Regular consumption following early introduction of allergenic foods and aggressive treatment of eczema are necessary for preventing the development of food allergy in children.

PURPOSE OF REVIEW: Over the past two decades, food allergy prevention strategies have shifted from 'delayed introduction' to 'no delayed introduction' to 'early introduction' of allergenic foods. This article reviews important research in this field published in the early 2020s to support future strategies for food allergy prevention. RECENT FINDINGS: Recent randomized controlled trials (RCTs), systematic reviews, meta-analyses, and real-world studies have reported that early allergenic food introduction, especially peanut and egg, are effective for preventing food allergies. However, there are also reports that food-induced anaphylaxis admission rates in infants are increasing. SUMMARY: Early allergenic food introduction by itself is not sufficient to prevent the development of food allergies. Recent RCTs (SPADE study and COMEET study) have demonstrated that continued regular cow's milk consumption after early introduction is important for preventing the onset of cow's milk allergy. Furthermore, an RCT (PACI study) reported that early and aggressive anti-inflammatory topical therapy for eczema can contribute to the prevention of egg allergy by suppressing percutaneous sensitization. Food allergies may be prevented through a combination of early food introduction, regular consumption, and active eczema treatment. Further research is needed to develop well tolerated, effective, and practical strategies to prevent food allergies.

Clinical outcome and component-specific antibody levels in egg allergic children after lightened oral immunotherapy

Objective: To evaluate the clinical outcome of lightened version of egg oral immunotherapy (OIT) and to analyze egg allergen component-specific antibody levels during short up-dosing with egg white powder and maintenance by egg in daily diet. Patients and methods: Eighteen egg-allergic children received egg powder with short up--dosing and they maintained tolerance using egg in daily diet. Seventeen egg-allergic children served as a control group. Component-resolved analysis of serum immunoglobulin E (IgE), IgA1, IgA2, and IgG4 levels were determined at inclusion, after up-dosing and after 1 year of immunotherapy. Skin-prick tests were performed at inclusion and after 1 year of therapy. Results: All 18 patients in the egg OIT group were successfully desensitized. Desensitization was achieved on average in 4.5 months. In the control group, only two children tolerated egg in oral food challenge after 1 year. Of the measured immune markers, smaller wheal diameters in skin-prick testing, reduction in component-specific IgE levels, and increase in component-specific IgA1, IgA2, and IgG4 levels were associated with desensitization. Conclusion: A lightened egg OIT is effective and safe in children with egg allergy. Increase in all egg component-specific IgA1, IgA2 and IgG4 levels and decrease in all egg component--specific IgE levels were observed after 12 months of OIT (AU)

The Combination of Binding Avidity of Ovomucoid-Specific IgE Antibody and Specific IgG4 Antibody Can Predict Positive Outcomes of Oral Food Challenges during Stepwise Slow Oral Immunotherapy in Children with Hen's Egg Allergy.

To increase the prediction accuracy of positive oral food challenge (OFC) outcomes during stepwise slow oral immunotherapy (SS-OIT) in children with a hen's egg (HE) allergy, we evaluated the predictive value of the combination of antigen-specific IgE (sIgE) with antigen binding avidity and sIgG4 values. Sixty-three children with HE allergy undergoing SS-OIT were subjected to repeated OFCs with HE. We measured the ovomucoid (OVM)-sIgE by ImmunoCAP or densely carboxylated protein (DCP) microarray, sIgG4 by DCP microarray, and the binding avidity of OVM-sIgE defined as the level of 1/IC50 (nM) measured by competitive binding inhibition assays. The OFC was positive in 37 (59%) patients undergoing SS-OIT. Significant differences in DCP-OVM-sIgE, CAP-OVM-sIgE, I/IC50, DCP-OVM-sIgG4, the multiplication products of DCP-OVM-sIgE, and the binding avidity of DCP-OVM-sIgE (DCP-OVM-sIgE/IC50) and DCP-OVM-sIgE/sIgG4 were compared between the negative and positive groups (p < 0.01). Among them, the variable with the greatest area under the receiver operating characteristic curve was DCP-OVM-sIgE/IC50 (0.84), followed by DCP-OVM-sIgE/sIgG4 (0.81). DCP-OVM-sIgE/IC50 and DCP-OVM-sIgE/sIgG4 are potentially useful markers for the prediction of positive OFCs during HE-SS-OIT and may allow proper evaluation of the current allergic status in the healing process during HE-SS-OIT.

