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.

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 American College of Radiology. Manual on Contrast Media. Available at: https://www.acr.org/Clinical-Resources/Contrast-Manual. Accessed March 1, 2021. Google Scholar 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 Laroche D Aimone-Gastin I Dubois F et al. Mechanisms of severe, immediate reactions to iodinated contrast material. Radiology. 1998; 209: 183-190 Crossref PubMed Scopus (210) Google Scholar and (2) their occurrence is idiosyncratic, often with no subsequent reaction with repeated exposure. Historical observations have demonstrated that ICM osmolarity was a risk factor for the reactions, with reported incidences decreasing by greater than or equal to 90% during the widespread transition from high-osmolar to low-osmolar ICMs. 1 American College of Radiology. Manual on Contrast Media. Available at: https://www.acr.org/Clinical-Resources/Contrast-Manual. Accessed March 1, 2021. Google Scholar ,3 Greenberger PA Patterson R. The prevention of immediate generalized reactions to radiocontrast media in high-risk patients. J Allergy Clin Immunol. 1991; 87: 867-872 Abstract Full Text PDF PubMed Scopus (236) Google Scholar ,4 Lieberman PL Seigle RL. Reactions to radiocontrast material. Anaphylactoid events in radiology. Clin Rev Allergy Immunol. 1999; 17: 469-496 Crossref PubMed Scopus (56) Google Scholar

Temozolomide is the most effective chemotherapy for malignant glioma. Hypersensitivity requiring interruption of therapy may significantly impact patient survival. We have successfully employed temozolomide desensitization followed by metronomic dosing of temozolomide. Our purpose was to report patient characteristics and outcomes in patients with glioma (Grade 2–4) and temozolomide hypersensitivity managed by desensitization and metronomic dosing. We performed an observational study of 15 patients at Mayo Clinic (Rochester) with a diagnosis of glioma who underwent temozolomide desensitization with subsequent metronomic dosing from May 2012 to January 2017. We calculated overall and progression-free survival using the Kaplan–Meier method, and log-rank analyses to assess for differences in survival by WHO Grade or treatment initiation. Median age at time of desensitization was 49.3 years (26.8–64.7 years). Median follow-up after desensitization was 35.5 months. One patient (6.7%) was unable to resume temozolomide due to recurrent allergy. The median time from first desensitization to discontinuation of metronomic temozolomide was 4.2 months (0–15.2 months). Median OS and PFS for the whole sample were 181.7 months and 44.9 months. For Grade 4, OS was 100% at 1 year, 40% at 3 years, 20% at 5 years; and PFS was 60% at 1 year, 40% at 3 years, and 20% at 5 years. Our results suggest that rapid-desensitization followed by metronomic temozolomide should be considered in patients with glioma who experience hypersensitivity. This strategy provides comparable outcomes to therapy with standard protocols, with the majority of patients able to tolerate temozolomide after desensitization with favorable disease control.

ommendations.This is crucial not only in the BRCA patient population, but, as multigene germline panel testing emerges, for patients with genetic alterations in other proteins important for DNA repair.In these patients, the traditional riskbenefit analyses for breast cancer screening are confounded by unique biologic profiles.Disclosures of Conflicts of Interest: M.E.

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) whoreceived 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 severeallergic-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. (C) RSNA, 2019

Temozolomide is an oral chemotherapy alkylating agent approved in the United States by Food and Drug Administration (FDA) for the treatment of brain tumors. Its utility as a first-line treatment for glioblastoma multiforme (GBM), second line for astrocytoma and some nonbrain tumors such as melanoma, has been published.1 Adverse reactions to this agent are common, but severe skin hypersensitivity including Stevens-Johnson syndrome, toxic epidermal necrolysis, or immediate hypersensitivity including anaphylaxis appears to be rare and reported in postmarketing surveys2 or isolated case reports.

