Immediate hypersensitivity reactions to iodinated contrast media: The diagnosis of allergy by skin testing.

Among 74 patients with an immediate hypersensitivity reaction (IHR) to iodinated contrast media (ICM), the rate of allergic patients confirmed by positive prick test or diluted intradermal test (IDT) was 8.1%. 12.5% of re-exposed patients had a recurrent IHR despite negative skin tests. Investigations on pure IDT to ICM and development of drug provocation test may provide additional safety nets to uncover recurrent ICM reactors. Agreements among allergists are needed to unify practices.

Efficacy and safety of oral immunotherapy with AR101 in European children with a peanut allergy (ARTEMIS): a multicentre, double-blind, randomised, placebo-controlled phase 3 trial.

BACKGROUND: Peanut allergy is the leading cause of food-related anaphylaxis. Current management options can negatively affect food allergy-related quality of life. We aimed to investigate the efficacy of an investigational oral biologic drug (AR101). METHODS: The AR101 Trial in Europe Measuring Oral Immunotherapy Success in peanut-allergic children (ARTEMIS) trial was a multicentre, double-blind, randomised, placebo-controlled phase 3 trial done at 18 hospitals in Ireland, France, Germany, Italy, Spain, Sweden, and the UK. Children and adolescents with peanut allergy, aged 4-17 years, who developed dose-limiting symptoms to 300 mg or less peanut protein (equivalent to approximately one peanut kernel) during a double-blind placebo-controlled food challenge test at study entry were enrolled. Participants were randomly assigned (3:1) to receive daily doses of either AR101 oral immunotherapy (AR101 group) or a taste-masked placebo (placebo group). All participants, investigators, and care providers were masked to treatment allocation until the study was completed. Doses were increased every 2 weeks over 6 months until a dose of 300 mg was reached and maintained for 3 months. The primary endpoint was the proportion of participants in the intention-to-treat or safety population (defined as those participants who had been randomly assigned and had received at least one dose of the assigned drug) who could consume a single dose of 1000 mg (cumulative dose 2043 mg) peanut protein without developing dose-limiting allergic symptoms at an exit double-blind placebo-controlled food challenge after 9 months of treatment. Additional endpoints included safety (ie, the frequency and severity of adverse events) and changes in food allergy-related quality of life, assessed by use of age-appropriate Food Allergy Quality of Life Questionnaires (FAQLQs) and the Food Allergy Independent Measure (FAIM). The study is registered with ClinicalTrials.gov, NCT03201003, and is completed. FINDINGS: Between June 12, 2017, and Feb 15, 2018, 227 patients were screened, of whom 175 were randomly assigned to the AR101 group (n=132) and the placebo group (n=43). All primary and secondary endpoints were met. 77 (58%) of 132 participants in the AR101 group tolerated 1000 mg peanut protein at the exit food challenge versus one (2%) of 43 participants in the placebo group (AR101-placebo treatment difference 56·0% [95% CI 44·1-65·2], p<0·0001). Adverse events were reported by almost all participants. The maximum severity of adverse events reported was mild or moderate for most participants who received AR101 (mild, 66 [50%] of 132 participants; moderate, 63 [48%]; and severe, one [1%]) or placebo (mild, 24 [56%] of 43 participants; moderate, 18 [42%]; severe, none). Participants aged 8-12 years in the AR101 group reported improvements that exceeded the minimum clinically important difference between the two groups across all FAQLQ domains. Additionally, participants in the AR101 group and their caregivers reported improvements that exceeded the minimum clinically important difference in FAIM domains related to the perceived likelihood and outcomes of a severe allergic reaction. INTERPRETATION: AR101 oral immunotherapy treatment led to rapid desensitisation to peanut protein, with a predictable safety profile that improved with treatment, and an associated improvement in self-reported and caregiver-reported food allergy-related quality of life. These patient-oriented outcomes provide invaluable data to help physicians, patients, and caregivers make informed, shared decisions on the management of peanut allergy. FUNDING: Aimmune Therapeutics.

Transcriptional frameshifts contribute to protein allergenicity.

Transcription infidelity (TI) is a mechanism that increases RNA and protein diversity. We found that single-base omissions (i.e., gaps) occurred at significantly higher rates in the RNA of highly allergenic legumes. Transcripts from peanut, soybean, sesame, and mite allergens contained a higher density of gaps than those of nonallergens. Allergen transcripts translate into proteins with a cationic carboxy terminus depleted in hydrophobic residues. In mice, recombinant TI variants of the peanut allergen Ara h 2, but not the canonical allergen itself, induced, without adjuvant, the production of anaphylactogenic specific IgE (sIgE), binding to linear epitopes on both canonical and TI segments of the TI variants. The removal of cationic proteins from bovine lactoserum markedly reduced its capacity to induce sIgE. In peanut-allergic children, the sIgE reactivity was directed toward both canonical and TI segments of Ara h 2 variants. We discovered 2 peanut allergens, which we believe to be previously unreported, because of their RNA-DNA divergence gap patterns and TI peptide amino acid composition. Finally, we showed that the sIgE of children with IgE-negative milk allergy targeted cationic proteins in lactoserum. We propose that it is not the canonical allergens, but their TI variants, that initiate sIgE isotype switching, while both canonical and TI variants elicit clinical allergic reactions.

Oral Immunotherapy for Hazelnut Allergy: A Single-Center Retrospective Study on 100 Patients.

