Tolerance induction through early feeding to prevent food allergy in infants and children with sensitization against food allergens (TIFFANI): rationale, study design, and methods of a randomized controlled trial.

BACKGROUND: Children with sensitization against foods have to be orally food-challenged before eating these foods for the first time. However, the waiting time for an oral food challenge (OFC) in Germany is about 3-6 months. In contrast, there are hints that an early introduction of allergenic foods might be protective regarding the development of food allergy. The aim of this clinical trial is therefore to investigate, whether an introduction and regular consumption of small amounts of food allergens is safe and will result in an increase of tolerance in children with sensitization against food allergens with unknown clinical relevance. METHODS: In this randomized, placebo-controlled, double-blind, single-center trial, 138 children (8 months to 4 years of age) sensitized to the target allergen(s) hen's egg, cow's milk, peanuts, and/or hazelnuts with unknown clinical relevance will be randomized in a 1:1 ratio to either an active or a placebo group, daily receiving a rusk-like biscuit powder with or without the target allergen(s) for 3-6 months until an OFC will be performed in routine diagnostics. The primary endpoint is an IgE-mediated food allergy to the primary target allergen, after the interventional period. DISCUSSION: Children with sensitization against food allergens with unknown clinical relevance often have to avoid the corresponding foods for several months until an OFC is performed. Therefore, the "window of opportunity" for an early preventive introduction of allergenic foods might be missed. This trial will assess whether an introduction of small allergen amounts will favor tolerance development in these children. TRIAL REGISTRATION: German Clinical Trials Register DRKS00032769. Registered on 02 October 2023.

An overview of a preliminary multicenter retrospective study on food and drug allergies in Moroccan pediatric population.

Introduction: this study aimed to investigate the prevalence and management of food allergies (FA) and drug allergies (DA) in Morocco. Sparse and conflicting epidemiological data exist on the exact prevalence of allergies in the country. The rise in allergies can be attributed to various factors. Methods: the study analyzed data from patients with suspected FA and DA who sought medical attention. Statistical tests were used to analyze the data, percentages were computed for qualitative variables, and for quantitative variables, medians or means accompanied by standard deviations (SD) were calculated. The Chi-square test was employed to assess categorical variables. A p-value < 0.05 was considered statistically significant. Results: Cow's milk was the most reported food allergen (58.2%), followed by egg and nuts (23.4% and 12.1%, respectively). The most affected age group was children under 5 years. Antibiotics were the leading cause of reported drug allergies (44.8%), particularly Beta-lactams. Immediate reactions were commonly associated with antibiotics and nonsteroidal anti-inflammatory drugs (NSAIDs). Symptoms of FA included acute urticaria, vomiting, anaphylactic shock, and facial edema. Urticaria was the most frequent symptom of DA. Antihistamines and corticosteroids were the main treatments used for both FA and DA. Conclusion: the prevalence of FA and DA in Morocco remains uncertain due to limited data. There is a need for centralized data collection and awareness among clinicians and the general population regarding allergies. The study highlights the importance of proper diagnosis and management of allergies to ensure patient safety. The findings emphasize the necessity of establishing a mandatory center for allergy care in Morocco to improve the understanding and management of allergic conditions.

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.

Perspectives in the validation of DEFASE: a paradigm shift in food allergy management.

PURPOSE OF REVIEW: To explore the groundbreaking international consensus on the DEFASE (DEfinition of Food Allergy Severity) project as a revolutionary grading system for IgE-mediated food allergy severity. Against the backdrop of the growing public health challenge posed by food allergy, this article delves into the importance of validating and implementing DEFASE in real-world clinical settings. RECENT FINDINGS: With new therapeutic options available for food allergy, including biologics alongside immunotherapy, it is urgent to properly support clinical decision-making in the management of the disease. The DEFASE score is the first international consensus-based grading system of severity associated with food allergy as a whole disease embracing multidisciplinary perspectives from different stakeholders involved. In its current version, this comprehensive scoring system has been developed to be used in research settings. SUMMARY: The review emphasizes the potential impact of DEFASE on patient outcomes, healthcare management, and resource allocation, underscoring its significance for the allergy scientific community. Future research should focus on internal and external validation of the scoring system, targeting these models to various food allergenic sources, populations, and settings.

