Assessment of the Frequency and Characteristics of Hypersensitivity Reactions to Contrast Media in Children: A Single-Center Experience

Assessment of the Frequency and Characteristics of Hypersensitivity Reactions to Contrast Media in Children: A Single-Center Experience | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Assessment of the Frequency and Characteristics of Hypersensitivity Reactions to Contrast Media in Children: A Single-Center Experience Ali Can Demirel¹, Candan İslamoğlu¹, Nadide Başak Gülleroğlu², and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7069205/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Hypersensitivity reactions to contrast media (CM) are rare, but can be life-threatening. The aim of this study was to evaluate the frequency, clinical features and diagnostic test results of contrast media-related hypersensitivity reactions in children. Method Patients aged 0-18 years who underwent computed tomography (CT) and magnetic resonance imaging (MRI) with CM were included. The characteristics of the reactions, diagnostic test results, and clinical findings of the patients who required reapplication of contrast media were recorded. Results During the study period, 2336 CT scans were performed with CM within one year. Immediate reactions developed in 8 patients (0.34%). Iohexol was used in all patients. Skin prick test (SPT) and intradermal test (IDT) performed with suspected CM were negative in these patients. One patient with urticaria was able to take the same CM without reaction. Iodine-based CM was not required in other patients. MRI was performed with gadoteric acid in 1848 patients. Immediate reactions developed in 4 patients (0.22%). No positive results were found in SPT and IDT. One patient with pruritus was able to use the same CM without reaction. Other patients were not exposed to CM thereafter. Conclusion In our study, the frequency of immediate reaction with CM application in paediatric patients was found to be 0.25%. No sensitisation was detected in any of the patients in diagnostic tests. Pediatric imaging contrast media immediate hypersensitivity children key Message Contrast media related immediate reaction frequency was found 0.25% in pediatric age group. This is the first study in our country investigating hypersensitivity reactions to contrast media in children. Further research is needed to better understand the nature of CM reactions. Introduction Contrast media (CM) are frequently used in radiological imaging and can lead to toxic reactions (Type A) (approximately 80%) and hypersensitivity (or allergic-like) reactions (Type B) (approximately 20%). Adverse reactions associated with CM can be classified based on the timing of their development into immediate (< 1 h) and non-immediate (≥ 1 h to 10 days). A small percentage of immediate reactions may be IgE-mediated, but most reactions occur due to direct mast cell release, kinin, or complement system activation. Non-immediate reactions primarily manifest as mild skin lesions, such as maculopapular exanthema, although severe reactions like Stevens-Johnson syndrome (SJS), acute generalized exanthematous pustulosis (AGEP), and generalized bullous fixed drug eruption (GBFIE) have also been reported infrequently.[ 1 ] Use of ionic, high-osmolarity CM was often associated with osmotoxicity-related immediate reactions before 1990s. [ 2 ] However, in recent years, the increase in the use of non-ionic, low-osmolarity CMs has led to a decrease in the frequency of such reactions. Immediate and non-immediate hypersensitivity reactions ranges from 0.5–3% with non-ionic, iodinated contrast media (ICM). [ 3 ] The frequency of severe reactions, such as anaphylaxis, occurs in the range of 0.02–0.04%, while the incidence of CM-related mortality is approximately 0.00001–0.00003. [ 4 ] The immediate reaction frequency with gadolinium-based CMs has been reported to be lower (0.004-0.7%).[ 5 ] Non-immediate reactions with gadolinium-based CMs are quite rare, with limited data available outside of case reports. [ 6 ] Although it is known that CM-related reactions are less frequent in children compared to adults, sufficient data is lacking.[ 7 ] In our country, approximately 300 million outpatient examinations, both emergency and non-emergency, are conducted annually, with 34.7 CT scans and 31.7 MRI scans performed per 1,000 examinations.[ 8 ] This study aims to evaluate the frequency of hypersensitivity reactions related to rcontrast agents in children, along with their clinical characteristics and diagnostic test results. Method Patients aged ≤ 17 years who underwent computed tomography (CT) and magnetic resonance imaging (MRI) with CM between June 1, 2021, and June 1, 2022, and who developed immediate reactions, were included in the study. The study was approved by the ethics committee of our hospital, and written consent was obtained from the parents of all the participants. Patients with immediate reactions were evaluated by a pediatric allergy specialist. The characteristics of reactions were recorded; categorized as isolated urticaria, angioedema, hypotension, rash, and anaphylaxis. The demographic characteristics of the patients, presence of allergic diseases in patients with reactions, previous exposure to CM, history of reactions with CM, and presence of chronic systemic diseases were recorded. Determining Reaction Severity The reactions in question were evaluated according to the classification by Brown and colleagues.