Transient pulmonary and gastric bleeding after iopamidol administration in a patient with marginal zone lymphoma: a case report.

BACKGROUND: Iopamidol is a non-ionic, water-soluble iodine contrast agent that is considered safe for intravenous or intra-arterial administration and is widely used both in the general population and in patients undergoing oncological treatment. While adverse reactions to iopamidol have been documented, to date, no pulmonary and gastric hemorrhages induced by iopamidol have been reported in oncology patients. We report the first case of this complication. CASE PRESENTATION: We report the case of a 60-year-old woman with marginal zone lymphoma who was receiving antineoplastic therapy. As part of the investigation for the condition, she underwent chest enhancement CT with iopamidol. Shortly thereafter(within five minutes), she experienced hemoptysis and hematemesis. She was intubated and admitted to the intensive care unit. Pre- and post-contrast images demonstrated the course of the hemorrhage. Flexible bronchoscopy and gastroscopy on the following day showed no active bleeding, and the patient recovered completely after antiallergy treatment. We speculate that contrast-induced hypersensitivity was the most likely cause of the transient pulmonary and gastric bleeding. CONCLUSION: Although rare, the complications of iopamidol, which may cause allergic reactions in the lungs and stomach, should be considered.

Clinical features and risk factors of iodinated contrast media (ICM)-induced anaphylaxis.

PURPOSE: To evaluate the clinical features and risk factors of iodinated contrast media (ICM)-induced anaphylaxis. METHODS: This retrospective study included all patients undergoing contrast-enhanced computed tomography (CT) with intravenous ICM administration (iopamidol, iohexol, iomeprol, iopromide, ioversol) at our hospital between April 2016 and September 2021. Medical records of patients who experienced anaphylaxis were reviewed, and the multivariable regression model using generalized estimating equations was employed to eliminate the effect of intrapatient correlation. RESULTS: Of the 76,194 ICM administrations (44,099 men [58 %] and 32,095 women; age, median, 68 years) to 27, 696 patients, anaphylaxis occurred in 45 cases in 45 different patients (0.06 % of administration and 0.16 % of patients), all with onset within 30 min after administration. Thirty-one (69 %) had no risk factors for ADRs, including 14 (31 %) who had previously used the same ICM that caused anaphylaxis. Thirty-one patients (69 %) had a history of ICM use without any ADRs. Four patients (8.9 %) received oral steroid premedication. The only factor associated with anaphylaxis was the type of ICM, with an odds ratio (OR) of 6.8 (p < 0.001) for iomeprol with iopamidol as a reference. No significant differences in OR of anaphylaxis were found for patients' age, sex, or premedication. CONCLUSION: The overall incidence of anaphylaxis due to ICM was very low. More than half of the cases had no risk factors for ADRs and had no ADRs on past ICM administration, although the ICM type was associated with a higher OR.

Contrast Agent Selection to Prevent Recurrent Severe Hypersensitivity Reaction to Iodinated Contrast Media Based on Nationwide Database.

OBJECTIVE: To investigate the incidence of severe iodinated contrast media (ICM)-related hypersensitivity reaction (HSR) and to find the optimal alternative ICM to reduce the risk of severe HSR recurrence. METHODS: We retrospectively reviewed 23,383,183 cases of ICM administration between January 2015 and December 2019 from the nationwide health insurance database. We classified ICMs based on generic profiles and the presence of N-(2,3-dihydroxypropyl) carbamoyl side chains. The incidence of severe and recurrent severe HSRs was calculated, and χ2 tests were performed to compare the prevalence of severe HSR according to ICM groups. In addition, logistic regression analyses were used to assess differences between ICM groups. RESULTS: The incidence of severe HSRs was 1.92% (450,067 of 23,282,183). Among 1,875,245 individuals who received ICM twice on different days, severe HSR occurred in 40,850 individuals, and severe HSR recurred in 3319 individuals (8.12%). The risk of recurrence significantly decreased when the ICM changed (9.24% vs 7.08%, P < 0.001), especially when the ICM changed to one with a different side chain (6.74%, P < 0.001). In addition, compared with the reuse of the culprit agent, using combinations of iobitridol/iohexol (odds ratio [OR], 0.696; P = 0.04), iohexol/iopamidol (OR, 0.757; P = 0.007), iopamidol/iohexol (OR, 0.447; P < 0.001), and ioversol/iohexol (OR, 0.683; P = 0.04) reduced the risk of recurrence of severe HSR. CONCLUSIONS: Changing the culprit ICM to that with a different side chain can reduce severe HSR recurrence. The optimal choice of an alternative ICM depends on the causative agent.

