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.

Role of biologics in severe food allergy.

PURPOSE OF REVIEW: This review examine the dynamic landscape of food allergy treatment within the context of emerging biologics. Our purpose is to comprehensively evaluate the potential benefits, challenges, and transformative impact associated with the utilization of biologics in comparison to conventional therapeutic modalities. RECENT FINDINGS: This document synthesizes recent scientific investigations to various biologics, such as omalizumab, ligelizumab, dupilumab, and tezepelumab, providing a nuanced understanding of their roles in oral immunotherapy, rapid desensitization, and overall food allergy management. Recent studies and clinical trials highlight the impact of anti-IgE treatment on food allergies, revealing critical findings such as dose-related efficacy, facilitation of rapid desensitization in peanut allergies, and the sustained positive outcomes observed in individuals with multifood allergies. SUMMARY: The use of biologics presents a groundbreaking approach in the treatment of food allergies. The multifaceted action of these agents, along with their potential to overcome the challenges associated with traditional therapies, marks a significant advancement. Despite the persisting challenges of economic constraints and the need for further safety studies, biologics offer a promising avenue for improving the quality of life for individuals with food allergies. Ongoing research and collaborative efforts are imperative to fully realize the transformative potential inherent in these emerging therapeutic frontiers.

Botanical Impurities in the Supply Chain: A New Allergenic Risk Exacerbated by Geopolitical Challenges.

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.

Reactivity to allergenic food contaminants: A study on products on the market.

BACKGROUND: The frequency and severity of reactions in food-allergic consumers exposed to unintentional food allergen contamination during production is unknown. To warn allergic consumers, it has been suggested for pre-packaged foods to be precautionary labelled when the food allergen contamination may exceed the amount to which 1%-5% of the population could react (ED01-ED05). ED01 for hazelnut and milk have been estimated at 0.1 and 0.2 mg, respectively, by the Voluntary Incidental Trace Allergen Labelling (VITAL) initiative. The respective reference doses recommended by the FAO/WHO Codex consultation are 3 and 2 mg. We evaluated the reactivity to potential traces of milk and hazelnut allergens in allergen-free pre-packaged products by children affected by severe allergies to milk and hazelnuts. METHODS: Oral Food Challenges with commercially available hazelnut-free wafer biscuits and milk-free chocolate pralines were administered to patients with severe food allergies to hazelnut and cow's milk, respectively. Contamination levels of milk or hazelnut allergens were measured using chromatographic separation interfaced with triple quadrupole mass spectrometry. RESULTS: No hazelnut allergic patient showed allergic reactions to exposure to biscuits, nor any milk allergic patient displayed allergic reactions to the dark chocolate praline. While no hazelnut trace was detected in biscuits, the praline was found to be contaminated by milk at concentrations ranging between 8 and 35 mg total protein/kg food. In our dose model, these amounts exceeded 1.5-10 times the VITAL ED01 and reached the threshold suggested by the FAO/WHO Codex consultation. CONCLUSIONS: Upon the consumption of food products available on the market, many patients with severe food allergies tolerate significantly higher doses of allergen than reference doses indicated in the VITAL system used for precautionary allergen labelling. These doses support the safety of the FAO/WHO recommended reference doses.

Biologicals in IgE-mediated food allergy.

PURPOSE OF REVIEW: A better understanding of the most recent scientific literature in the use of biological therapy in the treatment of patients with IgE-mediated food allergy. RECENT FINDINGS: A systematic review and meta-analysis demonstrated safety and effectiveness of omalizumab in the treatment of food allergy. The findings support the potential use of omalizumab as a monotherapy or as an adjunct to oral immunotherapy in IgE-mediated cow's milk allergy. The potential use of other biologics in the management of food allergy is subject of speculation. SUMMARY: Different biological therapies are under evaluation for food allergic patients. The advance in literature will guide for a personalized treatment in the near future. However, additional research is needed to better understand the best candidate for each treatment, the optimal dose and timing.

IgE-immunoadsorption for severe allergy to multiple foods: A case series of five children.

