Radiocontrast Media Hypersensitivity Reactions in Children.

Hypersensitivity reactions to radiocontrast media seem to be rare in children. Furthermore, the use of radiocontrast media in children remains quite safe in terms of the severity of reactions. Since pediatric guidelines are lacking, the diagnostic workup employed in adults could be adapted to children, taking into account that results have not yet been validated in this age group. Specific protocols for risk stratification and management of severe reactions have been proposed so far.

Anaphylaxis-a 2020 practice parameter update, systematic review, and Grading of Recommendations, Assessment, Development and Evaluation (GRADE) analysis.

Anaphylaxis is an acute, potential life-threatening systemic allergic reaction that may have a wide range of clinical manifestations. Severe anaphylaxis and/or the need for repeated doses of epinephrine to treat anaphylaxis are risk factors for biphasic anaphylaxis. Antihistamines and/or glucocorticoids are not reliable interventions to prevent biphasic anaphylaxis, although evidence supports a role for antihistamine and/or glucocorticoid premedication in specific chemotherapy protocols and rush aeroallergen immunotherapy. Evidence is lacking to support the role of antihistamines and/or glucocorticoid routine premedication in patients receiving low- or iso-osmolar contrast material to prevent recurrent radiocontrast media anaphylaxis. Epinephrine is the first-line pharmacotherapy for uniphasic and/or biphasic anaphylaxis. After diagnosis and treatment of anaphylaxis, all patients should be kept under observation until symptoms have fully resolved. All patients with anaphylaxis should receive education on anaphylaxis and risk of recurrence, trigger avoidance, self-injectable epinephrine education, referral to an allergist, and be educated about thresholds for further care.

Clinical implication of detecting sensitization to iodinated radiocontrast media in the basophil activation test by flow cytometry.

The use of iodinated radiocontrast media is necessary for visualization. A number of patients have adverse effects of various nature and severity when these drugs are administered. Routine allergy tests do not provide adequate diagnosis of reactions to drugs in this group. The aim of this work is to assess the capabilities of the basophil activation test to confirm sensitization to non-ionic iodinated radiocontrast media, as well as to select a safe alternative drug in patients with a burdened history. Basophil activation test by flow cytometry was performed in 184 patients The Nikiforov Russian Centre of Emergency and Radiation Medicine¼ EMERCOM of Russia and 32 volunteers using ultravist, omnipack, and optiray. The presence of sensitization was assessed based on the basophil activation index, as well as spontaneous and anti-IgE antibody-induced activation of basophils and the population of T-lymphocytes type 2 immune response. The volunteers showed no sensitization to iodinated radiocontrast media. In patients with a medium degree of hypersensitivity reaction in vivo, in vitro sensitization to drugs was detected 4 times more often than in patients with a mild degree (51% versus 13.5%). In patients with systemic reactions to the administration of a known drug, in vitro sensitization was confirmed in 86% of cases, while the frequency of detection of sensitization to drugs did not differ. Spontaneous activation of basophils in patients and type 2 T-lymphocytes were 2 times higher than in volunteers. Patients were more likely to have low (less than 30%) activation of basophils for anti-IgE antibodies. The specificity of the basophil activation test with iodinated radiocontrast media was 100% with a sensitivity of 94.1%. Most patients were able to select a non-sensitizing contrast. Inclusion in the algorithm of spontaneous and anti-IgE antibody-induced activation of basophils and a population of T-lymphocytes type 2 immune response will allow the doctor to carry out a personalized approach to the management of patients with a burdened history.

Adverse reactions to drugs and biologics in patients with clonal mast cell disorders: A Work Group Report of the Mast Cells Disorder Committee, American Academy of Allergy, Asthma & Immunology.

Providers caring for patients with mastocytosis are tasked with the decision to consider therapeutic options. This can come with some trepidation because information available in the public domain lists numerous mast cell (MC) activators based on data that do not discriminate between primates, rodents, and MC lines; do not consider dosage; and do not take into account previous exposure and resultant clinical findings. This being said, there is support in the literature for an enhanced MC response in some patients with mastocytosis and in cases in which there is a greater incidence of adverse reactions associated with certain antigens, such as venoms and drugs. Thus this report provides a comprehensive guide for those providers who must decide on therapeutic options in the management of patients with clonal MC disease.

Intradermal Testing With Radiocontrast Media to Prevent Recurrent Adverse Reactions.

