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Food allergy (FA) is a potentially life‐threatening chronic condition that is becoming an increasing public health problem worldwide. This systematic review (SR) was carried out to inform the development of clinical recommendations on the treatment of IgE‐mediated FA with biologics and/or IT for the update of the EAACI guidelines. A SR of randomized‐controlled trials or quasi‐controlled trials was carried out. Studies were identified via comprehensive search strategies in Medline, Embase, and Cochrane Library, up to April 2022. Population: Human adults, children, and adolescents with IgE‐mediated FA. Intervention: IT and/or biologics. Comparator: Placebo or standard‐of‐care (allergen avoidance). Outcome: Efficacy (desensitization, sustained unresponsiveness (SU), remission), quality of life, and safety (systemic and local adverse reactions (AR)). The Cochrane RoB tool was used to assess the risk of bias. It was reported according to PRISMA and registered in PROSPERO CRD4202229828. After screening, 121 studies were included (111 for IT and 10 for biologics). Most studies had a high risk of bias and showed high heterogeneity in design and results. Metanalysis showed a positive effect of biologics and IT in terms of relative risk (RR) for achieving tolerance to the culprit food compared to avoidance or placebo. Omalizumab for any FA showed a RR of 2.17 [95% confidence interval: 1.22, 3.85]. For peanut allergy, oral IT (OIT) had a RR of 11.94 [1.76, 80.84] versus avoidance or placebo, sublingual IT (SLIT) had a RR of 3.00 [1.04, 8.66], and epicutaneous IT (EPIT) of 2.16 [1.56, 3.00]. OIT had a RR of 5.88 [2.27, 15.18] for cow's milk allergy, and of 3.43 [2.24, 5.27] for egg allergy. There was insufficient data on SLIT or EPIT for the treatment of egg and milk allergies. Most ARs reported were mild. For OIT the most common AR involved the gastrointestinal system and for EPIT, AR's most commonly affected the skin. There was limited data on severe or life‐threatening ARs. There was limited evidence for long term efficacy and quality of life. In conclusion, biologics and IT, alone or in combination, are effective in achieving desensitization while on active treatment but more evidence is needed on long‐term tolerance as current evidence is not of high quality. Adverse events while on therapy are generally mild to moderate but a long‐term comprehensive safety profile is missing. There is a critical need to optimize and standardize desensitization protocols and outcome measures to facilitate our understanding of the efficacy and safety as well as to allow for comparison between interventions. [ABSTRACT FROM AUTHOR]

Background: Food allergen immunotherapy (FA‐AIT) practice is known to vary globally. This project aims to identify and characterize European centres performing FA‐AIT. Methods: An EAACI task force conducted an online survey to gather relevant information regarding FA‐AIT practice and setting‐specific resources after reviewing the published literature and congress abstracts throughout Europe. Results: We identified 102 FA‐AIT centres in 18 countries; only Spain (n = 39) and France (n = 16) had ≥10 such centres. Overall, most facilities were hospital‐based (77.5%), publicly funded (80.4%) and delivered FA‐AIT as routine clinical care (80.4%). On average, departments had 3 allergists/paediatric allergists and 2 nurses. Surveyed centres had provided FA‐AIT for a median of 9 years [1–24] to a median of 105 [5–2415] patients. The estimated total number of treated patients was 24875, of whom 41.3% received AIT for milk, 34.2% egg, 12.8% peanut and 11.7% other foods. Anaphylaxis to AIT doses requiring over 4–6 h of observation was reported by 70.6% of centres, ICU admissions by 10.8% and eosinophilic esophagitis by 45.1%. Quality of life and sustained unresponsiveness were evaluated in 20.6% and 54.9% of centres, respectively. The main contraindications for food AIT were severe asthma (57%‐63%), eosinophilic esophagitis (56%‐48%) and age below 5 years (47%‐41%). Conclusions: In Europe, FA‐AIT is provided mostly in clinical practice. Significant variation is seen in the number of centres per country, facility characteristics and inclusion/exclusion criteria, and in certain aspects of protocols. Potential inequality in access to AIT has been identified as well as the need for education and guidance for treatment standardization. [ABSTRACT FROM AUTHOR]