Differences in the Recurrence Rate of Immediate Adverse Drug Reactions According to the Components of Alternative Contrast Media: Analysis of Repetitive Computed Tomography Cases in a Single Tertiary Hospital.

INTRODUCTION: The recurrence rates of immediate adverse drug reactions (ADRs) to the alternative radiocontrast media (RCM) are not well known. Previous studies suggest selection of alternative RCM considering carbamoyl side chains; however, its usefulness for preventing the recurrence of ADRs has not been clearly verified. OBJECTIVE: The aim of this study was to verify the recurrence rate of immediate ADRs according to the alternative RCM. METHOD: This retrospective study analyzed 6420 contrast-enhanced computed tomography (CT) cases of 2009 patients registered in the ADR system from 861,664 CT cases in a single tertiary hospital between 2015 and 2020. Iohexol, iopromide, iobitridol, and iopamidol were used for CT. According to the carbamoyl side chains present, iohexol belongs to group 1, iopromide belongs to groups 1 and 2, iobitridol belongs to group 2, and iopamidol belongs to group 3. RESULTS: Replacing iobitridol with iopamidol (odds ratio [OR] 2.595, 95% confidence interval [CI] 1.48-4.550) or iopromide (OR 3.354, 95% CI 1.420-7.926) as the subsequent RCM was associated with increased recurrence, while replacing iopamidol with iobitridol (OR 0.506, 95% CI 0.282-0.908) and iopromide with iohexol (OR 0.355, 95% CI 0.177-0.711) was associated with decreased recurrence. Other changes did not influence the recurrence of ADRs. CONCLUSIONS: The recurrence of immediate ADRs increased in certain RCM combinations of preceding and subsequent CT scans, and the RCMs did not show cross-reactivity. Therefore, the clinical benefit of the alternative RCM considering cross-reactivity is limited. This result suggests that the side chains of RCM do not have an important role in the recurrence of immediate ADRs.

Non-immediate hypersensitivity reactions to iomeprol: Diagnostic value of skin tests and cross-reactivity with other iodinated contrast media.

BACKGROUND: Iodinated contrast media produce non-immediate hypersensitivity reactions (NIHR). The goal of this prospective study was to determine the utility of skin tests and the subsequent tolerance to negative skin-tested iodinated contrasts in patients with NIHR caused by iomeprol. METHODS: Prick and intradermal tests with iomeprol, iopamidol, iopromide, and iobitridol were performed in all patients. IV challenge with the causative contrast (iomeprol in 90%) was made if skin tests were negative. In case of a positive skin test with the causal contrast, or a positive challenge test with it, IV challenge test with an alternative, negative skin-tested contrast was performed in all patients. RESULTS: Skin tests were positive in 47.6% (20/42) of patients with NIHR induced by iomeprol. Of the 66 challenge tests performed with negative skin-tested iodinated contrasts, tolerance was confirmed in 35 (53%): 32 iomeron, 2 iobitridol, 1 iopamidol. Cross-reactivity between iomeprol and iopamidol was 22% (4/20 in patients with positive skin tests and 5/21 in patients with negative skin tests). CONCLUSIONS: Sensitivity of the skin tests was less than 50% NIHRs due to iomeprol, while the negative predictive value of skin tests in patients who tolerated challenges with alternative contrasts (mainly iopamidol) was 53% (35 tolerated out of 66 performed). The cross-reactivity between iomeprol and iopamidol is high.

Clinical and Imaging Features of Contrast-Induced Neurotoxicity After Neurointerventional Surgery.