[ 9 ] Diagnostic skin tests were performed on patients with reactions at 4–6 weeks after the reaction. Skin prick tests (SPT) were conducted using the CM itself. For patients with negative SPT results, intradermal tests (IDT) were performed at a 1/10 concentration, with readings taken 20 minutes after application. Drug provocation tests were not applied to patients; however, those requiring CM again during follow-up were monitored for reaction development. Patients were followed up for one year after the reaction to observe any reuse of CM and development of any reaction. Results During the study period, 2336 CT scans with CM were performed over one year. Number of reaction types and clinical characteristics of patients who reacted to iodinated CM was shown in Table 1 and Table 3 , respectively. Iohexol was used in 1876 of these patients, and iopamidol was used in 460 of them. One patient (17 years old; male) had a known history of allergic rhinitis and pollen allergy. No history of allergic diseases was reported in the other patients. Only one patient (15 years old; female) had a history of prior iohexol use. A total of 8 patients (0.34%) experienced immediate reactions, including pruritus in 4 patients, urticaria in 1 patient, angioedema in 1 patient, cough in 1 patient, and sneezing in 1 patient. All patients who developed skin symptoms and the patient who experienced sneezing were classified as "grade 1" according to the classification by Brown and colleagues. The patient who developed a cough did not experience respiratory distress or a drop in oxygen saturation. The severity of this patient's reaction was classified as "grade 2." In all patients who had reactions, iohexol, a non-ionic and low-osmolality agent, was used. Skin prick tests (SPT) and intradermal tests (IDT) performed with iohexol were negative. The patient who developed urticaria later received the same iodinated contrast medium (ICM) with premedication without any problems. In the other patients, there was no need for repeat iodine-based contrast agent use. During the study period, 1851 patients underwent MRI scans with gadoteric acid. Number of reaction types and clinical characteristics of patients who reacted to gadoteric acid was shown in Table 2 and Table 4 , respectively. One patient (9.5 years old; male) had a known history of asthma. Another patient (11 years old; male) had a history of urticaria following the administration of general anesthesia. A total of 4 patients (0.22%) experienced suspected immediate reactions, including urticaria in 1 patient, angioedema in 1 patient, erythema on the trunk in 1 patient, and shortness of breath in 1 patient. The reactions of the patients with skin symptoms and the patient who developed a cough were classified as "grade 1." The patient with shortness of breath did not experience a drop in oxygen saturation. The severity of this patient's reaction was classified as "grade 2." The SPT and IDT performed on these patients yielded negative results. The patient who developed erythema was later able to use the same agent with premedication without any issues. In the other patients, there was no need for repeat radicontrast media use. Table 1 Reactions to iodinated contrast media. Total number of iodinated CM used 2336 Number of immediate reactions (%) Pruritus Urticaria / angioedema Cough Dyspnea 8 (0,34) 4 2 1 1 Table 2 Reactions to gadoteric acid. Total number of gadoteric acid used 1851 Number of immediate reactions (%) Urticaria / angioedema Pruritus Dyspnea 4 (0,22) 2 1 1 Table 3 Descriptive features of patients reacted to iodinated contrast media Patient Age (year) Sex (F, M) CM Reaction Time interval between CM use and reaction History of allergic disease History of prior CM use History of prior reaction to CM SPT IDT Repeat use of CM after reaction 1 15, F İohexol Urticaria 2 hours Yes Yes No Negative Negative Yes. No reaction occured 2 2, M İohexol Angioedema 1 hour No No No Negative Negative No 3 17, M İohexol Sneezing 10 minutes Allergic rhinitis No No Negative Negative No 4 16, F İohexol Cough 30 minutes No No No Negative Negative No 5 4,M İohexol Pruritus 2 hours No No No Negative Negative No 6 5, F İohexol Pruritus, Erythema 1,5 hour No No No Negative Negative No 7 7, F İohexol Pruritus 50 minutes No No No Negative Negative No 8 6, M İohexol Pruritus 2 hours No No No Negative Negative No Table 4 Descriptive features of patients reacted to gadoteric acid Patient Age (year) Sex (F, M) CM Reaction Time interval between CM use and reaction History of allergic disease History of prior CM use History of prior reaction to CM SPT IDT Repeat use of CM after reaction 1 9,5; M Gadoteric acid Urticaria 45 minutes Asthma No No Negative Negative Yes. No reaction occured 2 11; M Gadoteric acid Urticaria 30 minutes Urticaria after general anesthesia Yes No Negative Negative No 3 12; M Gadoteric acid Erythema 2 hours No No No Negative Negative No 4 2 ; F Gadoteric acid Dyspnea 40 minutes No Yes No Negative Negative No Discussion We detected immediate reactions in a total of 12 patients, 8 of whom were given iohexol (0.34%) and 4 were given gadoteric acid (0.22%). There was not any positivity in skin tests performed on these 12 patients, and 2 of them were later able to receive contrast agents without any issues. Among the 8 reactions caused by iodinated contrast media, 6 presented with only skin symptoms, 1 patient experienced coughing, and another patient had sneezing. The reactions of 7 patients were classified as "mild/grade 1," and 1 patient’s reaction was classified as "moderate/grade 2." Of the reactions caused by gadolinium-based contrast media, 3 were limited to skin symptoms, while 1 patient experienced respiratory distress without a decrease in oxygen saturation, which was also classified as "moderate/grade 2." In a study by Dillman et al., reactions that developed after 11,306 doses of non-ionic, low-osmolality contrast agents were analyzed, and acute allergy-like reactions were reported in 20 pediatric patients (0.18%). [ 10 ] Of the 20 reactions, 16 were mild (urticaria in 7 patients, facial edema and sneezing in 2 patients, and sneezing, nasal discharge, widespread redness, asymptomatic tachycardia, isolated facial edema in other cases). One patient had a moderate reaction (acute bronchospasm), and three patients had severe reactions (progressive facial edema in one and anaphylaxis in two). It was noted that 2 patients with mild reactions had a history of reactions to contrast agents, and 3 out of 4 patients with moderate or severe reactions had a history of asthma. Fjelldal et al. reported a hypersensitivity reaction rate of 5/547 (0.9%) in children related to iohexol.