FPIN's Clinical Inquiries

Should Allele Testing Be Done Before Prescribing Allopurinol to Prevent Severe Cutaneous Adverse Reactions?


Am Fam Physician. 2021 Nov ;104(5):513-514.

Clinical Question

Should allele testing be done before prescribing allopurinol to prevent severe cutaneous adverse reactions (SCARs) such as Stevens-Johnson syndrome, toxic epidermal necrolysis, and drug reaction with eosinophilia and systemic symptoms?

Evidence-Based Answer

Moderate evidence supports allele testing for HLA-B*58:01 before initiating allopurinol to decrease the incidence of SCARs in higher risk populations. (Strength of Recommendation [SOR]: B, based on systematic review and meta-analysis of population-controlled studies, prospective cohort studies.) Patient populations who are not at increased risk should not be screened. (SOR: C, based on consensus recommendation.)

Evidence Summary

A 2015 nonrandomized prospective cohort study (n = 2,926) evaluated the use of prospective genotyping for HLA-B*58:01 before initiation of allopurinol to prevent SCARs, including Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms, and others.1 Historical incidence was used for the control group. The study included 15 medical centers in various regions across Taiwan from July 2009 to August 2014. Exclusion criteria included individuals who had a history of allopurinol-induced hypersensitivity, had a history of bone marrow transplant, or were not of self-described Han Chinese descent. HLAB*58:01 genotyping with real-time polymerase chain reaction was performed before starting treatment with allopurinol for all patients, and all patients were counseled on SCARs, with HLA-B*58:01-positive patients (n = 571) being recommended alternative treatments and non-carriers (n = 2,339) being started on allopurinol. The mean estimated historical incidence of allopurinol-induced SCARs in the control group from 2001 to 2004 was 0.30% per year (95% CI, 0.28% to 0.31%). This range of years was used to prevent confounding with early adopters of pretreatment genotyping. This study had a sufficient number of patients for a power of 86% to detect

Address correspondence to Elizabeth Close, MD, FAAFP, at elizabeth.close@erlanger.org. Reprints are not available from the authors.

Author disclosure: No relevant financial affiliations.


show all references

1. Ko TM, Tsai CY, Chen SY, et al.; Taiwan Allopurinol-SCAR Consortium. Use of HLA-B*58: 01 genotyping to prevent allopurinol induced severe cutaneous adverse reactions in Taiwan: national prospective cohort study. BMJ. 2015;351:h4848....

2. Park HW, Kim DK, Kim SH, et al. 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. J Allergy Clin Immunol Pract. 2019;7(4):1271–1276.

3. Somkrua R, Eickman EE, Saokaew S, et al. Association of HLA-B*5801 allele and allopurinol-induced Stevens Johnson syndrome and toxic epidermal necrolysis: a systematic review and meta-analysis. BMC Med Genet. 2011;12:118.

4. FitzGerald JD, Dalbeth N, Mikuls T, et al. 2020 American College of Rheumatology guideline for the management of gout [published corrections appear in Arthritis Care Res (Hoboken). 2020; 72(8): 1187 and Arthritis Care Res (Hoboken). 2021; 73(3): 458]. Arthritis Care Res (Hoboken). 2020;72(6):744–760.

5. Jutkowitz E, Dubreuil M, Lu N, et al. The cost-effectiveness of HLA-B*5801 screening to guide initial urate-lowering therapy for gout in the United States. Semin Arthritis Rheum. 2017;46(5):594–600.

6. Goodman CW, Brett AS. Race and pharmacogenomics—personalized medicine or misguided practice? JAMA. 2021;325(7):625–626.

Clinical Inquiries provides answers to questions submitted by practicing family physicians to the Family Physicians Inquiries Network (FPIN). Members of the network select questions based on their relevance to family medicine. Answers are drawn from an approved set of evidence-based resources and undergo peer review.

The complete database of evidence-based questions and answers is copyrighted by FPIN. If interested in submitting questions or writing answers for this series, go to http://www.fpin.org or email: questions@fpin.org.

This series is coordinated by John E. Delzell Jr., MD, MSPH, associate medical editor.

A collection of FPIN's Clinical Inquiries published in AFP is available at https://www.aafp.org/afp/fpin.



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