BACKGROUND: Contrast-induced neurotoxicity (CIN) is an infrequent complication of endovascular procedures, and its understanding remains poor. We aimed to study and characterize the clinical and imaging features of a case series of CIN after neurointerventional surgery. METHODS: We reviewed all neuroendovascular consecutive procedures from September 2014 to November 2018. CIN was defined as new onset of neurologic deficits that occurred postoperatively after excluding other conditions. All demographic, clinical, procedural, and radiologic data were retrospectively analyzed and collected. RESULTS: Eleven cases of CIN in 1587 patients were identified out of 2510 procedures. The median age was 76 years (interquartile range [IQR], 65-81). The most common comorbidity was hypertension (82%). Median procedure time was 100 minutes (IQR, 80-130.5 minutes). All patients showed wide variability in intraprocedural blood pressure (BP) recordings with fluctuations from the baseline BP. Systolic BP ranged from 83 mm Hg below the patient baseline to 80 mm Hg above baseline. The median symptom onset was 4 hours (IQR, 0.8-9.5 hours). The CIN signs and symptoms presented gradually, initially with encephalopathy and later with focal signs. All patients had an initial computed tomography scan, which showed ipsilateral cerebral edema in 82% of patients. Two had contrast enhancement. Complete resolution of CIN symptoms was obtained in a median time of 3 days (IQR, 2.5-3 days). CONCLUSIONS: CIN should be considered in the context of the progressive onset of neurologic deficits after neuroendovascular procedures. A distinct imaging pattern of ipsilateral hemisphere edema in the absence of ischemia is usually identified. Variability in procedural BP might be a predisposing factor.

Case 277: Iodide Mumps.

HistoryA 64-year-old woman with a medical history notable for hypertension, hyperlipidemia, cigarette smoking, type II diabetes mellitus, and end-stage renal disease requiring dialysis presented to the emergency department with tender swelling of her neck, which began 2 days prior to presentation.Four days prior to presentation, her dialysis catheter (Palindrome; Medtronic, Mannsfield, Mass) was partially pulled during dialysis. The next day, she underwent successful percutaneous transluminal balloon angioplasty with an iodinated contrast medium (20 mL Iopamiro; Bracco, Milano, Italy) via the existing right subclavian vein dialysis catheter because of stenosis in the superior vena cava. In addition, exchange of the dialysis catheter via guidewire was performed, without any reported complications. The following day, the patient underwent an uneventful scheduled hemodialysis treatment via the newly exchanged catheter.The patient denied trauma prior to the swelling. She had no known allergies, and prior exposure to iodinated contrast media on two occasions (2 months and 5 years before this presentation) was uneventful.Upon examination, the patient was fully alert and calm without any signs of distress and had bilateral submandibular firm nonpulsatile tender masses, each estimated at 3-4 cm in diameter.Because of a recent major vascular intervention, CT angiography of the neck was urgently performed.

Effect of Different Iodine Concentrations on Patient-Reported Discomfort in Contrast-Enhanced Computed Tomography: A Prospective Comparative Trial.

PURPOSE: Reducing contrast media injection speed while maintaining iodine flux is a promising workaround to lower or avoid contrast media-related discomfort during CT examinations. This approach demands contrast media with a higher concentration to guarantee excellent image quality. It remains unclear whether these concentration changes affect the patient's experience. Thus, the aim of this study was to evaluate the influence of different concentrations of intravenous iodinated contrast media on patient discomfort during and after contrast media delivery. MATERIALS AND METHODS: Patients were randomized to receive either Iomeprol 400 mg/ml (group A) or 300 mg/ml (group B) during routinely scheduled CT examinations at our department. The iodine delivery rate and injection time were kept constant in both groups. After examination, study subjects completed a digital questionnaire on different CM-related sensation items using digital visual analogue scales. RESULTS: 253 consecutive patients were enrolled in a 6-month period. Most of the patients reported heat sensation in both groups (mean VAS: 5.3 mm in group A vs. 5.0 mm in group B, p = 0.5). Taste sensation also did not differ significantly between both groups (2.4 mm vs. 2.0 mm, p = 0.08). Pain sensation was reported to be significantly lower in group B patients (1.3 mm vs. 1.0 mm, p = 0.005), even though pain sensation in general was reported on a very low level. Other injection-related sensations were rarely reported. CONCLUSION: Patient-reported discomfort during intravenous injection of high-concentration contrast media (400 mg/ml) was low and only marginally different when compared to the injection of contrast media with a lower concentration. The injection of highly concentrated contrast media showed comparable overall patient acceptance, allowing a reduction of the injection speed and volume during examinations. KEY POINTS: · Patient-reported, contrast-related discomfort was very low in this study.. · High-concentration contrast media (HCCM) showed comparable overall patient acceptance.. · HCCM allow a reduction of injection speeds while keeping iodine flux constant.. CITATION FORMAT: · Vahldiek JL, Schaafs LA, Niehues BK et al. Effect of Different Iodine Concentrations on Patient-Reported Discomfort in Contrast-Enhanced Computed Tomography: A Prospective Comparative Trial. Fortschr Röntgenstr 2020; 192: 945 - 951.

