Faculty Bibliography

It is well-established that food proteins, such as egg, soya, cow's milk and wheat, are detectable in breastmilk for many hours or days after ingestion. Exposure to these proteins is important to the process of developing tolerance but can also sometimes elicit IgE-mediated and non-IgE-mediated allergic symptoms in breastfed infants. Non-IgE-mediated allergy, outside of food protein-induced allergic proctocolitis and eosinophilic oesophagitis, is not well understood, leading to variations in the diagnosis and management thereof. A primary objective of the European Academy for Allergy and Clinical Immunology is to support breastfeeding in all infants, including those with food allergies. A Task Force was established, to explore the clinical spectrum of non-IgE-mediated allergies, and part of its objectives was to establish diagnosis and management of non-IgE-mediated allergies in breastfed infants. Eight questions were formulated using the Patient, Intervention, Comparison, Outcome (PICO) system and Scottish Intercollegiate Guideline Network (SIGN) criteria for data inclusion, and consensus was achieved on practice points through the Delphi method. This publication aims to provide a comprehensive overview on this topic with practice points for healthcare professionals.

Exopalaemon modestus (EM) is a shrimp delicacy that could cause food allergy, the major allergen of EM is Exo m 1. The amino acid (AA) sequence, IgE-binding epitopes and allergenic peptides in gastrointestinal (GI) digests of Exo m 1, and their effects on basophil function were investigated. Exo m 1 has an AA-sequence of high similarity with other shrimp tropomyosins, while not 100% matching. The IgE-binding epitopes of Exo m 1 are epitope 1 (43-59, VHNLQKRMQQLENDLDS), epitope 2 (85-105, VAALNRRIQLLEEDLERSEER), epitope 3 (131-164, ENRSLSDEERMDALENQLKEARFLAEEADRKYDE), epitope 4 (187-201, ESKIVELEEELRVVG) and epitope 5 (243-280, ERSVQKLQKEVDRLEDELVNEKEKYKSITDELDQTFSE). Among the thirty-three peptides of Exo m 1 identified in GI digests, two were highly recognized by IgE, twenty-four moderately or weakly bound IgE, and seven had no IgE-reactivities. These IgE-binding epitopes and GI digestion induced-allergenic peptides could activate basophil degranulation, and CD63 and CD203c expression, they could be potential peptide-based immunotherapy for shrimp allergic individuals.

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.

BACKGROUND:We sought to determine whether an extensively hydrolyzed formula (EHF) supplemented with two human milk oligosaccharides (HMO) was tolerated by infants with cow's milk protein allergy (CMPA). METHODS:A whey-based EHF (Test formula) containing 2'fucosyl-lactose (2'FL) and lacto-N-neotetraose (LNnT) was assessed for clinical hypoallergenicity and safety. The Control formula was a currently marketed EHF without HMO. Children with CMPA, aged 2 months to 4 years, were assessed by double-blind, placebo-controlled food challenges (DBPCFC) to both formulas, in randomized order. If both DBPCFC were negative, subjects participated in a one-week, open food challenge (OFC) with the Test formula. Symptoms and adverse events were recorded. Hypoallergenicity was accepted if at least 90% (with 95% confidence intervals) of subjects tolerated the Test formula. RESULTS:61). There was one allergic reaction to the Test, and one to the Control formula. On the mITT analysis, 63 out of 64 (98.4%; 95% CI lower bound 92.8%), and on the PP analysis 60 out of 61 (98.4%; 95% CI lower bound 92.5%) participants tolerated the Test formula, confirming hypoallergenicity. CONCLUSION/CONCLUSIONS:The whey-based EHF supplemented with 2'FL and LNnT met the clinical hypoallergenicity criteria and can be recommended for the management of CMPA in infants and young children.

The Milk Allergy in Primary (MAP) Care guideline was first published in 2013 in this journal. MAP aimed to provide simple and accessible algorithms for UK clinicians in primary care, detailing all the steps between initial presentation, through diagnosis, management and tolerance development. Despite its UK focus, it soon became clear that MAP was being accessed internationally and thus an updated International Milk Allergy in Primary Care (iMAP) guideline was published in 2017. Both guidelines used existing international consensus guidelines to develop accessible algorithms accompanied by patient information leaflets. In 2018, the guidelines were criticised for 3 distinct reasons: promoting the overdiagnosis of cow's milk allergy (CMA), negatively impacting breastfeeding and the possibility of industry influence on the guidelines. The authors address these criticisms using available evidence and, in the context of this and in consultation with patient groups, members of the General Practice Infant Feeding Network and other infant feeding healthcare leads, have collaboratively produced updated algorithms and an information leaflet to support breastfeeding. We believe iMAP is now closer to its original aim of facilitating early and accurate diagnosis of CMA, whilst minimising, as far as possible, any concerns around overdiagnosis or a risk to breastfeeding rates. We continue to welcome open and constructive engagement about how best to achieve these aims to provide evidence-based, practical guidelines for the primary care practitioner.

PURPOSE OF REVIEW/OBJECTIVE:To critically appraise the recent most relevant studies in the rapidly advancing field of food oral and sublingual immunotherapy. RECENT FINDINGS/RESULTS:Food allergen-specific immunotherapy via oral (OIT) and sublingual route (SLIT) increases the threshold of reactivity to peanut, cow's milk, egg, wheat, and many other foods in the majority of the treated individuals. This desensitized state is contingent upon the continued ingestion of the maintenance doses of the food. Permanent oral tolerance is achievable in a smaller subset of the treated individuals. The optimal duration of therapy has not been firmly established but is likely dependent on the phenotype (severity and persistence). Efficacy of food-OIT is superior compared with SLIT, whereas the safety of OIT is less favorable. Standardization of treatment protocols, maintenance dosing, duration of therapy, target populations and harmonization of the outcomes are top priorities at this stage. SUMMARY/CONCLUSIONS:OIT and SLIT represent two different routes of food allergen-specific immunotherapy. Although significant progress has been made in the last decade, both treatment modalities are still in the very early stages of development and further investigations are necessary to optimize the protocols and improve safety while maximizing efficacy.