[ 11 ] In a review including 11 studies, the rate of positive results in skin prick tests (SPT) or intradermal tests (IDT) in adults with a history of immediate reactions to iodinated contrast media was reported to range between 5.6% and 64.7%.[ 12 ] In the same study, reactions occurred at rates between 3.2% and 9.1% during provocation tests with the suspected drug or a skin tests negative alternative. We know that only a small percentage of immediate reactions are mediated by IgE mechanisms. Yoon et al reported the positivity rate of skin tests in mild reactions around 17%, whereas it was around 52% in severe reaction.[ 13 ] We did not observe any positivity in prick and intradermal tests performed on our patients, which we considered could be related to non-IgE mechanisms. The patient who developed sneezing 10 minutes after iohexol administration had a history consistent with allergic rhinitis. Later, in skin prick test conducted for inhalant allergens, pollen allergy was detected. The patient who developed urticaria 45 minutes after gadoteric acid administration had a history of asthma, but no inhalant allergen sensitivity was detected in this patient. Factors shown to increase the risk of reactions to contrast media include history of prior reaction to contrast media, allergies to other drugs, a history of atopic diseases, the simultaneous use of certain medications (such as ACE inhibitors, beta-blockers, or proton pump inhibitors), kidney and heart diseases, and female gender.[ 14 ] No significant risk factors have been reported specifically in children. [ 7 ] Among our patients who received gadoteric acid, only one had history of using gadoteric acid without any reaction. Except for one patient with asthma and another with allergic rhinitis, none of the other patients had chronic diseases or a history of regular medication use. We did not perform diagnostic provocation tests on our patients. There is no clear data in the literature regarding the dosage and protocol for provocation tests related to contrast media reactions. The EAACI's 2023 guidelines recommend performing diagnostic provocation under the supervision of an allergist in patients who develop anaphylaxis and suggest that patients who develop urticaria or maculopapular exanthema with negative skin tests may be administered contrast media by a radiologist based on allergist recommendations. [ 15 ] Two of our patients later received contrast media without any issues. In conclusion, we found comparable results in the frequency of immediate reactions to contrast media in pediatric patients which was 0.25%. Diagnostic tests did not reveal any sensitivities in any of the patients. More studies are needed on hypersensitivity reactions to contrast media in children. Declarations Conflict of Interest Statement The authors declare no conflict of interest in relation to this study. Funding No funding was received for conducting this study. Author Contribution All authors contributed the study design. A.C.D., D.Y., N.B.G., A.S.E. and C.İ. were responsible for the data curaton. A.C.D. and E.D.İ. wrote the main manuscript. All authors read and approved the final manuscript. References Egbert RE, De Cecco CN, Schoepf UJ, McQuiston AD, Meinel FG, Katzberg RW (2014) Delayed adverse reactions to the parenteral administration of iodinated contrast media. AJR Am J Roentgenol 203:1163–1170 Macy EM (2018) Current epidemiology and management of radiocontrast-associated acute- and delayed-onset hypersensitivity: A review of the literature. Perm J 22:17–072 Torres MJ, Trautmann A, Böhm I, Scherer K, Barbaud A, Bavbek S et al (2021) Practice parameters for diagnosing and managing iodinated contrast media hypersensitivity. Allergy 76:1325–1339 Brockow K, Sánchez-Borges M (2014) Hypersensitivity to contrast media and dyes. Immunol Allergy Clin North Am 34:547–564 viii Kodzwa R (2019) ACR manual on contrast media: 2018 updates. Radiol Technol 91:97–100 Doña I, Bogas G, Salas M, Testera A, Moreno E, Laguna JJ et al (2020) Hypersensitivity Reactions to Multiple Iodinated Contrast Media. Front Pharmacol 11:575437 Saretta F, Caimmi S, Mori F, Bianchi A, Bottau P, Crisafulli G et al (2022) Radiocontrast media hypersensitivity reactions in children. Medicina 58:517 Beştemi̇r A, Aydin H (2022) 300 million patient examinations per year; Evaluation of emergency and polyclinic services of 2nd and 3rd stage public health facilities in Turkey. Sak Med J 12:496–502 Brown SGA (2004) Clinical features and severity grading of anaphylaxis. J Allergy Clin Immunol 114:371–376 Dillman JR, Strouse PJ, Ellis JH, Cohan RH, Jan SC (2007) Incidence and severity of acute allergic-like reactions to i.v. nonionic iodinated contrast material in children. AJR Am J Roentgenol 188:1643–1647 Fjelldal A, Nordshus T, Eriksson J (1987) Experiences with iohexol (Omnipaque) at urography. Pediatr Radiol 17:491–492 Bansie RD, Karim AF, van Maaren MS, Hermans MA, van Daele PLA, van Gerth R et al (2021) Assessment of immediate and non-immediate hypersensitivity contrast reactions by skin tests and provocation tests: A review. Int J Immunopathol Pharmacol 35:20587384211015061 Yoon SH, Lee S-Y, Kang H-R, Kim J-Y, Hahn S, Park CM et al (2015) Skin tests in patients with hypersensitivity reaction to iodinated contrast media: a meta-analysis. Allergy 70:625–637 Rosado Ingelmo A, Doña Diaz I, Cabañas Moreno R, Moya Quesada MC, García-Avilés C, García Nuñez I et al (2016) Clinical Practice Guidelines for Diagnosis and Management of Hypersensitivity Reactions to Contrast Media. J Investig Allergol Clin Immunol 26:144–155 quiz 2 p following 155 Barbaud A, Garvey LH, Torres M, Laguna JJ, Arcolaci A, Bonadonna P et al (2024) EAACI/ENDA position paper on drug provocation testing. Allergy 79:565–579 Additional Declarations No competing interests reported. 