Phase 3 Trial of Epicutaneous Immunotherapy in Toddlers with Peanut Allergy.

BACKGROUND: No approved treatment for peanut allergy exists for children younger than 4 years of age, and the efficacy and safety of epicutaneous immunotherapy with a peanut patch in toddlers with peanut allergy are unknown. METHODS: We conducted this phase 3, multicenter, double-blind, randomized, placebo-controlled trial involving children 1 to 3 years of age with peanut allergy confirmed by a double-blind, placebo-controlled food challenge. Patients who had an eliciting dose (the dose necessary to elicit an allergic reaction) of 300 mg or less of peanut protein were assigned in a 2:1 ratio to receive epicutaneous immunotherapy delivered by means of a peanut patch (intervention group) or to receive placebo administered daily for 12 months. The primary end point was a treatment response as measured by the eliciting dose of peanut protein at 12 months. Safety was assessed according to the occurrence of adverse events during the use of the peanut patch or placebo. RESULTS: Of the 362 patients who underwent randomization, 84.8% completed the trial. The primary efficacy end point result was observed in 67.0% of children in the intervention group as compared with 33.5% of those in the placebo group (risk difference, 33.4 percentage points; 95% confidence interval, 22.4 to 44.5; P<0.001). Adverse events that occurred during the use of the intervention or placebo, irrespective of relatedness, were observed in 100% of the patients in the intervention group and 99.2% in the placebo group. Serious adverse events occurred in 8.6% of the patients in the intervention group and 2.5% of those in the placebo group; anaphylaxis occurred in 7.8% and 3.4%, respectively. Serious treatment-related adverse events occurred in 0.4% of patients in the intervention group and none in the placebo group. Treatment-related anaphylaxis occurred in 1.6% in the intervention group and none in the placebo group. CONCLUSIONS: In this trial involving children 1 to 3 years of age with peanut allergy, epicutaneous immunotherapy for 12 months was superior to placebo in desensitizing children to peanuts and increasing the peanut dose that triggered allergic symptoms. (Funded by DBV Technologies; EPITOPE ClinicalTrials.gov number, NCT03211247.).

Health-related quality of life of food-allergic children compared with healthy controls and other diseases.

BACKGROUND: Food allergy is a potentially life-threatening disease, affecting up to 10% of the pediatric population. OBJECTIVE: The aim of our study was to assess the health-related quality of life (HRQL) of food-allergic patients compared with the general population and patients with other chronic diseases with dietary or allergic burden, in a cross-sectional study. METHODS: We recruited patients aged 8-17 years diagnosed with food allergy and matched healthy controls recruited in schools. We also included patients with asthma, inflammatory bowel disease, celiac disease, diabetes, obesity, and eating disorders. We used the CHQ-CF87 questionnaire for generic HRQL assessment. Food allergy HRQL was also assessed using specific questionnaires: Food Allergy Quality of Life Questionnaire (FAQLQ) and Food Allergy Independent Measure (FAIM). RESULTS: One hundred and thirty-five food-allergic children, 255 children with chronic diseases, and 463 healthy controls were included in the analyses. Food-allergic patients had a better HRQL than healthy controls in the Behavior (BE), Bodily Pain (BP), Family Activities (FA), and Mental Health (MH) domains and a worse HRQL in the General Health Perception (GH) domain (p = .048). Food-allergic patients exhibited a better HRQL than patients affected by other chronic diseases, notably diabetes. Although an epinephrine autoinjector had been prescribed to 87.4% of the food-allergic children, only 54.2% of them carried it at all times. CONCLUSION: Food-allergic patients display overall good HRQL compared with the general population and those with other diseases with daily symptoms and treatments, in line with recent improvements in food allergy management.

[The child and his allergenic environment]. / L'enfant allergique et son environnement.

The child and his allergenic environment. Environment's allergens may promote sensitization and after that generate symptoms (allergy). Allergic diseases are frequent in childhood and food allergy increase. Environmental factors may be aeroallergens but also food allergens. The first step of the therapeutic possibilities is to avoid the allergens, with lifestyle modifications. Emergency plan is necessary for school. A first prevention level is feasible and probably useful for food allergy, but not for respiratory allergy.

L'enfant allergique et son environnement. L'environnement avec les allergènes qu'il contient est capable de générer chez l'enfant une sensibilisation. Des symptômes cliniques définissent l'allergie, maladie fréquente surtout en pédiatrie, et très contraignante en cas d'allergie alimentaire. En fonction des allergènes respiratoires, mais aussi alimentaires, des mesures d'éviction sont à proposer pour modifier cet environnement, parfois en changeant le mode de vie. Le projet d'accueil individualisé est indispensable en milieu scolaire. La prévention primaire qui viserait à éviter l'apparition de l'allergie a pu démontrer une certaine efficacité pour l'allergie alimentaire, mais pas pour les allergies respiratoires.