Heterogeneity of food protein-induced enterocolitis syndrome (FPIES).

Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE-mediated food allergy with gastrointestinal symptoms such as vomiting and diarrhea. The development of international consensus guidelines for the diagnosis and management of FPIES in 2017 enabled us to compare patients worldwide, regardless of geographic variation in disease features. As a result, it has become clear that there is heterogeneity among patients with FPIES or that there are cases that partly fit the diagnostic criteria for FPIES but have different characteristics. This review highlights the heterogeneity in FPIES characteristics in terms of trigger foods, the age of onset, differences in geographic regions, and symptoms; it further proposes four disease entities, including acute FPIES in children, acute FPIES in adults, chronic FPIES, and early-onset neonatal FPIES, depending on the age of onset and presumed pathophysiology. The major symptoms at onset and trigger foods differ in acute FPIES in children, acute FPIES in adults, and chronic FPIES, whereas the disease entities may share a similar pathophysiology. Early-onset neonatal FPIES may have a different pathophysiology than acute or chronic FPIES, and may not necessarily fulfil the full diagnostic criteria for acute or chronic FPIES described in the international consensus guidelines. Due to the similarity in symptoms, early-onset neonatal FPIES may sometimes be misdiagnosed as necrotizing enterocolitis. We aim to increase awareness of FPIES among medical staff in pediatrics, neonatology, and internal medicine and promote research, to gain a better understanding of the heterogeneity and pathophysiology of FPIES.

Core Outcome Set for IgE-mediated food allergy clinical trials and observational studies of interventions: International Delphi consensus study 'COMFA'.

BACKGROUND: IgE-mediated food allergy (FA) is a global health concern with substantial individual and societal implications. While diverse intervention strategies have been researched, inconsistencies in reported outcomes limit evaluations of FA treatments. To streamline evaluations and promote consistent reporting, the Core Outcome Measures for Food Allergy (COMFA) initiative aimed to establish a Core Outcome Set (COS) for FA clinical trials and observational studies of interventions. METHODS: The project involved a review of published clinical trials, trial protocols and qualitative literature. Outcomes found as a result of review were categorized and classified, informing a two-round online-modified Delphi process followed by hybrid consensus meeting to finalize the COS. RESULTS: The literature review, taxonomy mapping and iterative discussions with diverse COMFA group yielded an initial list of 39 outcomes. The iterative online and in-person meetings reduced the list to 13 outcomes for voting in the formal Delphi process. One more outcome was added based on participant suggestions after the first Delphi round. A total of 778 participants from 52 countries participated, with 442 participating in both Delphi rounds. No outcome met a priori criteria for inclusion, and one was excluded as a result of the Delphi. Thirteen outcomes were brought to the hybrid consensus meeting as a result of Delphi and two outcomes, 'allergic symptoms' and 'quality of life' achieved consensus for inclusion as 'core' outcomes. CONCLUSION: In addition to the mandatory reporting of adverse events for FA clinical trials or observational studies of interventions, allergic symptoms and quality of life should be measured as core outcomes. Future work by COMFA will define how best to measure these core outcomes.

Precision allergy molecular diagnosis applications in food allergy.

PURPOSE OF REVIEW: Precision medicine has become important in the diagnosis and management of food allergies. This review summarizes the latest information regarding molecular allergology, an essential component of food allergy managements. RECENT FINDINGS: Component-resolved diagnostics (CRD) can be used to investigate sensitization to allergens based on symptoms and to reveal co-sensitization and/or cross-sensitization in patients with allergies. The following allergen components are known to be associated with symptoms: ovomucoid from eggs, omega-5 gliadin from wheat, and many storage proteins (Gly m 8 from soy, Ara h 2 from peanut, Cor a 14 from hazelnut, Ana o 3 from cashew nut, Jug r 1 from walnut, and Ses i 1 from sesame). Recent studies on allergens of macadamia nuts (Mac i 1 and Mac i 2), almonds (Pru du 6), fish (parvalbumin and collagen), and shrimp (Pem m 1 and Pem m 14) have provided additional information regarding CRD. In addition, Pru p 7 is a risk factor for systemic reactions to peaches and has recently been found to cross-react with cypress and Japanese cedar pollen. SUMMARY: CRD provides information of individualized sensitization profiles related to symptoms and severity of allergies in patients. Clinical practice based on CRD offers many benefits, such as higher diagnostic accuracy and improved management of individual patients.