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This is the first study in our country investigating hypersensitivity reactions to contrast media in children. Further research is needed to better understand the nature of CM reactions.\u003c/p\u003e"},{"header":"Introduction","content":"\u003cp\u003eContrast media (CM) are frequently used in radiological imaging and can lead to toxic reactions (Type A) (approximately 80%) and hypersensitivity (or allergic-like) reactions (Type B) (approximately 20%). Adverse reactions associated with CM can be classified based on the timing of their development into immediate (\u0026lt; 1 h) and non-immediate (≥ 1 h to 10 days). A small percentage of immediate reactions may be IgE-mediated, but most reactions occur due to direct mast cell release, kinin, or complement system activation.\u003c/p\u003e\u003cp\u003eNon-immediate reactions primarily manifest as mild skin lesions, such as maculopapular exanthema, although severe reactions like Stevens-Johnson syndrome (SJS), acute generalized exanthematous pustulosis (AGEP), and generalized bullous fixed drug eruption (GBFIE) have also been reported infrequently.[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]\u003c/p\u003e\u003cp\u003eUse of ionic, high-osmolarity CM was often associated with osmotoxicity-related immediate reactions before 1990s. [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e] However, in recent years, the increase in the use of non-ionic, low-osmolarity CMs has led to a decrease in the frequency of such reactions.\u003c/p\u003e\u003cp\u003eImmediate and non-immediate hypersensitivity reactions ranges from 0.5–3% with non-ionic, iodinated contrast media (ICM). [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e] The frequency of severe reactions, such as anaphylaxis, occurs in the range of 0.02–0.04%, while the incidence of CM-related mortality is approximately 0.00001–0.00003. [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]\u003c/p\u003e\u003cp\u003eThe immediate reaction frequency with gadolinium-based CMs has been reported to be lower (0.004-0.7%).[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e] Non-immediate reactions with gadolinium-based CMs are quite rare, with limited data available outside of case reports. [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]\u003c/p\u003e\u003cp\u003eAlthough it is known that CM-related reactions are less frequent in children compared to adults, sufficient data is lacking.[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]\u003c/p\u003e\u003cp\u003eIn our country, approximately 300\u0026nbsp;million outpatient examinations, both emergency and non-emergency, are conducted annually, with 34.7 CT scans and 31.7 MRI scans performed per 1,000 examinations.[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e] This study aims to evaluate the frequency of hypersensitivity reactions related to rcontrast agents in children, along with their clinical characteristics and diagnostic test results.\u003c/p\u003e"},{"header":"Method","content":"\u003cp\u003ePatients aged ≤ 17 years who underwent computed tomography (CT) and magnetic resonance imaging (MRI) with CM between June 1, 2021, and June 1, 2022, and who developed immediate reactions, were included in the study. The study was approved by the ethics committee of our hospital, and written consent was obtained from the parents of all the participants.\u003c/p\u003e\u003cp\u003ePatients with immediate reactions were evaluated by a pediatric allergy specialist. The characteristics of reactions were recorded; categorized as isolated urticaria, angioedema, hypotension, rash, and anaphylaxis.\u003c/p\u003e\u003cp\u003eThe demographic characteristics of the patients, presence of allergic diseases in patients with reactions, previous exposure to CM, history of reactions with CM, and presence of chronic systemic diseases were recorded.\u003c/p\u003e\u003cp\u003e\u003cb\u003eDetermining Reaction Severity\u003c/b\u003e\u003c/p\u003e\u003cp\u003eThe reactions in question were evaluated according to the classification by Brown and colleagues.[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]\u003c/p\u003e\u003cp\u003eDiagnostic skin tests were performed on patients with reactions at 4–6 weeks after the reaction. Skin prick tests (SPT) were conducted using the CM itself. For patients with negative SPT results, intradermal tests (IDT) were performed at a 1/10 concentration, with readings taken 20 minutes after application.\u003c/p\u003e\u003cp\u003eDrug provocation tests were not applied to patients; however, those requiring CM again during follow-up were monitored for reaction development.\u003c/p\u003e\u003cp\u003ePatients were followed up for one year after the reaction to observe any reuse of CM and development of any reaction.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eDuring the study period, 2336 CT scans with CM were performed over one year. Number of reaction types and clinical characteristics of patients who reacted to iodinated CM was shown in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e and Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e, respectively.\u003c/p\u003e\u003cp\u003eIohexol was used in 1876 of these patients, and iopamidol was used in 460 of them.