Background A major drawback of oral immunotherapy for food allergy is the possibility of severe side-effects. We assessed both safety and efficacy of a low allergenic hydrolysed egg (HydE) preparation used in a double-blind placebo-controlled randomized study in egg allergic children. Methods In a pilot multicentre study, 29 egg allergic patients (aged 1-5.5 years) were administered daily for 6 months 9 g HydE or placebo in a blinded, randomized manner. Safety was verified by oral food challenge to assess tolerance towards HydE at the start and efficacy by an open oral food challenge ( OFC, primary outcome) at the end. Additionally, changes in basophil activation and specific IgE and IgG4 were assessed. Results All egg allergic patients randomized to HydE ( n = 15) tolerated the full dose at day 1 and received the maintenance dose from the start at home. No statistically significant difference was observed on the final OFC (36% and 21% had a negative OFC in the treatment and placebo groups, respectively). Specific IgG4 levels increased, while both CD203c+ and CD63+ basophils decreased significantly more over time in the treatment than in the placebo group. Conclusions HydE can be regarded as a safe, low allergenic product to use in children allergic to egg. Although not significant, HydE given for 6 months increased numerically the proportion of patients becoming tolerant to egg. HydE induced a modulation of the immune response towards better tolerance. A longer treatment period and/or a higher dose may improve the clinical outcome and should be evaluated. [ABSTRACT FROM AUTHOR]

Food allergies are believed to be on the rise, and currently, management relies on the avoidance of the food. Hen's egg allergy is after cow's milk allergy the most common food allergy; eggs are used in many food products and thus difficult to avoid. A technological process using a combination of enzymatic hydrolysis and heat treatment was designed to produce modified hen's egg with reduced allergenic potential. Biochemical ( SDS- PAGE, Size exclusion chromatography and LC- MS/ MS) and immunological ( ELISA, immunoblot, RBL-assays, animal model) analysis showed a clear decrease in intact proteins as well as a strong decrease of allergenicity. In a clinical study, 22 of the 24 patients with a confirmed egg allergy who underwent a double-blind food challenge with the hydrolysed egg remained completely free of symptoms. Hydrolysed egg products may be beneficial as low-allergenic foods for egg-allergic patients to extent their diet. [ABSTRACT FROM AUTHOR]

Cashew-allergic mice develop elevated walnut-specific Ig E upon oral feeding of walnut proteins. Ingestion of tree nuts in the presence of a known nut allergy could lead to additional sensitizations and anaphylaxis following subsequent exposure. [ABSTRACT FROM AUTHOR]

Background Sedation might improve tolerability and adherence to endoscopic procedures in patients with eosinophilic esophagitis ( Eo E). Propofol administration is often contraindicated in patients with hypersensitivity to egg, soy, or peanut. Objective To investigate the safety of propofol administration for procedural sedation in Eo E patients sensitized/allergic to egg, soy, peanut. Methods A retrospective observational study in adult Eo E patients undergoing esophagogastroduodenoscopy with propofol sedation was conducted between January 2009 and March 2013. Food-specific serum Ig E and skin prick tests for egg, soy, peanut, and cross-reactant foods were performed in all patients. Results Sixty Eo E adult patients, mostly on food elimination diets (91%), were evaluated (age: 28 years (14-56), male gender (90%)). Atopy was present in 88% of patients, being the most prevalent comorbidities rhinoconjunctivitis (78%) and asthma (67%). Fifty-two patients (86%) were sensitized to either egg, soy, or peanut. Eighteen patients (28%) had a history of allergic reactions to egg, legumes, and nuts and strictly avoided these foods. A total of 404 upper endoscopies were performed under propofol sedation. No allergic adverse events were reported, except a transient bronchospasm after orotracheal intubation in an asthmatic adolescent receiving multiple drugs for anesthesia, in whom no sensitization to either propofol or its lipid vehicle was confirmed. Conclusions Propofol was safely administered for procedural sedation in a large series of adult Eo E patients multisensitized to egg, soy, peanut, showing one-third clinical allergy to these foods. [ABSTRACT FROM AUTHOR]

