Immediate Allergic Reactions to Gadolinium-based Contrast Agents: A Systematic Review and Meta-Analysis

Abstract

Purpose To perform a systematic review and meta-analysis to determine if there are differences in rates of immediate allergic events between classes of gadolinium-based contrast agents (GBCAs). Materials and Methods PubMed and Google Scholar databases were searched for studies in which rates of immediate adverse events to GBCAs were reported. The American College of Radiology classification system was used to characterize allergic-like events as mild, moderate, or severe, and the total number of administrations of each GBCA was recorded. Where necessary, authors of studies were contacted to clarify data and eliminate physiologic reactions. Relative risks of GBCA types were estimated by using the Mantel-Haenszel type method. Results Nine studies in which immediate reactions to GBCA were recorded from a total of 716 978 administrations of GBCA met the criteria for inclusion and exclusion. The overall rate of patients who had immediate allergic-like reactions was 9.2 per 10 000 administrations and the overall rate of severe immediate allergic-like reactions was 0.52 per 10 000 administrations.. The nonionic linear chelate gadodiamide had the lowest rate of reactions, at 1.5 (95% confidence interval [CI]: 0.74, 2.4) per 10 000 administrations, which was significantly less than that of linear ionic GBCAs at 8.3 (95% CI: 7.5, 9.2) per 10 000 administrations (relative risk, 0.19 [95% CI: 0.099, 0.36]; P< .00001) and less than that for nonionic macrocyclic GBCAs at 16 (95% CI: 14, 19) per 10 000 administrations (relative risk, 0.12 [95% CI: 0.05, 0.31]; P < .001). GBCAs known to be associated with protein binding had a higher rate of reactions, at 17 (95% CI: 15, 20) per 10 000 administrations compared with the same chelate classification without protein binding, at 5.2 (95% CI: 4.5, 6.0) per 10 000 administrations (relative risk, 3.1 [95% CI: 2.4, 3.8]; P < .0001). Conclusion These data show the lowest rate of immediate allergic adverse events with use of the nonionic linear GBCA gadodiamide in comparison with those of ionic linear or nonionic macrocyclic GBCAs. A higher rate of immediate allergic adverse events was associated with ionicity, protein binding, and macrocyclic structure. RSNA, 2017 An earlier incorrect version of this article appeared online. This article was corrected on August 31, 2017.

Fatal gadolinium-induced encephalopathy following accidental intrathecal administration: a case report and a comprehensive evidence-based review

“…For all four categories, genetic and immune roles have been implicated 27. Immediate hypersensitivity reactions to GBCAs are rare and range from 1.5, 8.3 or 16 immediate allergic like adverse events per 10 000 administrations for linear non-ionic, linear ionic and macrocyclic non-ionic GBCAs, respectively 4. Although rare, the immediate hypersensitivity reactions can be fatal 30.…”

Analysis of retention of gadolinium by brain, bone, and blood following linear gadolinium‐based contrast agent administration in rats with experimental sepsis

“…Gadolinium‐based contrast agents have been used clinically for decades and have enhanced the diagnostic efficacy of MRI. Historically, toxicity concerns have focused on allergic reactions, and in patients with advanced renal failure, on nephrogenic systemic fibrosis . Since 2014, additional concerns have been raised, based on increased T 1 signal and supported by mass spectroscopy, that Gd deposition occurs in the brain following GBCA administration as a result of dechelation of linear, rather than macrocyclic, formulations .…”

“…Historically, toxicity concerns have focused on allergic reactions, and in patients with advanced renal failure, on nephrogenic systemic fibrosis. [2][3][4] Since 2014, additional concerns have been raised, based on increased T 1 signal and supported by mass spectroscopy, that Gd deposition occurs in the brain following GBCA administration as a result of dechelation of linear, rather than macrocyclic, formulations. [5][6][7][8][9][10][11][24][25][26][27][28][29][30][31][32][33][34] This has been challenged by observations that unenhanced T 1 signal intensity increases with normal myelination as children mature, and by underlying pathological processes, which may complicate the interpretation of increasing unenhanced T 1 signal intensity as indicative of Gd deposition in patients who undergo multiple MRI examinations over time.…”

“…The initial concept that these agents are biologically inert has been recently challenged . Gadolinium‐based contrast agents were initially noted to be associated with allergic reactions . Subsequently, concerns that these agents could lead to systemic nephrogenic sclerosis in patients with severe renal insufficiency resulted in the near‐complete cessation of use of GBCA in this vulnerable population .…”

Low‐dose provocation and skin tests in patients with hypersensitivity to gadolinium‐based contrast agents

“…The severity of the immediate HS was grade I and grade II according to Ring and Messmer severity classification, for respectively four and eight out of 12 patients and one delayed HS occurred with exanthema and dyspnoea more than 6 hours after GBCA injection for cerebral MRI (see Table 1). A positive allergological work-up was found in 5/14 patients, with positive GBCA intradermal tests in three cases (Figure 1) and positive IPT in two cases.Culprit GBCA were negative either with skin tests, or with lowdose IPT in five of them (No. 6,8,(12)(13)(14).…”