Subclinical Contrast-Induced Acute Kidney Injury in Patients Undergoing Cerebral Computed Tomography.

INTRODUCTION: The nephrotoxicity of modern contrast media remains controversial. Novel biomarkers of kidney damage may help in identifying a subclinical structural renal injury not revealed by widely used markers of kidney function. OBJECTIVE: The aim of this study was to investigate clinical (contrast-induced acute kidney injury [CI-AKI]) and subclinical CI-AKI (SCI-AKI) after intra-arterial administration of Iodixanol and Iopamidol in patients with an estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2. METHODS: This is a prospective observational monocentric study. Urinary sample was collected at 4-8 h after contrast medium exposure to measure neutrophil gelatinase associated lipocalin (NGAL) and the product tissue inhibitor of metalloproteinase-2 and insulin-like growth factor-binding protein 7 ([TIMP-2] × [IGFBP7]), while blood samples were collected at 24 and 48 h after exposure to measure serum creatinine. RESULTS: One hundred patients were enrolled, of whom 53 were exposed to Iodixanol and 47 to Iopamidol. Patients in Iodixanol and Iopamidol groups were comparable in terms of demographics, pre-procedural and procedural data. No patient developed CI-AKI according KDIGO criteria, while 13 patients reported SCI-AKI after exposure to iodine-based medium contrast (3 patients in Iodixanol group and 10 patients in Iopamidol group), defined by positive results of NGAL and/or [TIMP-2] × [IGFBP7]. A positive correlation was found between NGAL and [TIMP-2] × [IGFBP7] in the analysed population (Spearman's rho 0.49, p < 0.001). In logistic regression analysis, Iopamidol exposure showed higher risk for SCI-AKI compared to Iodixanol (OR 4.5 [95% CI 1.16-17.52], p = 0.030), even after controlling for eGFR and volume of contrast medium used. CONCLUSIONS: This study showed that intra-arterial modern contrast media administration may have a nephrotoxic effect in a population without pre-existing chronic kidney disease. Further investigations on larger scale are warranted to confirm if Iopamidol exposed patients to increased risk of SCI-AKI compared to Iodixanol.

Ventricular Fibrillation During Optical Coherence Tomography/Optical Frequency Domain Imaging　- A Large Single-Center Experience.

BACKGROUND: The risks of ventricular fibrillation (Vfib) associated with frequency-domain optical coherence tomography (OCT)/optical frequency domain imaging (OFDI) remain undetermined.Methods and Results:We retrospectively studied the occurrence of Vfib during OCT/OFDI for unselected indications. The frequency of Vfib and patient and procedural characteristics were investigated. A total of 4,467 OCT/OFDI pullback examinations were performed in 1,754 patients (median of 2.0 [2.0-3.0] pullbacks for 1.0 [1.0-1.3] vessels). OCT/OFDI was performed during PCI in 899 patients (51.3%). The contrast injection volume per pullback was 14.4 (11.7-17.2) mL with a flow rate of 3.4 (3.2-3.5) mL/s. Vfib occurred in 31 pullbacks (0.69%) in 30 patients (1.7%). No cases of Vfib occurred when using low-molecular-weight dextran. On multivariate analysis, contrast volume was the only independent factor for predicting Vfib (odds ratio, 1.080; 95% confidence interval, 1.008-1.158, P=0.029). The best cutoff value of contrast volume for predicting Vfib was 19.2 mL (area under the curve, 0.713, P<0.001; diagnostic accuracy, 87.1%). CONCLUSIONS: The present large, single-center registry study indicated that Vfib during OCT/OFDI was rare for unselected indications. Contrast injection volume used to displace blood should be limited to avoid Vfib.

Low dose contrast CT for transcatheter aortic valve replacement assessment: Results from the prospective SPECTACULAR study (spectral CT assessment prior to TAVR).

