Patients with hypersensitivity to iodinated contrast media exhibit broad cross-reactivity

Key takeaways:

• Eleven patients reported 22 reactions during intradermal testing.
• Nine of 11 patients displayed cross-reactivity between iohexol and iodixanol.
• Results of ELISpot testing were inconsistent.

SAN ANTONIO — Patients with a history of delayed hypersensitivity to iodinated contrast media exhibited a broad cross-reactivity pattern, according to data presented at the American Academy of Allergy, Asthma & Immunology Annual Meeting.

Also, interferon-gamma enzyme-linked ImmunoSpot (ELISpot) assays were inconsistently helpful, possible because of cytotoxicity induced by the iodinated contrast media, Ana Copaescu, MD, FRCP, researcher with the Centre for Antibiotic Allergy and Research, department of infectious diseases, Austin Health, Heidelberg, Australia, said during her presentation.

“The role of intradermal testing and ex vivo testing for delayed reactions that occur more than 6 hours is not well understood,” Copaescu said. “The aim of the study was to evaluate the role of in vivo and ex vivo diagnostic tools for delayed reactions following intravenous low-osmolality contrast media.”

The researchers prospectively recruited 11 patients with delayed hypersensitivity associated with iodinated contrast media from two adult allergy clinics in Australia and Canada. Next, the researchers performed intradermal tests with 1:10 and 1:1 implicated iodinated contrast media on these patients.

Media included iohexol and iodixanol in both centers; iopromide (Ultravist, Bayer Healthcare), ioversol (Optiray, Guerbet) and iobitridol (Xenetix, Guerbet) in Australia; and iopamidol (Isovue, Bracco Diagnostics) in Canada.

Using photographs shared by the patients, the researchers performed readings at 24 and 48 hours. Also, the researchers completed ELISpot assays using each patient’s peripheral blood mononuclear cells stimulated with the relevant contrast media concentrations.

Ten of the patients had a positive delayed intradermal test to the culprit iodinated contrast media. One patient had a positive intravenous rechallenge to iohexol.

“This patient had previous negative intradermals, and he had received no premedication before his challenge,” Copaescu said.

The index agents included iohexol (77%) and iodixanol (23%). There were 22 reported reactions, including 17 cases of non-severe maculopapular exanthem (MPE), three cases of severe MPE and two cases of drug reaction with eosinophilia and systemic symptoms. The average time since the reaction was 653 days.

The researchers found cross-reactivity between iohexol and iodixanol in nine of 11 patients, iohexol and iopromide in two of seven patients, iohexol and ioversol in two of seven patients and iohexol and iopamidol in two of four patients.

One patient who reacted to iodixanol did not have any cross-reactivity with the other media. Also, two patients who tested positive for iohexol and iodol tolerated intravenous doses of iobitrodol.

Further, the researchers performed ELISpot in four patients across a range of concentrations. One patient with two non-severe MPE reactions to iohexol had a positive delayed intradermal test for iohexol and iodixnol while tolerating ioversol.

“However, his ex vivo testing showed a marked interferon gamma secretion for ioversol,” Copaescu said.

The other three patients had inconsistent results as well. The researchers attributed these inconsistencies to possible cytotoxicity induced by the iodinated contrast media.

“In conclusion, in patients with a history of delayed hypersensitivity to contrast media, a broad cross-reactivity pattern was demonstrated using delayed intradermal testing,” Copaescu said. “Interferon-gamma ELISpot was, unfortunately, inconsistently helpful, possibly due to contrast media cytotoxicity.”