Effect of moderate to severe atopic dermatitis on the prognosis of egg allergy resolution

BACKGROUND: Few studies have examined the effect of atopic dermatitis (AD) on the resolution of food allergies in Asia, and the predictors of egg allergy resolution are not yet well defined. OBJECTIVE: We evaluated whether AD severity could predict the resolution of egg allergy. METHODS: This retrospective cohort study included infants under 24 months of age diagnosed with IgE-mediated egg white allergy. We included subjects who completed a 60-month follow-up. Open oral food challenges (OFCs) and serologic tests were performed at the time of initial diagnosis and at 36 ± 3 and 60 ± 3 months. RESULTS: We analyzed 68 patients (39 boys and 29 girls). OFCs were performed in 88.2% of the patients. The egg allergy remission rates were 23.5% and 47.1% by 3 and by 5 years of age, respectively. Persistent egg allergy was significantly associated with moderate to severe AD and house dust mite sensitization. Kaplan-Meier curve analysis revealed that patients with moderate to severe AD had higher persistent egg allergy rates than patients with no and mild AD (p = 0.012). Multivariable analysis identified moderate to severe AD as strongly associated with persistent egg allergy (p = 0.001). CONCLUSIONS: In this study, 47.1% of infants had resolved egg white allergies at 60 months. Moderate to severe AD may be a practical and important prognostic factor for persistent egg allergy in clinical settings.

Are There Hidden Dangers Associated With Milk and Egg Dietary Advancement Therapy?

Dietary advancement therapies (DATs) constitute a continuum spanning extensively heated item ingestion, progressive milk or egg ladders, and oral immunotherapy (OIT). These represent an evolution in food allergy management from strict avoidance to an active therapy that may modulate the immune system to develop tolerance to particular forms of the allergen. Many egg or milk individuals are tolerant to baked egg or milk at baseline, and regular consumption (at home ingestion) of baked milk or egg is a safe process with potential quality of life and immunologic benefit. Milk and egg ladders, developed for non-IgE mediated allergy, are increasingly being adapted to IgE-mediated allergy as a potentially safe at-home option for gradual dietary advancement. However, data are limited regarding how safe and effective these approaches are or what patient is best suited for which DAT. It is also unclear whether extensively heated allergen consumption and ladders are susceptible to the same patient-specific factors that affect day-to-day tolerance and safety in OIT. Several recent events involving near-fatal or fatal reactions to milk or egg products (all among patients with asthma) have highlighted that DATs are not risk-free, and that physician guidance in these therapies is essential. Such guidance may include obtaining informed consent before starting any DAT and instituting the same safe dosing rules for OIT across any form of DAT. This rostrum discusses practical concerns about the safety of DAT, and considerations regarding how clinicians can maximize patient protection while defining the safety and efficacy of real-world implementation of these concepts.

Natural History of Allergy to Hen's Egg: A Prospective Study in Children Aged 6 to 12 Years.

