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Background: Food protein-induced enterocolitis syndrome (FPIES) is a food allergy primarily affecting infants, often leading to vomiting and shock. Due to its poorly understood pathophysiology and lack of specific biomarkers, diagnosis is frequently delayed. Understanding FPIES genetics can shed light on disease susceptibility and pathophysiology-key to developing diagnostic, prognostic, preventive and therapeutic strategies. Using a well-characterised cohort of patients we explored the potential genome-wide susceptibility factors underlying FPIES., Methods: Blood samples from 41 patients with oral food challenge-proven FPIES were collected for a comprehensive whole exome sequencing association study., Results: Notable genetic variants, including rs872786 (RBM8A), rs2241880 (ATG16L1) and rs2289477 (ATG16L1), were identified as significant findings in FPIES. A weighted SKAT model identified six other associated genes including DGKZ and SIRPA. DGKZ induces TGF-β signalling, crucial for epithelial barrier integrity and IgA production; RBM8A is associated with thrombocytopenia absent radius syndrome, frequently associated with cow's milk allergy; SIRPA is associated with increased neutrophils/monocytes in inflamed tissues as often observed in FPIES; ATG16L1 is associated with inflammatory bowel disease. Coexpression correlation analysis revealed a functional correlation between RBM8A and filaggrin gene (FLG) in stomach and intestine tissue, with filaggrin being a known key pathogenic and risk factor for IgE-mediated food allergy. A transcriptome-wide association study suggested genetic variability in patients impacted gene expression of RBM8A (stomach and pancreas) and ATG16L1 (transverse colon)., Conclusions: This study represents the first case-control exome association study of FPIES patients and marks a crucial step towards unravelling genetic susceptibility factors underpinning the syndrome. Our findings highlight potential factors and pathways contributing to FPIES, including epithelial barrier dysfunction and immune dysregulation. While these results are novel, they are preliminary and need further validation in a second cohort of patients., (© 2024 The Author(s). Clinical & Experimental Allergy published by John Wiley & Sons Ltd.)

Background: The supply chains of food raw materials have recently been heavily influenced by geopolitical events. Products that came from, or transited through, areas currently in conflict are now preferentially supplied from alternative areas. These changes may entail risks for food safety., Methods: We review the potential allergenicity of botanical impurities, specifically vegetable contaminants, with particular attention to the contamination of vegetable oils. We delve into the diverse types of botanical impurities, their sources, and the associated allergenic potential. Our analysis encompasses an evaluation of the regulatory framework governing botanical impurities in food labeling., Results: Unintended plant-derived contaminants may manifest in raw materials during various stages of food production, processing, or storage, posing a risk of allergic reactions for individuals with established food allergies. Issues may arise from natural occurrence, cross-contamination in the supply chain, and contamination at during production. The food and food service industries are responsible for providing and preparing foods that are safe for people with food allergies: we address the challenges inherent in risk assessment of botanical impurities., Conclusions: The presence of botanical impurities emerges as a significant risk factor for food allergies in the 2020s. We advocate for regulatory authorities to fortify labeling requirements and develop robust risk assessment tools. These measures are necessary to enhance consumer awareness regarding the potential risks posed by these contaminants.

Purpose of Review: In the last years, the interest of the scientific community toward food protein-induced enterocolitis syndrome (FPIES) has grown exponentially. We review here the peculiar characteristics of this syndrome., Recent Findings: The recent publication of the First International Consensus Guidelines allowed a positive interaction between different research groups with the aim of improving the diagnosis and management of patients affected by FPIES., Summary: Several fixed points have been placed on the diagnosis and management, but further studies are needed to clarify the many shadows that still surround different aspects of the syndrome, especially regarding the pathophysiology.

Purpose of Review: To perform a nonsystematic review of the literature on the microbiota in the different types of non-IgE-mediated food allergy., Recent Findings: The commonest non-IgE-mediated disorders managed by allergists include: eosinophilic esophagitis, food protein-induced enteropathy, food protein-induced enterocolitis syndrome, and food protein-induced allergic proctocolitis. The review of the literature describes how at phylum level we observe an increase of Proteobacteria in eosinophilic esophagitis esophageal microbiota and in food protein-induced enterocolitis syndrome, and food protein-induced allergic proctocolitis gut microbiota, while we observe an increase of Bacteroidetes in healthy controls. Several studies endorse the concept that a bloom of Proteobacteria in the gut reflects dysbiosis or an unstable gut microbial community structure. In several studies, the type of diet, the use of probiotics and in a single experience the use of fecal microbiota transplantation has produced significant variations of the microbiota., Summary: Genetic factors alone cannot account for the rapid rise in food allergy prevalence and the microbiome might be contributing to allergy risk. Our review showed that common features of the pathological microbiota among different types of non-IgE-mediated food allergy can be identified. These evidences suggest a possible role of the microbiota in the pathogenesis and non-IgE-mediated food allergies and the need to understand the effects of its modulation on the disorders themselves.