Pru p 7 sensitization is a predominant cause of severe, cypress pollen-associated peach allergy.

BACKGROUND: Peach is a common elicitor of food allergic reactions. Peach-induced immediate reactions may occur as benign pollen-food syndromes, usually due to birch pollen-related PR-10 cross-reactivity in temperate climates, and as potentially severe primary food allergies, predominantly related to nsLTP Pru p 3 in Mediterranean regions. The newly described peach allergen Pru p 7 has gained recent attention as a potential peach allergy severity marker. Sensitization to Pru p 7 and its allergenic homologues of the gibberellin-regulated protein family occurs in areas with high Cupressaceae tree pollen exposure. OBJECTIVE: We sought to investigate the distribution, clinical characteristics and molecular associations of Pru p 7 sensitization among subjects with suspected peach allergy in different regions of France. METHODS: Subjects with suspected peach allergy (n = 316) were included. Diagnostic work-up was performed according to current guidelines, including open food challenge when required. IgE antibody measurements and competition experiments were performed using the ImmunoCAP assay platform. RESULTS: Sensitization to Pru p 7 was present in 171 (54%) of all subjects in the study and in 123 of 198 (62%) diagnosed as peach allergic, more than half of whom were sensitized to no other peach allergen. Frequency and magnitude of Pru p 7 sensitization were associated with the presence of peach allergy, the clinical severity of peach-induced allergic reactions and the level of cypress pollen exposure. Cypress pollen extract completely outcompeted IgE binding to Pru p 7. Pru p 7 was extremely potent in basophil activation tests. CONCLUSION AND CLINICAL RELEVANCE: A subtype of Cupressaceae pollinosis, characterized by Pru p 7 sensitization, can be an underlying cause of severe peach allergy.

Effect of Varying Doses of Epicutaneous Immunotherapy vs Placebo on Reaction to Peanut Protein Exposure Among Patients With Peanut Sensitivity: A Randomized Clinical Trial.

Importance: Epicutaneous immunotherapy may have potential for treating peanut allergy but has been assessed only in preclinical and early human trials. Objective: To determine the optimal dose, adverse events (AEs), and efficacy of a peanut patch for peanut allergy treatment. Design, Setting, and Participants: Phase 2b double-blind, placebo-controlled, dose-ranging trial of a peanut patch in peanut-allergic patients (6-55 years) from 22 centers, with a 2-year, open-label extension (July 31, 2012-July 31, 2014; extension completed September 29, 2016). Patients (n = 221) had peanut sensitivity and positive double-blind, placebo-controlled food challenges to an eliciting dose of 300 mg or less of peanut protein. Interventions: Randomly assigned patients (1:1:1:1) received an epicutaneous peanut patch containing 50 µg (n = 53), 100 µg (n = 56), or 250 µg (n = 56) of peanut protein or a placebo patch (n = 56). Following daily patch application for 12 months, patients underwent a double-blind, placebo-controlled food challenge to establish changes in eliciting dose. Main Outcomes and Measures: The primary efficacy end point was percentage of treatment responders (eliciting dose: ≥10-times increase and/or reaching ≥1000 mg of peanut protein) in each group vs placebo patch after 12 months. Secondary end points included percentage of responders by age strata and treatment-emergent adverse events (TEAEs). Results: Of 221 patients randomized (median age, 11 years [quartile 1, quartile 3: 8, 16]; 37.6% female), 93.7% completed the trial. A significant absolute difference in response rates was observed at month 12 between the 250-µg (n = 28; 50.0%) and placebo (n = 14; 25.0%) patches (difference, 25.0%; 95% CI, 7.7%-42.3%; P = .01). No significant difference was seen between the placebo patch vs the 100-µg patch. Because of statistical testing hierarchical rules, the 50-µg patch was not compared with placebo. Interaction by age group was only significant for the 250-µg patch (P = .04). In the 6- to 11-year stratum, the response rate difference between the 250-µg (n = 15; 53.6%) and placebo (n = 6; 19.4%) patches was 34.2% (95% CI, 11.1%-57.3%; P = .008); adolescents/adults showed no difference between the 250-µg (n = 13; 46.4%) and placebo (n = 8; 32.0%) patches: 14.4% (95% CI, -11.6% to 40.4%; P = .40). No dose-related serious AEs were observed. The percentage of patients with 1 or more TEAEs (largely local skin reactions) was similar across all groups in year 1: 50-µg patch = 100%, 100-µg patch = 98.2%, 250-µg patch = 100%, and placebo patch = 92.9%. The overall median adherence was 97.6% after 1 year; the dropout rate for treatment-related AEs was 0.9%. Conclusions and Relevance: In this dose-ranging trial of peanut-allergic patients, the 250-µg peanut patch resulted in significant treatment response vs placebo patch following 12 months of therapy. These findings warrant a phase 3 trial. Trial Registration: clinicaltrials.gov Identifier: NCT01675882.

