Allergic-like Reactions Research Articles

Allergic-like Hypersensitivity Reactions to Gadolinium-based Contrast Agents: An 8-year Cohort Study of 154 539 Patients.

Background With the widespread use of gadolinium-based contrast agents (GBCAs), the incidence of allergic-like hypersensitivity reactions (HSRs) to GBCAs is increasing. Research on the incidence and risk factors for HSRs to GBCAs is needed for their safe use. Purpose To determine the incidence of acute and delayed reactions to GBCAs and to discuss the risk factors and strategies for the prevention of HSRs to GBCAs. Materials and Methods All cases of HSRs to contrast media that occurred at the Seoul National University Hospital from July 1, 2012, to June 30, 2020, were assessed. Information including age, sex, GBCA type, onset, and severity of HSRs was retrospectively analyzed. Results Among the 331070 cases of GBCA exposure in 154539 patients, 1304 cases of HSRs (0.4%) were reported. Acute HSRs accounted for 1178 cases (0.4%), while 126 cases (0.04%) were delayed HSRs. While both premedication (odds ratio [OR] = 0.7, P = .041) and changing the type of GBCA (OR = 0.2, P < .001) showed preventative effects in patients with a history of acute HSRs, only premedication (OR = 0.2, P = .016) significantly reduced the incidence of HSRs in patients with a history of delayed reactions. The risk of an HSR to GBCA was higher in those with a history of an HSR to iodinated contrast media (OR = 4.6, P < .001). Conclusion The rate of hypersensitivity reactions (HSRs) to gadolinium-based contrast agents (GBCAs) was 0.4%. The absence of premedication, repeated exposures to the culprit GBCA, and a history of HSRs to iodinated contrast media and GBCAs were risk factors for HSRs to GBCAs. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Kallmes and McDonald in this issue.

Hypersensitivity to Pegylated E.coli asparaginase as first-line treatment in contemporary paediatric acute lymphoblastic leukaemia protocols: a meta-analysis of the Ponte di Legno Toxicity working group

BackgroundHypersensitivity reactions to asparaginase challenge its use and occur frequently (30–75%) after native Escherichia Coli (E.coli) asparaginase. Comparison of incidence of allergic reactions to pegylated E.coli asparaginase (PEGasparaginase) across contemporary paediatric acute lymphoblastic leukaemia (ALL) protocols is lacking. Method and patientsQuestionnaires were sent to all members of the international ALL Ponte di Legno Toxicity Working Group. Meta-analyses were conducted to estimate the incidence of three types of hypersensitivity (allergy, allergic-like reaction and silent inactivation). Information on protocol level regarding PEGasparaginase dosing regimen, administration route and use of therapeutic drug monitoring was collected for risk analysis. ResultsNewly diagnosed patients with ALL (n = 5880), aged 1–24 years old, were enrolled in seven different upfront ALL protocols using PEGasparaginase as first-line treatment. The incidence of allergic reactions (sum of allergies and allergic-like reactions) [95% confidence interval] was 2% [1%; 3%] during induction and 8% [5%; 11%] during postinduction. Route of administration, number of doses, dosage and number of PEGasparaginase-free weeks did not significantly influence risk of hypersensitivity. Multivariate meta-regression analysis suggests that initiation of PEGasparaginase in postinduction and higher number of PEGasparaginase-free intervals increased the risk for allergic reactions. 9–16% and 23–29% of all hypersensitivities were allergic-like reactions and silent inactivation, respectively. ConclusionThe incidence of allergic reactions is lower in protocols using PEGasparaginase as first-line treatment compared with that reported for E.coli asparaginase or PEGasparaginase after E.coli asparaginase.Postinduction phase, a higher number of PEGasparaginase-free intervals, and initiation of PEGasparaginase in postinduction phase are risk factors for allergic reactions. These results are important for planning of PEGasparaginase administrations in future frontline therapy.

Safety of COVID-19 vaccination in patients with polyethylene glycol allergy: A case series

Safety of COVID-19 vaccination in patients with polyethylene glycol allergy: A case series

A Meta-Analysis of Hypersensitivity to Pegylated Escherichia coli Asparaginase Used As First-Line Treatment in Contemporary Pediatric Acute Lymphoblastic Leukemia Protocols