Background: Children with severe food allergy may present high risk of fatal anaphylaxis and a highly impaired quality of life. Anti IgE-treatment has been shown to be a promising approach as monotherapy for severe allergy to multiple foods. However, very high serum total IgE levels may limit its use.This study aims to assess the efficacy of IgE-selective immunoadsorption (IgE-IA) on total IgE levels and threshold of reactivity to the culprit foods in children with history of severe anaphylaxis due to multiple foods and allergic comorbidities. Methods: In this single-center, prospective, open-label efficacy study we evaluated children with severe asthma, allergy to 2+foods and total IgE levels >2300 kUI/L. To establish the food reactivity threshold, each patient underwent oral food challenges (OFCs) before and after IgE-IA. Results: Five patients (4 males; age, 12.2 ± 5 years, mean ± SD) underwent an average of 3 (range 2-4) sessions of IgE-IA. Each session reduced IgE levels by a mean of 1958.87 kUI/L. After the IgE-IA cycle, serum total IgE dropped from 3948 ± 1652.7 (mean ± SD) to 360.8 ± 71.9 kUI/L (-10.9 folds; p = 0.01). The threshold of reactivity (No Observed Adverse Effect Level, NOAEL) tested at OFCs for the culprit foods (4 baked-milk + 2 baked-egg + 1 lentil + 2 hazelnut + 1 wheat) increased overall from 21.5 (median, IQR 1.5-82.6) protein milligrams to 1115 (837.2-4222.8) milligrams (p < 0.001), ie, up to 51.8 times higher than baseline. 8/10 OFCs were negative after IgE-IA. Conclusions: IgE-IA increased food threshold quickly. It can be considered in well-selected patients with severe food allergies and high IgE-levels especially if otherwise eligible to anti IgE treatment.

Management of IgE-mediated food allergy in the 21st century.

The 21st century has seen the propulsion of research in the field of food allergy, which has driven real changes in the clinical approach. Allergen immunotherapy has been recommended for the active management of food allergy. Data have shown promising additional methods of treatment, including biologics. Efforts have been devoted to the risk stratification of food allergy and the standardization of the assessment of food-allergic severity. Alternative routes of administration of epinephrine are under investigation to minimize any mechanical issue and the fear of injections. Evidence-based guidelines have been published by the main international societies in the field of anaphylaxis and food allergy management and new updates are in preparation. In the coming years, treatment options that are currently in pre-clinical or early clinical evaluation will hopefully lead to safe and effective disease-modifying therapies for food allergy in clinical practice. The identification of reliable biomarkers and the standardization of definitions and measurement approaches, alongside a shared decision-making with patients and families, will be key for the development of personalized care and to help minimize the substantial burden of food allergy.

Cow's milk allergy.

PURPOSE OF REVIEW: To highlight the most recent insights on cow's milk allergy (CMA), its treatment, and management. RECENT FINDINGS: CMA is one of the most common food allergies among children. Burdened by the risk for fatal reaction, CMA may imply also a severe impairment of health-related quality of life at individual and family level as well as well as individual and societal costs. The updated Diagnosis and Rationale for Action against Cow's Milk Allergy series is going to provide a series of manuscripts that will offer a comprehensive state-of-the-art specifically on CMA, including international evidence-based recommendations. The current results from randomized clinical trials highlight that oral immunotherapy may be effective by itself in providing desensitization. Preliminary data suggest that biologicals such as omalizumab may be able to increase the threshold of reactivity to milk or several foods (if multiple food allergies) without requiring allergen exposure. Breastfeeding is the first choice for infants with CMA. Extensively hydrolyzed formula and amino-acid formula are valid alternatives and may be particularly helpful when eliminating multiple foods, with severe complex gastrointestinal food allergies, eosinophilic esophagitis, severe eczema, or symptoms while exclusively breastfeeding. Heed is needed to ensure the formula is nutritionally sufficient. Due to a high degree of cross-reactivity with cow's milk proteins and risk for allergic reactions, goats' milk or other mammals' milk should not be used. SUMMARY: The adoption and implementation of evidence-based recommendations may guide a proper diagnostics and management and awaited advances in knowledge will allow the development of a personalized treatment tailored on the specific CMA patient's profile.