Background: The effects of omalizumab on food allergy thresholds have been little studied., Objective: To assess the real-life effects of omalizumab on food threshold tolerability in children treated for severe asthma., Methods: In this observational, real-life, efficacy study, we reviewed the food allergen thresholds of patients with severe asthma, as well as their immediate reactions to 2+ foods before and after a 4-month treatment with omalizumab. We also evaluated their control of asthma and their quality of life, as measured by Pediatric Quality of Life Inventory (PedsQL)., Results: Fifteen children, allergic to 37 foods, were evaluated. Omalizumab induced an increase in the allergen threshold for milk, egg, wheat, and hazelnut from a mean 1012.6 ± 1464.5 mg protein to 8727 ± 6463.3 eliciting dose (P < .001). A total of 70.4% of subjects tolerated the complete challenge dose after 4 months of treatment with omalizumab. These foods were reintroduced in the patients' diet without the need for any oral immunotherapy procedures. The remaining foods were partially tolerated. The number of reactions to the unintended ingestion of allergenic foods over 4 months dropped from 47 to 2. The PedsQL increased from 61 ± 5.32 to 87 ± 7.33 (parental judgment; P < .001) and from 65 ± 7.39 to 90 ± 4.54 (patients' judgment; P < .001). The mean cost of omalizumab was €1311.63 per month., Conclusions: During treatment with omalizumab for severe uncontrolled asthma, the food allergen threshold increases to 8.6 times its original value. The quality of life of patients also increased, due to a better asthma control and a reduction in dietary restrictions. The cost/benefit ratio of such treatment for selected cases of food allergy remains to be evaluated., (Copyright © 2019 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Purpose of Review: In the last years, food allergy treatment is moving away from food avoidance to interventional treatments. We review here the recent developments on immunotherapy with food allergens., Recent Findings: Oral immunotherapy remains the best studied form of food immunotherapy. In 2017, further evidence has been added to its efficacy. Its mechanisms of action are under scrutiny. To reduce its side effects, studies have been dedicated to the simultaneous use of biologics, in particular omalizumab. Among the other forms of food immunotherapy that are being developed, the epicutaneous application of food allergens is promising., Summary: The immunologic trajectories of the development of food tolerance may be intercepted by different forms of food immunotherapy. Research efforts aim to make these therapies feasible at the clinical level.

Purpose of Review: The prevalence of food allergy is increasing. More children are being diagnosed with food allergies, and it is taking longer to outgrow them, among those who develop tolerance. The aim of this review is to draw the profile of the persistent food allergic, so that prevention strategies can be developed and active treatment set up., Recent Findings: Many determinants are involved in food allergy prognosis: ethnicity and sex, type of food, innate immune system, eliciting dose, sensitization status and other biomarkers determination, gut microbiome composition, and the presence of comorbidities. Once identified, a persistent food allergy could be conveyed to active treatments, such as oral immunotherapy or the use of biologics, always taking into account their experimental nature., Summary: A better understanding of prognostic factors and phenotypes of food allergy is crucial in decision-making when it comes to food allergy prevention and management. A good classification of the allergic patient allows to determine the degree of exclusion diets and the timing of the reintroduction of avoided food when possible. In the cases of persistent and severe food allergy, many promising interventions are emerging which could improve prognosis and quality of care.

