The Presence of HLA-B75, DR13 Homozygosity, or DR14 Additionally Increases the Risk of Allopurinol-Induced Severe Cutaneous Adverse Reactions in HLA-B*58:01 Carriers
- Authors
- Shim, Ji-Su; Yun, James; Kim, Mi-Yeong; Chung, Soo Jie; Oh, Ji Hyun; Kang, Dong-Yoon; Jung, Jae-Woo; Cho, Sang-Heon; Kang, Hye-Ryun
- Issue Date
- Apr-2019
- Publisher
- ELSEVIER SCIENCE BV
- Keywords
- Allopurinol; Stevens-Johnson syndrome; Toxic epidermal necrolysis; Drug hypersensitivity syndrome; Human leukocyte antigen; Koreans
- Citation
- JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE, v.7, no.4, pp 1261 - 1270
- Pages
- 10
- Journal Title
- JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE
- Volume
- 7
- Number
- 4
- Start Page
- 1261
- End Page
- 1270
- URI
- https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/18090
- DOI
- 10.1016/j.jaip.2018.11.039
- ISSN
- 2213-2198
2213-2201
- Abstract
- BACKGROUND: Although HLA-B*58:01 is a well-known risk factor for the development of allopurinol-induced severe cutaneous adverse reactions (SCARs), most of the HLA-B*58:01 carriers do not suffer from SCARs despite a long-term use of allopurinol. This suggests that there are other risk factors that determine the fate of HLA-B*58:01 carriers. OBJECTIVE: The aim of this study was to investigate the additional genetic factors that increase the risk of allopurinol-induced SCARs in HLA-B*58:01 carriers. METHODS: The incidence of allopurinol-induced SCARs was investigated according to coexisting HLA alleles in all subjects with HLA-B*58:01 who took allopurinol between 2003 and 2017. The allopurinol tolerant group was defined as a group who took allopurinol for more than 60 days without developing hypersensitivity and was compared with the allopurinol-induced SCAR group. RESULTS: Among the retrospective cohort consisting of 367 HLA-B*58:01 carriers treated with allopurinol, 11 (3.0%) were diagnosed with allopurinol-induced SCARs. When HLA-B75, DR13 homozygosity, or DR14 was present, the incidence of SCARs increased up to 22.2% (odds ratio [OR], 19.568; P = .015), 20.0% (OR, 38.458; P = .001), and 10.7% (OR, 19.355; P = .004), respectively. Among the 153 HLA-B*58:01 carriers with chronic renal insufficiency (CRI), the incidence of SCARs doubled to 6.5% and further increased to 40%, 30%, and 37.5% in the presence of HLA-B75, DR13 homozygosity, or DR14, respectively. CONCLUSIONS: Secondary screening with HLA-B75, DR13 homozygosity, and DR14 in addition to primary screening with HLA-B*58:01 would enable a more accurate prediction of SCAR occurrence, especially in patients with CRI. (C) 2018 American Academy of Allergy, Asthma & Immunology
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