Immediate reactions to iodinated contrast media

doi:10.1016/j.anai.2017.08.014

Annals of Allergy, Asthma & Immunology

Volume 119, Issue 6, December 2017, Pages 553-557

https://doi.org/10.1016/j.anai.2017.08.014 Get rights and content

Abstract

Background

Immediate hypersensitivity reactions (IHRs) to iodinated contrast media (ICMs) remain a common clinical concern. Positive skin test and basophil activation test results suggest a specific IgE-mediated mechanism in some cases. Skin test and controlled challenge test (CCT) are useful to manage these patients.

Objective

To study clinical and allergologic features of IHRs to ICMs in a Spanish tertiary hospital during a 7-year period.

Methods

Demographic and clinical data concerning the reaction were recorded. Patients treated at the Allergy Department of Hospital General Universitario Gregorio Marañón, Madrid, Spain, underwent skin tests. In those with positive results, CCTs with an alternative skin-test-negative ICM was performed. Global reaction rate was calculated and compared for each ICM.

Results

A total of 342 reactions occurred in 329 patients. Cutaneous symptoms were the most common (87.7%). A total of 196 patients underwent an allergy workup, 15 (7.6%) of whom had positive skin test results. Reactions were more severe in patients with positive vs negative skin test results (grade 1, 46.7% vs 73.6%; grade 2, 33.3% vs 20.9%; grade 3, 20% vs 5.46%; P < .05). Three patients had cross-reactivity to 3 ICMs, all including ioversol and iomeprol. Six patients allergic to iopamidol tolerated ioversol and 1 tolerated iomeprol. Four patients allergic to ioversol and 1 allergic to iomeprol tolerated iopamidol. The global reaction rate was 0.2%, differing for each ICM (iopamidol, 0.14%; ioversol, 0.2%; and iomeprol, 0.4%; P < .001). Positive skin test results were found in a low percentage of patients in whom skin test–based CCT identified an alternative non–cross-reactive ICM. Low-grade cross-reactivity was found, especially between iopamidol and ioversol. Reactions were more severe in patients with positive skin test results. The reaction rate was greater for iomeprol compared with iopamidol (reaction rate, 2.8%) and ioversol (reaction rate, 2%).

Conclusion

This study identified a possible underlying specific IgE-mediated mechanism by positive skin test result in a low percentage of patients with IHRs to ICMs. In these patients, the CCT based on skin test results was useful for identifying an alternative non–cross-reactive ICM. More studies are needed to investigate the underlying mechanism in patients with IHRs and negative skin test results.

Introduction

Immediate hypersensitivity reactions (IHRs) to iodinated contrast media (ICMs) are those which occur within 1 hour after administration.¹ Cutaneous mild reactions are the most common, but severe anaphylaxis or even death can occur in 1 per 100,000 administrations.² These reactions were classically considered nonallergic and explained by nonspecific mast cell and basophil activation. However, positive skin test and basophil activation test results have been reported, suggesting a specific allergic mechanism in some cases.[3], [4], [5], [6], [7], [8], [9] In addition, specific IgE to ICMs has been detected using radioimmunoassay techniques.¹⁰

Skin tests are useful tools for the evaluation and diagnosis of IHRs to ICMs, and guidelines for this procedure have been published.¹¹ Skin test sensitivity is not well established, and positivity rates vary widely in different populations.[3], [4], [5], [6], [7], [8], [9], [12] The controlled challenge test (CCT) is useful for the evaluation of these patients with positive skin test results to identify an alternative non–cross-reactive ICM.[7], [8]

We report the study of IHRs to ICMs occurring in a tertiary hospital in Spain during a 7-year period assaying their clinical features and their allergy workup. Reaction rate was calculated and compared for different ICMs.

Section snippets

Methods

This prospective study included all adult patients with an IHR to ICMs in the Radiology Department of Hospital General Universitario Gregorio Marañón, Madrid, Spain, from January 2008 to December 2014. The total number of radiologic procedures using ICMs performed in the Radiology Department in the same period was also reported to calculate the reaction rate (RR). Patient personal data and symptoms, ICM administrated, and required treatment were recorded by the Radiology Quality Service at the

Results

From January 2008 to December 2014, a total of 342 reactions occurred in 329 patients. Of the patients, 157 were male (47.7%) and 172 female (52.3%). The mean (SD) age was 58.1 (22.0) years (range, 18–93 years). Atopy was recorded in 14.3%, asthma in 5.9%, drug allergy in 13.2%, renal insufficiency in 7.9%, β-blocker treatment in 7.9%, and ACEI treatment in 13.2% of patients. A total of 206 patients (59.7%) were being studied because of an oncologic disease, 51 (15%) for a urologic disease, 41

Discussion

Currently, despite the generalized use of low-osmolar nonionic agents, IHRs to ICM remain a common clinical concern. The mechanism underlying these reactions is still unclear in many cases.