Background: Oral challenge is widely used for diagnosing food allergy but variable interpretation of subjective symptoms may cause error. Facial thermography was evaluated as a novel, objective and sensitive indicator of challenge outcome. Methods: A total of 24 children with a history of egg allergy underwent oral challenge, which were scored positive when objective symptoms occurred or negative after all doses were consumed without reaction. Facial temperatures were recorded at baseline and 10-min intervals. The difference between mean and baseline temperature (ΔT), maximum ΔT during challenge (ΔTmax) and area under curve of ΔT against time (ΔTAUC) were calculated for predefined nasal, oral and forehead areas, and related to objective challenge outcome. Results: There were 13 positive and 11 negative challenges. Median nasal ΔTAUC and ΔTmax were greater in positive compared with negative challenges (231- and 5-fold, respectively; P < 0.05). In positive challenges, nasal temperatures showed an early transient rise at 20 min, preceding objective symptoms at median 67 min. There was a sustained temperature increase from 60 min, which was reduced by antihistamines. A cut-off for nasal ΔTmax of 0.8°C occurring within 20 min of the start of the challenge predicted outcome with 91% sensitivity (positive predictive value [PPV] 100%) and 100% specificity (negative predictive value [NPV] 93%). Subjective symptoms occurred in four of 13 positive and three of 11 negative challenges. Conclusions: Facial thermography consistently detects a significant early rise in nasal temperature during positive compared with negative food challenges, which is evident before objective symptoms occur. Thermography may therefore provide a sensitive method to determine outcome of food challenges and investigate the pathophysiology of food allergic reactions. [ABSTRACT FROM AUTHOR]

Background: The aim of this paper was to investigate whether a statistical model could be developed to estimate a “threshold” dose for foods eliciting allergic reactions in susceptible patients. The threshold dose is defined to be one that elicits allergic reactions in a given (small) proportion of susceptible patients, using data from published studies. Methods: Based on data available from the literature, we developed a statistical model using the actual allergen content in the four foods, where data for allergen content are available (peanut, soy, egg, milk). Results: The model demonstrated that the threshold doses giving a reaction of one in a million in susceptible patients were within the same order of magnitude for egg, milk and soy, but were an order of magnitude lower for peanut flour: 0.005 mg of cow's milk, 0.002 mg of fresh hen's egg, 0.0007 mg of peanut, or 0.0013 mg of soy flour. Conclusions: Although several assumptions were made in creating this statistical model, we demonstrated that the previously published differences in threshold doses for various foods can be largely eliminated by comparing actual allergen content; this may therefore serve as a model for further studies. Background: The aim of this paper was to investigate whether a statistical model could be developed to estimate a “threshold” dose for foods eliciting allergic reactions in susceptible patients. The threshold dose is defined to be one that elicits allergic reactions in a given (small) proportion of susceptible patients, using data from published studies. Methods: Based on data available form the literature, we developed a statistical model using the actual allergen content in the four foods, where data for allergen content are available (peanut, soy, egg, milk). Results: The model demonstrated that the threshold doses giving a reaction of one in a million in susceptible patients were within the same order of magnitude for egg, milk and soy, but... [ABSTRACT FROM AUTHOR]

Background: The aim of the present study was to estimate the prevalence of adverse reactions to egg, as population-based prevalence estimates based on objective diagnostic procedures are lacking. Methods: The parents of 2721 children in a population-based birth cohort completed questionnaires on the occurrence of any reaction to food at 12, 18, and 24 months of age. Children with parentally reported reactions to eggs at the age of 2 years were selected for further examination. A stepwise diagnostic procedure was developed that included diet trials at home, skin prick tests, and open and double-blind, placebo-controlled food challenges. The mean age of the children at the time of the examination was 2.5 years (CI 2.5–2.6). A sample of children without perceived reactions to egg was also selected for assessment of unrecognized reactions. Results: The estimated point prevalence of allergy to egg in children aged 2½ years was 1.6% (CI 1.3–2.0%), with an upper estimate of the cumulative incidence by this age calculated roughly at 2.6% (CI 1.6–3.6). Almost all reactions were IgE mediated. In general, two-thirds of the parentally perceived reactions were verified. However, the positive predictive value of a parentally perceived reaction depended on the number of times it had been reported, and increased from 50% to 100%, for reactions reported one and three times, respectively. Unrecognized reactions were infrequent. Conclusions: This study confirms that allergy to egg is frequent in a child population. [ABSTRACT FROM AUTHOR]

