Role of serum-specific immunoglobulin E in egg allergy: a comprehensive study of Portuguese pediatric patients.

INTRODUCTION: Food allergies represent a growing public health concern, particularly among children. This study aims to examine egg allergy in pediatric patients and analyze the value of serum-specific immunoglobulin E (sIgE) levels as predictive biomarkers for oral food challenge (OFC) outcomes. METHODS: Retrospective study, involving pediatric patients with suspected IgE-mediated egg allergy, conducted at a tertiary hospital. RESULTS: Data from 176 pediatric patients were analyzed, revealing a higher male prevalence (59.1%). Most cases (40.3%) presented symptoms in the first year of life, predominantly mucocutaneous symptoms (46%). OFC results varied across various forms of egg presentation, with cooked egg being the most frequently tested food. Positive OFCs were observed in 14.6% (n = 36) of cases. The study identified specific egg protein biomarkers for positive OFC, with ovalbumin for raw egg (sIgE > 1.28 KUA/L; area under the curve [AUC] = 0.917; sensitivity [S] 100%; and specificity [Sp] 92%), ovomucoid for cooked egg (sIgE > 0.99 KUA/L; AUC = 0.788, 95%; S: 79%; and Sp: 74%), and ovomucoid for baked egg (sIgE> 4.63 KUA/L; AUC = 0.870; S: 80%; and Sp: 85%) showing predictive capacities. CONCLUSIONS: The findings underscore the importance of considering various forms of egg presentation in the diagnosis and management of egg allergy. The findings highlight the valuable discriminatory capacity and provided reliable biomarkers, such as ovalbumin for raw egg and ovomucoid for cooked and baked egg in risk assessment, aiding in predicting OFC outcomes and helping clinicians to make informed decisions in diagnosing and managing egg allergies, thus improving patient care and quality of life.

Design of the Intervention to Reduce Early Peanut Allergy in Children (iREACH): A practice-based clinical trial.

BACKGROUND: Introducing peanut products early can prevent peanut allergy (PA). The "Addendum guidelines for the prevention of PA in the United States" (PPA guidelines) recommend early introduction of peanut products to low and moderate risk infants and evaluation prior to starting peanut products for infants at high risk for PA (those with severe eczema and/or egg allergy). Rapid adoption of guidelines could aid in lowering the prevalence of PA. The Intervention to Reduce Early (Peanut) Allergy in Children (iREACH) trial was designed to promote PPA guideline adherence by pediatric clinicians. METHODS: A two-arm, cluster-randomized, controlled clinical trial was designed to measure the effectiveness of an intervention that included clinician education and accompanying clinical decision support tools integrated in electronic health records (EHR) versus standard care. Randomization was at the practice level (n = 30). Primary aims evaluated over an 18-month trial period assess adherence to the PPA guidelines using EHR documentation at 4- and 6-month well-child care visits aided by natural language processing. A secondary aim will evaluate the effectiveness in decreasing the incidence of PA by age 2.5 years using EHR documentation and caregiver surveys. The unit of observation for evaluations are individual children with clustering at the practice level. CONCLUSION: Application of this intervention has the potential to inform the development of strategies to speed implementation of PPA guidelines.

Oral administration of egg ovalbumin allergen induces dysregulation of tryptophan metabolism in sensitized BALB/c mice.

Food allergy (FA), triggered by specific dietary allergens, has emerged as a substantial global concern for food safety and public health. While studies have elucidated changes in immune cells and cytokines associated with allergen exposure, a comprehensive analysis of the host's metabolic features and the interaction between metabolites and the gut microbiota has not been conducted. In this study, egg allergen ovalbumin (OVA) was administered by the oral route to sensitized BALB/c mice to faithfully replicate key aspects of human FA, including severe allergic diarrhea, mast cell infiltration, and elevated levels of serum IgE, mMCPT-1, and Th2 cell hallmark cytokines (such as IL-4, IL-5, and IL-13). Furthermore, the untargeted and targeted metabolomic analyses indicated that FA in mice precipitated a substantial decrease in the tryptophan metabolites indole-3-acrylic acid (IA) and indole-3-lactic acid (ILA). The integration of shotgun metagenome and metabolome data further unveiled that the dysregulation of indole metabolism is related to a decline in the abundance of beneficial bacteria such as Lactobacillus and Bifidobacterium. Additionally, disruption of the tryptophan indole derivative pathway compromises the maintenance of intestinal mucosal function through the AHR signaling pathway, manifested by decreased expression of Reg3g and IL22. Taken together, this study demonstrated that the anaphylaxis triggered by oral ingestion of food allergens can lead to disruptions in tryptophan metabolism, consequently impairing intestinal immune homeostasis.

