korea.

Abstract

BACKGROUND:

Thus far, human leukocyte antigen (HLA)-B58:01 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-B58:01 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-B58:01 allele. Of these, 503 HLA-B58:01-negative patients (92.8% of total) were treated with allopurinol, and 39 HLA-B58:01-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-B58:01 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

PMID:
30580048
DOI:
10.1016/j.jaip.2018.12.012

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