HLA-A*32:01 is strongly associated with vancomycin-induced drug reaction with eosinophilia and systemic symptoms

Publication date: Available online 16 February 2019

Source: Journal of Allergy and Clinical Immunology

Author(s): Katherine C. Konvinse, Jason A. Trubiano, Rebecca Pavlos, Ian James, Christian M. Shaffer, Cosmin A. Bejan, Ryan J. Schutte, David A. Ostrov, Mark A. Pilkinton, Misha Rosenbach, Jeffrey P. Zwerner, Kristina B. Williams, Jack Bourke, Patricia Martinez, Francois Rwandamuriye, Abha Chopra, Mark Watson, Alec J. Redwood, Katie D. White, Simon A. Mallal

Abstract

Background

Vancomycin is a prevalent cause of the severe hypersensitivity syndrome drug reaction with eosinophilia and systemic symptoms (DRESS) which leads to significant morbidity and mortality and commonly occurs in the setting of combination antibiotic therapy which impacts future treatment choices. Variations in human leukocyte antigen (HLA) class I in particular have been associated with serious T-cell mediated adverse drug reactions which has led to preventive screening strategies for some drugs.

Objective

To determine if variation in the HLA region is associated with vancomycin-induced DRESS.

Methods

Probable vancomycin DRESS cases were matched 1:2 with tolerant controls based on sex, race, and age using BioVU, Vanderbilt's deidentified electronic health record database. Associations between DRESS and carriage of HLA class I and II alleles were assessed by conditional logistic regression. An extended sample set from BioVU was utilized to conduct a time-to-event analysis of those exposed to vancomycin with and without the identified HLA risk allele.

Results

Twenty-three individuals met inclusion criteria for vancomycin-associated DRESS. 19/23 (82.6%) cases carried HLA-A*32:01 compared to 0/46 (0%) of the matched vancomycin tolerant controls (p=1x10^-8) and 6.3% of the BioVU population (n=54,249) (p=2x10^-16). Time-to-event analysis of DRESS development during vancomycin treatment among the HLA-A*32:01 positive group indicated that 19.2% developed DRESS and did so within four weeks.

Conclusions

HLA-A*32:01 is strongly associated with vancomycin DRESS in a population of predominantly European ancestry. HLA-A*32:01 testing could improve antibiotic safety, help implicate vancomycin as the causal drug and preserve future treatment options with co-administered antibiotics.

Graphical abstract

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