Rash decisions: Unmasking a risk phenotype in adults with persistent delayed penicillin allergy sensitized during historic infection with Epstein-Barr virus

Background: Penicillin-associated exanthems in the setting of infectious mononucleosis caused by Epstein-Barr virus (EBV) are often viewed as a transient event, not a true allergy. Recent evidence challenges this and suggests that a notable subset of patients retain penicillin hypersensitivity. Obje...

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Main Authors: Fionnuala Cox, BA Hons, PhD, MB, BCh, BAO, MRCPI, FRCPath, Natasha E. Holmes, MBBS, PhD, Jamie Lee Waldron, MD, Jason A. Trubiano, MBBS, PhD
Format: Article
Language:English
Published: Elsevier 2024-11-01
Series:Journal of Allergy and Clinical Immunology: Global
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Online Access:http://www.sciencedirect.com/science/article/pii/S2772829324001164
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author Fionnuala Cox, BA Hons, PhD, MB, BCh, BAO, MRCPI, FRCPath
Natasha E. Holmes, MBBS, PhD
Jamie Lee Waldron, MD
Jason A. Trubiano, MBBS, PhD
author_facet Fionnuala Cox, BA Hons, PhD, MB, BCh, BAO, MRCPI, FRCPath
Natasha E. Holmes, MBBS, PhD
Jamie Lee Waldron, MD
Jason A. Trubiano, MBBS, PhD
author_sort Fionnuala Cox, BA Hons, PhD, MB, BCh, BAO, MRCPI, FRCPath
collection DOAJ
description Background: Penicillin-associated exanthems in the setting of infectious mononucleosis caused by Epstein-Barr virus (EBV) are often viewed as a transient event, not a true allergy. Recent evidence challenges this and suggests that a notable subset of patients retain penicillin hypersensitivity. Objective: We investigated the occurrence and predictors of persistent adulthood hypersensitivity in those with penicillin-associated rash occurring in the setting of EBV infection. Methods: Retrospective analysis of data of patients referred for penicillin allergy testing to an Australian tertiary-care hospital captured from 2015 to 2023 was carried out. Results: Of 2066 patients, 23 (1%) had penicillin-associated rash during an historic EBV infection; 16 (70%) were female; and median (interquartile range) age was 18 (16-20) years at index reaction and 38 (33.5-57) years at allergy testing. Skin prick testing and delayed intradermal testing to a penicillin panel were performed, followed by oral provocation challenge in those testing negative. Persistent sensitization was shown in 6 (26%) of 23; 4 (67%) of 6 positive delayed intradermal testing; and 3 (50%) of 6 had positive oral challenge test. Notably, 5 (83%) of 6 had a severe maculopapular exanthem with facial swelling, including 2 (33%) of 6 with probable drug reaction with eosinophilia and systemic symptoms (aka DRESS) during the index reaction, compared to 0 of 17 in patients tolerating penicillin on reexposure. Conclusion: This study highlights the requirement of allergy testing in adult patients reporting a penicillin-associated severe maculopapular exanthem in the setting of EBV, even if it occurred during childhood or adolescence.
