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.

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 increases 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 to the allopurinol-induced SCARs 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 = 0.015], 20.0% [OR, 38.458; P = 0.001], and 10.7% [OR, 19.355; P = 0.004], 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.

CONCLUSION: 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.