PURPOSEAsparaginase is a key component of acute lymphoblastic leukemia (ALL) therapy. Hypersensitivity reactions challenge its use and occur frequently (30-75%) after native Escherichia. Coli (E.coli) asparaginase (Appel et al., 2008; Muller et al., 2001; Panosyan et al., 2004; Silverman et al., 2001). The international ALL Ponte di Legno Toxicity Work Group (PTWG) classifies hypersensitivity to asparaginase as (i) allergy in case of symptoms of allergy (always associated with undetectable asparaginase activity levels), (ii) allergic-like reactions in case of symptoms without inactivation, and (iii) silent inactivation (SI) with inactivation of asparaginase activity, but without hypersensitivity symptoms (Schmiegelow et al., 2016). Allergic-like reactions and SI can only be diagnosed with monitoring of asparaginase activity levels. A meta-analysis was performed based on data from the PTWG to estimate the incidence of hypersensitivity and risk factors for hypersensitivity to asparaginase in ALL protocols using pegylated E.coli asparaginase (PEGasparaginase) as first line of treatment.PATIENTS AND METHODSQuestionnaires were sent to all members of the PTWG. Information on protocol level regarding PEGasparaginase dose, dosing regimen (e.g. dosing frequency, total number of doses, PEGasparaginase-free intervals(s)), administration route, total induction and post-induction hypersensitivity rates per protocol and per risk group and use of therapeutic drug monitoring (TDM). To facilitate comparison between protocols with and without TDM, we defined allergic reactions as the sum of allergies and allergic-like reactions. Silent inactivation was analyzed separately.RESULTSA total of 5880 patients with newly diagnosed ALL, aged 1 to 24 years old, were enrolled in seven different upfront ALL protocols using PEGasparaginase as first-line treatment. The overall incidence of allergic reactions along with 95% confidence interval (CI) were 9% [6%; 13%], 2% [1%; 3%] and 8% [5%; 11%] in the overall protocol, induction and post-induction, respectively (Figure 1). Severity of allergic reactions were described, according to the CTCAE version 3.0 or 4.03, per protocol. 47% of the reactions were classified as grade 3/4.Univariate meta-regression analysis showed a positive association between the incidence of allergic reactions and number of PEGasparaginase-free intervals (P=0.005). High risk group stratification (P<0.001), post-induction treatment phase (P<0.001) and start of PEGasparaginase treatment in post-induction (P=0.006) were also associated with a higher incidence of allergic reactions. Route of administration (IV (8.9%, range 8.6-10.5%) versus IM (6.5%, range 5.5-14.8%)) did not significantly influence risk of hypersensitivity. Number of doses, duration of first PEGasparaginase-free interval and dosage did not significantly influence risk of hypersensitivity. Multivariate meta-regression analysis showed a positive association between the incidence of allergic reactions and the number of PEGasparaginase-free intervals (P=0.006) and start of PEGasparaginase in the post-induction treatment phase (P=0.02).Two out of seven study groups reported an incidence of allergic reactions of 1.6-2.0%, which was 9-16% of all hypersensitivity. Three out of seven study groups reported an incidence of SI of 3.7-4.1%, which was 23-29% of all hypersensitivity reactions.All protocols prescribed a switch to Erwinia asparaginase in case of clinical hypersensitivity and/or SI. 308 out of 348 (89%) of the patients with hypersensitivity to PEGasparaginase received Erwinia asparaginase. 19 out of these 308 (6%) exposed patients had an allergic reaction to Erwinia asparaginase, of which 7 out of 19 (37%) were grade 3/4.CONCLUSIONThe incidence of allergic reactions is lower in protocols using PEGasparaginase as first-line treatment compared to that reported for native E.coli asparaginase or PEGasparaginase after native E.coli asparaginase. Post-induction phase, a higher number of PEGasparaginase-free intervals, and initiation of PEGasparaginase in post-induction phase are risk factors for allergic reactions. These results are important for planning of PEGasparaginase administrations in future frontline therapy. [Display omitted] DisclosuresAlbertsen: Erytech: Honoraria, Speakers Bureau; Servier: Speakers Bureau; BKA: Other: Sponsor of the investigator-initiated trial NOR-GRASPALL2016.

Effect of Extrinsic Warming of Low-Osmolality CT Contrast Media (Iohexol 350) on Extravasations and Patient Reaction Rates: A Retrospective Study.

