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Title: The role of in vivo and ex vivo diagnostic tools in severe delayed immune-mediated adverse antibiotic drug reactions.
Austin Authors: Copaescu, Ana ;Mouhtouris, Effie ;Vogrin, Sara;James, Fiona;Chua, Kyra Y L ;Holmes, Natasha E ;Douglas, Abby;Slavin, Monica A;Cleland, Heather;Zubrinich, Celia;Aung, Ar Kar;Goh, Michelle ;Phillips, Elizabeth J;Trubiano, Jason A 
Affiliation: Medicine (University of Melbourne)
Department of Dermatology, Alfred Health, Melbourne, Victoria, Australia
Department of Dermatology, St Vincent's Hospital, Fitzroy, Victoria, Australia
Burns Unit, Alfred Health, Melbourne, Victoria, Australia
Centre for Antibiotic Allergy and Research
Department of General Medicine, Alfred Health, Melbourne, Victoria, Australia
Department of Medicine, St Vincent's Hospital, University of Melbourne, Fitzroy, Victoria, Australia
Clinical Immunology and Allergy, McGill University Health Center, Montréal, Canada.
Institute for Immunology and Infectious Diseases, Murdoch University, Murdoch, Western Australia, Australia
Department of Infectious Diseases, Vanderbilt University Medical Centre, Nashville, Tennessee, USA
Department of Medicine and Radiology, Melbourne Medical School, The University of Melbourne, Parkville, Victoria, Australia
Department of Infectious Diseases and Infection Prevention, Peter MacCallum Cancer Centre, The University of Melbourne, Parkville, Victoria, Australia
The National Centre for Infections in Cancer, Peter MacCallum Cancer Centre, Parkville, Victoria, Australia
Department of Oncology, Peter MacCallum Cancer Centre, The University of Melbourne, Parkville, Victoria, Australia
Allergy, Asthma and Clinical Immunology, Alfred Health, Melbourne, Victoria, Australia
School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia
Infectious Diseases
Issue Date: 13-Jan-2021 2021-01-13
Publication information: The Journal of Allergy and Clinical Immunology. In Practice 2021; online first: 13 January
Abstract: The use of in vivo and ex vivo diagnostic tools for delayed immune-mediated adverse drug reactions (IM-ADR) is currently ill defined. To determine if the combination of skin testing and/or interferon-γ (IFN-γ) enzyme-linked immunoSpot assay (ELISpot) can aid diagnosis of these allergy phenotypes. Patients with antibiotic-associated severe delayed IM-ADR hypersensitivity, including SJS and TEN, DRESS, AGEP, GBFDE and severe MPE, were prospectively recruited. In vivo testing was completed to the implicated drug(s) and ex vivo testing was performed with the patient's PBMC stimulated with the relevant antibiotic concentrations for IFN-γ release ELISpot measurement. Eighty-one patients met the inclusion with DRESS (42; 51.9%) accounting for the majority of cases. Among the 63 (78%) who had an ELISpot assay performed, 34 (54%) were positive to at least one implicated antibiotic (median spot forming units/ million cells, 99.5; [IQR], 68-187) with glycopeptide being a strong predictor of positivity (aOR 6.11 95% CI 1.74, 21.42). In combination (in vivo and ex vivo), 51 (63%) of those tested were positive to an implicated antibiotic. For DRESS and severe MPE associated with penicillins and cephalosporins, this combination confirmed the culprit agent in 11/12 of the cases and in 6/7 for DRESS associated with glycopeptides. This study demonstrates that using in vivo in combination with ex vivo testing can enhance the diagnostic approach in these severe phenotypes by assisting with the identification of possible culprit antibiotics.
DOI: 10.1016/j.jaip.2020.12.052
PubMed URL: 33453452
Type: Journal Article
Subjects: Severe cutaneous adverse reaction (SCAR)
T-cell mediated hypersensitivity
adverse drug reaction (ADR)
delayed hypersensitivity
ex vivo diagnostic
in vitro diagnostic
interferon-γ enzyme-linked immunoSpot assay
intradermal testing
skin testing
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