Case-control study measuring the association between HLA-B*13:01 and dapsone hypersensitivity syndrome in Indian patients

Objectives: Dapsone hypersensitivity syndrome (DHS) is associated with HLA-B*13:01 in Chinese and south-east Asians. This association has not been studied among Indians. The objective was to study the association between HLA-B*13:01 and DHS in Indian patients. Methodology: A case – control study was done in south India (January 2016 to March 2018). Prevalence of HLA-B*13:01 in 8 DHS cases was compared to its prevalence in 324 controls (113 patient controls, 211 population controls). HLA-B*13 typing was done in 2 steps: First, HLA-B*13 positivity was determined using intermediate resolution PCR (SSOP HLA typing kit, Luminex platform) in the 332 study participants followed by Sanger sequence-based typing on 17 HLA-B*13 positive patients (7cases, 10 patient controls). 1 DHS case (HLA-B*13:01 negative) was also screened for HLA-DRB*15:01 and 16:02. Odds ratio, CI and population attributable risk were calculated. Results: There were 8 cases of DHS and 324 controls including 113 patient controls and 211 population controls. 7/8 cases (87.5%) of DHS and 9/113 of patient controls (7.96%) were HLA-B*13:01 positive. Among those in whom high resolution typing was done, 1/17 (5.7%) were HLA-B*13:02 positive. Among population controls, 9.9% (21/211) were HLA-B*13 positive. HLA-DRB*15:01 and 16:02 were negative in the 1 patient tested. Two HLA-B*13:01 positive patient controls were dapsone tolerant. HLA-B*13 and specifically HLA˙B*13:01 was significantly associated with DHS. (Odds ratio of 66.16 for HLA-B*13 and 80.89 for HLA-B*13:01). Population attributable risk was 86.2%. Conclusion: HLA-B*13:01 appears to be a significant risk factor for DHS in Indians. Implementation of a pre-treatment screening strategy may decrease the incidence of DHS.