BACKGROUND: Computed tomographic angiography (CTA) based planning for transcatheter aortic valve replacement (TAVR) is essential for reduction of periprocedural complications. Spectral CT based imaging provides several advantages, including better contrast/signal to noise ratio and increased soft tissue contrast, permitting better delineation of contrast filled structures at lower doses of iodinated contrast media. The aim of this prospective study was to assess the initial feasibility of a low dose iodinated contrast protocol, utilizing monoenergetic 40 keV reconstruction, using a dual-layer CT scanner (DLCT) for CTA in patients undergoing TAVR planning. METHODS: 116 consecutive TAVR patients underwent a gated chest and a non-gated CTA of the abdomen and pelvis. 40 keV virtual monoenergetic images (VMI) were reconstructed and compared with conventional polychromatic images (CI). The proximal aorta and access vessels were scored for image quality by independent experienced cardiovascular imagers. RESULTS: Proximal aortic image quality as assessed by signal to noise (SNR) and contrast to noise ratio (CNR), were significantly better with 40 keV VMI relative to CI (SNR 14.65 ±â€¯7.37 vs 44.16 ±â€¯22.39, p < 0.001; CNR 15.84 ±â€¯9.93 vs 59.8 ±â€¯40.83, p < 0.001). Aortic root dimensions were comparable between the two approaches with a bias towards higher measurements at 40 keV (Bland Altman). SNR and CNR in all access vessel segments at 40 keV were substantially better (p < 0.001 for all peripheral access vessel segments) with comparable image quality. CONCLUSION: 40 keV VMI with low dose contrast dose spectral imaging is feasible for comprehensive preprocedural evaluation of access vessels and measurements of aortic root dimensions in patients undergoing TAVR.

A case of contrast-induced encephalopathy.

The differential diagnosis of the patient with encephalopathy is broad and remains a common yet challenging problem for critical care physicians. A case is presented of contrast-induced encephalopathy in an 81-year-old man undergoing a left heart catheterisation after receiving iopamidol, a low-osmolar contrast agent. Immediately after receiving contrast, our patient experienced severe headache, agitation, altered mentation and significant skin hypersensitivity. This rare, acute and reversible neurological disturbance can be associated with administration of intra-arterial, osmotic, iodinated contrast. Although uncommon, it is important to recognise the various presentations, risk factors and treatment of this condition.

Voiding cystography: an unusual route of induced hypothyroidism by iodine overdose in two newborns with chronic kidney disease.

BACKGROUND: Iatrogenic induced hypothyroidism had been described in newborns and more particularly in preterm infants after cutaneous or intravenous exposure to iodine. CASE-DIAGNOSIS : We reported a new risk of iodine intoxication with the cases of two newborns who developed hypothyroidism after intra vesical iodine injection during a cystography, which was performed to confirm antenatal diagnosis of posterior urethral valves (PUV). The newborns both developed transient hypothyroidism due to an iodine overdose. CONCLUSIONS: These two observations suggest that voiding cystourethrography (VCUG) should be carefully considered in newborns with severe uropathy, particularly in the case of renal insufficiency. If indicated, thyroid function should be monitored in the following weeks, and in case of hypothyroidism treatment should be started.

Acute Adverse Reactions to Nonionic Iodinated Contrast Media: A Meta-Analysis.

OBJECTIVES: We aimed to meta-analytically compare the incidence of acute adverse reactions (AARs) to nonionic iodinated contrast media (ICM) according to the type of ICM in patients who underwent radiologic examinations with administration of ICM via intravascular route. MATERIALS AND METHODS: A systematic literature search identified studies evaluating the incidence of AARs to 7 nonionic ICM (iobitridol, iohexol, iomeprol, iopamidol, iopromide, ioversol, and iodixanol) with extractable outcomes. These outcomes were pooled using a random-effects model, and the effect of ICM type on the incidence of overall and severe AARs was evaluated using meta-regression analysis. RESULTS: Thirty studies with 1,360,488 exposures to ICM were included. The pooled incidences of overall and severe AARs to nonionic ICM were 1.03% (95% confidence interval [CI], 0.81%-1.30%; I = 0.99) and 0.0141% (95% CI, 0.0108%-0.0183%; I = 0.56), respectively. Iomeprol had the highest overall AAR incidence (1.74%; 95% CI, 0.79%-3.76%; I = 0.99), followed by iohexol (1.21%; 95% CI, 0.67%-2.17%; I = 0.99), iopamidol (1.10%; 95% CI, 0.60%-2.03%; I = 0.99), ioversol (0.88%; 95% CI, 0.43%-1.83%; I = 0.96), iodixanol (0.85%; 95% CI, 0.36%-1.95%; I = 0.99), iopromide (0.82%; 95% CI, 0.43%-1.55%; I = 0.99), and iobitridol (0.77%; 95% CI, 0.36%-1.62%; I = 0.99). Multivariable meta-regression analysis revealed that study design (P = 0.0014) and premedication (P = 0.0230) were statistically significant determinants affecting the incidence of overall AARs. Iodinated contrast media type did not affect the incidence of overall and severe AARs (P = 0.1453 and 0.4265, each). CONCLUSIONS: The varying pooled incidences of overall and severe AARs to specific types of nonionic ICM do not remain as significant after adjusting confounders. Our results may support nonrestriction of certain types of nonionic ICM in the context of AAR avoidance.