\u003c/p\u003e\u003cp\u003eOne patient (17 years old; male) had a known history of allergic rhinitis and pollen allergy. No history of allergic diseases was reported in the other patients. Only one patient (15 years old; female) had a history of prior iohexol use.\u003c/p\u003e\u003cp\u003eA total of 8 patients (0.34%) experienced immediate reactions, including pruritus in 4 patients, urticaria in 1 patient, angioedema in 1 patient, cough in 1 patient, and sneezing in 1 patient. All patients who developed skin symptoms and the patient who experienced sneezing were classified as \"grade 1\" according to the classification by Brown and colleagues. The patient who developed a cough did not experience respiratory distress or a drop in oxygen saturation. The severity of this patient's reaction was classified as \"grade 2.\"\u003c/p\u003e\u003cp\u003eIn all patients who had reactions, iohexol, a non-ionic and low-osmolality agent, was used. Skin prick tests (SPT) and intradermal tests (IDT) performed with iohexol were negative. The patient who developed urticaria later received the same iodinated contrast medium (ICM) with premedication without any problems. In the other patients, there was no need for repeat iodine-based contrast agent use.\u003c/p\u003e\u003cp\u003eDuring the study period, 1851 patients underwent MRI scans with gadoteric acid. Number of reaction types and clinical characteristics of patients who reacted to gadoteric acid was shown in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e and Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e, respectively.\u003c/p\u003e\u003cp\u003eOne patient (9.5 years old; male) had a known history of asthma. Another patient (11 years old; male) had a history of urticaria following the administration of general anesthesia.\u003c/p\u003e\u003cp\u003eA total of 4 patients (0.22%) experienced suspected immediate reactions, including urticaria in 1 patient, angioedema in 1 patient, erythema on the trunk in 1 patient, and shortness of breath in 1 patient. The reactions of the patients with skin symptoms and the patient who developed a cough were classified as \"grade 1.\" The patient with shortness of breath did not experience a drop in oxygen saturation. The severity of this patient's reaction was classified as \"grade 2.\" The SPT and IDT performed on these patients yielded negative results.\u003c/p\u003e\u003cp\u003eThe patient who developed erythema was later able to use the same agent with premedication without any issues. In the other patients, there was no need for repeat radicontrast media use.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eReactions to iodinated contrast media.\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"2\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTotal number of iodinated CM used\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2336\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNumber of immediate reactions (%)\u003c/p\u003e\u003cp\u003ePruritus\u003c/p\u003e\u003cp\u003eUrticaria / angioedema\u003c/p\u003e\u003cp\u003eCough\u003c/p\u003e\u003cp\u003eDyspnea\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e8 (0,34)\u003c/p\u003e\u003cp\u003e4\u003c/p\u003e\u003cp\u003e2\u003c/p\u003e\u003cp\u003e1\u003c/p\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eReactions to gadoteric acid.\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"2\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTotal number of gadoteric acid used\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1851\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNumber of immediate reactions (%)\u003c/p\u003e\u003cp\u003eUrticaria / angioedema\u003c/p\u003e\u003cp\u003ePruritus\u003c/p\u003e\u003cp\u003eDyspnea\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4 (0,22)\u003c/p\u003e\u003cp\u003e2\u003c/p\u003e\u003cp\u003e1\u003c/p\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eDescriptive features of patients reacted to iodinated contrast media\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"11\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c11\" colnum=\"11\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePatient\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAge (year)\u003c/p\u003e\u003cp\u003eSex\u003c/p\u003e\u003cp\u003e(F, M)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eCM\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eReaction\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eTime interval between CM use and reaction\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003eHistory of allergic disease\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u003cp\u003eHistory of prior CM use\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c8\"\u003e\u003cp\u003eHistory of prior reaction to CM\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c9\"\u003e\u003cp\u003eSPT\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c10\"\u003e\u003cp\u003eIDT\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c11\"\u003e\u003cp\u003eRepeat use of CM after reaction\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e15, F\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eİohexol\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eUrticaria\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e2 hours\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eNegative\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eNegative\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eYes.