Background: An increasing number of infants are diagnosed with food protein-induced enterocolitis syndrome (FPIES), a non-IgE-mediated food allergy. Until now, T-cell, food-specific mechanisms have been hypothesized., Methods: Sixteen children (11M, 5F), affected by FPIES from cow's milk, wheat, fruit, rice, and others, experienced 25 acute episodes managed at our emergency department (ED) and eight FPIES reactions during oral food challenges (OFC). We compared the laboratory data in resting conditions, in the absence of infectious diseases, with data collected during the 25 acute ED episodes (blood samples drawn at 2-12 hours) and the eight positive OFCs (three samples at 2, 6, and 12 hours). The onset of symptoms was used as a reference time point., Results: In basal conditions, total IgE, WBC, neutrophil and eosinophil count, CRP, and SGPT were found normal. LDH and SGOT values were high (627.81±97.88 and 45.75±10.26 UI/L, respectively). During ED reactions, LDH and SGOT increased to 794.21±247.28 (P=.028) and 51.08±16.99 UI/L (P=.14) and neutrophils count and CRP to 8.44±3.82×10 3 /μL (P=.0009) and 3.27±5.73 mg/dL (P=.0014), respectively. During positive OFC, LDH and SGOT did not vary significantly; CRP increased from 0.14±0.18 to 2.49±3.65 mg/dL (P=.00189) and neutrophil count from 2.79±1.42 to 7.10±3.98×10 3 /μL (P=.00096)., Conclusions: FPIES reactions are characterized by neutrophilia and by a time-dependent, significant increase in CRP, indicating that inflammatory mechanisms are in place. This suggests new directions for research on FPIES pathogenesis., (© 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Purpose of Review: Severe cases of food allergy account for the majority of the burden in terms of risks, quality of life, and resource expenditure. The traditional approach to these forms has been strict avoidance. More recently, Oral ImmunoTherapy (OIT) has gained a role in their management. However, in severe food allergies OIT is often infeasible., Recent Findings: Case reports, observational, and prospective studies have recently proposed different approaches to severe food allergy. The majority of them include the use of biologics. Omalizumab has been the most studied drug for severe food allergies, and its role as adjuvant treatment to OIT is well established. Interest has been raised on other biologics, as dupilumab, reslizumab, and mepolizumab. Toll-like receptor agonists, and gene therapy using adeno-associated virus coding for Omalizumab are promising alternatives., Summary: The recent studies are deeply influencing the clinical practice. We review the modifications of the clinical approach to severe food allergies so far available. We indicate the possible evolutions of treatment with biologics in severe food allergies.

Purpose of Review: there are accruing evidences on the role of the intestinal microbiota in the development of allergic diseases among infants. Elaborating on this theoretical basis, studies did assess the possibilities to prevent allergic diseases in infancy through manipulation of the intestinal microbiota. We review here such studies., Recent Findings: interventional studies led to conflicting conclusions on the possible role of probiotics and prebiotics in allergy prevention. Two metanalyses published in 2015 did reconcile all data. Guidelines have been predicated on such studies using the GRADE methodology., Summary: the guidelines for allergy prevention suggest for the first time the use of probiotics and prebiotics. The existing evidences stand for a use of such supplementation in particular for the prevention of eczema. As there is no evidence so far of superiority of one probiotic strand over the others, they should be considered as class and not as individual products.

Background: Data on specific IgE sensitization prevalence in children with allergy-like symptoms seen in the primary care setting are rare. Early diagnosis of allergic diseases is important to prevent clinical manifestations, exacerbations or expansion of allergic diseases to other organ systems. The present study aims to assess the usefulness of early serological diagnosis in children with common allergic symptoms., Methods: 532 children (<15 years of age), with at least one of ten allergy-like symptoms, from 21 primary care centers in two geographic areas of Italy and Spain were included in the study. Patients were tested with, either Phadiatop® Infant (0-5 years of age) or Phadiatop® and food mix (fx5e) (>5 years of age) to discriminate atopic from non-atopic subjects. A blood sample of atopic subjects was taken for additional 6-26 specific IgE antibody determinations from a predefined panel using the ImmunoCAP® System., Results: 267 children (50.2 %) were positive in the initial test and were classified as atopic. 14 % were mono-sensitized, 37 % were sensitized to 2-3 allergens and 49 % to more than 3 allergens. The average number of symptoms in the atopic group was 3.3 vs 2.8 in the non-atopic group. The prevalence of sensitization to single allergens was highest for grass and ragweed pollen and house-dust mites (19-28 %). Sensitization to tree allergens was highest for olive tree (16.5 %). Cow's milk and egg white were the most sensitizing foods (~15 %). Food allergen sensitization predominated in younger children (OR = 2.8) whereas the inverse occurred with inhalant allergens (OR = 2.5 to 5.6). A significant positive correlation between patient age and the number of sensitizations was found., Conclusions: Specific IgE sensitization in children with allergy-like symptoms is common. Multiple sensitization is predominating. Number of clinical symptoms was higher in the atopic group compared to the non-atopic without a correlation with the number of positive allergens. Age seems to play a crucial role in the development of sensitization with a significant positive correlation between patient age and the number of sensitizations.

Food allergy is a matter of concern because it affects about 0.5-3.8% of the paediatric population and 0.1-1% of adults, and as well may cause life-threatening reactions. Skin prick testing with food extracts and with fresh foods, the measurement of food-specific IgE, elimination diets and a double-blind, placebo-controlled food challenge are the main diagnostic procedures; many non-validated procedures are available, creating confusion among patients and physicians. The treatment of food allergy is still a matter of debate. Antihistamines, corticosteroids and, if necessary (in case of anaphylaxis), epinephrine, are the drugs of choice for the treatment of symptoms of food allergy. Sodium cromolyn may be used prophylactically even though there are no controlled studies certifying its efficacy. The only etiologic treatment of food allergy is specific desensitization. Sublingual-oral-specific desensitization has been used by our group for the treatment of food-allergic patients with a high percentage of success.