BACKGROUND. Extrinsic warming of iodinated CT contrast media to body temperature reduces viscosity and injection pressures. However, studies examining the effect of extrinsic warming on clinical adverse events are limited in number and provide conflicting results. Therefore, consensus practice recommendations have been sparse. OBJECTIVE. The purpose of this study is to compare rates of extravasation, allergic and allergiclike reactions, and physiologic reactions between iohexol 350 mg I/mL warmed to body temperature (37°C) versus this agent maintained at room temperature. METHODS. This retrospective study compared adult patients who received CT examinations using IV iohexol 350 that had either been warmed to body temperature or maintained at room temperature. At our institution, contrast media had historically been warmed to body temperature before a protocol change unrelated to this investigation. Information on the patient and CT examination was extracted from the electronic medical record. Adverse events, including extravasations, allergic and allergiclike reactions, and physiologic reactions, were compared between groups. RESULTS. A total of 3939 patients received contrast media warmed to body temperature before the protocol change; 3933 patients received contrast media at room temperature after the protocol change. The body temperature group experienced 11 (0.28%; 95% CI, 0.14-0.50%) adverse events, all extravasations; the allergic and allergic-like reaction rate was 0.00% (97.5% CI, 0.00-0.09%). The room temperature group experienced 17 (0.43%; 95% CI, 0.25-0.69%) adverse events: 13 (0.33%; 95% CI, 0.17-0.56%) extravasations and four (0.10%; 95% CI, 0.03-0.26%) allergic and allergiclike reactions. No physiologic reaction occurred in either group. The two groups were not different in terms of overall reaction rate (p = .19), extravasation rate (p = .69), allergic and allergiclike reaction rate (p = .06), or physiologic reaction rate (p > .99). Logistic regression adjusting for patient and CT characteristics (age, sex, conventional CT vs CTA, contrast media volume, injection location) showed no significant association of patient group and adverse reaction rate (odds ratio, 2.19; 95% CI, 0.68-7.00). Multivariable regression modeling showed an excess of 0.27 adverse events per 100 patients within the room temperature group, which is below a 0.6% noninferiority margin. CONCLUSION. The data suggest that maintaining iohexol 350 at room temperature is noninferior to warming the agent to body temperature before injection. CLINICAL IMPACT. The resources involved to prewarm iohexol 350 before injection may not be warranted.

Prevention of Allergic-like Reactions at Repeat CT: Steroid Pretreatment versus Contrast Material Substitution

Background It is unclear whether steroid premedication is an effective means of preventing repeat allergic-like reactions in high-risk patients with a previous allergic-like reaction to iodinated contrast material (ICM). Purpose To compare the effectiveness of ICM substitution (ie, using iohexol in a patient with a previous iopromide reaction) with 12- and 2-hour steroid premedication for preventing repeat acute allergic-like reactions in high-risk patients. Materials and Methods This retrospective study identified all high-risk (ie, having a previous allergic-like reaction) adult and pediatric patients who underwent a contrast-enhanced CT examination at the institution from June 1, 2009, to May 9, 2017. Prophylactic treatments and repeat reactions were identified using chart review. The effectiveness of prophylactic treatments on repeat reaction rates was examined with multivariable regression models that used generalized estimating equations. Results A total of 1973 high-risk patients who underwent 4360 subsequent ICM-enhanced CT examinations were included. Of the 4360 examinations, a total of 280 allergic-like reactions occurred (6%) in 224 of the 1973 patients (11% of patients), with only 19 of 280 reactions (7%) that were more severe than the previous reaction being demonstrated. After adjustment, patients who received a different ICM with and without steroid premedication had a significantly lower rate of repeat reactions than did patients who received steroid premedication and the same ICM (same ICM and steroid premedication: 80 of 423 examinations [19%]; different ICM and no steroid premedication: 10 of 322 examinations [3%]; odds ratio [OR], 0.14 [95% CI: 0.06, 0.33]; P < .001; different ICM and steroid premedication: five of 166 patients [3%]; OR, 0.12 [95% CI: 0.04, 0.36]; P < .001). When examining the first scan only, patients who received the same ICM had a similar risk of repeat reactions regardless of whether they received steroid premedication (steroid premedication: 44 of 172 patients [26%] vs no premedication: 73 of 298 patients [25%]; OR, 1.00 [95% CI: 0.64, 1.57]; P = .99). Conclusion In this cohort, using an iodinated contrast material (ICM) substitution was more effective for preventing repeat allergic-like reactions than using steroid premedication and the same ICM that caused the previous reaction. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Davenport and Weinstein in this issue.

Prospective multicenter assessment of patient preferences for properties of gadolinium-based contrast media and their potential socioeconomic impact in a screening breast MRI setting