BACKGROUND: Oral immunotherapy (OIT) protects patients with IgE-mediated food allergies from food-induced allergic reactions due to accidental exposure and may improve their quality of life. This approach has never been evaluated for hazelnut, a major cause of food allergy in Europe. OBJECTIVE: To determine the proportion of hazelnut-desensitized patients after 6 months of OIT and to identify predictors of successful desensitization. METHODS: In a retrospective single-center study, we included patients younger than 18 years who underwent at least 6 months of hazelnut OIT for IgE-mediated allergy, defined by history of hypersensitivity reaction after hazelnut ingestion, positive hazelnut skin prick test result or specific IgE, and positive double-blind, placebo-controlled food challenge. Patients able to tolerate 1635 mg of hazelnut protein (∼8 hazelnuts) were considered to be hazelnut desensitized. We determined the proportion of desensitized patients after 6 months of OIT, searched for associations between baseline variables and successful desensitization, and estimated the frequency and severity of OIT-related adverse reactions. RESULTS: One hundred patients were included (64% males; median age, 5 years). History of severe reactions was noted in 7% of cases. At 6 months, the proportion of desensitized patients was 34% (95% CI, 25-44). The median eliciting dose (defined as the amount of hazelnut protein provoking a hypersensitivity reaction during the double-blind, placebo-controlled food challenge) increased from 106 mg (interquartile range, 51-249) at baseline to 523 mg (interquartile range, 190-1635) after 6 months of OIT (P < .0001). With longer therapy, the proportion of desensitized patients increased. Using multivariate analysis, successful desensitization was associated with older age (odds ratio [OR], 1.5; 95% CI, 1.2-2.2), smaller hazelnut skin prick test wheal diameter (OR, 0.61; 95% CI, 0.4-0.8), lower hazelnut specific IgE level (OR, 0.86; 95% CI, 0.72-0.98), and absence of cashew allergy (OR, 0.42; 95% CI, 0.12-0.64). Adverse reactions occurred in 30% of patients; none were severe. CONCLUSIONS: In a cohort of 100 patients aged 3 to 9 years, our results show for the first time that hazelnut OIT is associated with hazelnut desensitization and may be safe in most patients undergoing this therapy.

Phenotypical characterization of peanut allergic children with differences in cross-allergy to tree nuts and other legumes.

BACKGROUND: Peanut allergy in children is often associated with allergies to tree nuts and/or legumes. The aim of this study was to analyze in cluster a cohort of children allergic to peanuts and assessed for cross-reactivity to nuts and legumes and to identify different phenotypes. METHODS: We included retrospectively 317 children with peanut allergy evaluated at the Allergy Unit of the Saint Vincent Hospital of Lille in the last 12 years. A complete workup for peanut allergy and nuts and legumes was carried out for each patient. A hierarchical agglomerative clustering method was used to search for clusters of individuals in the evaluated cohort. RESULTS: Cross-allergy to TN and/or other legumes was identified in 137 patients (43.2%), atopic dermatitis being a major risk factor (adjusted OR = 16 [95% CI: 7.4-37]; p < 0.001). Three phenotypes emerged from cluster analysis. Cluster 1 (72 patients) is characterized by high level of rAra h 2, low threshold reactive doses for peanut and high proportion of asthma; Cluster 2 (93 patients) is characterized by high threshold reactive doses for peanut and the lowest proportion of cross-allergy to TN and/or legumes; Cluster 3 (152 patients) has a high risk of cross-allergy to TN and/or legumes and most patients suffer from eczema. CONCLUSIONS: The three phenotypes highlighted by this study could be useful to identify children with high risk of cross-allergic reaction to TNs and legumes early after PA diagnosis.

Intestinal permeability and fecal eosinophil-derived neurotoxin are the best diagnosis tools for digestive non-IgE-mediated cow's milk allergy in toddlers.

BACKGROUND: Food allergy is a common problem in France involving 4%-6% of toddlers. As opposed to IgE-mediated cow's milk allergy (CMA), delayed-onset CMA, mostly, non-IgE-mediated, remains difficult to diagnose in toddlers. Our study assessed the diagnostic performances of intestinal permeability and of fecal markers, in comparison with the standard allergic work-up in children referred for CMA diagnosis. METHODS: Twenty-five consecutive children, mean age (standard deviation) 6.3 months (4.8) with digestive and/or extra-digestive manifestations suggesting CMA, were prospectively studied based on a standardized allergic work-up (specific cow's protein IgE and IgG, skin prick test, atopy patch test and oral open cow's milk challenge) and digestive work-up including fecal microbiota analysis, intestinal permeability determination (urinary lactitol/mannitol ratio) and fecal markers measurement, i.e., α(1)-antitrypsin, tumor necrosis factor-α, calprotectin, ß-defensin2, secretory IgA and eosinophil-derived neurotoxin (EDN). Receiver operating characteristic (ROC) curves were calculated for all markers in order to define cut-off levels. RESULTS: The cow's milk challenge was positive in 11 children and negative in 14. The global test performances, i.e., the number of true positive+negative cases/the total number of cases, were 76% for intestinal permeability; 72% for fecal EDN; contrasting with atopy patch test, 68%; IgE, 60%; skin prick test, 55% and IgG, 52%. CONCLUSIONS: In this routine diagnosis allergy work-up for CMA in toddlers, the best efficacy was seen for intestinal permeability compared to IgE, IgG, skin prick test and atopy patch test. Moreover, fecal EDN in a single spot sample displayed a similar performance.