INTRODUCTION: There are limited reports on the natural history of hen's egg (HE) allergy (HEA) in children <6 years. We aimed to investigate the natural history of HEA in children aged 6-12 years and the factors affecting its tolerance acquisition. METHODS: Using the database in our hospital, a total of 137 patients diagnosed with a definitive immediate-type reaction to HE when they turned 6 years were enrolled, and the natural course of HEA was prospectively examined until patients turned 12 years. Tolerance was defined as being able to pass an oral food challenge to consume a half or whole heated HE or consume heated HE freely without symptoms. Thirty patients (21.9%) who were enrolled for oral immunotherapy and 21 (15.3%) who discontinued follow-up were considered dropouts. Kaplan-Meier estimation was used to evaluate the rate of tolerance. RESULTS: Fifty-five of the 137 patients (40.1%) had a previous HE anaphylaxis history; 61 (44.5%) patients had acquired tolerance to HE by age 12 years; and 25 (18.2%) continued total or partial HE elimination. The estimated acquired tolerance rates by ages 7, 9, and 12 years were 14.6%, 40.8%, and 60.5%, respectively. A previous history of HE anaphylaxis before 6 years of age, reacting to small amounts of heated HE by 6 years of age, and higher ovomucoid-specific immunoglobulin E values at the same age were associated with persistent HEA. CONCLUSION: This study provides important insights into the natural course of HEA beyond early childhood, with the acquisition of HE tolerance continuing throughout the duration of the study.

Diet supplementation with commercial enzymatically-hydrolyzed egg white peptides ameliorates the severity of allergy in a mouse model of egg white allergy.

BACKGROUND: Commercial spray-dried egg white (S-EW) is often used for oral immunotherapy (OIT). Peptifine® (PF), a commercial preparation of enzymatically-hydrolyzed egg white (EW) peptides, is considered safe OIT food. OBJECTIVE: Here, we examined the therapeutic effect of PF or S-EW in a mouse model of EW allergy. METHODS: Sensitized female BALB/c mice underwent 4-week OIT by supplementation of 19% casein diet with 1% PF (PF group) or S-EW (S-EW group), and non-supplementation of 20% casein diet (non-OIT group). Non-sensitized mice acted as the non-allergy group. Oral and intraperitoneal EW challenges were performed and allergic biomarkers were determined. RESULTS: Changes in rectal temperature after oral challenge were comparable in the allergy groups. However, after intraperitoneal challenge, rectal temperature decrease in the PF and S-EW groups was lower than in the non-OIT group. After 4 weeks, plasma levels of ovalbumin- and ovomucoid-specific antibodies were assessed; IgE levels in the PF and S-EW groups were lower than those in the non-OIT group. Interleukin-4 secretion after EW challenge was significantly lower in splenocyte cultures derived from PF and S-EW groups than in the non-OIT group. Furthermore, the percentage of CD4+ Foxp3+ splenocytes in the PF group was significantly higher than that in the non-OIT and S-EW groups. Oral gavage of 40 mg PF did not induce an allergic response in sensitized mice with EW. CONCLUSIONS: Diet supplementation with 1% PF mildly ameliorated the severity of allergy in mouse with EW allergy, indicating that PF is a safe OIT food.

Oral Immunotherapy in Patients with IgE Mediated Reactions to Egg White: A Clinical Trial Study.

BACKGROUND: Oral immunotherapy (OIT) is under consideration as a promising treatment for desensitization of egg-allergic patients. The objective of this study was to assess the effectiveness of egg-white OIT in patients with IgE-mediated allergy to egg white and to compare the clinical and laboratory findings before and after OIT. METHODS: This clinical trial was performed from February to August 2018 in Rasool e Akram Hospital, Tehran, Iran. Patients' selection criteria included a history of allergic symptoms, skin prick test (SPT) reactivity to egg white, and the inability to pass the Oral Food Challenge (OFC). Egg-white OIT was done for eight patients in the OIT group for 6 months while egg-white-free products were administrated for controls. The SPT reactivity, specific IgE, and IgG4 for egg white and ovomucoid were evaluated before and after OIT. RESULTS: Hundred percent of the subjects in OIT group were desensitized and tolerated 40 cc raw egg white following 6-month maintenance whereas none of the controls was able to pass the OFC. The findings obtained from the evaluations indicated a significant decrease in the wheal size and specific IgE to egg white after OIT (P = .001). Furthermore, a significant decrease of IgE/IgG4 ratio to egg white was found in OIT group (P = .01). CONCLUSION: This OIT protocol was successful as all OIT patients were able to continue 6-month OIT process and the reaction threshold to egg white increased in the OIT group. Therefore, it could be regarded as an effective and safe protocol to treat egg-allergic patients.

