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Food allergies are common and are associated with substantial morbidity; the only approved treatment is oral immunotherapy for peanut allergy. In this trial, we assessed whether omalizumab, a monoclonal anti-IgE antibody, would be effective and safe as monotherapy in patients with multiple food allergies. Persons 1 to 55 years of age who were allergic to peanuts and at least two other trial-specified foods (cashew, milk, egg, walnut, wheat, and hazelnut) were screened. Inclusion required a reaction to a food challenge of 100 mg or less of peanut protein and 300 mg or less of the two other foods. Participants were randomly assigned, in a 2:1 ratio, to receive omalizumab or placebo administered subcutaneously (with the dose based on weight and IgE levels) every 2 to 4 weeks for 16 to 20 weeks, after which the challenges were repeated. The primary end point was ingestion of peanut protein in a single dose of 600 mg or more without dose-limiting symptoms. The three key secondary end points were the consumption of cashew, of milk, and of egg in single doses of at least 1000 mg each without dose-limiting symptoms. The first 60 participants (59 of whom were children or adolescents) who completed this first stage were enrolled in a 24-week open-label extension. Of the 462 persons who were screened, 180 underwent randomization. The analysis population consisted of the 177 children and adolescents (1 to 17 years of age). A total of 79 of the 118 participants (67%) receiving omalizumab met the primary end-point criteria, as compared with 4 of the 59 participants (7%) receiving placebo (P<0.001). Results for the key secondary end points were consistent with those of the primary end point (cashew, 41% vs. 3%; milk, 66% vs. 10%; egg, 67% vs. 0%; P<0.001 for all comparisons). Safety end points did not differ between the groups, aside from more injection-site reactions in the omalizumab group. In persons as young as 1 year of age with multiple food allergies, omalizumab treatment for 16 weeks was superior to placebo in increasing the reaction threshold for peanut and other common food allergens. (Funded by the National Institute of Allergy and Infectious Diseases and others; ClinicalTrials.gov number, NCT03881696.).

Egg allergy is a common and difficult pediatric problem. In this trial, the investigators found that oral treatment with escalating doses of egg protein enabled about one in four children with known egg allergy to eat egg without allergic symptoms. In the United States, 4% of children have a food allergy, 1 which affects health and quality of life. 2 Egg allergy has a cumulative prevalence of approximately 2.6% by 2.5 years of age, 3 with allergic reactions varying in severity from mild urticaria to systemic anaphylaxis. Severe allergic reactions can occur with a single bite of cooked egg (approximately 70 mg of egg protein). Children with egg allergy are placed on egg-free diets, but total avoidance of egg is difficult. Avoidance places a constant responsibility on patients and caregivers, leaves patients vulnerable to unintentional ingestion and anaphylaxis, and influences quality of life. . . .

Purpose of Review To review current and future treatment options for IgE-mediated food allergy. Recent Findings Recent years have seen major developments in both allergen-specific and allergen-non-specific treatment options, with the first FDA-approved peanut oral immunotherapy (OIT) product becoming available in 2020. In addition to OIT, other immunotherapy modalities, biologics, adjunct therapies, and novel therapeutics are under investigation. Summary Food allergy is a potentially life-threatening condition associated with a significant psychosocial impact. Numerous products and protocols are under investigation, with most studies focusing on OIT. A high rate of adverse events, need for frequent office visits, and cost remain challenges with OIT. Further work is needed to unify outcome measures, develop treatment protocols that minimize adverse events, establish demographic and clinical factors that influence candidate selection, and identify patient priorities.

Marc Rothenberg, John Harley and colleagues present the results of a genome-wide association study of eosinophilic esophagitis. They discover an association with variants near CAPN14 and show that CAPN14 is expressed specifically in the esophagus and is upregulated in esophageal biopsies of individuals with active disease. Eosinophilic esophagitis (EoE) is a chronic inflammatory disorder associated with allergic hypersensitivity to food. We interrogated >1.5 million genetic variants in EoE cases of European ancestry and subsequently in a multi-site cohort with local and out-of-study control subjects. In addition to replicating association of the 5q22 locus (meta-analysis P = 1.9 × 10 −16 ), we identified an association at 2p23 spanning CAPN14 ( P = 2.5 × 10 −10 ). CAPN14 was specifically expressed in the esophagus, was dynamically upregulated as a function of disease activity and genetic haplotype and after exposure of epithelial cells to interleukin (IL)-13, and was located in an epigenetic hotspot modified by IL-13. Genes neighboring the top 208 EoE-associated sequence variants were enriched for esophageal expression, and multiple loci for allergic sensitization were associated with EoE susceptibility (4.8 × 10 −2 < P < 5.1 × 10 −11 ). We propose a model to explain the tissue-specific nature of EoE that involves the interplay of allergic sensitization with an EoE-specific, IL-13–inducible esophageal response involving CAPN14.

Purpose Food allergy management places a daily psychosocial burden on patients and their caregivers. New food allergy treatments may positively impact their lives, but also introduce new stressors. The purpose of this paper is to provide an overview of the current state of the literature regarding patients’ and caregivers’ food allergy experiences and needs within the United States as well as a set of recommendations regarding how best to proceed with patient-centered development and evaluation of new food allergy treatments. Recent findings The first pharmaceutical-grade product for peanut oral immunotherapy was approved in the United States for children aged 4–17 years following a successful international Phase 3 trial. This new treatment is only the first of several food allergy treatments currently under development. Patients will soon be presented with multiple options for food allergy treatment and will need to make decisions about what treatment is best for them. Summary Allergy researchers and providers are encouraged to consider patients’ perspectives and needs when developing and evaluating new food allergy treatments. Recommendations regarding next steps include the development of new patient-reported outcome tools, focus on psychosocial support, health disparities, and financial implications, and research harmonization and interdisciplinary collaboration.