ObjectiveIt is unknown how patients prioritize gadolinium-based contrast media (GBCM) benefits (detection sensitivity) and risks (reactions, gadolinium retention, cost). The purpose of this study is to measure preferences for properties of GBCM in women at intermediate or high risk of breast cancer undergoing annual screening MRI.MethodsAn institutional reviewed board-approved prospective discrete choice conjoint survey was administered to patients at intermediate or high risk for breast cancer undergoing screening MRI at 4 institutions (July 2018–March 2020). Participants were given 15 tasks and asked to choose which of two hypothetical GBCM they would prefer. GBCMs varied by the following attributes: sensitivity for cancer detection (80–95%), intracranial gadolinium retention (1–100 molecules per 100 million administered), severe allergic-like reaction rate (1–19 per 100,000 administrations), mild allergic-like reaction rate (10–1000 per 100,000 administrations), out-of-pocket cost ($25–$100). Attribute levels were based on published values of existing GBCMs. Hierarchical Bayesian analysis was used to derive attribute “importance.” Preference shares were determined by simulation.ResultsResponse (87% [247/284]) and completion (96% [236/247]) rates were excellent. Sensitivity (importance = 44.3%, 95% confidence interval = 42.0–46.7%) was valued more than GBCM-related risks (mild allergic-like reaction risk (19.5%, 17.9–21.1%), severe allergic-like reaction risk (17.0%, 15.8–18.1%), intracranial gadolinium retention (11.6%, 10.5–12.7%), out-of-pocket expense (7.5%, 6.8–8.3%)). Lower income participants placed more importance on cost and less on sensitivity (p < 0.01). A simulator is provided that models GBCM preference shares by GBCM attributes and competition.ConclusionsPatients at intermediate or high risk for breast cancer undergoing MRI screening prioritize cancer detection over GBCM-related risks, and prioritize reaction risks over gadolinium retention.Key Points• Among women undergoing annual breast MRI screening, cancer detection sensitivity (attribute “importance,” 44.3%) was valued more than GBCM-related risks (mild allergic reaction risk 19.5%, severe allergic reaction risk 17.0%, intracranial gadolinium retention 11.6%, out-of-pocket expense 7.5%).• Prospective four-center patient preference data have been incorporated into a GBCM choice simulator that allows users to input GBCM properties and calculate patient preference shares for competitor GBCMs.• Lower-income women placed more importance on out-of-pocket cost and less importance on cancer detection (p < 0.01) when prioritizing GBCM properties.

Abstract No. 471 Allergy testing for verification of contrast allergy prior to radiology procedures

Allergy to contrast material can limit the diagnostic and therapeutic options for patients, especially if the reaction to contrast media is listed as anaphylaxis (IgE-mediated allergic reactions). Many patients with physiologic response to contrast are labeled as being allergic to contrast because the patient or caregiver do not understand the differences between dose-related responses and allergy. Other patients with a history suggesting only a mild reaction may be at risk for anaphylaxis. Our goal is to provide appropriate documentation for the existences or lack of contrast allergy which facilitate best therapeutic and diagnostic options for the patient. Pre-procedure patients with written documentation of contrast allergy were, at the discretion of a licensed independent practitioner, referred to the Allergy and Immunology department for contrast media testing. Patients were tested using an established protocol. Based on reaction clinical history and skin testing patients were classified into four groups: Nonallergic (Negative skin testing, and negative clinical evaluation), predominantly histamine mediated reaction (Negative skin testing, clinical evaluation consistent with histamine mediated symptoms), allergic- like reaction (Negative skin testing, convincing clinical allergic-like reaction), and IgE- mediated allergic reaction (Positive skin testing and positive clinical history) Ten patients completed contrast allergy testing. Referral to allergy and immunology changed the management as follows: avoided steroids in 8/10 (80%) and avoided premedication completely in 6/10 (60%). The testing also confirmed IgE mediated reaction to contrast (Risk of anaphylactic reaction) in 1 patient (10%). Testing in this preliminary patient population suggests significant clinical benefit from referral to allergy and immunology for contrast media testing in patients with reported contrast allergy. Standardization of patient testing may reduce procedure cancellations, excessive use of steroids and potentially the risk of contrast induced anaphylaxis.

Immunologic biomarker changes in patients exposed to intravenous iodinated contrast material

Iodinated contrast material (ICM) is an integral component of computed tomography (CT) examinations, cardiac catheterizations, and other diagnostic imaging procedures, often providing crucial clinical information that would otherwise not be available with other imaging examinations. Allergic-like reactions after ICM exposure, ranging in severity from pruritis to anaphylaxis, are a known complication with an incidence of 0.6%.1 The mechanisms of these reactions remain poorly understood because: (1) they are not considered true allergic reactions owing to inconsistent activation of immunoglobulin E (IgE)–mediated pathways and the lack of immunologic memory,2 and (2) their occurrence is idiosyncratic, often with no subsequent reaction with repeated exposure.

Gadolinium-based contrast agents: What we learned from acute adverse events, nephrogenic systemic fibrosis and brain retention.