Skin tests are useful to manage IHRs to ICMs because a specific IgE–mediated mechanism may be involved in some cases. However, positivity rates vary widely in different studied populations from 4.2% to 73%.[3], [4], [5], [6], [7], [8], [9] The cause of these discrepancies is not well known, but they could be

Acknowledgment

Jose María Bellón Cano provided the statistical analysis.

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Skin Test Reactivity Patterns in Patients Allergic to Iodinated Contrast Media: A Refined View
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Two-dimensional (2D) classifications of iodinated contrast media (ICM) are insufficient to explain the observed skin test (ST) reactivity patterns in patients with drug hypersensitivity reactions (DHRs) to ICM.
To refine the current view on allergic DHRs to ICM by analyzing ST reactivity patterns in patients with previous reactions to ICM.
Patients with a history of DHR to ICM and positive STs, who presented at the University Hospital of Montpellier between 2004 and 2022, were included in the study. The relative difference between every two ICM products was measured by Manhattan distance and odds ratios were computed for all pairs of products in the immediate reaction (IR) and non-immediate reaction (NIR) ST groups.
A total of 181 patients were included in the study. Odds ratio analysis identified significant associations between classical cross-reactive ICM, such as iohexol-ioversol, iohexol-iomeprol, iomeprol-ioversol, and iohexol-iodixanol in the IR ST group and iohexol-ioversol, iopromide-iohexol, and iomeprol-ioversol in the NIR ST group. We also identified uncommon associations, such as ioxitalamate-amidotrizoate in the IR ST group and amidotrizoate-iopamidol and amidotrizoate-ioxitalamate in the NIR ST group. The results were reflected by the Manhattan distance, which suggested the existence of clusters containing the same classically associated ICM as well as uncommon associations, which we hypothesize to be related to similarities in the 3D structure of the respective ICM.
Current chemical (2D) classifications cannot explain all observed ST reactivity patterns. Whether the 3D structure can be integrated into the current classifications to interpret the observed ST reactivity patterns and predict tolerance to alternative ICM requires further research.
Skin Test–Guided Strategy to Select Alternative Iodinated Contrast Media in Patients With Immediate Hypersensitivity Reaction: A Prospective Confirmative Study
2023, Journal of Allergy and Clinical Immunology: In Practice
Iodinated contrast media (ICM) are a common cause of drug-induced immediate hypersensitivity reaction (IHR). Repeated use of ICM is often necessary; therefore, a standardized protocol to prevent recurrence of IHR is required.
We aimed to propose an intradermal skin test (IDT)–guided strategy for previous reactors to prevent recurrence of IHR.
We conducted a prospective multicenter study from May 2018 to December 2020 and recruited patients who had experienced IHR to ICM. Once enrolled, the participants underwent IDT with a causative ICM. The alternatives for reexposure were selected using the following protocol: (1) if the IDT with the culprit ICM was positive, further skin tests with other available ICM were conducted to choose IDT-negative agents as alternatives, and (2) if the IDT with the culprit ICM was negative, a randomly changed ICM was used without additional skin tests. The recurrence and severity of hypersensitivity were assessed in subsequent computed tomography examinations. Premedication was administered according to the severity of the index event in all cases.
A total of 496 participants were enrolled, and 299 were reexposed to ICM. Among 269 participants who followed the protocol, 228 (84.8%) completed computed tomography examinations without adverse reactions, and IHR recurred in 16 of 30 participants (53.3%) who did not follow the protocol (P < .001). In addition, application of the protocol reduced the severity of IHR in recurred cases (P = 0.003).
Our IDT-guided strategy not only reduced recurrence of IHR to ICM but also mitigated the severity in recurred cases. This provides evidence for recommending an IDT to diagnose ICM allergy and find safe alternatives.
Validation of Practical Pathway in Patients With Anaphylaxis to Low Osmolar Contrast Media: A Retrospective Cohort Study
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An optimal strategy for choosing safe alternative low osmolar contrast media (LOCM) has not yet been established in patients with a history of LOCM-induced anaphylaxis.
To validate the practical pathway in patients with anaphylaxis to LOCMs and to compare 2 different doses of challenge testing with skin test-negative LOCM.
A retrospective cohort study was performed in patients with LOCM-induced anaphylaxis. Patients were challenged with intravenous LOCMs showing negativity in the skin test according to 2 different protocols: low-dose and high-dose (maximum dose 10 and 30 mL, respectively). Challenge-negative LOCMs were selected for use during computed tomography scans, and patients received intravenous pretreatment with 4 mg chlorpheniramine and 40 mg methylprednisolone.