Eosinophilic esophagitis (EoE) is a chronic inflammatory disease of the esophagus triggered by immune hypersensitivity to food. Herein, we tested whether genetic risk factors for known, non-allergic, immune-mediated diseases, particularly those involving autoimmunity, were associated with EoE risk. We used the high-density Immunochip platform, encoding 200,000 genetic variants for major auto-immune disease. Accordingly, 1214 subjects with EoE of European ancestry and 3734 population controls were genotyped and assessed using data directly generated or imputed from the previously published GWAS. We found lack of association of EoE with the genetic variants in the major histocompatibility complex (MHC) class I, II, and III genes and nearly all other loci using a highly powered study design with dense genotyping throughout the locus. Importantly, we identified an EoE risk locus at 16p13 with genome-wide significance (Pcombined=2.05 × 10−9, odds ratio = 0.76−0.81). This region is known to encode for the genes CLEC16A, DEXI, and CIITI, which are expressed in immune cells and esophageal epithelial cells. Suggestive EoE risk were also seen 5q23 (intergenic) and 7p15 (JAZF1). Overall, we have identified an additional EoE risk locus at 16p13 and highlight a shared and unique genetic etiology of EoE with a spectrum of immune-associated diseases.

This Anaphylaxis Manifesto calls on communities to prioritise 10 practical actions to improve the lives of people at risk of serious allergic reactions. The Global Allergy and Asthma European Network and the European Federation of Allergy and Airways Diseases Patients' Associations (EFA) compiled patient‐centric priorities. We used qualitative consensus methods, research evidence and feedback from over 200 patient groups, stakeholder organisations and healthcare professionals. We encourage healthcare, education and food organisations to collaborate with people at risk of serious allergic reactions to tackle safety, anxiety and financial burdens for individuals and societies. Key priorities for prevention include awareness‐raising campaigns for the public and professionals, school and workplace initiatives and mandatory precautionary allergen labels on food. Priorities for improving immediate and long‐term management include educating healthcare professionals, patients and schools about when and how to use adrenaline, funding two approved adrenaline devices for everyone at risk, and facilitating access to allergy specialists. Integrated care pathways should include clinical and non‐clinical management options such as individualised risk assessment and quality of life assessment, self‐management plans, dietetic and psychosocial support and peer support. Organisations around the world are committing to work together towards these priorities.

[...]most but not all studies assess desensitization by performing oral food challenges (OFC) intended to provoke clinical reactions, and these are not standardized either. The reason that this is important is that some participants achieving SU after OIT may have simply outgrown their allergy naturally while being treated, as has been shown to occur in rigorously controlled randomized studies of OIT and sublingual peanut IT [14,19-20]. [...]controlled trials address primary end points uniformly in all randomized arms, the occurrence of spontaneous resolution will obscure the effect of OIT in producing desired long-term outcomes.

Background Immunoglobulin E (IgE) and immunoglobulin G4 (IgG4) to peanut and its components may influence the clinical reactivity to peanut. Allergen‐specific immunotherapy is known for modifying both IgE and IgG4. Peanut oral immunotherapy may influence these serological parameters. Methods Exploratory analyses of serological data from participants receiving peanut (Arachis hypogaea) allergen powder‐dnfp (PTAH) and placebo in the double‐blind, randomized, phase 3 PALISADE trial were conducted to evaluate potential relationships between peanut‐specific and peanut component–specific (Ara h 1, Ara h 2, Ara h 3, Ara h 6, Ara h 8, and Ara h 9) IgE and IgG4 levels and clinical outcomes. Results A total of 269 participants (PTAH, n = 202; placebo, n = 67) were analyzed. No relationship was observed between specific IgE and IgG4 levels at screening and maximum tolerated peanut protein dose during screening or response status during exit double‐blind placebo‐controlled food challenge (DBPCFC). In PTAH‐treated participants, no relationship was observed between IgE and IgG4 levels at screening and maximum symptom severity during exit DBPCFC. Postscreening ratios (ie, postscreening/screening) in the PTAH group were significant at the end of updosing and exit visit for most components. Postscreening changes in specific IgE levels were more pronounced with PTAH versus placebo for most components. Conclusions Specific IgE and IgG4 levels at screening are not correlated with screening or exit DBPCFC results, and are not predictive of clinical response to PTAH. Peanut (Arachis hypogaea) allergen powder‐dnfp contains the relevant and immunodominant allergens, inducing immunological changes with the treatment. Clinical Trial Registration ClinicalTrials.gov identifier: NCT02635776.

In the US and other developed countries, food allergy is a growing epidemic in pediatric populations with a substantial impact on health-related quality of life. As such, there are great efforts underway to unravel the mechanisms of oral mucosal tolerance and to better define the factors related to host and allergen exposure that contribute to the aberrant immune response leading to sensitization and clinical food allergy. Although more research is needed to eventually develop targeted treatment and prevention strategies, this review highlights our current understanding of the pathogenesis of IgE-mediated food allergy.