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HLA-B*58:01 screening to prevent allopurinol-induced severe cutaneous adverse reactions in Chinese patients with chronic kidney disease

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Abstract

Human leukocyte antigen (HLA)-B*58:01 allele is a significant risk factor for allopurinol-induced severe cutaneous adverse reactions (SCARs) which is potentially fatal. In some studies, chronic kidney disease (CKD) was also implicated to compound the risk of SCARs. We aim to investigate if pre-treatment HLA-B*58:01 screening can prevent allopurinol-induced SCARs in Chinese patients with CKD and its cost-effectiveness. We prospectively recruited Chinese CKD patients who required allopurinol during 2011–2015 and performed pre-treatment HLA testing (HLA screening group). Patients tested positive for HLA-B*58:01 were refrained from allopurinol while those tested negative were prescribed allopurinol. The incidence of SCARs in the HLA screening group was compared with the historical control in previous 5 years and the cost-effectiveness of HLA testing was analyzed. In the historical control (2006–2010), 3605 patients on allopurinol were screened, 22 out of 1027 (2.14%) CKD Chinese patients newly started on allopurinol developed SCARs, including 6 SJS/TEN. In the HLA screening group, 28 out of 192 patients (14.6%) tested HLA-B*58:01 positive were advised to avoid allopurinol; 156 out of 164 HLA-B*58:01-negative patients received allopurinol and none developed SCARs. The incidence rate of SCARs was significantly lower in the HLA screening group compared with controls (0% vs 2.14% respectively, p = 0.037*). The targeted HLA screening approach was associated with lower healthcare costs compared with no HLA screening (US$ 92,430 vs US$ 281,226). Pre-treatment HLA-B*58:01 screening is cost-effective to target on patients with CKD in Chinese to prevent allopurinol-induced SCARs.

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Acknowledgements

The authors would like to extend the appreciation to Dr. Kendrick Co Shih who reviewed and advised on SJS/TEN cases with ocular complications in the study.

Funding

This project was funded by the S.K. Yee Medical Foundation (Project number 212218).

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Authors and Affiliations

  1. Division of Dermatology, Department of Medicine, The University of Hong Kong, Hong Kong SAR, China

    Christina Sze-Man Wong, Chi-Keung Yeung, Chun-Yin Chan & Henry Hin-Lee Chan

  2. Division of Nephrology, Department of Medicine, The University of Hong Kong, Hong Kong SAR, China

    Desmond Yat-Hin Yap & Sydney Chi-Wai Tang

  3. Division of Clinical Pharmacology, Department of Medicine, The University of Hong Kong, Hong Kong SAR, China

    Bernard Man-Yung Cheung

  4. Division of Transplantation and Immunogenetics, Department of Pathology, Queen Mary Hospital, Hong Kong SAR, China

    Janette Siu-Yin Kwok

  5. Dermatology and Laser Centre, 1 Wellington Street, Central, Hong Kong SAR, China

    Henry Hin-Lee Chan

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Wong, C.SM., Yeung, CK., Chan, CY. et al. HLA-B*58:01 screening to prevent allopurinol-induced severe cutaneous adverse reactions in Chinese patients with chronic kidney disease. Arch Dermatol Res 314, 651–659 (2022). https://doi.org/10.1007/s00403-021-02258-3

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