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

Copaescu, A.M., Chua, K.Y.L., Mouhtouris, E. et al. Allergy Asthma Clin Immunol 21, 35 (2025). https://doi.org/10.1186/s13223-025-00982-3

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

Examples of delayed positive intradermal skin testing and intravenous challenges

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.

PDF