\u003c/p\u003e\u003cp\u003eNo reaction occured\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2, M\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eİohexol\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eAngioedema\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e1 hour\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eNegative\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eNegative\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e17, M\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eİohexol\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eSneezing\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e10 minutes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eAllergic rhinitis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eNegative\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eNegative\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e16, F\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eİohexol\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eCough\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e30 minutes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eNegative\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eNegative\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4,M\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eİohexol\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003ePruritus\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e2 hours\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eNegative\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eNegative\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5, F\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eİohexol\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003ePruritus,\u003c/p\u003e\u003cp\u003eErythema\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e1,5 hour\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eNegative\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eNegative\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e7, F\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eİohexol\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003ePruritus\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e50 minutes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eNegative\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eNegative\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e6, M\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eİohexol\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003ePruritus\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e2 hours\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eNegative\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eNegative\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eDescriptive features of patients reacted to gadoteric acid\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"11\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c11\" colnum=\"11\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePatient\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAge (year)\u003c/p\u003e\u003cp\u003eSex\u003c/p\u003e\u003cp\u003e(F, M)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eCM\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eReaction\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eTime interval between CM use and reaction\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003eHistory of allergic disease\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u003cp\u003eHistory of prior CM use\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c8\"\u003e\u003cp\u003eHistory of prior reaction to CM\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c9\"\u003e\u003cp\u003eSPT\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c10\"\u003e\u003cp\u003eIDT\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c11\"\u003e\u003cp\u003eRepeat use of CM after reaction\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e9,5; M\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eGadoteric acid\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eUrticaria\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e45 minutes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eAsthma\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eNegative\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eNegative\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eYes.\u003c/p\u003e\u003cp\u003eNo reaction occured\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e11; M\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eGadoteric acid\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eUrticaria\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e30 minutes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eUrticaria after general anesthesia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eNegative\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eNegative\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e12; M\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eGadoteric acid\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eErythema\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e2 hours\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eNegative\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eNegative\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2 ; F\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eGadoteric acid\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eDyspnea\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e40 minutes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eNegative\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eNegative\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eWe detected immediate reactions in a total of 12 patients, 8 of whom were given iohexol (0.34%) and 4 were given gadoteric acid (0.22%). There was not any positivity in skin tests performed on these 12 patients, and 2 of them were later able to receive contrast agents without any issues.