Radiologists have been administering gadolinium-based contrast agents (GBCA) in magnetic resonance imaging for several decades, so that there is abundant experience with these agents regarding allergic-like reactions, nephrogenic systemic fibrosis (NSF) and gadolinium retention in the brain. This review is based on a selective literature search and reflects the current state of research on acute adverse effects of GBCA, NSF and brain retention of gadolinium. Due to the frequent use of GBCA, data on adverse effects of these compounds are available in large collectives. Allergic-like reactions occurred rarely, whereas severe acute reactions were very rarely observed. Systemic changes in NSF also occur very rarely, although measures to avoid NSF resulted in a significantly reduced incidence of NSF. Due to gadolinium retention in the body after administration of linear MR contrast agents, only macrocyclic preparations are currently used with few exceptions. Clear clinical correlates of gadolinium retention in the brain could not be identified so far. Although the clinical added value of GBCA is undisputed, individual risks associated with the injection of GBCA should be identified and the use of non-contrast enhanced MR techniques should be considered. Alternative contrast agents such as iron oxide nanoparticles are not clinically approved, but are currently undergoing clinical trials. GBCA have a very good risk profile with a low rate of adverse effects or systemic manifestations such as NSF. Gadolinium retention in the brain can be minimized by the use of macrocyclic GBCA, although clear clinical correlates due to gadolinium retention in the brain following administration of linear GBCA could not be identified yet. · Acute adverse effects are predominantly mild/moderate, rarely severe reactions occur.. · International guidelines resulted in significant reduction of nephrogenic systemic fibrosis.. · Application of macrocyclic contrast agents minimizes gadolinium retention in the brain.. · Bäuerle T, Saake M, Uder M. Gadolinium-based contrast agents: What we learned from acute adverse events, nephrogenic systemic fibrosis and brain retention. Fortschr Röntgenstr 2021; 193: 1010 - 1018.

Safety of gadoterate meglumine in children younger than 2years of age.

Few studies on the safety of gadolinium-based contrast agents have been performed in children with even fewer focusing on children younger than 2years of age. To assess the safety of gadoterate meglumine (Dotarem) in patients younger than 2years of age by evaluating adverse events following contrast administration. Pediatric patients younger than 2years of age undergoing magnetic resonance imaging (MRI) with and without contrast were prospectively enrolled and received a weight-based intravenous dose of gadoterate meglumine (0.1mmol/kg). The occurrence of adverse events was assessed at the time of injection, 2h after MRI, and by phone contact using a standard questionnaire 24h after MRI. Adverse events were documented including the time of onset, duration of symptoms, intensity, causality and subsequent outcome. Descriptive statistics were used to characterize patient information. One hundred fifty exams were completed in 150 patients (median age: 12.1months, age range: 0.25-23months; males: 56%). Almost all patients (97.3%) received sedation/anesthesia before and during MRI. Thirty-four adverse events were reported in 23 patients overall (15.3%; male: 73.9%; median age: 11months, age range: 3-23months). Within the initial 2h after the injection, there was one report of transient flushing/warmth and one report of vomiting, the latter of which was related to drinking formula too soon after anesthesia. Twenty-two patients (14.7%), who had all received sedation/anesthesia, experienced minor adverse events within 24h, most physiological. Fourteen patients (9.3%) reported emesis, eight (5.3%) reported transient flushing/warmth, seven (4.7%) reported nausea, one (0.7%) reported altered taste and one (0.7%) reported dizziness. No patient experienced anaphylaxis. Two patients (1.3%) reported allergic-like reactions, which consisted of wheezing or sneezing. No patient experienced adverse events directly related to gadoterate meglumine. Only two adverse events were reported to have occurred in the initial 2h after the exam, while the rest were reported on the 24-h follow-up call. The higher reported rate of adverse events in this study may be related to concomitant sedation/anesthesia as well as to overreporting from parents on the 24-h follow-up questionnaire. The study confirms a good safety profile for gadoterate meglumine in this very sensitive population.

Individualized Asparaginase Dosing in Childhood Acute Lymphoblastic Leukemia.