Allergen-specific T cells and clinical features of food allergy: Lessons from CoFAR immunotherapy cohorts.

BACKGROUND: Allergen-specific IL-4+ and IL-13+ CD4+ cells (type 2 cells) are essential for helping B cells to class-switch to IgE and establishing an allergic milieu in the gastrointestinal tract. The role of T cells in established food allergy is less clear. OBJECTIVE: We examined the food allergen-specific T-cell response in participants of 2 food allergen immunotherapy trials to assess the relationship of the T-cell response to clinical phenotypes, including response to immunotherapy. METHODS: Blood was obtained from 84 participants with peanut allergy and 142 participants with egg allergy who underwent double-blind placebo-controlled food challenges. Peanut- and egg-responsive T cells were identified by CD154 upregulation after stimulation with the respective extract. Intracellular cytokines and chemokine receptors were also detected. The response to peanut epicutaneous immunotherapy (Peanut Epicutaneous Phase II Immunotherapy Clinical Trial [CoFAR6]; 49 participants receiving epicutaneous immunotherapy) and egg oral immunotherapy or a baked egg diet (Baked Egg or Egg Oral Immunotherapy for Children With Egg Allergy [CoFAR7]; 92 participants) was monitored over time. RESULTS: Peanut-specific type 2 and CCR6+ T cells were negatively correlated with each other and differently associated with immune parameters, including specific IgE level and basophil activation test result. At baseline, type 2 cells, but not CCR6+ cells, were predictive of clinical parameters, including a successfully consumed dose of peanut and baked egg tolerance. Exposure to peanut or egg immunotherapy was associated with a decrease in type 2 cell frequency. At baseline, high egg-specific type 2 cell frequency was the immune feature most predictive of oral immunotherapy failure. CONCLUSION: Food-specific type 2 T cells at baseline are informative of threshold of reactivity and response to immunotherapy.

Inmunoterapia oral con huevo en un hospital comarcal / Oral immunotherapy with egg in a regional hospital

Introducción y objetivos. La inmunoterapia oral (ITO) es una alternativa a la dieta de evitación en algunas alergias alimentarias. El objetivo de este trabajo es evaluar la eficacia y seguridad de la ITO con huevo en una consulta de alergia pediátrica. Material y métodos. Estudio observacional, longitudinal y retrospectivo de pacientes pediátricos con alergia al huevo persistente sometidos a ITO. Para la inducción se utilizó proteína de clara de huevo deshidratada administrada diariamente y con incrementos semanales hasta alcanzar una dosis de 4 gramos. Para la fase de mantenimiento se indicó una ingesta de al menos dos o tres huevos a la semana. Resultados. Se trataron 14 pacientes (6 niñas), de entre 5 y 13 años (mediana 5,5 años). Se consiguió desensibilización completa al final de la inducción en 11 pacientes (78,6%), que se mantuvo en todos ellos tras una mediana de tiempo de seguimiento de 29 meses. Durante la inducción los síntomas más frecuentes fueron: prurito orofaríngeo (9/14), dolor abdominal (7/14) y rinoconjuntivitis (6/14). Se emplearon antihistamínicos en 8 casos (57,1%) y ninguno precisó adrenalina. Entre los pacientes que consiguieron desensibilización se observó una tendencia al descenso de las IgE específicas, siendo estadísticamente significativo para las IgE a huevo completo (p = 0,047), clara de huevo (p = 0,031) y ovoalbúmina (p = 0,016). Conclusiones. La ITO con clara de huevo deshidratada resultó ser un tratamiento muy eficaz y bien tolerado en población pediátrica con alergia al huevo (AU)

