Assessment of immediate and non-immediate hypersensitivity contrast reactions by skin tests and provocation tests: A review

Abstract

Introduction: Allergic and nonallergic hypersensitivity reactions to iodinated contrast media (ICM) and gadolinium-based contrast media are classified as immediate or non-immediate hypersensitivity reactions (IHR and NIHR), respectively. Skin tests and provocation tests are recommended for the evaluation of hypersensitivity reactions to contrast agents; however provocations are not common in clinical practice. Methods: A MEDLINE search was conducted to investigate studies comprising both skin tests and provocation tests that evaluated hypersensitivity reactions to ICM. Results: Nineteen studies were identified that reported on skin tests, followed by provocations. In the case of IHR to ICM, 65/69 (94%) patients with a positive skin test for the culprit media tolerated a challenge with a skin-test-negative alternative ICM. In IHR to ICM with a negative skin test for the culprit media, provocations were positive in 3.2%–9.1% patients. In the case of a NIHR to ICM with a positive skin test, provocation with a skin-test-negative agent was tolerated in 75/105 (71%) of cases. In NIHR with a negative skin test for the culprit agent, re-exposure to the culprit or an alternative was positive in 0%–34.6% patients. Provocations with the same ICM in skin test positive patients with IHR or NIHR were positive for a majority of the patients, although such provocation tests were rarely performed. Data on hypersensitivity reactions, skin tests and provocations with gadolinium-based contrast media were limited; however, they exhibited a pattern similar to that observed in ICM. Conclusion: In both ICM and gadolinium-based contrast media, the risk of an immediate repeat reaction is low when skin tests are negative. In contrast, a provocation with a skin-test-positive contrast medium showed a high risk of an immediate repeat hypersensitivity reaction. Therefore, a thorough medical history is necessary, followed by skin tests. A provocation is recommended, for diagnostic work-up, when the diagnosis is uncertain.

Radiocontrast Media Hypersensitivity Reactions in Children

“…Among all adverse reactions to RCM, the frequency of TAr is greater than 80% [5]. In a recent review [6], the frequency of HRs to ICM varied from 1% to 12%, with severe reactions (mainly anaphylaxis) accounting for 0.01-0.2% of total reactions. The frequency of HRs to ionic ICM is higher (3.8-12.7%) [7] than nonionic ICM (0.5-3%) [8].…”

“…Skin and mucous involvement characterized by erythema and urticaria with or without angioedema affects up to 70% of patients with reactions to ICM [16]. According to a recent review, severe reactions account for 0.01% to 0.2% of all reactions [6]. Only a small proportion of immediate reactions seems to be IgE mediated, but these data could change according to the studied population, being much higher in studies analyzing patients with severe reactions [18,20].…”

“…Therefore, these types of adverse reactions can be defined as pseudoallergic instead of allergic since an underlying hypersensitivity mechanism is lacking, which could also explain why some patients experience severe reactions to ICM following first exposure. Nonimmediate HRs develop in 0.5% to 23% of patients [6]. These are commonly mild skin reactions (30-90% of cases) with mainly urticaria/angioedema and maculopapular exanthema such as skin eruptions [16].…”

“…If the patient observes a positive reaction at the skin test site at other time points, additional readings should be performed up to 7 days for the IDT and at 102 h for the patch test [20]. In adults with a diagnosis of immediate HRs to ICM confirmed by a provocation test or re-exposure to the culprit ICM, the positive rate of skin tests (SPT and/or IDT) ranged between 5.6 and 64.7% [6]. This discrepancy may be explained by several factors, including skin test technique, type of ICM, severity of reaction, and interval time between reaction and tests.…”

Hypersensitivity to gadolinium-based contrast

“…There is evidence for this activation by in-vivo test (skin testing) with case reports or short series published [1,[22][23][24][25] and recently by in-vitro test (basophil activation testing) to gadobutrol [26]. In contrast, the evidence supporting the non-IgE mediated mechanisms is scarce [27], including the direct effect of the GBCA on the cell membrane, the activation of the complement (increased levels of C3a and C4a have been identified in patients with severe immediate HSR [28]) and the generation of bradykinin [29,30].…”