In the DCOG ALL-11 protocol, polyethylene glycol-conjugated Escherichia coli asparaginase (PEGasparaginase) and Erwinia asparaginase treatment of pediatric acute lymphoblastic leukemia are individualized with therapeutic drug monitoring (TDM). The efficacy of TDM and its effect on asparaginase-associated toxicity are reported. After induction with 3 fixed intravenous doses of 1,500 IU/m2 PEGasparaginase, medium-risk patients (n = 243) received 14 individualized doses that targeted trough levels of 100-250 IU/L, standard-risk patients (n = 108) received 1 individualized dose, and high-risk patients (n = 18) received 2-5 fixed administrations (1,500 IU/m2). After a neutralizing hypersensitivity reaction, patients were started with 20,000 IU/m2 Erwinia asparaginase 3 times per week, and l-asparagine was measured to monitor asparaginase efficacy. Several asparaginase-associated toxicities were studied. The final median PEGasparaginase dose was lowered to 450 IU/m2. Overall, 97% of all trough levels of nonallergic patients were > 100 IU/L. Asparagine was < 0.5 μM in 96% and 67% of the PEGasparaginase and Erwinia asparaginase levels > 100 IU/L, respectively. Ten percent developed a neutralizing hypersensitivity reaction to PEGasparaginase, of which 40% were silent inactivations. The cumulative incidence of grade 3-4 pancreatitis, central neurotoxicity, and thromboses was 12%, 4%, and 6%, respectively, and not associated with asparaginase activity levels. During medium-risk intensification, 50% had increased ALT and 3% hyperbilirubinemia (both grade 3/4 and correlated with asparaginase activity levels), and 37% had grade 3/4 hypertriglyceridemia. Hypertriglyceridemia occurred less in intensification compared with ALL-10 (37% v 47%), which is similar to ALL-11 but with higher asparaginase levels during intensification. TDM of asparaginase results in a significant reduction of the PEGasparaginase dose with adequate asparaginase activity levels and sufficient asparagine depletion. In addition, with TDM, silent inactivation and allergic-like reactions were identified. However, the effect of reduced asparaginase activity levels on toxicity is limited.

Multicenter Safety and Practice for Off-Label Diagnostic Use of Ferumoxytol in MRI.

Background Ferumoxytol is approved for use in the treatment of iron deficiency anemia, but it can serve as an alternative to gadolinium-based contrast agents. On the basis of postmarketing surveillance data, the Food and Drug Administration issued a black box warning regarding the risks of rare but serious acute hypersensitivity reactions during fast high-dose injection (510 mg iron in 17 seconds) for therapeutic use. Whereas single-center safety data for diagnostic use have been positive, multicenter data are lacking. Purpose To report multicenter safety data for off-label diagnostic ferumoxytol use. Materials and Methods The multicenter ferumoxytol MRI registry was established as an open-label nonrandomized surveillance databank without industry involvement. Each center monitored all ferumoxytol administrations, classified adverse events (AEs) using the National Cancer Institute Common Terminology Criteria for Adverse Events (grade 1-5), and assessed the relationship of AEs to ferumoxytol administration. AEs related to or possibly related to ferumoxytol injection were considered adverse reactions. The core laboratory adjudicated the AEs and classified them with the American College of Radiology (ACR) classification. Analysis of variance was used to compare vital signs. Results Between January 2003 and October 2018, 3215 patients (median age, 58 years; range, 1 day to 96 years; 1897 male patients) received 4240 ferumoxytol injections for MRI. Ferumoxytol dose ranged from 1 to 11 mg per kilogram of body weight (≤510 mg iron; rate ≤45 mg iron/sec). There were no systematic changes in vital signs after ferumoxytol administration (P > .05). No severe, life-threatening, or fatal AEs occurred. Eighty-three (1.9%) of 4240 AEs were related or possibly related to ferumoxytol infusions (75 mild [1.8%], eight moderate [0.2%]). Thirty-one AEs were classified as allergiclike reactions using ACR criteria but were consistent with minor infusion reactions observed with parenteral iron. Conclusion Diagnostic ferumoxytol use was well tolerated, associated with no serious adverse events, and implicated in few adverse reactions. Registry results indicate a positive safety profile for ferumoxytol use in MRI. © RSNA, 2019 Online supplemental material is available for this article.

Acute Adverse Events Following Gadolinium-based Contrast Agent Administration: A Single-Center Retrospective Study of 281 945 Injections.