OBJECTIVE. Adverse drug reactions (ADRs) to radiocontrast media are a significant social and economic burden and are difficult to predict. Because some ADRs to radiocontrast media may be immunologically induced, a skin test with diluted 1:10 radiocontrast media has been used to predict ADRs. However, using this test in clinical practice is difficult because of its low sensitivity. SUBJECTS AND METHODS. This study enrolled 36 patients with a history of immediate ADR to radiocontrast media who visited the Allergy and Asthma Clinic of Severance Hospital from 2017 to 2018. Patients underwent intradermal testing (IDT) with five types of diluted (1:10) and undiluted radiocontrast media (iohexol, iobitridol, iopamidol, iopromide, and iodixanol). The IDT result was regarded as positive if at least one radiocontrast medium elicited a positive reaction. Positivity of IDT and sensitivity to the culprit radiocontrast medium were calculated and compared. For subsequent CT examinations with a radiocontrast medium, the contrast agent eliciting a negative skin reaction in IDT was selected, excluding the previous culprit radiocontrast medium. RESULTS. IDT positivity and sensitivity for the culprit radiocontrast medium at 1:10 dilution were 47.2% and 47.2%, respectively, whereas the positivity and sensitivity for the undiluted radiocontrast medium were 86.1% and 75.0%, respectively. The positivity and sensitivity were higher with frequent radiocontrast medium use or with severe reaction. Of 22 patients who underwent another CT examination with the contrast medium selected on the basis of IDT results, 21 (95.5%) did not experience an ADR. CONCLUSION. IDT to prevent ADR should be performed with undiluted radiocontrast medium. Selecting an alternative radiocontrast agent on the basis of IDT results can be clinically useful to prevent recurrent ADRs to radiocontrast media.

Varied incidence of immediate adverse reactions to low-osmolar non-ionic iodide radiocontrast media used in computed tomography.

BACKGROUND: Low-osmolar non-ionic radiocontrast media (RCMs) are commonly used throughout hospitals. However, the incidence of immediate adverse drug reactions (ADRs) to various low-osmolar non-ionic RCMs is not well studied. We compared the incidence of immediate ADRs among different low-osmolar non-ionic RCMs used in computed tomography (CT). METHODS: Severance Hospital has collected data for adverse reactions occurring in-hospital using an internally developed system. Using this data, we reviewed 1969 immediate ADRs from 286 087 RCM-contrasted CT examinations of 142 099 patients and compared the immediate ADRs of iobitridol, iohexol, iopamidol, and iopromide. We analysed the incidence of immediate ADRs to different RCMs, as well as the effect of single or multiple CT examinations per day. RESULTS: Iopromide showed the highest incidence of immediate ADRs (1.03%) and was followed by iopamidol (0.67%), iohexol (0.64%), and iobitridol (0.34%). In cases of anaphylaxis, iopromide also showed the highest incidence (0.041%), followed by iopamidol (0.023%), iohexol (0.018%), and iobitridol (0.012%). Risk of immediate ADR due to multiple CT examinations (1.19%) was significantly higher than the risk due to a single CT examination (0.63%). Risk of anaphylaxis was also higher for multiple CT examinations (0.052%) than for a single CT examination (0.020%). CONCLUSIONS AND CLINICAL RELEVANCE: The incidence of immediate ADRs varied according to the low-osmolar non-ionic RCM used. Iopromide-induced immediate ADRs were more frequent, while iobitridol was associated with fewer immediate ADRs than other RCMs. Multiple CT examinations per day resulted in a higher incidence of immediate ADRs and anaphylaxis than a single CT examination. Clinicians should consider these risk differences of immediate ADRs when prescribing contrasted CT examinations.

MRI-CEST assessment of tumour perfusion using X-ray iodinated agents: comparison with a conventional Gd-based agent.

