DRESS Syndrome in Patients With Drug-Induced Liver Injury: Characteristics and HLA Risk Factors

INTRODUCTION Drug reaction with eosinophilia and systemic symptoms (DRESS) can sometimes occur in patients with drug-induced liver injury (DILI). However, detailed studies of DRESS in patients with DILI from the United States are lacking. We investigated the characteristics and human leukocyte antigen (HLA) risks for DILI who also developed DRESS. METHODS Patients with definite, highly likely, or probable DILI enrolled into US DILI Network studies between September 2004 and August 2023 were included. DRESS was defined based on modified RegiSCAR criteria. HLA alleles were compared between DILI-DRESS cases and 2 control groups (DILI with non-DRESS rash [n = 244] and DILI without rash [n = 1,637]). RESULTS Of 2,121 participants with DILI during the study period, 128 participants had DRESS (6%). The most frequently implicated drugs causing DRESS were trimethoprim/sulfamethoxazole, lamotrigine, phenytoin, allopurinol, and vancomycin. Compared with 1993 patients with DILI without DRESS, patients with DILI + DRESS were younger (mean age 42.3 years vs 50.6 years), were more likely to be Black (26% vs 12%), and had shorter latency (median 31 days vs 47 days), higher frequency of rash (100% vs 13%), eosinophilia (55% vs 13%), and fever (76% vs 16%) ( P < 0.001 for all). Compared with DILI without DRESS, DILI + DRESS had more severe liver injury (severe/fatal: 45% vs 21.5%, P < 0.001) and higher overall (15.6% vs 6.3%, P < 0.001) and liver-related (9% vs 2.3%, P < 0.001) mortality. HLA A*32:01 , HLA B*53:01 , and HLA B*58:01 were significantly enriched in DILI-DRESS cases, compared with control groups. DISCUSSION Patients with DILI and DRESS are younger, are more likely to be Black, have shorter time to DILI onset with more severe liver injury and higher overall and liver-related mortality. HLA A*32:01 , HLA B*53:01 , and HLA B*58:01 are risk factors for DILI-DRESS.