Omalizumab for the Treatment of Multiple Food Allergies.

BACKGROUND: Food allergies are common and are associated with substantial morbidity; the only approved treatment is oral immunotherapy for peanut allergy. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.).

Precautionary Allergen Labeling: Avoidance for All?

PURPOSE OF REVIEW: Precautionary allergen labeling (PAL) suggests the risk of unintended allergen presence (UAP) in food but is unregulated in most countries and inconsistently applied by food manufacturers. This review evaluates the current use of PAL, its relevance to allergic consumers, and weighs possible advantages and disadvantages of avoiding products with PAL. RECENT FINDINGS: In most countries, manufacturers are free to decide whether, when, and how to apply PAL resulting in inconsistencies and consumer confusion. Patients with food allergy often interpret PAL incorrectly and without guidance from their health care providers. Health care providers are also prone to misinterpreting PAL, indicating a need for better education. Consumers desire guidance on whether to avoid products with PAL or not. Until further regulatory guidance is available, shared decision-making between patient and provider is required to offer individualized, rather than one-size-fits-all, approaches to PAL.

The immune-supportive diet in allergy management: A narrative review and proposal.

The role of nutrition is increasingly recognized in the management of chronic immune diseases. However, the role of an immune-supportive diet as adjuvant therapy in the management of allergic disease has not been similarly explored. This review assesses the existing evidence for a relationship between nutrition, immune function, and allergic disease from a clinical perspective. In addition, the authors propose an immune-supportive diet to enhance dietary interventions and complementing other therapeutic options for allergic disease from early life to adulthood. A narrative review of the literature was conducted, to determine the evidence of the relationship between nutrition and immune function, overall health, epithelial barrier function, and gut microbiome, particularly in relation to allergy. Studies on food supplements were excluded. The evidence was assessed and utilized to develop a sustainable immune-supportive diet to complement other therapies in allergic disease. The proposed diet consists of a highly diverse range of fresh, whole, and minimally processed plant-based and fermented foods supplemented with moderate amounts of nuts, omega-3-rich foods and animal-based products in proportional amounts of the EAT-Lancet diet, such as (fatty) fish, (fermented) milk products which may be full-fat and eggs, lean meat or poultry, which may be free-range or organic.

Detection and management of milk allergy: Delphi consensus study.

BACKGROUND: There is significant overdiagnosis of milk allergy in young children in some countries, leading to unnecessary use of specialized formula. This guidance, developed by experts without commercial ties to the formula industry, aims to reduce milk allergy overdiagnosis and support carers of children with suspected milk allergy. METHODS: Delphi study involving two rounds of anonymous consensus building and an open meeting between January and July 2021. Seventeen experts in general practice, nutrition, midwifery, health visiting, lactation support and relevant areas of paediatrics participated, located in Europe, North America, Middle East, Africa, Australia and Asia. Five authors of previous milk allergy guidelines and seven parents provided feedback. FINDINGS: Participants agreed on 38 essential recommendations through consensus. Recommendations highlighted the importance of reproducibility and specificity for diagnosing milk allergy in children with acute or delayed symptoms temporally related to milk protein ingestion; and distinguished between children directly consuming milk protein and exclusively breastfed infants. Consensus was reached that maternal dietary restriction is not usually necessary to manage milk allergy, and that for exclusively breastfed infants with chronic symptoms, milk allergy diagnosis should only be considered in specific, rare circumstances. Consensus was reached that milk allergy diagnosis does not need to be considered for stool changes, aversive feeding or occasional spots of blood in stool, if there is no temporal relationship with milk protein ingestion. When compared with previous guidelines, these consensus recommendations resulted in more restrictive criteria for detecting milk allergy and a more limited role for maternal dietary exclusions and specialized formula. INTERPRETATION: These new milk allergy recommendations from non-conflicted, multidisciplinary experts advise narrower criteria, more prominent support for breastfeeding and less use of specialized formula, compared with current guidelines.

Evaluation of the introduction of allergen-containing foods: Feeding Infants and Toddlers Study 2016.