Background Acute allergic-like and physiologic reactions occur following administration of gadolinium-based contrast agents (GBCAs) for MRI examinations. Because these reactions are uncommon, it is challenging to compare reaction rates between GBCAs and to determine risk factors. Purpose To compare reaction rates between the four GBCAs gadodiamide, gadobutrol, gadobenate dimeglumine, and gadoterate meglumine, and to determine potential risk factors for reactions. Materials and Methods This retrospective study identified all intravenous GBCA injections for MRI examinations performed at a single institution from June 1, 2009, to May 9, 2017. Reactions were identified by reviewing records from the MRI technologist, MRI nursing staff, radiologist, emergency department, and provider. Reactions were classified as allergic-like or physiologic and as mild, moderate, or severe by using American College of Radiology criteria. GBCA reaction rates and other potential risk factors were examined by using multivariable regression models with generalized estimating equations. Results Analysis included a total of 158 100 patients (median age, 55 years [interquartile range, 40-67 years], 51% women) who received a total of 281 945 GBCA injections (140 645 gadodiamide, 94 109 gadobutrol, 39 138 gadobenate, and 8053 gadoterate). At multivariate analysis, gadobenate or gadobutrol had higher rates of allergic-like reactions compared with gadodiamide (gadobenate: odds ratio [OR], 3.9 [95% confidence interval {CI}: 3.0, 5.1]; P < .001; gadobutrol: OR, 2.3 [95% CI: 1.8, 2.9]; P < .001) or gadoterate (gadobenate: OR, 4.8 [95% CI: 1.0, 23]; P = .049; gadobutrol: OR, 2.8 [95% CI: 0.6, 14]; P = .20). Physiologic reactions were more frequently observed with gadoterate (OR, 7.7 [95% CI: 2.3, 25; P = .001), gadobenate (OR, 1.8 [95% CI: 1.3, 2.5; P < .001), and gadobutrol (OR, 1.6 [95% CI: 1.3, 2.1; P < .001) administration compared with gadodiamide. Six severe allergic-like reactions (three gadobutrol, three gadobenate) occurred requiring hospitalization. Patient age (P values .025 to < .001), sex (P < .001), location (P = .006), and MRI type (P = .003 and P = .006) were associated with acute reactions. Conclusion Gadobenate and gadobutrol are associated with higher rates of allergic-like reactions compared with gadodiamide or gadoterate, and gadoterate, gadobenate, and gadobutrol are associated with higher rates of physiologic reactions compared with gadodiamide. Patient sex, age, location, and MRI type correlate with acute reaction rates. © RSNA, 2019 Online supplemental material is available for this article.

Practical administration of intravenous contrast media in children: screening, prophylaxis, administration and treatment of adverse reactions.

Administration of intravenous contrast media to children is a routine practice at many clinical imaging centers, that can involve special considerations. In this paper, we provide practical information to facilitate optimal performance and oversight of this task. We provide targeted screening questions that can help to identify high-risk pediatric patients for both iodine-based and gadolinium-based intravenous contrast media administration. These include children at risk for allergic-like reactions, thyroid dysfunction, contrast-induced nephropathy, and nephrogenic systemic fibrosis. We make recommendations for addressing "yes" responses to screening questions using risk stratification schema that are specific to children. We also present criteria for selecting children for premedication prior to intravenous contrast administration, and suggest pediatric regimens. Additionally, we discuss practical nuances of intravenous contrast media administration to children and provide a quick-reference table of appropriate treatments with pediatric dosages for adverse contrast reactions.

Single-Center Retrospective Analysis of Breakthrough Allergic-Like Reactions to Gadobutrol.

The purpose of this study was to assess the rate and severity of breakthrough allergic-like reactions to gadobutrol. Under a waiver from our institutional review board, we performed a key word search of our institutional PACS (Picture Archiving and Communication System) database to identify all allergic-like reactions, which occurred in the setting of gadobutrol administration between December 2009 and August 2018, encompassing approximately 25,000 gadobutrol injections. Patients with an index allergic-like reaction who underwent a subsequent gadobutrol-enhanced magnetic resonance imaging after a standard 13-hour corticosteroid and antihistamine premedication protocol before repeat injection were identified. Patient characteristics, volume of gadobutrol injected, and severity of index and breakthrough reactions were recorded and compared by χ test, t test, and Spearman correlation. The index allergic-like reaction rate to gadobutrol was 0.28% (69/25000). Of the patients who had an index allergic-like reaction, 45% (31/69) had a subsequent magnetic resonance imaging with gadobutrol injection and premedication with a breakthrough reaction rate of 35% (11/31). Most index reactions were mild in severity (91% [63/69]), and most breakthrough reactions were also typically mild (91% [10/11]). One patient escalated from a mild index reaction to a moderate breakthrough reaction despite premedication. There was no correlation between volume of gadobutrol injected (ρ = -0.004, P = 0.98) or association with age (P = 0.74), although female patients had higher breakthrough reaction rates (P = 0.007). Allergic-like reactions to gadobutrol are rare; however, breakthrough reactions occur with moderate frequency despite premedication, and although generally of mild severity, in our series, one breakthrough reaction escalated in severity.

