Single-cell immunopathology of recurrent acute generalized exanthematous pustulosis associated with vancomycin
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 characteriz...
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2025-05-01
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| Series: | Journal of Allergy and Clinical Immunology: Global |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S277282932500027X |
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| author | Eric M. Mukherjee, MD, PhD Andrew Gibson, PhD Matthew S. Krantz, MD Rama Gangula, MS Amy M. Palubinsky, PhD Alan S. Boyd, MD Jeffrey P. Zwerner, MD, PhD Anna K. Dewan, MD, MS Nontaya Nakkam, PhD Katherine C. Konvinse, MD, PhD Yueran Li, PhD Ramesh Ram, PhD Abha Chopra, PhD Elizabeth J. Phillips, MD |
| author_facet | Eric M. Mukherjee, MD, PhD Andrew Gibson, PhD Matthew S. Krantz, MD Rama Gangula, MS Amy M. Palubinsky, PhD Alan S. Boyd, MD Jeffrey P. Zwerner, MD, PhD Anna K. Dewan, MD, MS Nontaya Nakkam, PhD Katherine C. Konvinse, MD, PhD Yueran Li, PhD Ramesh Ram, PhD Abha Chopra, PhD Elizabeth J. Phillips, MD |
| author_sort | Eric M. Mukherjee, MD, PhD |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-229dcdfa235d4967bcb1141c3b175cf6 |
| institution | Kabale University |
| issn | 2772-8293 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Allergy and Clinical Immunology: Global |
| spelling | doaj-art-229dcdfa235d4967bcb1141c3b175cf62025-02-08T05:01:45ZengElsevierJournal of Allergy and Clinical Immunology: Global2772-82932025-05-0142100426Single-cell immunopathology of recurrent acute generalized exanthematous pustulosis associated with vancomycinEric M. Mukherjee, MD, PhD0Andrew Gibson, PhD1Matthew S. Krantz, MD2Rama Gangula, MS3Amy M. Palubinsky, PhD4Alan S. Boyd, MD5Jeffrey P. Zwerner, MD, PhD6Anna K. Dewan, MD, MS7Nontaya Nakkam, PhD8Katherine C. Konvinse, MD, PhD9Yueran Li, PhD10Ramesh Ram, PhD11Abha Chopra, PhD12Elizabeth J. Phillips, MD13Department of Medicine, Center for Drug Safety and Immunology, Vanderbilt University Medical Center, Nashville, Tenn; Department of Dermatology, Vanderbilt University Medical Center, Nashville, TennInstitute for Immunology and Infectious Diseases (IIID), Murdoch University, Perth, AustraliaDepartment of Medicine, Center for Drug Safety and Immunology, Vanderbilt University Medical Center, Nashville, TennDepartment of Medicine, Center for Drug Safety and Immunology, Vanderbilt University Medical Center, Nashville, TennDepartment of Medicine, Center for Drug Safety and Immunology, Vanderbilt University Medical Center, Nashville, TennDepartment of Dermatology, Vanderbilt University Medical Center, Nashville, TennDepartment of Dermatology, Vanderbilt University Medical Center, Nashville, TennDepartment of Dermatology, Vanderbilt University Medical Center, Nashville, TennDepartment of Pharmacology, Faculty of Medicine, Khon Kaen University, Khon Kaen, ThailandDepartment of Pediatrics, Stanford University School of Medicine, Stanford University, Stanford, CalifInstitute for Immunology and Infectious Diseases (IIID), Murdoch University, Perth, AustraliaInstitute for Immunology and Infectious Diseases (IIID), Murdoch University, Perth, AustraliaInstitute for Immunology and Infectious Diseases (IIID), Murdoch University, Perth, AustraliaDepartment of Medicine, Center for Drug Safety and Immunology, Vanderbilt University Medical Center, Nashville, Tenn; Institute for Immunology and Infectious Diseases (IIID), Murdoch University, Perth, Australia; Department of Dermatology, Vanderbilt University Medical Center, Nashville, Tenn; Corresponding author: Elizabeth J. Phillips, MD, Vanderbilt University Medical Center, 1211 Medical Center Dr, Nashville, TN 37232.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.http://www.sciencedirect.com/science/article/pii/S277282932500027XAcute generalized exanthematous pustulosisvancomycindrug reaction analysismultiomic analysisT-cell response |
| spellingShingle | Eric M. Mukherjee, MD, PhD Andrew Gibson, PhD Matthew S. Krantz, MD Rama Gangula, MS Amy M. Palubinsky, PhD Alan S. Boyd, MD Jeffrey P. Zwerner, MD, PhD Anna K. Dewan, MD, MS Nontaya Nakkam, PhD Katherine C. Konvinse, MD, PhD Yueran Li, PhD Ramesh Ram, PhD Abha Chopra, PhD Elizabeth J. Phillips, MD Single-cell immunopathology of recurrent acute generalized exanthematous pustulosis associated with vancomycin Journal of Allergy and Clinical Immunology: Global Acute generalized exanthematous pustulosis vancomycin drug reaction analysis multiomic analysis T-cell response |
| title | Single-cell immunopathology of recurrent acute generalized exanthematous pustulosis associated with vancomycin |
| title_full | Single-cell immunopathology of recurrent acute generalized exanthematous pustulosis associated with vancomycin |
| title_fullStr | Single-cell immunopathology of recurrent acute generalized exanthematous pustulosis associated with vancomycin |
| title_full_unstemmed | Single-cell immunopathology of recurrent acute generalized exanthematous pustulosis associated with vancomycin |
| title_short | Single-cell immunopathology of recurrent acute generalized exanthematous pustulosis associated with vancomycin |
| title_sort | single cell immunopathology of recurrent acute generalized exanthematous pustulosis associated with vancomycin |
| topic | Acute generalized exanthematous pustulosis vancomycin drug reaction analysis multiomic analysis T-cell response |
| url | http://www.sciencedirect.com/science/article/pii/S277282932500027X |
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