An egg protein, lysozyme, is a still unlabeled additive currently used in cheese preparation. Furthermore, the WHO-FAO committee considers it innocuous. However, 31% of children and 8% of adults with food allergies are allergic to eggs. This work aimed to determine the percentage of patients sensitized to lysozyme from a population of egg-allergic patients. Specific IgE was determined with Cap RAST in 52 patients clinically allergic to egg. Thirty-five percent of egg-allergic patients had antilysozyme IgE. Given this high incidence of lysozyme sensitization, it seems that the presence of lysozyme should be indicated on food labels. [ABSTRACT FROM AUTHOR]

A microfiberglass-based histamine assay (HRM) was compared with an automated fluorometric histamine assay (HRA). Twenty-four subjects with and 24 without a case history (CH) of milk and/or egg allergy were tested by HRM and HRA, skin prick test (SPT), and specific serum IgE (RAST). Six different concentrations of milk, egg, and anti-IgE were used to stimulate washed leukocytes (250 μl for HRA) and whole blood samples (25 μl for HRM) in parallel. When we compared scores representing basophil sensitivity, correlation coefficients (rs) were positive (r(anti-IgE) = 0.88, r(egg) = 0.95, r(milk) = 0.88, P < 0.001), but no significant correlations were found after exclusion of the negatives in both tests. In some individual dose-response curves, the scores obtained by HRM were shifted to higher allergen and anti-IgE concentrations. A high degree of concordance was found in positive and negative responses between the two tests: anti-IgE 91%, egg 92%, milk 86%. Finally, we found a good concordance between, on one side, HRM and, on the other, CH, SPT, and RAST (HRM vs. CH/SPT/RAST): egg 92/82/82%; milk 89/74/67%. We conclude that HRM is in good qualitative, but poor quantitative, agreement with the autoanalyzer-based fluorometric histamine assay. [ABSTRACT FROM AUTHOR]

The intestinal permeability test is a noninvasive method which, when done during a food provocation procedure, can detect the deleterious effect of food on the intestinal mucosa in allergic children. We report on a 1-month-old breast-fed boy with a history of regurgitation, diarrhea, difficult feeding, and malaise suggesting food allergy. Intestinal permeability tests were done with the mother's milk and showed breast-milk-induced alterations of intestinal permeability. No improvement occurred in the child's clinical symptoms or in the results of the intestinal permeability test when the mother withdrew dairy products from her diet. Disappearance of the child's symptoms and normalization of intestinal permeability during provocation with the milk were obtained after elimination of egg and pork from the mother's diet. This observation suggests that dietary proteins different from cow's milk antigens may be transferred to breast milk and induce adverse reactions in hypersensitive infants. [ABSTRACT FROM AUTHOR]

The article discusses the tolerance in cooking an egg in an egg allergic population. The study has showed that egg allergy has been the most frequent food allergy in pediatric practice, although its allergic reaction tends to decrease and even disappear with age. It has indicated that between January 1998 and May 2006, 60 children allergic to eggs had performed an oral food challenge to cooked eggs, the result showed that 73 percent of the egg allergic children tolerated egg in its cooked form.

The past few decades have witnessed an increasing understanding of the role of food allergy in human disease. Nevertheless, controversies still exist in several aspects of this area. One such controversy concerns the body systems that can be the target of food hypersensitivity reactions. Another is the role of noningestant exposure to food in a nonoccupational setting. Both of these aspects are vividly demonstrated in the case presented here. [ABSTRACT FROM AUTHOR]