BACKGROUND: Guidelines on the early introduction of allergen-containing foods are evolving; however, little national data exist defining current allergen-feeding practices. OBJECTIVE: To investigate the consumption rates of foods containing egg and peanut among infants and toddlers before the guideline changes in 2017. METHODS: The Feeding Infants and Toddlers Study 2016 was conducted nationally among 3235 caregivers with a child under 4 years of age. The 24-hour dietary recalls were reviewed for peanut or egg ingredients. Participants were categorized as "consuming peanut or egg-containing foods" or "not consuming peanut or egg-containing foods." Data on physician-diagnosed food allergies and avoidance were collected. RESULTS: The consumption rates of peanut- and egg-containing foods were low. For the age group of 4 to 5.9 months, 0.3% reported peanut consumption and 2.4% reported egg consumption. For the age group of 6 to 8.9 months, 0.9% reported eating peanut-containing foods and 13.0% egg, and for the age group of 9 to 11.9 months, 5.5% were consuming peanut-containing foods and 33.2% egg-containing foods. Peanut or egg ingredients were identified in the diet of children whose caregivers reported avoidance. CONCLUSION: Before the publication of the 2017 Addendum Guidelines for the Prevention of Peanut Allergy, there were low rates of reported peanut consumption across the study population with less than 1% of any age group before 9 months of age and less than 6% in any age group before 12 months of age consuming peanut on the 24-hour recall day. In addition, reported egg consumption was low and increased with age. These results serve as an important baseline comparison for future studies evaluating the implementation and impact of early peanut and egg introduction.

The practical dietary management of food protein-induced enterocolitis syndrome.

OBJECTIVE: Food protein-induced enterocolitis syndrome (FPIES) is a non-immunoglobulin E-mediated food allergy with potential risk of malnutrition related to the early onset of disease, frequent avoidance of cow's milk, and the possibility of multiple food triggers. This publication is aimed at providing an evidence-based, practical approach to the dietary management of FPIES. DATA SOURCES: This is a narrative review summarizing information from national and international guidelines, retrospective studies, population studies, review articles, case reports, and case series to evaluate for nutritional risk and develop guidance for risk reduction in children with FPIES. STUDY SELECTIONS: We have included retrospective clinical cohort studies, population-based studies, case reports, and case studies. We did not exclude any studies identified owing to the small number of studies addressing the nutritional management of individuals with FPIES. RESULTS: Children with FPIES are at risk of malnutrition owing to suboptimal oral intake, limited food choices, and knowledge deficits related to feeding. In particular, children with 3 or more FPIES triggers seem to be at increased risk for poor weight gain and developing food aversion. Caregivers of children with FPIES also report a high degree of psychosocial burden. CONCLUSION: Appropriate dietary management entails the following 3 essential components: supporting normal growth and development, avoidance of allergens, and advancement of complementary foods. Education to avoid the trigger food and assisting caregivers in creating an individualized, well-designed complementary feeding plan to meet the infant's nutritional needs for optimal growth and development are essential management strategies.

Dietary factors during pregnancy and atopic outcomes in childhood: A systematic review from the European Academy of Allergy and Clinical Immunology.

RATIONALE: Allergic diseases are an increasing public health concern, and early life environment is critical to immune development. Maternal diet during pregnancy has been linked to offspring allergy risk. In turn, maternal diet is a potentially modifiable factor, which could be targeted as an allergy prevention strategy. In this systematic review, we focused on non-allergen-specific modifying factors of the maternal diet in pregnancy on allergy outcomes in their offspring. METHODS: We undertook a systematic review of studies investigating the association between maternal diet during pregnancy and allergic outcomes (asthma/wheeze, hay fever/allergic rhinitis/seasonal allergies, eczema/atopic dermatitis (AD), food allergies, and allergic sensitization) in offspring. Studies evaluating the effect of food allergen intake were excluded. We searched three bibliographic databases (MEDLINE, EMBASE, and Web of Science) through February 26, 2019. Evidence was critically appraised using modified versions of the Cochrane Collaboration Risk of Bias tool for intervention trials and the National Institute for Clinical Excellence methodological checklist for cohort and case-control studies and meta-analysis performed from RCTs. RESULTS: We identified 95 papers: 17 RCTs and 78 observational (case-control, cross-sectional, and cohort) studies. Observational studies varied in design and dietary intakes and often had contradictory findings. Based on our meta-analysis, RCTs showed that vitamin D supplementation (OR: 0.72; 95% CI: 0.56-0.92) is associated with a reduced risk of wheeze/asthma. A positive trend for omega-3 fatty acids was observed for asthma/wheeze, but this did not reach statistical significance (OR: 0.70; 95% CI: 0.45-1.08). Omega-3 supplementation was also associated with a non-significant decreased risk of allergic rhinitis (OR: 0.76; 95% CI: 0.56-1.04). Neither vitamin D nor omega-3 fatty acids were associated with an altered risk of AD or food allergy. CONCLUSIONS: Prenatal supplementation with vitamin D may have beneficial effects for prevention of asthma. Additional nutritional factors seem to be required for modulating the risk of skin and gastrointestinal outcomes. We found no consistent evidence regarding other dietary factors, perhaps due to differences in study design and host features that were not considered. While confirmatory studies are required, there is also a need for performing RCTs beyond single nutrients/foods.