Of the 110 challenge tests, there were 4 (3.6%) positive challenges. Among 106 enhanced computed tomography scans performed using challenge-negative LOCMs, breakthrough reactions occurred in 8 (7.6%). Breakthrough reaction rates were not statistically different between the 2 protocols (8.9% and 6.0% in the low-dose challenge and the high-dose challenge, respectively). Compared with the low-dose protocol, the number needed to test of the high-dose challenge test decreased 2.5-fold. Moreover, none of the patients in the high-dose challenge group incurred severe reactions during computed tomography scans with challenge-negative LOCM, whereas 80% of reactions were severe in the low-dose challenge group.
We validated a pathway consisting of a battery of skin testing to LOCMs and challenge with skin test-negative LOCM in patients with LOCM-induced anaphylaxis.
Mas-Related G Protein–Coupled Receptor-X2 and Its Role in Non-immunoglobulin E–Mediated Drug Hypersensitivity
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Citation Excerpt :
The incidence of DHRs to ICM ranges from 0.2% to 3%.78–80 Although mild cutaneous symptoms represent the most common ICM hypersensitivity reaction, severe anaphylaxis can occur with an estimated death rate of 1 per 100,000 administrations.77,81 MC-derived mediators such as histamine and tryptase have been implicated in immediate, anaphylaxis-like reactions caused by ICM.82
Anaphylaxis in the Radiology Suite
2020, Journal of Allergy and Clinical Immunology: In Practice
Citation Excerpt :
A different approach, not fully coincident with Lerondeau et al's classification, was proposed by Rosado Ingelmo et al41 as follows: RCM with strong association: iodixanol and iohexol; RCM with frequent association: iodixanol, iohexol, iopentol, ioversol, and iomeprol; RCM with limited association: ioxaglate, iopamidol, iobitridol, and iopromide. According to various investigators, immunologic cross-reactivity between RCM is commonly observed, and reported proportions of patients with cross-reactions range from 20% up to 75%.31,42-44 Nevertheless, there is some evidence that iobitridol has a comparatively low tendency to cross-react with other RCM.42,43,45,46
Contrast media are crucial for modern medical imaging. Contrast agents are generally well tolerated. However, patients may present with adverse reactions, which can be divided into pharmacological effects or hypersensitivity reactions. We present a vignette of a patient with a past history of urticaria after radiocontrast media exposure for coronary angiography. He returns for evaluation for radiocontrast media because he needs another coronary angiography. There are no validated methods for predicting such reactions yet. Mechanisms behind adverse contrast media reactions are still not well understood. Because of unknown contrast agent, the patient was successfully pretreated with corticosteroids and an H1 antihistamine.
A mast-cell-specific receptor mediates Iopamidol induced immediate IgE-independent anaphylactoid reactions
2019, International Immunopharmacology
Iopamidol is a radiographic contrast media which caused a very high incidence of anaphylactic reactions. Mast cells are sentinel cells in host defense reactions during immediate hypersensitivity responses and anaphylactic responses. Mas-related G protein-coupled receptor X2 (MRGPRX2) is a kind of mast cell specific receptor, which triggers mast cell degranulation in anaphylactic reactions. Mice MrgprB2 is a homologous gene of MRGPRX2. We sought to better understand the anaphylactic reactions induced by Iopamidol and the mechanisms involving MRGPRX2. The MRGPRX2-related anaphylactic reactions induced by Iopamidol were investigated using the hindpaw swelling and extravasation assay in vivo and a calcium imaging assay was used for mast cell intracellular calcium responses detection and mast cell release of anaphylactic mediators, such as β-hexosaminidase, histamine and TNF-α, was also detected in vitro. The mast cell deficient Kit^W-sh/W-sh mice and MrgprB2 knockout mice exhibited a reduced Iopamidol-induced inflammation effect compared with wild type mice. Furthermore, human mast cells that express MRGPRX2 were activated by Iopamidol in a dose-dependent manner, meanwhile MRGPRX2 knockdown mast cells showed reduced intracellular calcium responses and anaphylactic mediators release effect. It could be concluded that Iopamidol-induced anaphylactoid reactions were MRGPRX2 mediated to provoke mast cells Ca²⁺ mobilization and degranulation.

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: Disclosures: Authors have nothing to disclose.

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Original ArticleSystemic Allergic DisordersImmediate reactions to iodinated contrast media

Abstract

Background

Objective

Methods

Results

Conclusion

Introduction

Section snippets

Methods

Results

Discussion

Acknowledgment

Immunol Allergy Clin North Am

J Allergy Clin Immunol

Management of hypersensitivity reactions to iodinated contrast media

Allergy

Anaphylactoid reactions to radiocontrast media

Curr Allergy Asthma Rep

Diagnosis of iodinated contrast media hypersensitivity: results of a 6-year period

Clin Exp Allergy

Anaphylaxis to iodinated contrast material: nonallergic hypersensitivity or IgE-mediated allergy?

AJR Am J Roentgenol

Skin testing in patients with hypersensitivity reactions to iodinated contrast media: a European multicenter study

Allergy

Allergy and contrast media

Allergy

Original Article
Systemic Allergic Disorders
Immediate reactions to iodinated contrast media