OBJECTIVES: X-ray iodinated contrast media have been shown to generate contrast in MR images when used with the chemical exchange saturation transfer (CEST) approach. The aim of this study is to compare contrast enhancement (CE) capabilities and perfusion estimates between radiographic molecules and a Gd-based contrast agent in two tumour murine models with different vascularization patterns. METHODS: MRI-CEST and MRI-CE T1w images were acquired in murine TS/A and 4 T1 breast tumours upon sequential i.v. injection of iodinated contrast media (iodixanol, iohexol, and iopamidol) and of gadoteridol. The signal enhancements observed in the two acquisition modalities were evaluated using Pearson's correlation, and the correspondence in the spatial distribution was assessed by a voxelwise comparison. RESULTS: A significant, positive correlation was observed between iodinated contrast media and gadoteridol for tumour contrast enhancement and perfusion values for both tumour models (r = 0.51-0.62). High spatial correlations were observed in perfusion maps between iodinated molecules and gadoteridol (r = 0.68-0.86). Tumour parametric maps derived by iodinated contrast media and gadoteridol showed high spatial similarities. CONCLUSIONS: A good to strong spatial correlation between tumour perfusion parameters derived from MRI-CEST and MRI-CE modalities indicates that the two procedures provide similar information. KEY POINTS: • Gd-based agents are the standard of reference for contrast-enhanced MRI. • Iodinated contrast media provides MRI-CEST contrast enhancement in animal tumour models. • Contrast enhancements were positively correlated between iodinated agents and gadoteridol. • Tumour perfusion map showed similar spatial distribution between iodinated agents and gadoteridol. • MRI-CEST with iodinated agents provide similar information to gadoteridol.

[Choosing wisely recommendations in nephrology]. / Klug-entscheiden-Empfehlungen in der Nephrologie.

The German Society of Internal Medicine ("Deutsche Gesellschaft für Innere Medizin", DGIM) founded the Choosing wisely initiative in order to address diagnostic and therapeutic procedures that are frequently inappropriately applied, whether this be in terms of over-, under-, or misuse of health services. The German Society of Nephrology ("Deutsche Gesellschaft für Nephrologie," DGfN) strongly supports the initiative and has contributed five positive and five negative recommendations. These ten recommendations are discussed in the current publication. The positive recommendations reflect the importance of early recognition of renal disease via simple blood and urine tests, the use of radiocontrast media in cases of impaired renal function, as well as the problems associated with low vaccination rates. Three of the negative recommendations are focused on hydration and diuretics. The remaining two negative recommendations concern angioplasty in cases of renal artery stenosis and the unconsidered use of nonsteroidal anti-inflammatory drugs.

Should patients with risk factors be tested for hypersensitivity to contrast media: a prospective study.

BACKGROUND: Previous hypersensitivity reactions to contrast media (CM), atopy, atopic disease, drug allergy, and age (20-29 or >55) are risk factors for CM hypersensitivity reactions. Our aim was to evaluate whether these risk factors should prompt skin testing for diagnosing CM allergy. METHODS: The study was conducted among patients referred for allergy testing with CM. Skin tests were performed with non ionic or gadolinium CM, recommended by a radiologist. After completion of tests patients were telephonically queried on their symptoms of reactions. RESULTS: 151 risk patients (53 men, 98 women; mean age 55.2) were included in the study. Only 13 (9 %) had a history of hypersensitivity reaction to CM. Compared with the other patients, atopy was significantly more common in patients with a history of CM hypersensitivity reactions. Female gender and mean age were also higher, but not significant. All of the tests with CMs were negative. Only one patient reported urticaria within 1-2 min after administration of CM (telephonically). CONCLUSIONS: Atopy can increase the risk of CM allergy. However, skin tests with CMs may be inefficient, unnecessary, and time-consuming, except in cases with a history of CM allergy. Premedication protocols appear to be beneficial in patients with a history of CM allergy and cannot be recommended for patients with well-controlled asthma, rhinitis, atopic dermatitis or history of drug allergy.

Circulating tumour necrosis factor receptors 1 and 2 predict contrast-induced nephropathy and progressive renal dysfunction: a prospective cohort study.