Food protein-induced enterocolitis syndrome.

Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE-mediated gastrointestinal food allergic disorder that has gained a major interest the past decade. FPIES prevalence, which still needs to be accurately determine in different populations, appears to be higher than previously thought (ie up to 0.7% in infants in the 1st year of life). FPIES to seafood in adults is also increasingly reported; limited data suggest that adult FPIES is most commonly triggered by shellfish, tends to affect females more than men, is characterized by a significant delay in diagnosis and a prolonged course. The first international consensus guidelines on diagnosis and management of FPIES have been published in 2017, proposing new diagnostic criteria as well as new criteria for a positive oral food challenge. However, there is a need to develop new biomarkers to improve the diagnosis and management of FPIES patients, and this requires a better understanding of the pathophysiology. Recently, the role of T cells has been questioned and a major role of innate immune cells has been suggested in acute FPIES. Regarding the treatment of acute FPIES reaction, ondansetron has emerged as an adjunct to intravenous rehydration in moderate-severe reactions and as a first-line treatment in mild reactions. Important information regarding the nutritional management of FPIES patients that might be complex has also been provided in the international guidelines. In this review, we discuss recent advances regarding all those different aspects.

New developments in patients with eosinophilic gastrointestinal diseases presented at the CEGIR/TIGERS Symposium at the 2018 American Academy of Allergy, Asthma & Immunology Meeting.

The Consortium of Eosinophilic Gastrointestinal Diseases and the International Gastrointestinal Eosinophil Researchers organized a day-long symposium at the recent 2018 Annual Meeting of the American Academy of Allergy, Asthma & Immunology, which was coupled for the first time with the World Allergy Organization meeting to create an international platform. The symposium featured experts in many facets of eosinophilic gastrointestinal diseases, including allergy, immunology, gastroenterology, pathology, and nutrition, and was a well-attended event. The basic science, genetics, cellular immunology, and clinical features of the diseases, with a focus on epithelial, eosinophil, and mast cell responses, as well as current and emerging treatment options, were reviewed. Here we briefly review some of the highlights of the material presented at the meeting.

International consensus guidelines for the diagnosis and management of food protein-induced enterocolitis syndrome: Executive summary-Workgroup Report of the Adverse Reactions to Foods Committee, American Academy of Allergy, Asthma & Immunology.

Food protein-induced enterocolitis (FPIES) is a non-IgE cell- mediated food allergy that can be severe and lead to shock. Despite the potential seriousness of reactions, awareness of FPIES is low; high-quality studies providing insight into the pathophysiology, diagnosis, and management are lacking; and clinical outcomes are poorly established. This consensus document is the result of work done by an international workgroup convened through the Adverse Reactions to Foods Committee of the American Academy of Allergy, Asthma & Immunology and the International FPIES Association advocacy group. These are the first international evidence-based guidelines to improve the diagnosis and management of patients with FPIES. Research on prevalence, pathophysiology, diagnostic markers, and future treatments is necessary to improve the care of patients with FPIES. These guidelines will be updated periodically as more evidence becomes available.