\u003c/p\u003e\u003cp\u003eAmong the 8 reactions caused by iodinated contrast media, 6 presented with only skin symptoms, 1 patient experienced coughing, and another patient had sneezing. The reactions of 7 patients were classified as \"mild/grade 1,\" and 1 patient\u0026rsquo;s reaction was classified as \"moderate/grade 2.\" Of the reactions caused by gadolinium-based contrast media, 3 were limited to skin symptoms, while 1 patient experienced respiratory distress without a decrease in oxygen saturation, which was also classified as \"moderate/grade 2.\"\u003c/p\u003e\u003cp\u003eIn a study by Dillman et al., reactions that developed after 11,306 doses of non-ionic, low-osmolality contrast agents were analyzed, and acute allergy-like reactions were reported in 20 pediatric patients (0.18%). [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e] Of the 20 reactions, 16 were mild (urticaria in 7 patients, facial edema and sneezing in 2 patients, and sneezing, nasal discharge, widespread redness, asymptomatic tachycardia, isolated facial edema in other cases). One patient had a moderate reaction (acute bronchospasm), and three patients had severe reactions (progressive facial edema in one and anaphylaxis in two). It was noted that 2 patients with mild reactions had a history of reactions to contrast agents, and 3 out of 4 patients with moderate or severe reactions had a history of asthma.\u003c/p\u003e\u003cp\u003eFjelldal et al. reported a hypersensitivity reaction rate of 5/547 (0.9%) in children related to iohexol.[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]\u003c/p\u003e\u003cp\u003eIn a review including 11 studies, the rate of positive results in skin prick tests (SPT) or intradermal tests (IDT) in adults with a history of immediate reactions to iodinated contrast media was reported to range between 5.6% and 64.7%.[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e] In the same study, reactions occurred at rates between 3.2% and 9.1% during provocation tests with the suspected drug or a skin tests negative alternative.\u003c/p\u003e\u003cp\u003eWe know that only a small percentage of immediate reactions are mediated by IgE mechanisms. Yoon et al reported the positivity rate of skin tests in mild reactions around 17%, whereas it was around 52% in severe reaction.[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e] We did not observe any positivity in prick and intradermal tests performed on our patients, which we considered could be related to non-IgE mechanisms.\u003c/p\u003e\u003cp\u003eThe patient who developed sneezing 10 minutes after iohexol administration had a history consistent with allergic rhinitis. Later, in skin prick test conducted for inhalant allergens, pollen allergy was detected. The patient who developed urticaria 45 minutes after gadoteric acid administration had a history of asthma, but no inhalant allergen sensitivity was detected in this patient.\u003c/p\u003e\u003cp\u003eFactors shown to increase the risk of reactions to contrast media include history of prior reaction to contrast media, allergies to other drugs, a history of atopic diseases, the simultaneous use of certain medications (such as ACE inhibitors, beta-blockers, or proton pump inhibitors), kidney and heart diseases, and female gender.[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e] No significant risk factors have been reported specifically in children. [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e] Among our patients who received gadoteric acid, only one had history of using gadoteric acid without any reaction. Except for one patient with asthma and another with allergic rhinitis, none of the other patients had chronic diseases or a history of regular medication use.\u003c/p\u003e\u003cp\u003eWe did not perform diagnostic provocation tests on our patients. There is no clear data in the literature regarding the dosage and protocol for provocation tests related to contrast media reactions. The EAACI's 2023 guidelines recommend performing diagnostic provocation under the supervision of an allergist in patients who develop anaphylaxis and suggest that patients who develop urticaria or maculopapular exanthema with negative skin tests may be administered contrast media by a radiologist based on allergist recommendations. [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e] Two of our patients later received contrast media without any issues.\u003c/p\u003e\u003cp\u003eIn conclusion, we found comparable results in the frequency of immediate reactions to contrast media in pediatric patients which was 0.25%. Diagnostic tests did not reveal any sensitivities in any of the patients. More studies are needed on hypersensitivity reactions to contrast media in children.\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eConflict of Interest Statement\u003c/h2\u003e\u003cp\u003eThe authors declare no conflict of interest in relation to this study.\u003c/p\u003e\u003ch2\u003eFunding\u003c/h2\u003e\u003cp\u003eNo funding was received for conducting this study.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eAll authors contributed the study design. A.C.D., D.Y., N.B.G., A.S.E. and C.İ. were responsible for the data curaton. A.C.D. and E.D.İ. wrote the main manuscript. All authors read and approved the final manuscript.