AIM: Contrast-induced nephropathy (CIN) is an important cause of hospital-acquired acute kidney injury. An accurate understanding of the pathogenesis of CIN is crucial. The aim of this study was to evaluate the clinical role of circulating tumour necrosis factor receptors (cTNFRs) in CIN. METHODS: From May 2013 to February 2014, 262 patients who underwent coronary angiography and/or percutaneous coronary intervention at Seoul National University Boramae Medical Center were enrolled. CIN was defined as either an increase in serum creatinine ≥ 22.1 µmol/L or ≥ 25% within 48 h after the procedure. RESULTS: Diabetes and chronic kidney disease accounted for 27.5% and 17.6% of the patients, respectively, and the mean age was 65 years. All patients received fluid therapy, and 36.3% underwent percutaneous coronary intervention. A total of 4.2% of the patients developed CIN; younger age, underlying diseases (e.g., stroke and chronic kidney disease), the use of N-acetylcysteine, and elevated concentrations of ln(cTNFRs) were associated with development of CIN. Increased values of ln(cTNFR1) (OR 6.32, 95% CI 2.46-16.28, P < 0.001) and ln(cTNFR2) (OR 3.24, 95% CI 1.26-8.31, P = 0.015) were significantly associated with CIN after adjusting for other risk factors, including baseline renal function. Moreover, an increase of cTNFRs levels was independently correlated with the deterioration of renal function. CONCLUSION: Markedly elevated concentrations of circulating TNFRs were correlated with the occurrence of CIN and significantly associated with prolonged renal dysfunction regardless of the development of CIN.

Differential activation of signaling pathways by low-osmolar and iso-osmolar radiocontrast agents in human renal tubular cells.

Radiocontrast media (RCM)-induced nephrotoxicity (CIN) is a major clinical problem accounting for 12% of all hospital-acquired cases of acute kidney injury (AKI). The pathophysiology of AKI due to RCM is not well understood, but direct toxic effects on renal cells have been postulated as contributing to CIN. It is believed that iso-osmolar RCM (IOCM) are less nephrotoxic than low-osmolar RCM (LOCM) but clinical data have been controversial. We have investigated the intracellular signaling pathways that may be affected by the LOCM iomeprol (IOM) and the IOCM iodixanol (IOD). Both IOM and IOD caused a dramatic decrease in phosphorylation of the kinase Akt at Ser473 and Thr308 in human renal tubular (HK-2) cells, with IOM having a greater effect; IOM also caused a greater decrease in cell viability. IOM also had a greater effect on phosphorylation of p38 MAP kinases, JNKs, and NF-kB (Ser276), and caused a marked decrease in the phosphorylation of forkhead box O3a (FOXO3a) and signal transducer and activator of transcription 3 (STAT3). However, IOD caused a greater decrease in the phosphorylation of mTOR (Ser2448) and phospho-ERK 1/2 while both RCM caused a similar decrease in the phosphorylation of phospho-p70S6 kinase (Ser371). In vivo studies showed that both IOM and IOD caused a significant decrease in both pAkt (Ser473) and pERK 1/2 in rat kidneys. Our study gives an insight into the possible mechanism of toxicity of RCM via their action on intracellular signaling pathways and may help in developing pharmacological interventions for their side-effects.

Diagnosis of immediate hypersensitivity reactions to radiocontrast media.

BACKGROUND: No consensus exists on the diagnostic approach for immediate hypersensitivity reactions (IHR) to radiocontrast media (RCM). We analyzed the diagnostic value of a skin test (ST), drug provocation test (DPT) and basophil activation test (BAT) in patients with symptoms compatible with IHR to RCM. METHODS: Ninety patients with symptoms suggestive of IHR to RCM were evaluated. ST with a panel of RCM was performed, and if negative, DPT was carried out with the culprit RCM. If ST or DPT were positive, tolerance was assessed with an alternative RCM and BAT was carried out with the same panel used for ST. RESULTS: Eight (8.9%) cases were confirmed as having IHR, 5 (62.5%) by ST and 3 (37.5%) by DPT. Five from those confirmed as IHR (62.5%) had a positive BAT. CONCLUSIONS: Hypersensitivity to RCM was confirmed in 9%, by ST or DPT. BAT proved a valuable method for diagnosis.

Effects of ebselen on radiocontrast media-induced hepatotoxicity in rats.

Oxidative stress is accepted as a potential responsible mechanism in the pathogenesis of radiocontrast media (RCM)-induced hepatotoxicity. Therefore, we aimed to investigate the protective effects of ebselen against RCM-induced hepatotoxicity by measuring tissue oxidant/antioxidant parameters and histological changes in rats. Wistar albino rats were randomly separated into four groups consisting of eight rats per group. Normal saline was given to the rats in control group (group 1). RCM was given to the rats in group 2, and both RCM and ebselen were given to the rats in group 3. Only ebselen was given to the rats in group 4. Liver sections of the killed animals were analyzed to measure the levels of malondialdehyde (MDA) and activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px), as well as histopathological changes. In RCM group, SOD and CAT levels were found increased. In RCM-ebselen group, MDA, SOD and CAT levels were found decreased. In RCM-ebselen group, however, GSH-Px activities of liver tissue increased. All these results indicated that ebselen produced a protective mechanism against RCM-induced hepatotoxicity and took part in oxidative stress.