[The allergic child and his environment]. / L'enfant allergique et son environnement

Allergic diseases are frequent, and often begin during childhood. Environmental factors may promote allergy (sensitization) in atopic children, and after that generate symptoms (allergic hypersensitivity). One of the therapeutic possibilities is to avoid, when possible, the contact with allergens. Its usefulness has been demonstrated at the tertiary prevention level, and is discussed at the secondary prevention level. However, the question remains open to know whether this is feasible and useful at the first prevention level.

L'allergie est une maladie fréquente, dont le début est très souvent pédiatrique. L'environnement peut agir chez l'enfant en initiant la réaction immunitaire d'hypersensibilité qui définit le terrain atopique (sensibilisation) puis entretient les symptômes cliniques (allergie). Une des modalités de prise en charge en pédiatrie est d'agir quand cela est possible en fonction des allergènes sur cet environnement en prévention tertiaire, secondaire et idéalement primaire par des mesures d'éviction. La prévention primaire qui viserait à éviter l'apparition de l'allergie est la plus intéressante, mais la plus aléatoire quant à ses résultats.

Frey Syndrome.

OBJECTIVE: To describe the features of Frey syndrome (auriculotemporal nerve dysfunction with gustatory flushing) in childhood. STUDY DESIGN: A multicenter, retrospective, descriptive observational national case series study was conducted with the help of French academic societies. Diagnostic criteria were based on clinical history, and sometimes also on photographs or provocation tests. RESULTS: Forty-eight cases were identified, with 2 subtypes: 35 unilateral and 13 bilateral. Associated sweating was reported in only 10% of cases. Diagnosis was made in only 20% of children at the first consultation and inappropriate dietary restriction was prescribed for 21%. Instrumented vaginal delivery was significantly associated with unilateral forms (OR [unilateral vs bilateral] = 29; 95% CI 3.99-311.58; P < .001). The outcome was favorable overall with 57% regression, 20% recovery, and only 23% persistence of initial symptoms. Regression was more frequent in unilateral forms (OR = 6.60; 95% CI 1.23-44.04; P = .016), observed in 69% of unilateral forms at a median age of 27 (24-48) months. Recovery predominated in bilateral forms (OR = 0.05; 95% CI 0-0.38; P = .001), observed in 58% of bilateral cases at a median age of 8 (7-9) months. CONCLUSIONS: Frey syndrome in childhood is a rare but benign condition with mild symptoms and a favorable outcome in most cases. Unilateral forms are mostly associated with instrumented delivery. Pediatricians should be familiar with this disorder in order to avoid misdiagnosis, mainly as food allergy, and unnecessary referrals and tests.

Distinct epithelial gene expression phenotypes in childhood respiratory allergy.

Epithelial cell contribution to the natural history of childhood allergic respiratory disease remains poorly understood. Our aims were to identify epithelial pathways that are dysregulated in different phenotypes of respiratory allergy. We established gene expression signatures of nasal brushings from children with dust mite-allergic rhinitis, associated or not associated with controlled or uncontrolled asthma. Supervised learning and unsupervised clustering were used to predict the different subgroups of patients and define altered signalling pathways. These profiles were compared with those of primary cultures of human nasal epithelial cells stimulated with either interleukin (IL)-4, IL-13, interferon (IFN)-α, IFN-ß or IFN-γ, or during in vitro differentiation. A supervised method discriminated children with allergic rhinitis from healthy controls (prediction accuracy 91%), based on 61 transcripts, including 21 T-helper cell (Th) type 2-responsive genes. This method was then applied to predict children with controlled or uncontrolled asthma (prediction accuracy 75%), based on 41 transcripts: nine of them, which were down-regulated in uncontrolled asthma, are directly linked to IFN. This group also included GSDML, which is genetically associated with asthma. Our data revealed a Th2-driven epithelial phenotype common to all children with dust mite allergic rhinitis. It highlights the influence of epithelially expressed molecules on the control of asthma, in association with atopy and impaired viral response.