Drug hypersensitivity to tolperisone – case report

Introduction. Drug hypersensitivity, now a worldwide health problem, undoubtedly has gained significance in the last years due to the increasing number of patients categorized as drug allergic. We underline unpredictable adverse reactions (type B reactions) after administration of tolperisone. The severity of anaphylaxis ranged from urticarial reactions to shock with arterial hypotension that was treated at the Emergency Room. Aim. In clinical practice, there is an increase in the number of cases with a positive history of anaphylactic events due to administration of tolperisone. The purpose was to raise awareness among medical practitioners and take in consideration these frequent side effects when prescribing tolperisone. Materials and method. Our case report involved a middle aged woman who took tolperisone for chronic muscular pain. Reactions occurred within 15 to 20 minutes after oral intake of this drug frequently prescribed in our country. Discussion. Consulting medical articles and literature, the reporting of adverse reactions to tolperisone are scarce, possibly due to lack of commercialization in many countries. At the Emergency Department of the Emergency County Hospital of Târgu-Mureş we found several (almost 2-3 per year) presentations with suspicion of severe allergic reaction due to tolperisone, without further investigations. Conclusions. Our research and the frequency of anaphylactic occurrences suggest that anaphylaxis to tolperisone is not uncommon, varying from urticaria and angioedema to more major reactions such as dyspnea and hypotension. Often, severe allergic reactions are likely to appear when tolperison is taken in combination with nonsteroidal anti-inflammatory drugs (NSAIDs). In Romania, tolperisone remains a popular myorelaxant agent often bought without medical prescription. The mechanism of these allergic-like reactions remains unclear.

Extrinsic warming of low-osmolality iodinated contrast media to 37°C reduced the rate of allergic-like reaction.

Background: Although there is good evidence that warming of contrast media changes the bolus kinetics and injection pressure of iodinated contrast media, there has been little evidence that it affects clinical adverse event rates in a meaningful way. Objective: To determine whether the extrinsic warming of low-osmolality iodinated contrast media to 37°C reduced adverse reactions. Methods: Data on adverse reactions were collected from two cohorts, one of which used contrast media at room temperature and the other in which contrast media were warmed to 37°C before administration. Adverse reactions, including allergic-like and physiological reactions, were reviewed. We compared the incidence rates of adverse reactions between the two cohorts by using the χ2 test. Results: A total of 70,446 injections in cohort 1 and 203,873 injections in cohort 2 were included. Extrinsic warming reduced the rate of allergic-like reactions to iopromide 370, iopamidol 370, and iohexol 350 (0.32% in cohort 1 versus 0.21% in cohort 2, p = 0.003; 0.14% versus 0.10%, p = 0.046; and 0.32% versus 0.13%, p = .003, respectively). However, the physiological reaction rates could not be reduced (p = 0.057, p = 0.107, and p = 0.962, respectively). The extrinsic warming of iopromide 300 could not reduce adverse reaction rates (allergic-like reaction rates: 0.21% versus 0.16%, p = 0.407; physiological reaction rates: 0.17% versus 0.13%, p = 0.504). Conclusion: Extrinsic warming to 37°C before intravenous administration was associated with a reduction in the rate of allergic-like reactions to iopromide 370, iopamidol 370, and iohexol 350.

Safety of animal traditional Chinese medicine (TCM) injections

Animal medicine injection is an important part of traditional Chinese medicine (TCM) injections. All or part of animals with a significant curative effect and little side reactions as raw materials as well as modern technology are used to produce traditional Chinese medicine injections with a reliable and rapid drug efficacy and high bioavailability. Due to the complex composition of traditional Chinese medicine injections, imperfect quality standards, and unreasonable clinical use, the incidence of adverse reactions of traditional Chinese medicine injections has been significantly higher than that of traditional Chinese medicine for oral use. Animal medicine injections contain rich protein and fat, and heteroproteins are the main sensitization source in animal medicine injections. At present, the adverse reactions of animal medicine injections are mainly manifested in the anaphylaxis-like reactions at skin, mucous membranes and organ systems. The adverse reactions that occur during the first medication are more common. Specific causes for allergic-like adverse reactions in animal injections and related substances in traditional Chinese medicine injections made of animals that induce allergies or anaphylactoid reactions are currently not specifically reported. This article reviews the current adverse reactions of animal TCM injections, allergies and pseudoallergic reactions of animal TCM injections, the pharmacokinetics of animal TCM injections, and the combined use of drugs, in order to improve the quality standards of Chinese medicine injections for animals and provide reference for further safety related research.

Allergic-like contrast media reaction management in children.

The use of contrast materials as part of imaging examinations is common in children of all ages, as these compounds increase image contrast, lesion detection and lesion characterization. Though modern iodinated, gadolinium-based and ultrasound microbubble contrast materials generally are quite safe, acute physiological and allergic-like reactions are possible. The majority of acute contrast reactions in children are mild and self-limited; however, life-threatening reactions can occur. It is our obligation as radiologists to recognize and manage these adverse reactions. The objective of this article is to review the frequency, manifestations and appropriate treatment of acute contrast reactions in the pediatric population.