The role of skin testing, drug challenge and IFN-γ ELISpot in delayed hypersensitivity to iodinated contrast media

Ana Maria Copaescu; Kyra Y L Chua; Effie Mouhtouris; Natasha E Holmes; Moneerah AlGassim; Ibtihal Al Otaibi; Florian Stehlin; Ghislaine A C Isabwe; Christos Tsoukas; Jean-Francois Toupin; Derek Lee; Moshe Ben-Shoshan; Elizabeth J Phillips; Jason A Trubiano

doi:10.1186/s13223-025-00982-3

The role of skin testing, drug challenge and IFN-γ ELISpot in delayed hypersensitivity to iodinated contrast media

Allergy Asthma Clin Immunol. 2025 Aug 14;21(1):35. doi: 10.1186/s13223-025-00982-3.

Authors

Ana Maria Copaescu^{1

2

3

4}, Kyra Y L Chua^{1

4}, Effie Mouhtouris¹, Natasha E Holmes^{1

4}, Moneerah AlGassim^{5

6}, Ibtihal Al Otaibi^{2

7}, Florian Stehlin^{2

8}, Ghislaine A C Isabwe^{2

3}, Christos Tsoukas^{2

3}, Jean-Francois Toupin⁹, Derek Lee¹⁰, Moshe Ben-Shoshan^{3

11}, Elizabeth J Phillips^{12

13}, Jason A Trubiano^{1

4

14}

Affiliations

¹ Centre for Antibiotic Allergy and Research, Department of Infectious Diseases, Austin Health, Heidelberg, VIC, Australia.
² Department of Medicine, Division of Allergy and Clinical Immunology, McGill University Health Centre (MUHC), McGill University, Montreal, QC, Canada.
³ The Research Institute of the McGill University Health Centre, McGill University, McGill University Health Centre (MUHC), Montreal, QC, Canada.
⁴ Department of Infectious Diseases, University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia.
⁵ Department of Medicine, Division of Allergy and Clinical Immunology, McGill University Health Centre (MUHC), McGill University, Montreal, QC, Canada. mneera.algassim@hotmail.com.
⁶ Montreal General Hospital, 1650 Cedar Ave, Montreal, QC, H3G 1A4, Canada. mneera.algassim@hotmail.com.
⁷ Division of Allergy and Clinical Immunology Department of Pediatrics, Central Second Health Cluster, Ministry of Health, Riyadh, Saudi Arabia.
⁸ Division of Clinical Immunology and Allergy, Department of Medicine, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland.
⁹ Department of Diagnostic Radiology, McGill University Health Centre (MUHC), McGill University, Montreal, QC, Canada.
¹⁰ Pharmacy Department, Montreal General Hospital, Montreal, QC, Canada.
¹¹ Division of Allergy, Immunology and Dermatology, Montreal Children's Hospital, McGill University Health Centre (MUHC), McGill University, Montreal, QC, Canada.
¹² Institute for Immunology and Infectious Diseases, Murdoch University, Murdoch, WA, Australia.
¹³ Center for Drug Safety and Immunology, Department of Medicine, Dermatology, Pathology, Microbiology & Immunology, Vanderbilt University Medical Centre, Nashville, TN, USA.
¹⁴ The National Centre for Infections in Cancer, Peter MacCallum Cancer Centre, Parkville, VIC, Australia.

Abstract

Background: The use of in vivo and ex vivo diagnostic tools for delayed hypersensitivity reactions (DHRs) associated with iodinated contrast media (ICM) is currently ill-defined.

Objective: To evaluate the role of in vivo and ex vivo diagnostic tools for DHRs occurring >6 h following intravenous low-osmolality ICM.

Methods: We conducted a prospective, multicenter, international cohort study. The patients were recruited from two tertiary care adult allergy clinics, Austin Health, Australia and the McGill University Health Centre, Canada. Eligible participants were adults who reported a DHR after receiving ICM. In vivo testing (skin testing and intravenous challenge) was performed to identify an alternative agent. Ex vivo testing using interferon-γ enzyme-linked ImmunoSpot assay was performed in four Australian patients to explore its diagnostic performance.

Results: The culprit ICM was identified by dIDT in 17/20 (85%) while in 3/20 (15%) a challenge was necessary to confirm delayed hypersensitivity. All patients with a positive dIDT to iohexol were positive to iodixanol (15/15; 100%) while 3/4 (75%), 3/4 (75%), 4/6 (67%), and 3/5 (60%) were positive to iopromide, ioversol, iopamidol, and iobitridol, respectively. Overall, 7/20 (35%) patients tolerated a challenge with an alternative ICM. The IFN-γ release assay was negative for the implicated ICM in 4 patients with confirmed DHR through a positive dIDT.

Conclusion: dIDT allowed confirmation of T cell-mediated allergy to the implicated ICM in 85% of patients with a strong clinical suspicion of DHR and identification of non-cross-reactive ICM in 35% of patients. The IFN-y ELISpot was not useful in the four patients tested.

Keywords: Delayed hypersensitivity reactions; Drug reaction with eosinophilia and systemic symptoms; Ex vivo diagnostic tools; In vivo diagnostic tools; Iodinated contrast media; Maculopapular exanthema.