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spelling doaj-art-cdca1bc91df04269b3bb01fcf351355d2025-08-20T02:14:50ZengElsevierJournal of Allergy and Clinical Immunology: Global2772-82932024-11-013410032010.1016/j.jacig.2024.100320Rash decisions: Unmasking a risk phenotype in adults with persistent delayed penicillin allergy sensitized during historic infection with Epstein-Barr virusFionnuala Cox, BA Hons, PhD, MB, BCh, BAO, MRCPI, FRCPath0Natasha E. Holmes, MBBS, PhD1Jamie Lee Waldron, MD2Jason A. Trubiano, MBBS, PhD3Department of Infectious Diseases, Centre for Antibiotic Allergy and Research, Austin Health, Heidelberg, Victoria, Australia; Corresponding author: Fionnuala Cox, BA Hons, PhD, MB, BCh, BAO, MRCPI, FRCPath, Department of Infectious Diseases, Centre for Antibiotic Allergy and Research, Austin Health, Heidelberg VIC 3084, Australia.Department of Infectious Diseases, Centre for Antibiotic Allergy and Research, Austin Health, Heidelberg, Victoria, Australia; Department of Infectious Diseases, The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Victoria, AustraliaDepartment of Medicine, Division of Allergy and Immunology, Massachusetts General Hospital, and Harvard Medical School, Boston, MassDepartment of Infectious Diseases, Centre for Antibiotic Allergy and Research, Austin Health, Heidelberg, Victoria, Australia; Department of Infectious Diseases, The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Victoria, AustraliaBackground: Penicillin-associated exanthems in the setting of infectious mononucleosis caused by Epstein-Barr virus (EBV) are often viewed as a transient event, not a true allergy. Recent evidence challenges this and suggests that a notable subset of patients retain penicillin hypersensitivity. Objective: We investigated the occurrence and predictors of persistent adulthood hypersensitivity in those with penicillin-associated rash occurring in the setting of EBV infection. Methods: Retrospective analysis of data of patients referred for penicillin allergy testing to an Australian tertiary-care hospital captured from 2015 to 2023 was carried out. Results: Of 2066 patients, 23 (1%) had penicillin-associated rash during an historic EBV infection; 16 (70%) were female; and median (interquartile range) age was 18 (16-20) years at index reaction and 38 (33.5-57) years at allergy testing. Skin prick testing and delayed intradermal testing to a penicillin panel were performed, followed by oral provocation challenge in those testing negative. Persistent sensitization was shown in 6 (26%) of 23; 4 (67%) of 6 positive delayed intradermal testing; and 3 (50%) of 6 had positive oral challenge test. Notably, 5 (83%) of 6 had a severe maculopapular exanthem with facial swelling, including 2 (33%) of 6 with probable drug reaction with eosinophilia and systemic symptoms (aka DRESS) during the index reaction, compared to 0 of 17 in patients tolerating penicillin on reexposure. Conclusion: This study highlights the requirement of allergy testing in adult patients reporting a penicillin-associated severe maculopapular exanthem in the setting of EBV, even if it occurred during childhood or adolescence.http://www.sciencedirect.com/science/article/pii/S2772829324001164Penicillin allergyEBVMaculopapular exanthemaDRESSdelayed drug rashallergy testing
spellingShingle Fionnuala Cox, BA Hons, PhD, MB, BCh, BAO, MRCPI, FRCPath
Natasha E. Holmes, MBBS, PhD
Jamie Lee Waldron, MD
Jason A. Trubiano, MBBS, PhD
Rash decisions: Unmasking a risk phenotype in adults with persistent delayed penicillin allergy sensitized during historic infection with Epstein-Barr virus
Journal of Allergy and Clinical Immunology: Global
Penicillin allergy
EBV
Maculopapular exanthema
DRESS
delayed drug rash
allergy testing
title Rash decisions: Unmasking a risk phenotype in adults with persistent delayed penicillin allergy sensitized during historic infection with Epstein-Barr virus
title_full Rash decisions: Unmasking a risk phenotype in adults with persistent delayed penicillin allergy sensitized during historic infection with Epstein-Barr virus
title_fullStr Rash decisions: Unmasking a risk phenotype in adults with persistent delayed penicillin allergy sensitized during historic infection with Epstein-Barr virus
title_full_unstemmed Rash decisions: Unmasking a risk phenotype in adults with persistent delayed penicillin allergy sensitized during historic infection with Epstein-Barr virus
title_short Rash decisions: Unmasking a risk phenotype in adults with persistent delayed penicillin allergy sensitized during historic infection with Epstein-Barr virus
title_sort rash decisions unmasking a risk phenotype in adults with persistent delayed penicillin allergy sensitized during historic infection with epstein barr virus
topic Penicillin allergy
EBV
Maculopapular exanthema
DRESS
delayed drug rash
allergy testing
url http://www.sciencedirect.com/science/article/pii/S2772829324001164
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