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eEgbert RE, De Cecco CN, Schoepf UJ, McQuiston AD, Meinel FG, Katzberg RW (2014) Delayed adverse reactions to the parenteral administration of iodinated contrast media. AJR Am J Roentgenol 203:1163\u0026ndash;1170\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMacy EM (2018) Current epidemiology and management of radiocontrast-associated acute- and delayed-onset hypersensitivity: A review of the literature. Perm J 22:17\u0026ndash;072\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eTorres MJ, Trautmann A, B\u0026ouml;hm I, Scherer K, Barbaud A, Bavbek S et al (2021) Practice parameters for diagnosing and managing iodinated contrast media hypersensitivity. Allergy 76:1325\u0026ndash;1339\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBrockow K, S\u0026aacute;nchez-Borges M (2014) Hypersensitivity to contrast media and dyes. Immunol Allergy Clin North Am 34:547\u0026ndash;564 viii\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKodzwa R (2019) ACR manual on contrast media: 2018 updates. Radiol Technol 91:97\u0026ndash;100\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eDo\u0026ntilde;a I, Bogas G, Salas M, Testera A, Moreno E, Laguna JJ et al (2020) Hypersensitivity Reactions to Multiple Iodinated Contrast Media. Front Pharmacol 11:575437\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSaretta F, Caimmi S, Mori F, Bianchi A, Bottau P, Crisafulli G et al (2022) Radiocontrast media hypersensitivity reactions in children. Medicina 58:517\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBeştemi̇r A, Aydin H (2022) 300 million patient examinations per year; Evaluation of emergency and polyclinic services of 2nd and 3rd stage public health facilities in Turkey. Sak Med J 12:496\u0026ndash;502\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBrown SGA (2004) Clinical features and severity grading of anaphylaxis. J Allergy Clin Immunol 114:371\u0026ndash;376\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eDillman JR, Strouse PJ, Ellis JH, Cohan RH, Jan SC (2007) Incidence and severity of acute allergic-like reactions to i.v. nonionic iodinated contrast material in children. AJR Am J Roentgenol 188:1643\u0026ndash;1647\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eFjelldal A, Nordshus T, Eriksson J (1987) Experiences with iohexol (Omnipaque) at urography. Pediatr Radiol 17:491\u0026ndash;492\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBansie RD, Karim AF, van Maaren MS, Hermans MA, van Daele PLA, van Gerth R et al (2021) Assessment of immediate and non-immediate hypersensitivity contrast reactions by skin tests and provocation tests: A review. Int J Immunopathol Pharmacol 35:20587384211015061\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eYoon SH, Lee S-Y, Kang H-R, Kim J-Y, Hahn S, Park CM et al (2015) Skin tests in patients with hypersensitivity reaction to iodinated contrast media: a meta-analysis. Allergy 70:625\u0026ndash;637\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eRosado Ingelmo A, Do\u0026ntilde;a Diaz I, Caba\u0026ntilde;as Moreno R, Moya Quesada MC, Garc\u0026iacute;a-Avil\u0026eacute;s C, Garc\u0026iacute;a Nu\u0026ntilde;ez I et al (2016) Clinical Practice Guidelines for Diagnosis and Management of Hypersensitivity Reactions to Contrast Media. J Investig Allergol Clin Immunol 26:144\u0026ndash;155 quiz 2 p following 155\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBarbaud A, Garvey LH, Torres M, Laguna JJ, Arcolaci A, Bonadonna P et al (2024) EAACI/ENDA position paper on drug provocation testing. Allergy 79:565\u0026ndash;579\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Pediatric imaging, contrast media, immediate hypersensitivity, children","lastPublishedDoi":"10.21203/rs.3.rs-7069205/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7069205/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eBackground\u003c/p\u003e\n\u003cp\u003eHypersensitivity reactions to contrast media (CM) are rare, but can be life-threatening. The aim of this study was to evaluate the frequency, clinical features and diagnostic test results of contrast media-related hypersensitivity reactions in children.\u003c/p\u003e\n\u003cp\u003eMethod\u003c/p\u003e\n\u003cp\u003ePatients aged 0-18 years who underwent computed tomography (CT) and magnetic resonance imaging (MRI) with CM were included. The characteristics of the reactions, diagnostic test results, and clinical findings of the patients who required reapplication of contrast media were recorded.\u003c/p\u003e\n\u003cp\u003eResults\u003c/p\u003e\n\u003cp\u003eDuring the study period, 2336 CT scans were performed with CM within one year.\u003c/p\u003e\n\u003cp\u003eImmediate reactions developed in 8 patients (0.34%). Iohexol was used in all patients. Skin prick test (SPT) and intradermal test (IDT) performed with suspected CM were negative in these patients. One patient with urticaria was able to take the same CM without reaction. Iodine-based CM was not required in other patients.\u003c/p\u003e\n\u003cp\u003eMRI was performed with gadoteric acid in 1848 patients. Immediate reactions developed in 4 patients (0.22%). No positive results were found in SPT and IDT. One patient with pruritus was able to use the same CM without reaction. Other patients were not exposed to CM thereafter.\u003c/p\u003e\n\u003cp\u003eConclusion\u003c/p\u003e\n\u003cp\u003eIn our study, the frequency of immediate reaction with CM application in paediatric patients was found to be 0.25%. No sensitisation was detected in any of the patients in diagnostic tests.\u003c/p\u003e","manuscriptTitle":"Assessment of the Frequency and Characteristics of Hypersensitivity Reactions to Contrast Media in Children: A Single-Center Experience","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-07-24 15:58:12","doi":"10.21203/rs.3.rs-7069205/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"9c31e0cc-8fd6-4606-926b-96669cd88fdd","owner":[],"postedDate":"July 24th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-11-11T09:24:29+00:00","versionOfRecord":[],"versionCreatedAt":"2025-07-24 15:58:12","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7069205","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7069205","identity":"rs-7069205","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}