Management of food allergy based on oral food challenge.

PURPOSE OF REVIEW: Food allergy is a growing health problem that affects both patients and society in multiple ways. Despite the emergence of novel diagnostic tools, such as component-resolved diagnostics (CRD) and basophil activation tests (BAT), oral food challenge (OFC) still plays an indispensable role in the management of food allergies. This review aimed to highlight the indications and safety concerns of conducting an OFC and to provide insights into post-OFC management based on recent findings. RECENT FINDINGS: Standardized OFC protocols have regional diversification, especially in Japan and Western countries. Recent studies suggested that the interval between doses should be at least more than an hour. Furthermore, applying a stepwise method tailored to the patient's specific immunoglobulin E level and history of anaphylaxis seems to mitigate these risks. Recent surveys have shown that, following a positive OFC, options other than strict avoidance are also selected. SUMMARY: OFC serves diverse purposes, yet the risks it carries warrant caution. The stepwise protocol appears promising for its safety. Subthreshold consumption following OFC shows potential; however, further research on its efficacy and safety is required. Management following OFC should be tailored and well discussed between clinicians and patients.

Immunoassay Testing of Alpha-Gal Specific Immunoglobulin-E: Data from a National Reference Laboratory.

BACKGROUND: Immunoassay measurements of serum alpha-gal (AG) specific IgE (sIgE) enable antibody detection and quantification with high sensitivity and specificity and are essential for AG syndrome diagnosis and patient management. We here present and analyze results from over 15 000 patient serum samples tested using the ImmunoCAP (Thermo/Phadia) assay. METHODS: AG-sIgE levels and positivity rates were correlated to patient age, gender, geographic location, repeat testing results, sIgE levels to co-tested red meat whole allergen extracts, and Rocky Mountain spotted fever (RMSF) serology performed on a subset of patient samples. RESULTS: Of the tested samples, 36.7% contained detectable (>0.1 KUA/L) AG-sIgE. Antibody levels were higher in patients of older age, in samples submitted from lower midwestern and southern states, and during the June-December period of the year. Specific IgE to co-tested red meat whole allergens showed moderate to strong correlation to AG-sIgE and were of lower levels. Samples with positive RMSF IgG titers (≥1:64) were of overall higher AG-IgE levels. CONCLUSION: Findings are consistent with the role of lone star ticks in AG syndrome pathogenesis. Levels of measured sIgE to AG are higher than co-tested sIgE to red meat whole allergen, consistent with the improved diagnostic performance of component-resolved testing.

Allergy to Gibberellin-regulated proteins in an adolescent: A case of orange-induced anaphylaxis mediated by cofactors.

This report is a case of anaphylaxis in an adolescent due to allergy to gibberellin-regulated proteins mediated by cofactors, in probable relation to a pollen/food allergy syndrome. It should also emphasizes the importance of obtaining a faithful clinical history, especially when it comes to adolescent patients as they tend to initiate toxic habits.

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.).

Current and future perspectives on the consensus guideline for food protein-induced enterocolitis syndrome (FPIES).

Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE mediated food allergy presenting with delayed onset of projectile vomiting in the absence of cutaneous and respiratory symptoms. The pathophysiology of FPIES remains poorly characterized. The first international consensus guidelines for FPIES were published in 2017 and provided clinicians with parameters on the diagnosis and treatment of FPIES. The guidelines have served as a resource in the recognition and management of FPIES, contributing to an increased awareness of FPIES. Since then, new evidence has emerged, shedding light on adult-onset FPIES, the different phenotypes of FPIES, the recognition of new food triggers, center-specific food challenge protocols and management of acute FPIES. Emerging evidence indicates that FPIES impacts both pediatric and adult population. As a result, there is growing need to tailor the consensus guidelines to capture diagnoses in both patient groups. Furthermore, it is crucial to provide food challenge protocols that meet the needs of both pediatric and adult FPIES patients, as well as the subset of patients with atypical FPIES. This review highlights the evolving clinical evidence relating to FPIES diagnosis and management published since the 2017 International FPIES Guidelines. We will focus on areas where recent published evidence may support evolution or revision of the guidelines.