Anaphylaxis Following Contrast-Enhanced CT with Iodixanol: A Case Report and Literature Review.

Background: Iodixanol-induced anaphylactic reaction is a well-known adverse event of contrast agents, which are generally well-tolerated and reversible. Serious and fatal reactions such as anaphylactic shock after computed tomography (CT) enhancement have been described. However, there is no data on these events in the literature. Objective: This report describes a case of a serious anaphylactic reaction, possibly related to iodixanol and provides an overview of case reports. Case Summary: A 47-year-old women who experienced persistent abdominal pain for more than one month, was proposed of hiatal hernia with CT images taken two weeks previously and was admitted to the gastrointestinal surgery department. The patient underwent contrast-enhanced abdominal CT for the evaluation of multiple intraperitoneal hemodynamic features. A few minutes after abdominal enhanced CT scan, the patient was pale, sweating, had muscle tension and trembling, even coma and profound hypotension with 90/43 mm Hg. Immediately she was supported with oxygen inhalation, was treated with adrenaline subcutaneously, dexamethasone intravenously, and rapid intravenous drip of compound sodium chloride. Ten minutes later, the patient was in respiratory and cardiac arrest and the pupils were dilated. CPR and intermittant static push of 1 mg adrenaline were immediately carried. After endotracheal intubation, the patient's spontaneous heart rate and pupils recovered, and her blood pressure recovered to 105/53 mm Hg. It was suggested that the patient was suffering from iodixanol-induced anaphylactic shock and nephropathy, and she was transferred to the intensive care unit. Despite immediate treatment, the patient died. Conclusion: A 47-year-old female patient with no history of allergies developed severe fatal anaphylactic shock after receiving iodixanol. Although contrast agents induced anaphylactoid/anaphylactic reactions do not often occur, clinicians should be conscious of the potentially serious anaphylactic reaction, which could lead to a life-threatening or fatal event.

Successful Desensitization to the Radiocontrast Material Iohexol (Omnipaque™).

Adverse reactions to radiocontrast media (RCM) are rare and occur predominantly in association with intravenous administration but may also occur with intra-arterial and nonvascular injections (e.g., retrograde pyelography, intra-articular injections) of RCM. This article reports the case of a 52-year-old lady who was known to have amyloidosis secondary to rheumatoid arthritis and was on regular renal replacement therapy. She was under follow-up for regular angioplasties to manage the central vein stenosis that was affecting her right brachiocephalic arteriovenous fistula (AVF) and was referred to our Immunology service when she developed an allergic reaction after her AVF angioplasty (central venoplasty). Despite being dialysed immediately post-angioplasty, she complained of skin rash and itching with hoarseness of voice that developed almost six to eight hours post-angioplasty. We decided to arrange the iodinated non-ionic iso-osmolar contrast agent iodixanol (Visipaque™) for her instead, as it is known to be better tolerated in patients with reactions to Omnipaque™ due to its lower osmolarity as compared to Omnipaque™. However, since it was the first time to request this contrast in our hospital, it was not possible due to logistical reasons. It was necessary that our patient continued to undergo angioplasty every three months, however, she was developing more severe and earlier symptoms with each subsequent exposure to the radiocontrast medium. After her latest reaction of generalized itching and angioedema with shortness of breath during the procedure despite premedication, it was decided for her to undergo desensitization to Omnipaque™. In the absence of a published protocol for this, we used a protocol used for desensitization to Visipaque™. She showed an excellent response and completed her remaining angioplasties until Visipaque™ became available. Hence, desensitization to Omnipaque™ using the published protocol to Visipaque™ is likely to help patients allergic to Omnipaque™ or where Visipaque™ is not available or non-affordable in low/middle-income countries.

Hypersensitivity reactions to iodinated radiocontrast media: Cluster analysis reveals distinct clinical phenotypes.

