Investigation Details Hypersensitivity Reactions Linked to Gadolinium-Based Contrast Agents

Louise Gagnon

February 24, 2022

An 8-year cohort study published in Radiology suggests exposure to specific gadolinium-based contrast agents (GBCAs) can produce allergic-like hypersensitivity reactions (HSRs) in patients. Authors of the study recommend a two-pronged strategy to avoid the development of HSRs when possible: avoid the culprit GBCAs linked to HSRs, and initiate prophylactic use of medications prior to MRI.

Hye-Ryun Kang, MD, PhD, professor in the Department of Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea, and colleagues retrospectively looked at 331,070 cases of exposure to GBCAs in 154,539 patients. The investigators found that 1304 cases of HSRs (0.4%) were reported. Most were acute (1178), and the rest were delayed (126). The authors note that the figures are consistent with previous studies.

They identified the biggest GBCA culprits as gadobutrol, gadoterate meglumine, gadoxetate disodium, and gadoteridol. Premedications included intravenous chlorpheniramine and intravenous methylprednisolone.

"Our study showed that patients with a history of HSRs to iodinated contrast media (ICM) are at risk for HSRs to GBCAs," said Kang in an email response to queries from Medscape Medical News. "All patients receiving magnetic resonance imaging exams with GBCA exposure should provide a detailed history of previous HSRs to both ICM and GBCAs. When necessary, appropriate prevention measures such as using premedication and switching to different types of GBCAs should be implemented."

HSRs to GBCAs were classified as mild, moderate, or severe. Mild reactions included limited urticaria or pruritus, nasal congestion, cutaneous edema, and throat discomfort. Moderate reactions included diffuse urticaria or pruritus, diffuse erythema, and mild wheezing. Severe reactions included diffuse edema with dyspnea, diffuse erythema with hypotension, laryngeal edema with stridor or hypoxia, wheezing or bronchospasms with hypoxia, and anaphylactic shock.

Investigators divided the patients into four groups to examine the effects of switching to a different GBCA or using a premedication with respect to recurrence. Recurrence was highest, at 31% (37 of 188), in patients who did not switch to a different GBCA nor use a premedication, and it was lowest, at 5% (21 of 441), for patients who switched to a different GBCA and received premedication. The other two groups consisted of patients who were exposed to the same GBCA but used premedication and patients who were switched to a different GBCA but did not use premedication.

The investigators also note that the risk of HSRs with GBCAs was higher in those with a history of HSRs to ICM (odds ratio = 4.6; P < .001). They postulate that genetics may explain why some individuals are at increased risk of developing HSRs.

"Although the exact mechanism behind our findings is yet to be elucidated, we believe a genetic predisposition to developing Th2 reactions may have a role in increasing the risk of HSRs across different types of contrast media regardless of chemical structure or composition," Kang wrote.

Asked for independent comment on the study, Jennifer McDonald, PhD, associate professor of radiology at the Mayo Clinic in Rochester, Minnesota, told Medscape that little has been published about delayed reactions after MRI, which occur from 1 hour to 1 week after contrast exposure.

Responding to recommendations from the study authors, McDonald emphasized that the decision to use alternative contrast agents for imaging is problematic.

"The biggest challenge lies with switching to a different type of GBCA, as the specific GBCA that caused the prior reaction is frequently not documented in the medical record, and patients typically don't recall what GBCA they received," McDonald wrote in an email. "Going forward, we can help overcome this obstacle by proactively recording these details in the medical record every time an allergic-like reaction occurs."

With respect to the use of premedications to prevent HSRs, McDonald noted that this practice is not universally endorsed. "The use of premedication in patients with a prior allergic-like reaction is still widely debated and has limited evidence supporting its efficacy," she said.

McDonald added that at her own institution, for patients who have had a prior allergic-like reaction to ICM, the recommendation is to switch to a different type of ICM when possible.

Kang has received grants from the Ministry of Food and Drug Safety of South Korea and Bayer.McDonald has received research grants from GE Healthcare, serves as scientific advisor and consultant for a variety of contrast safety studies, and is member of the American College of Radiology Committee on Drugs and Contrast Media.

Radiology. Published online February 22, 2022. Full text

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