A rare case of lysozyme-induced anaphylaxis in a child with egg allergy.

We report an unusual case of anaphylaxis induced by the lysozyme-containing over-the-counter-drug Lysopaine®, which contains 20 mg lysozyme hydrochloride and 1.5 mg cetylpyridinium chloride, in a 9-year-old child with allergy to hen's egg as well as multiple IgE-mediated food allergies. The involvement of lysozyme was confirmed by positive skin prick tests for Lysopaine® and the presence of specific IgE against lysozyme. Our case highlights the importance of properly educating allergic patients to recognize allergens, even minor ones. Despite the presence of lysozyme in various food and drug products, it is not necessarily perceived as an allergenic protein by patients with egg allergy, and the labeling may be misleading, thereby exposing patients to potentially severe reactions.

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.

Variation in the Allergenicity of Scrambled, Boiled, Short-Baked and Long-Baked Egg White Proteins.

BACKGROUND: Hen's egg white (HEW) is the most common cause of food allergy in children which induces mild to fatal reactions. The consultation for a proper restriction is important in HEW allergy. We aimed to identify the changes in HEW allergenicity using diverse cooking methods commonly used in Korean dishes. METHODS: Crude extract of raw and 4 types of cooked HEW extracts were produced and used for sodium dodecyl-sulfate polyacrylamide gel electrophoresis (SDS-PAGE), enzyme-linked immunosorbent assay (ELISA), and ELISA inhibition assays using 45 serum samples from HEW allergic and tolerant children. Extracts were prepared; scrambled without oil for 20-30 seconds in frying pan without oil, boiled at 100°C for 15 minutes, short-baked at 180°C for 20 minutes, and long-baked at 45°C for 12 hours with a gradual increase in temperature up to 110°C for additional 12 hours, respectively. RESULTS: In SDS-PAGE, the intensity of bands of 50-54 kDa decreased by boiling and baking. All bands almost disappeared in long-baked eggs. The intensity of the ovalbumin (OVA) immunoglobulin E (IgE) bands did not change after scrambling; however, an evident decrease was observed in boiled egg white (EW). In contrast, ovomucoid (OM) IgE bands were darker and wider after scrambling and boiling. The IgE binding reactivity to all EW allergens were weakened in short-baked EW and considerably diminished in long-baked EW. In individual ELISA analysis using OVA+OM+ serum samples, the median of specific IgE optical density values was 0.435 in raw EW, 0.476 in scrambled EW, and 0.487 in boiled EW. Conversely, it was significantly decreased in short-baked (0.406) and long-baked EW (0.012). Significant inhibition was observed by four inhibitors such as raw, scrambled, boiled and short-baked HEW, but there was no significant inhibition by long-baked HEW (IC50 > 100 mg/mL). CONCLUSION: We identified minimally reduced allergenicity in scrambled EW and extensively decreased allergenicity in long-baked EW comparing to boiled and short-baked EW as well as raw EW. By applying the results of this study, we would be able to provide safer dietary guidence with higher quality to egg allergic children.

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)

Safety of Oral Food Challenge for Individuals with Low Egg White and Ovomucoid-Specific IgE Antibodies.

INTRODUCTION: During an oral food challenge (OFC), there is a risk of adverse reactions, including anaphylaxis. Therefore, the physician should carefully conduct the OFC. This study aimed to evaluate the OFC results in individuals with low levels of egg white (EW)- and ovomucoid (OVM)-specific immunoglobulin E (sIgE) and the safety of a hen's egg (HE) OFC in these individuals. METHODS: A total of 2,058 individuals with low EW- or OVM-sIgE underwent HE-OFC at two institutions in Kumamoto prefecture, located in the western area of Japan, between January 1, 2017, and December 31, 2021, within 1 year of recorded sIgE measurements. The ImmunoCAP systems were used to measure sIgEs. The HE-OFC test was performed according to the 2017 Food Allergy Guidelines in an open and unblinded method. RESULTS: Five hundred and one individuals (24.3%) had low EW-sIgE levels (class 2 or lower), and 926 (45.0%) had low OVM-sIgE levels (class 2 or lower). Individuals with low EW-sIgE had lower total IgE and OVM-sIgE than did those with high EW-sIgE (greater than class 2). Those with low OVM-sIgE had lower total IgE and EW-sIgE than did those with high OVM-sIgE (greater than class 2). Among the individuals with low EW-sIgE, 86.4% (433/501 cases) passed the OFC without symptoms. Among the individuals with low OVF-sIgE, 82.6% (765/926 cases) passed the OFC without symptoms. CONCLUSION: More than 80% of individuals with suspected IgE-dependent HE allergy and low levels of EW- or OVM-specific IgE were able to consume at least a small amount of HE. As the OFC results are independent of the loading dose in cases with low EW- or OVM-sIgE, a medium-dose HE-OFC may be performed safely in individuals with no history of anaphylaxis.