Background: Drug hypersensitivity reaction (DHR) to iodinated radiocontrast media (iRCM) is reported in 1%-3% of injections. Risk assessment of patients with suspicion of DHR to iRCM relies solely on clinical phenotyping and drug allergy workup. Using a novel unsupervised TwoStep cluster analysis, we aimed to identify prototypic patterns within a large cohort of patients evaluated for a potential iRCM DHR. Methods: A retrospective study was conducted using data from the Drug Allergy and Hypersensitivity Database of the Allergy Unit, University Hospital of Montpellier, Montpellier, France. All referred patients during February 2001 to December 2019 with suspicion of iRCM DHR with either confirmed positive or confirmed negative skin tests were included in the analysis. Results: A total of 1439 patients were evaluated. The chronology of the index reaction was immediate and nonimmediate in 77.1% and 22.4%, respectively. Cluster analysis categorized the total study population in 5 clusters. Cluster 1 compiled all nonimmediate and cluster 2-5 almost all immediate reactors. Cluster 1 and 2 had recent reactions (<1 y) with mostly known iRCMs and the highest iRCM allergy prevalence (16-17%). In the other clusters, more remote reactions, unknown iRCMs and a lower allergy prevalence (3-8%) was observed. Chronology and semiology of the index reaction were the factors most strongly differentiated among clusters. History of anaphylactic shock and chronology of immediate hypersensitivity reactions were shown to be independent predictors of allergy with adjusted OR (aOR) of 4.68 (95%CI: 3.01-7.27, p < 0.001) and 2.51 (95%CI: 1.67-3.78, p < 0.001), respectively. Conclusions: Unsupervised cluster analysis identified 5 prototypic patterns within patients with a suspected DHR to iRCMs. Well-phenotyped patients cluster together in 2 groups in which the prevalence of allergy is approximately 1 in 6. However, this value decreases for patients with reactions dating back to more than a decade.

Evaluating pharmacists' knowledge, attitude, and practices toward amiodarone cross-reactivity with iodine: a cross-sectional pilot study.

Introduction: Iodine is a vital mineral of the human body that acts by maintaining the health of the thyroid gland. Research has shown that iodine-rich food allergy (i.e., seafood allergy) is not caused by iodine itself; instead, it is caused by other proteins including tropomyosin and parvalbumin in shellfish and fish, respectively. Amiodarone is a commonly used antiarrhythmic agent containing a significant amount of iodine. Objective: This study's objective was to assess pharmacists' knowledge, attitude, and practices toward the misconception of iodine allergy and the cross-reactivity with amiodarone. Methods: In February 2020, a cross-sectional study was conducted by sending out an online survey to three pharmaceutical organizations (Saudi Pharmaceutical Society, Kuwait Pharmaceutical Association, and Oman Pharmaceutical Society). Additionally, an electronic questionnaire was administered to pharmacists attending the Dubai International Pharmaceuticals and Technologies Conference and Exhibition 2020 (DUPHAT). Chi-square or Fisher's exact test, when appropriate, were used to compare categorical variables. The statistical analyses were carried out using SPSS software. Results: Data were collected from 66 respondents. However, only 61 (92.4%) were included in the final analysis following the exclusion of incomplete responses. The mean age of participants was 35 ± 8.48 years. The majority of participants did not have the Board of Pharmacy Specialties Certification (54.1%). Moreover, (41%) of participants licensed as pharmacists with more than 10 years of initial pharmacy licensure. Forty-three (70.5%) of participants had the misconception that iodine allergy should be considered before amiodarone administration, 20/32 (62.5%) of whom considered iodine allergy alone thought that premedication with corticosteroids and/or antihistamines is necessary. Concerning iodine allergy and amiodarone use, there was no significant difference in knowledge between the pharmacists who have board certification and those who did not. Conclusion: Pharmacists' misconception concerning iodine allergy and cross-reactivity with amiodarone was evident. Implementation of educational programs targeting pharmacists is necessary to correct these misconceptions.

Allergy to Radiocontrast Dye.

Radiocontrast media (RCM) are common elicitors of immediate and nonimmediate hypersensitivity reactions, manifesting predominantly as urticaria/anaphylaxis or exanthems, respectively. In the minority of patients with immediate hypersensitivity reactions to RCM allergy is demonstrated by positive skin tests. However, data show that assessment by an allergist/immunologist is beneficial for managing patients with previous immediate and nonimmediate hypersensitivity reactions. For future RCM-enhanced examinations in patients with previous reactions, structurally different, skin test-negative preparations should be applied. The efficacy of this strategy is confirmed by drug provocation tests or exposures confirming or excluding RCM hypersensitivity and demonstrating tolerability of alternative RCM.