Background and objective. Oral immunotherapy (OIT) is an alternative to strict avoidance for the management of some food allergies. The aim of this study is to assess the efficacy and safety of egg OIT in a paediatric allergy outpatient service. Methods. Retrospective, longitudinal observational study in children with persistent hen egg allergy who received egg OIT. For the build-up phase, dehydrated egg white was used daily. Updosing was performed weekly at the allergy unit, up to a final dose of 4 grams. Maintenance phase was carried out with a daily intake of one egg at least two or three times a week. Results. 14 patients (6 girls), whose ages ranged from 5 to 13 years (median 5.5 years) were treated with egg OIT. Eleven subject (78.6%) reached total desensitization, and all of them remained desensitized after a median follow-up time of 29 months. The most frequent adverse effects detected during the build-up phase were: oropharyngeal pruritus (9/14), abdominal pain (7/14), and rhinoconjuntivitis (6/14). Eight patients (57.1%) required oral antihistamines, and none received adrenaline. In those subjects that reached total desensitization, a trend to lower specific IgE levels was observed. That trends were statistically significand for whole egg (p = 0.047), egg white (p = 0.031), and ovalbumin (p = 0.016). Conclusions. Egg OIT was an effective and well tolerated treatment in children with egg allergY (AU)

BSACI 2021 guideline for the management of egg allergy.

This guideline advises on the management of patients with egg allergy. Most commonly egg allergy presents in infancy, with a prevalence of approximately 2% in children and 0.1% in adults. A clear clinical history will confirm the diagnosis in most cases. Investigation by measuring egg-specific IgE (by skin prick testing or specific IgE assay) is useful in moderate-severe cases or where there is diagnostic uncertainty. Following an acute allergic reaction, egg avoidance advice should be provided. Egg allergy usually resolves, and reintroduction can be achieved at home if reactions have been mild and there is no asthma. Patients with a history of severe reactions or asthma should have reintroduction guided by a specialist. All children with egg allergy should receive the MMR vaccine. Most adults and children with egg allergy can receive the influenza vaccine in primary care, unless they have had anaphylaxis to egg requiring intensive care support. Yellow Fever vaccines should only be considered in egg-allergic patients under the guidance of an allergy specialist. This guideline was prepared by the Standards of Care Committee (SOCC) of the British Society for Allergy and Clinical Immunology (BSACI) and is intended for allergists and others with a special interest in allergy. The recommendations are evidence based. Where evidence was lacking, consensus was reached by the panel of specialists on the committee. The document encompasses epidemiology, risk factors, diagnosis, treatment, prognosis and co-morbid associations.

Study protocol of a phase 2, dual-centre, randomised, controlled trial evaluating the effectiveness of probiotic and egg oral immunotherapy at inducing desensitisation or sustained unresponsiveness (remission) in participants with egg allergy compared with placebo (Probiotic Egg Allergen Oral Immunotherapy for Treatment of Egg Allergy: PEAT study).

INTRODUCTION: Egg allergy is the most common food allergy in children but recent studies have shown persistence or delayed resolution into adolescence. As there is currently no effective long-term treatment, definitive treatments that improve quality of life and prevent fatalities for food allergies are required. We have previously shown that a novel treatment comprising a combination of the probiotic Lactobacillus rhamnosus CGMCC 1.3724 with peanut oral immunotherapy (OIT) is highly effective at inducing sustained unresponsiveness, with benefit persisting to 4 years after treatment cessation in the majority of initial treatment responders. In this study, we plan to extend the probiotic food OIT platform to another allergen, namely egg. We describe the protocol for a phase 2, dual-centre, randomised, controlled trial evaluating the effectiveness of probiotic and egg OIT at inducing desensitisation or sustained unresponsiveness (remission) in participants with egg allergy compared with placebo. METHODS AND ANALYSIS: 80 participants aged 5-30 years of age with current egg allergy confirmed by double-blind placebo-controlled food challenge at study screening will be recruited from Australia and Singapore. There are two intervention arms-probiotic and egg OIT (active) or placebo. Interventions are administered once daily for 18 months. The primary outcome is the proportion of participants who attain 8-week sustained unresponsiveness in the active group versus placebo group. ETHICS AND DISSEMINATION: This study has been approved by the Human Research Ethics Committees at the Royal Children's Hospital (HREC 2019.082) and the National Healthcare Group Domain Specific Review Board (2019/00029). Results will be published in peer-reviewed journals and disseminated via presentations at international conferences. TRIAL REGISTRATION NUMBER: ACTRN12619000480189.