Biologics as treatment options for anaphylaxis.

PURPOSE OF REVIEW: To provide the most recent insights in the use of biologicals in the treatment of patients with anaphylaxis. RECENT FINDINGS: There is evidence that biologics such as omalizumab may be safe and effective in preventing anaphylactic reactions in patients at high risk mainly because of severe food allergy or desensitization procedures to food, airborne allergen, drugs, or hymenoptera venom. SUMMARY: Further knowledge will guide the adoption and implementation of any new therapy including biologics for anaphylaxis according to the stratification of risk/benefits.

Omalizumab as monotherapy for food allergy.

PURPOSE OF REVIEW: To familiarize the reader with the most recent insights in the use of Omalizumab (monoclonal anti-immunoglobulin E) monotherapy in the treatment of patients with severe food allergy. RECENT FINDINGS: The current data from early stage clinical trials show that Omalizumab may be safe and effective by itself in providing desensitization to one or several foods without requiring allergen exposure. SUMMARY: In the near future, advances in knowledge will guide the adoption and implementation of any new therapy for food allergy and allow the development of a personalized treatment tailored on the specific patient's profile.

Food protein-induced allergic proctocolitis in infants: Literature review and proposal of a management protocol.

Food protein-induced allergic proctocolitis (FPIAP) is a condition characterized by inflammatory changes in the distal colon in response to one or more foreign food proteins because of immune-mediated reactions. FPIAP prevalence estimates range widely from 0.16% in healthy children and 64% in patients with blood in stools. In clinical practice, FPIAP is diagnosed when patients respond positively to the elimination of a suspected triggering food allergen. Nevertheless, significant proportions of infants get misdiagnosed with IgE mediated allergy and undergo unnecessary dietary changes. Diagnosis is based on clinical symptoms, a good response to an allergen-free diet and the recurrence of symptoms during the "allergy challenge test". Sometimes clinical features may be non-specific and the etiology of rectal bleeding in childhood may be heterogeneous. Therefore, it is crucial to exclude a variety of other possible causes of rectal bleeding in the pediatric age group, including infection, anal fissure, intestinal intussusception and, in infants, necrotizing enterocolitis and very early onset inflammatory bowel disease. The diagnostic workup includes in those cases invasive procedures such as sigmoidoscopy and colonoscopy with biopsies. The high prevalence of FPIAP contrasts with the lack of known information about the pathogenesis of this condition. For this reason and due to the absence of a review of the evidence, a literature review appears necessary to clarify some aspects of allergic colitis. The aim of the review is to fill this gap and to lay the foundations for a subsequent evidence-based approach to the condition.

Vitamin D levels in children affected by vernal keratoconjunctivitis.

BACKGROUND: Vernal keratoconjunctivitis (VKC) is a chronic and often severe bilateral conjunctivitis. VKC etiology still remains unclear although endocrine, genetic, neurogenic and environmental factors have been implicated. Vitamin D is a fat-soluble prohormone whose main function is the regulation of calcium and phosphate metabolism. The aim of this study was to evaluate serum vitamin D in children affected by VKC compared to the healthy children and investigate the relationship between its levels and disease severity. METHODS: A total of 110 children, 47 affected by VKC, aged between 5 and 12 years were enrolled at the Department of Pediatrics, Division of Allergy and Immunology, "Sapienza" University of Rome. Used as controls were 63 healthy children with negative skin prick test (SPT), without allergic, ocular and systemic disease. Serum samples were obtained in April from all the children included in the study. Vitamin D dosage was repeated in October in 20 patients after therapy and in 20 controls. A conjunctival scraping was performed in all children affected by VKC. RESULTS: Children affected by VKC had lower vitamin D levels compared to healthy controls and we found an increase in vitamin D levels after therapy with cyclosporine eye drops 1% although this increase was lower than that of healthy controls. Moreover we found significant correlations between vitamin D level and the severity of the disease. CONCLUSIONS: The study shows that children affected by VKC have lower vitamin D levels when compared to healthy controls and highlights a significant correlation between its levels and disease severity.