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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 L ;Chua, Kyra Y L ;Holmes, Natasha E ;Douglas, Abby;Slavin, Monica A;Cleland, Heather;Zubrinich, Celia;Aung, Ar Kar;Goh, Michelle S Y;Phillips, Elizabeth J;Trubiano, Jason A 
Affiliation: Department of Medicine and Radiology, Melbourne Medical School, The University of Melbourne, Parkville, VIC, Australia
Department of General Medicine, Alfred Health, Melbourne, VIC, Australia
Medicine (University of Melbourne)
Centre for Antibiotic Allergy and Research
Department of Medicine, St Vincent's Hospital, University of Melbourne, Fitzroy, VIC, Australia
Burns Unit, Alfred Health, Melbourne, VIC, Australia
Clinical Immunology and Allergy, McGill University Health Center, Montréal, QC, Canada.
Department of Dermatology, Alfred Health, Melbourne, VIC, Australia
Department of Dermatology, St Vincent's Hospital, Fitzroy, VIC, Australia
Institute for Immunology and Infectious Diseases, Murdoch University, Murdoch, WA, Australia
Department of Infectious Diseases, Vanderbilt University Medical Centre, Nashville, Tenn..
Department of Infectious Diseases and Infection Prevention, Peter MacCallum Cancer Centre, The University of Melbourne, Parkville, VIC, Australia
The National Centre for Infections in Cancer, Peter MacCallum Cancer Centre, Parkville, VIC, Australia
Department of Oncology, Peter MacCallum Cancer Centre, The University of Melbourne, Parkville, VIC, Australia
Allergy, Asthma and Clinical Immunology, Alfred Health, Melbourne, VIC, Australia
School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia
Infectious Diseases
Issue Date: May-2021 2021-01-13
Publication information: The Journal of Allergy and Clinical Immunology. In Practice 2021; 9(5): 2010-2015.e4
Abstract: The use of in vivo and ex vivo diagnostic tools for delayed immune-mediated adverse drug reactions is currently ill defined. To determine whether the combination of skin testing and/or IFN-γ enzyme-linked immunoSpot assay (ELISpot) can aid diagnosis of these allergy phenotypes. Patients with antibiotic-associated severe delayed immune-mediated adverse drug reaction hypersensitivity, including Stevens-Johnson syndrome and toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms (DRESS), acute generalized exanthematous pustulosis, generalized bullous fixed drug eruption, and severe maculopapular exanthema, were prospectively recruited. In vivo testing was completed to the implicated drug(s), and ex vivo testing was performed with the patient's PBMCs stimulated with the relevant antibiotic concentrations for IFN-γ release ELISpot measurement. Eighty-one patients met the inclusion criteria, with DRESS (42; 51.9%) accounting for most cases. Among the 63 (78%) who had an ELISpot assay performed, 34 (54%) were positive to at least 1 implicated antibiotic (median spot-forming units/million cells, 99.5; interquartile range, 68-187), with glycopeptide being a strong predictor of positivity (adjusted odds ratio, 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 maculopapular exanthema associated with penicillins and cephalosporins, this combination confirmed the culprit agent in 11 of the 12 cases and in 6 of 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: Adverse drug reactions (ADRs)
Delayed hypersensitivity
Ex vivo diagnostic
IFN-γ enzyme-linked immunoSpot assay
Intradermal testing
Severe cutaneous adverse reactions (SCARs)
Skin testing
T-cell–mediated hypersensitivity
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