Low incidence of nephrotoxicity following intravenous administration of iodinated contrast media: a prospective study.

OBJECTIVES: To estimate the incidence of contrast-induced acute kidney injury (CI-AKI) after intravenous (iv) iodinated contrast material (ICM) exposure. METHODS: This prospective cohort study included all consecutive patients who underwent radiological investigations using low-osmolar iopamidol 370 mg/ml in a regional hospital over a period of 36 months, without any exclusion criteria. The estimated glomerular filtration rate (eGFR) was evaluated using the MRDR equation before (2-10 days) and after (24-36 h) radiological investigations. CI-AKI was defined as a ≥ 25% decrease in eGFR from baseline. CI-AKI incidence was estimated using a binomial distribution. The association between CI-AKI and demographic and clinical characteristics was modeled using logistic regression. RESULTS: The study included 1541 patients with a median age of 68 (1st-3rd quartiles 58-76) years with various comorbidities, 30% of whom had pre-existing CKD. Patients affected by stage III or IV chronic kidney disease (CKD) received an infusion of 0.9% normal saline (1.0-1.5 ml/kg/h) before and after iso-osmolar iodixanol administration. CI-AKI was observed in 33 patients (2.1%, 95% CI 1.5-3.0). The logistic regression analysis showed that antibiotic and statin therapies were significantly associated with CI-AKI. The probability of developing CI-AKI decreased by 80% in patients taking statins (OR = 0.20, 95% CI 0.03; 0.68) and increased approximately three times in patients with antibiotic therapy compared with those who did not take statins and antibiotics (OR = 2.92, 95% CI 1.21; 6.36). CONCLUSIONS: Our data suggest that low-osmolar iopamidol carries a low incidence of nephrotoxicity, even in subjects with various comorbid conditions or reduced renal function. KEY POINTS: • IV administration of ICM carries a low incidence of nephrotoxicity, which was transient in observed patients. • Statin therapy is negatively associated with AKI in patients exposed to ICM. • Pre-existing impairment of renal function is not associated with AKI in patients exposed to ICM.

Radiocontrast Media Hypersensitivity: Skin Testing Differentiates Allergy From Nonallergic Reactions and Identifies a Safe Alternative as Proven by Intravenous Provocation.

BACKGROUND: Hypersensitivity reactions occurring within minutes after intravascular injection of iodinated radiocontrast media (RCM) are not rare and have been previously considered to be nonallergic. However, in the last decades, evidence is increasing that genuine RCM allergy may present as either full-blown anaphylaxis or delayed exanthematous skin reaction. OBJECTIVES: We aimed to assess whether allergy diagnostics including skin and provocation testing can differentiate between nonallergic and allergic RCM hypersensitivity by identifying the causative RCM as well as tolerated alternative RCM. METHODS: We retrospectively evaluated clinical and diagnostic data from 45 consecutive patients with RCM hypersensitivity. RESULTS: Immediate nonallergic RCM hypersensitivity was diagnosed in 21 patients, immediate-type RCM allergy in 11, delayed-type RCM allergy in 11, and delayed-type iodine allergy in 2. All patients with immediate-type RCM allergy had a history of moderate to severe anaphylaxis. Eleven of 13 patients with delayed-type allergic reactions including the 2 cases of iodine allergy suffered from maculopapular exanthem developing several hours to days after exposure, 1 was a systemic hypersensitivity syndrome, and 1 a fixed drug eruption. Of 18 RCM-allergic patients tested, all tolerated an alternative RCM in the intravenous provocation. CONCLUSIONS: The diagnostic sensitivity of intradermal RCM testing to identify allergic patients is high in both immediate-type and delayed-type RCM allergy. Intravenous provocation with a skin test-negative RCM is safe and enables identification of a tolerated alternative RCM. Additional skin testing of iodine solution is required to identify patients with iodine allergy.