Efficacy of a 4-Food Elimination Diet for Children With Eosinophilic Esophagitis.

BACKGROUND & AIMS: A 6-food elimination diet induces remission in most children and adults with eosinophilic esophagitis (EoE). The effectiveness of empiric elimination of only 4 foods has not been studied in children. We performed a prospective observational outcome study in children with EoE treated with dietary exclusion of cow's milk, wheat, egg, and soy. The objective was to assess the clinical, endoscopic, and histologic efficacy of this treatment in EoE. METHODS: We recruited children (1-18 years old, diagnosed per consensus guidelines) from 4 medical centers. Study participants (n = 78) were given a proton pump inhibitor twice daily and underwent a baseline esophagogastroduodenoscopy. Subjects were instructed on dietary exclusion of cow's milk, wheat, egg, and soy. Clinical, endoscopic, and histologic assessments were made after 8 weeks. Responders had single foods reintroduced for 8 weeks, with repeat endoscopy to assess for recurrence of active disease. The primary endpoint was histologic remission (fewer than 15 eosinophils per high-powered field). Secondary endpoints included symptom and endoscopic improvements and identification of foods associated with active histologic disease. RESULTS: After 8 weeks on 4-food elimination diet, 50 subjects were in histologic remission (64%). The subjects' mean baseline clinical symptoms score was 4.5, which decreased to 2.3 after 8 weeks of 4-food elimination diet (P < .001). The mean endoscopic baseline score was 2.1, which decreased to 1.3 (P < .001). After food reintroduction, the most common food triggers that induced histologic inflammation were cow's milk (85%), egg (35%), wheat (33%), and soy (19%). One food trigger that induced recurrence of esophageal inflammation was identified in 62% of patients and cow's milk-induced EoE was present in 88% of these patients. CONCLUSIONS: In a prospective study of children with EoE, 8 weeks of 4-food elimination diet induced clinical, endoscopic, and histologic remission in more than 60% of children with EoE. Although less restrictive than 6-food elimination diet, 4-food elimination diet was nearly as effective, and can be recommended as a treatment for children with EoE.

Growth comparison in children with and without food allergies in 2 different demographic populations.

OBJECTIVE: To examine the effects of food avoidance on the growth of children with food allergies. STUDY DESIGN: A retrospective chart review was performed for children with and without food allergies followed at 2 New York City general pediatric practices. Charts were selected based on codes from the International Classification of Diseases, 9th Revision, for well child visit, food allergy, anaphylaxis, and/or epinephrine autoinjector prescriptions. Heights and weights were obtained to calculate body mass index, height, and weight z-scores. RESULTS: Of the 9938 children seen, 439 (4.4%) were avoiding one or more foods. Of those with commercial insurance, children with food allergies were significantly shorter (mean height z-score = 0.06; P = .01) and weighed less (mean weight z-score -0.1; P = .006) than children without food allergies (mean height z-score = 0.42; mean weight z-score = 0.07). In contrast, children with food allergies and state insurance were not smaller in height or weight compared with children without food allergies. Among white subjects, there was a significant effect of food allergies on height and weight (ANOVA for height P = .012, for weight P = .0036) that was not observed for Hispanic/Latino, black, or Asian subjects. Children with allergies to milk weighed significantly less than children without milk allergies (P = .0006). CONCLUSIONS: Children with food allergies and commercial insurance have significant impairment in growth compared with those without food allergies. Additionally, children avoiding all forms of milk are shorter and weigh less than matched counterparts. Therefore, height and weight measurements should be assessed routinely in children with food allergies because there is risk for growth impairment in this population.

Dietary Management of Eosinophilic Esophagitis.

Eosinophilic esophagitis (EoE) is a chronic immune-mediated food allergy-driven disease characterized by eosinophilic inflammation of the esophagus leading to symptoms of esophageal dysfunction. Prior studies have supported the key role of food allergen exposure as the main driver behind the etiopathogenesis showing that removal of food antigens can result in disease remission in both children and adults. These landmark studies serve as the basis for the rising interest and evolution of dietary therapy in EoE. This article will focus on the rationale for dietary therapy in EoE and provide helpful tools for the implementation of dietary therapy in practice.