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Journal article
Single-cell immunopathology of recurrent acute generalized exanthematous pustulosis associated with vancomycin
The journal of allergy and clinical immunology. Global, Vol.4(2), 100426
2025
Abstract
Background
Acute generalized exanthematous pustulosis (AGEP) is a severe cutaneous adverse reaction to medication that presents within 72 hours of exposure with erythematous papules and plaques with overlying pustules. The immunopathogenesis and predisposing factors of AGEP are not well characterized.
Objective
To better understand the genetic risk factors and single-cell immunopathogenesis of AGEP, we longitudinally characterized a patient with recurrent AGEP after an initial episode triggered by vancomycin.
Methods
A clinical timeline over an 8-year period was paired with skin testing, histopathology, and immunogenetic and other testing at 3 time points. Skin biopsies performed on affected skin (positive vancomycin-delayed intradermal testing [IDT]) and unaffected control skin 8 years after the initial event were subjected to single-cell sequencing to measure gene and protein expression.
Results
The patient was HLA-A∗32:01 positive, which has been associated with vancomycin-induced drug reaction with eosinophilia and systemic symptoms. IDT remained positive over time, despite recurrent reactions without drug exposure. Clinical features and histopathology of IDT-positive skin were consistent with AGEP. Single-cell analysis of affected skin showed polyclonal TH17-like cells with gene expression signatures similar to T-cell response during prevalent infectious diseases.
Conclusions
This patient exhibited persistent vancomycin-positive IDT despite distinct nondrug episodes of ALEP/AGEP. This suggests that AGEP may be triggered by both antigen-specific and non–antigen-specific factors. AGEP-affected skin showed an inflammatory infiltrate with a TH17-like effector population, which may represent potentially actionable targets for therapeutic intervention. The presence of HLA-A∗32:01, a defined risk factor for vancomycin-induced drug reaction with eosinophilia and systemic symptoms, may indicate a shared predisposition, warranting further study.
Details
- Title
- Single-cell immunopathology of recurrent acute generalized exanthematous pustulosis associated with vancomycin
- Authors/Creators
- Eric M. Mukherjee - Vanderbilt University Medical CenterAndrew Gibson - Murdoch University, Centre for Molecular Medicine and Innovative TherapeuticsMatthew S. Krantz - Vanderbilt University Medical CenterRama Gangula - Vanderbilt University Medical CenterAmy M. Palubinsky - Vanderbilt University School of MedicineAlan S. Boyd - Department of Dermatology, Vanderbilt University Medical Center, Nashville, TennJeffrey P. Zwerner - Department of Dermatology, Vanderbilt University Medical Center, Nashville, TennAnna K. Dewan - Department of Dermatology, Vanderbilt University Medical Center, Nashville, TennNontaya Nakkam - Department of Pharmacology, Faculty of Medicine, Khon Kaen University, Khon Kaen, ThailandKatherine C. Konvinse - Department of Pediatrics, Stanford University School of Medicine, Stanford University, Stanford, CalifYueran Li - Institute for Immunology and Infectious Diseases (IIID), Murdoch University, Perth, AustraliaRamesh Ram - Institute for Immunology and Infectious Diseases (IIID), Murdoch University, Perth, AustraliaAbha Chopra - Murdoch University, Centre for Molecular Medicine and Innovative TherapeuticsElizabeth J. Phillips - Vanderbilt University
- Publication Details
- The journal of allergy and clinical immunology. Global, Vol.4(2), 100426
- Publisher
- Elsevier Inc. on behalf of the American Academy of Allergy, Asthma & Immunology.; AMSTERDAM
- Number of pages
- 10
- Identifiers
- 991005741586607891
- Copyright
- © 2025 The Author(s).
- Murdoch Affiliation
- Institute for Immunology and Infectious Diseases; Centre for Molecular Medicine and Innovative Therapeutics
- Language
- English
- Resource Type
- Journal article
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