A Randomized, Open-Label Trial of Hen's Egg Oral Immunotherapy: Efficacy and Humoral Immune Responses in 50 Children.

BACKGROUND: Egg allergy is the second most common food allergy in children. Persistent food allergy increases the risk of anaphylaxis and reduces the quality of life. OBJECTIVE: To determine the efficacy of oral immunotherapy (OIT) with raw egg white powder and study its effects on humoral responses in children with persistent egg allergy. METHODS: Fifty children aged 6 to 17 years with egg allergy, diagnosed by double-blind, placebo-controlled food challenge, were randomized 3:2 to 8 months of OIT with a maintenance dose of 1 g of egg white protein or 6 months of avoidance after which the avoidance group crossed over to OIT. We examined changes in IgE, IgG4, and IgA concentrations to Gal d 1-4 during OIT compared with avoidance and assessed clinical reactivity at 8 and 18 months. RESULTS: After 8 months, 22 of 50 children (44%) on OIT and 1 of 21 (4.8%) on egg avoidance were desensitized to the target dose, 23 of 50 (46%) were partially desensitized (dose <1 g), and 5 of 50 (10%) discontinued. IgG4 concentrations to Gal d 1-4 and IgA to Gal d 1-2 increased significantly, whereas IgE to Gal d 2 decreased. A heatmap analysis of the IgE patterns revealed 3 distinct clusters linked with the clinical outcome. High baseline egg white-specific IgE and polysensitization to Gal d 1-4 related with failure to achieve the maintenance dose at 8 months. After 18 months of treatment, 36 of 50 patients (72%) were desensitized and 8 of 50 (16%) partially desensitized. CONCLUSIONS: OIT with raw egg enables liberation of egg products into the daily diet in most patients. Subjects with high egg white-specific IgE concentrations and sensitization to multiple egg allergen components at baseline benefit from prolonged treatment.

Evaluation of baked egg oral immunotherapy in French children with hen's egg allergy.

BACKGROUND: Introduction and gradual incremental escalation of a low dose of baked egg may accelerate the resolution of severe hen's egg (HE) allergy for some children. The purpose of our study was to evaluate the efficacy and safety of baked egg oral immunotherapy (OIT) in children with HE allergy after a low-dose baked egg oral food challenge (OFC). METHODS: In a retrospective analysis of OFC performed between 2013 and 2018 at the Children's Hospital of Toulouse (France), we identified 71 children with HE allergy and high egg-white (EW) and ovomucoid specific IgE levels, who underwent a total of 164 OFC (71 baked egg, then 93 unbaked egg). Mean age at first low-dose baked egg OFC was 6 years. Median EW specific IgE was 14.0 kUA/L, and median ovomucoid specific IgE was 11.7 kUA/L. RESULTS: Most children were treated with baked egg OIT. Our study shows that 78.9% of the children did not react to first low-dose baked egg OFC (702 mg of HE protein). 8.7% of children discontinued OIT at home. Finally, desensitization to unbaked HE was achieved in 47 children (66.2% of children allergic to HE). Children with lower EW specific IgE levels had a significantly higher probability of becoming desensitized to HE. We did not report any anaphylactic reactions to baked egg OIT. CONCLUSION: Most children with HE allergy and high egg-white (EW) and ovomucoïd specific IgE levels tolerate the introduction of baked egg. Baked egg OIT is safe, and anaphylaxis to baked egg OIT has not been observed.