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

Sahand Rahnama-Moghadam1, Nitin Arora1, Raj Vuppalanchi1

  • 1Indiana University School of Medicine, Indianapolis, Indiana, USA.

The American Journal of Gastroenterology
|June 12, 2025
PubMed
Summary
This summary is machine-generated.

Drug reaction with eosinophilia and systemic symptoms (DRESS) in drug-induced liver injury (DILI) patients are younger, more likely Black, and have higher mortality. Specific HLA alleles (A*32:01, B*53:01, B*58:01) are identified as risk factors.

Keywords:
DILIDRESSLamotriginePhenytoinTrimethoprim-Sulfamethoxazole

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Area of Science:

  • Pharmacovigilance
  • Hepatology
  • Immunogenetics

Background:

  • Drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe adverse drug reaction that can co-occur with drug-induced liver injury (DILI).
  • Limited data exists on DILI-DRESS characteristics and genetic risk factors within the US population.

Purpose of the Study:

  • To investigate the clinical characteristics of DILI patients who develop DRESS.
  • To identify Human Leukocyte Antigen (HLA) alleles associated with an increased risk of DILI-DRESS.

Main Methods:

  • Analysis of 2,121 DILI patients from US DILI Network studies (2004-2023).
  • DRESS diagnosis based on modified RegiSCAR criteria.
  • Comparison of HLA alleles between DILI-DRESS cases and DILI patients with or without rash.

Main Results:

  • 128 (6%) DILI patients had DRESS. Common culprits included trimethoprim/sulfamethoxazole, lamotrigine, phenytoin, allopurinol, and vancomycin.
  • DILI-DRESS patients were younger, more likely Black, had shorter latency, and presented with higher rates of rash, eosinophilia, and fever compared to DILI without DRESS.
  • DILI-DRESS was associated with more severe liver injury (45% vs 21.5%) and higher overall (15.6% vs 6.3%) and liver-related (9% vs 2.3%) mortality.
  • HLA A*32:01, HLA B*53:01, and HLA B*58:01 were significantly enriched in DILI-DRESS cases.

Conclusions:

  • DILI-DRESS patients exhibit distinct demographic and clinical profiles, including younger age, higher prevalence in Black individuals, and increased mortality.
  • Specific HLA alleles, namely HLA A*32:01, HLA B*53:01, and HLA B*58:01, are identified as significant genetic risk factors for developing DILI-DRESS.