Barbara, David W.; Ronan, Kevin P.; Maddox, Daniel E.; Warner, Mark A. Author Information

The purpose of this study was to determine whether premedication of patients with a history of urticaria after low osmolality contrast media (LOCM) results in fewer subsequent reactions, and if a benefit is seen, to determine which premedication regimen results in the fewest reactions.

Angioedema is a potentially life-threatening condition that may present at any point in the perioperative care of patients. It requires prompt recognition and diagnosis; the primary concern during acute attacks is airway management. The pathophysiology, various causes of angioedema, and treatment strategies according to underlying etiology are presented.

Background: Sublingual immunotherapy (SLIT) has become established in Europe, and its efficacy is being evaluated in the United States. The doses used for SLIT in Europe today are difficult to evaluate, because each manufacturer expresses the potency of its extracts differently.Objectives: To compare in vitro European SLIT maintenance solutions against US licensed standardized allergenic extract concentrates and to determine the monthly SLIT doses delivered expressed in bioequivalent allergy units ([B]AU).Methods: We studied Dermatophagoides pteronyssinus, timothy grass pollen, cat (hair) and short ragweed pollen allergen extracts. The SLIT maintenance solutions of 4 leading European manufacturers and standardized concentrate extracts of 3 US manufacturers were analyzed with the following assays: protein content, relative potency (immunoglobulin E [IgE]-binding enzyme-linked immunosorbent assay [ELISA] inhibition) and major allergen content. The relative monthly allergen dose in (B)AU was calculated for each recommended SLIT schedule.Results: Relative potency was approximately 10 times higher for US concentrate standardized extracts which are meant to be diluted than for European SLIT maintenance solutions of D pteronyssinus and timothy grass pollen. For cat (hair) and short ragweed pollen, the difference was less. Measurements of relative potency and major allergen content correlated well. In our assays, European mite extracts contain a very low quantity of Der p 2 compared with US mites.Conclusion: Recommended SLIT doses in Europe vary widely among the manufacturers, but are consistently lower (Eurl) or higher (Eur4) over all four allergens tested. SLIT efficacy probably depends on additional factors apart from the exact dose. SLIT dose finding studies should be done for each product. Ann Allergy Asthma Immunol. 2011;107:448-458.

We used high throughput sequencing to examine the structure and composition of the T cell receptor β chain in Common Variable Immune Deficiency (CVID). TCRβ CDR3 regions were amplified and sequenced from genomic DNA of 44 adult CVID subjects and 22 healthy adults, using a high-throughput multiplex PCR. CVID TCRs had significantly less junctional diversity, fewer n-nucleotide insertions and deletions, and completely lacked a population of highly modified TCRs, with 13 or more V-gene nucleotide deletions, seen in healthy controls. The CVID CDR3 sequences were significantly more clonal than control DNA, and displayed unique V gene usage. Despite reduced junctional diversity, increased clonality and similar infectious exposures, DNA of CVID subjects shared fewer TCR sequences as compared to controls. These abnormalities are pervasive, found in out-of-frame sequences and thus independent of selection and were not associated with specific clinical complications. These data support an inherent T cell defect in CVID.

Medications are a major source of acute kidney injury, especially in critically ill patients. Medication-induced renal injury can occur through a number of mechanisms. We present two cases of acute kidney injury (AKI) where inactive cytochrome P450 (CYP) polymorphism may have played a role. The first patient developed a biopsy-proven allergic interstitial nephritis following urethrotomy. Genetic testing revealed the patient to be heterozygous for an inactivating polymorphism CYP2C9*3 and homozygous for an inactivating polymorphism CYP2D6*4. Patient had received several doses of promethazine, which is metabolized by CYP2D6*4. Another patient developed AKI on several occasions after exposure to lansoprazole and allopurinol. CYP testing revealed the patient to be homozygous for inactivating polymorphism CYP2C19*2, which is responsible for the metabolism of lansoprazole. These are the first two cases of AKI associated with non-functional polymorphisms of cytochrome P450 superfamily. While the exact mechanism has not been worked out, it introduced the possibility of a new source of kidney injury.