Basophil activation test as predictor of severity and threshold of allergic reactions to egg.

BACKGROUND: Identifying patients at risk of severe allergic reactions and/or low threshold of reactivity is very important, particularly for staple foods like egg. METHODS: One hundred and fifty children underwent double-blind placebo-controlled food challenge (DBPCFC) to baked egg (BE), skin prick testing and blood collection for serology and basophil activation test (BAT). Patients who passed BE DBPCFC underwent loosely cooked egg (LCE) DBPCFC. Severity of allergic reactions was classified following Practall guidelines and threshold dose was determined during DBPCFC. RESULTS: Sixty out of 150 (40%) children reacted to BE and 16 out of 77 (21%) to LCE on DBPCFC. Considering DBPCFC to BE, 23 children (38%) had severe reactions and 33 (55%) reacted to 0.13 g or less of egg protein (low threshold group). Two children (2 out of 16 = 12%) had severe reactions to LCE. Demographic, clinical and most immunological features were not significantly different between severe/non-severe BE reactors or low/high threshold groups. Severe BE reactors had higher ovomucoid-sIgE (p = .009) and higher BAT to BE (p = .001). Patients with lower threshold to BE had higher IgE-specific activity (p = .027) and BAT to egg (p = .007) but lower severity score (p = .008). Optimal cut-offs for ovomucoid-sIgE had 100% sensitivity, 35% specificity and 60% accuracy and for BAT 76% sensitivity, 74% specificity and 75% accuracy to identify BE severe reactors. Optimal cut-offs for specific activity had 70% sensitivity, 68% specificity and 69% accuracy and for BAT 70% sensitivity, 72% specificity and 71% accuracy to identify low threshold patients. CONCLUSIONS: BAT was the best biomarker to predict severity and threshold of allergic reactions to BE and can be useful when making decisions about management of egg allergy.

Egg allergy and yellow fever vaccination.

OBJECTIVE: Evaluate biomarkers capable of safely guiding Yellow fever vaccine (YFV) vaccination among individuals suspicious of hen's egg allergy, and identify factors associated with a higher risk for adverse events after immunization (AEAI). METHODS: Patients underwent skin prick test (SPT) for standardized allergens: whole egg, egg white, egg yolk; YFV (1:10 dilution; Biomanguinhos-Fiocruz), and intradermal test (IDT; YFV 0.02 mL, 1:100 dilution) and positive and negative controls. Serum levels of specific IgE (sIgE) for a whole egg, egg white, egg yolk, egg albumin, ovomucoid, lysozyme, and conalbumin (ImmunoCap®; ThermoFisher®) were obtained. Patients sensitized to YFV were submitted to YFV desensitization, and those negatives received YFV (0.5mL) and remained under surveillance for at least one hour. RESULTS: 103 patients were enrolled, 95% under 12 years old. 71% (81/103) of patients had reactions: 80% immediate, 11% mixed, and 9% delayed. There was an association between positive skin test results with YFV and the severity of the reaction (OR:7.64; 95%CI:1.61-36.32; p = 0,011). Only the presence of sIgE to ovomucoid was associated with clinical symptoms (p = 0,025). Thirty patients underwent the YFV desensitization protocol. CONCLUSION: There is a relationship between the positivity of the egg's components and the severity of the clinical reaction. Furthermore, the relationship between the positivity of the tests with the YFV and egg's components may show a tendency to look at ovomucoid and conalbumin, but it is not a certainty. Therefore, further studies are needed to confirm these associations, and for now, the authors still recommend using the vaccine for testing when necessary.

Rates of New Peanut Allergy and Discontinuation Following Introduction in High-Risk Infants.

BACKGROUND: Peanut introduction guidelines recommend that infants with severe eczema and/or egg allergy consume 6 g of peanut protein weekly to prevent peanut allergy. Rates of new peanut allergy after introduction and adherence remain under study. OBJECTIVE: To determine compliance with peanut introduction guidelines, rates of new peanut allergy, and reasons for discontinuation of peanut consumption in a cohort of high-risk infants. METHODS: A prospective cohort of 4- to 11-month-old high-risk infants (defined as moderate-severe eczema or non-peanut food allergy or a first-degree relative with peanut allergy) with no prior peanut exposure who were determined to not be peanut allergic were recommended to introduce 6 g of peanut protein weekly. Participants were followed to 30 months with 2 in-person visits and monthly questionnaires. RESULTS: Two hundred seventy-seven infants were followed. At last follow-up, 245 (88%) were consuming some peanut protein with median weekly consumption of 3 g (interquartile range: 1-5 g). New peanut allergy developed in 6 (2%), with 2 of those cases consistent with food protein-induced enterocolitis syndrome. Fear of reaction in another household member was the most common reason for peanut discontinuation. Reactions to peanut after introduction in the index infant occurred in <2% of peanut-allergic siblings and in 20% of peanut-allergic parents. CONCLUSION: We found low rates of new peanut allergy and generally low rates of peanut discontinuation after introduction in our high-risk cohort. However, families of high-risk infants require significant support with introduction, especially those with another peanut-allergic member.

Systematic review and meta-analyses on the accuracy of diagnostic tests for IgE-mediated food allergy.

The European Academy of Allergy and Clinical Immunology (EAACI) is updating the Guidelines on Food Allergy Diagnosis. We aimed to undertake a systematic review of the literature with meta-analyses to assess the accuracy of diagnostic tests for IgE-mediated food allergy. We searched three databases (Cochrane CENTRAL (Trials), MEDLINE (OVID) and Embase (OVID)) for diagnostic test accuracy studies published between 1 October 2012 and 30 June 2021 according to a previously published protocol (CRD42021259186). We independently screened abstracts, extracted data from full texts and assessed risk of bias with QUADRAS 2 tool in duplicate. Meta-analyses were undertaken for food-test combinations for which three or more studies were available. A total of 149 studies comprising 24,489 patients met the inclusion criteria and they were generally heterogeneous. 60.4% of studies were in children ≤12 years of age, 54.3% were undertaken in Europe, ≥95% were conducted in a specialized paediatric or allergy clinical setting and all included oral food challenge in at least a percentage of enrolled patients, in 21.5% double-blind placebo-controlled food challenges. Skin prick test (SPT) with fresh cow's milk and raw egg had high sensitivity (90% and 94%) for milk and cooked egg allergies. Specific IgE (sIgE) to individual components had high specificity: Ara h 2-sIgE had 92%, Cor a 14-sIgE 95%, Ana o 3-sIgE 94%, casein-sIgE 93%, ovomucoid-sIgE 92/91% for the diagnosis of peanut, hazelnut, cashew, cow's milk and raw/cooked egg allergies, respectively. The basophil activation test (BAT) was highly specific for the diagnosis of peanut (90%) and sesame (93%) allergies. In conclusion, SPT and specific IgE to extracts had high sensitivity whereas specific IgE to components and BAT had high specificity to support the diagnosis of individual food allergies.

Clinical Features of Quail Egg Ingestion in Patients with Acquired Tolerance to Hen Eggs: A Case Series Study.

INTRODUCTION: Patients with hen's egg allergy are often instructed to avoid consuming other avian eggs, such as quail eggs. However, it is unclear whether patients with an acquired tolerance to hen eggs continue to avoid consuming quail eggs. This study aimed to evaluate the clinical features of quail egg ingestion. METHODS: This prospective case series included children aged ≥1 year with hen's egg allergy who were recruited between October 2019 and February 2021 in our hospital. We conducted an oral food challenge (OFC) with three boiled quail eggs to evaluate the clinical features of quail egg ingestion in patients with acquired tolerance to hen eggs. The primary outcome was a positive OFC after ingesting three quail eggs. Secondary outcomes were cross-antigenicity between hen and quail eggs observed through the skin prick test (SPT) and pattern of quail egg allergy, comprising the onset of reaction, and severity. The correlation between the diameters of the wheals with SPT in hen and quail eggs was evaluated using the Pearson product-moment correlation coefficient. RESULTS: A total of 62 patients underwent the quail egg OFC. The median (interquartile range) age of the participants was 3 (2-5) years. Thirty-three (53%) patients had a history of anaphylaxis due to hen eggs. The median total immunoglobulin E (IgE) level in patients who underwent the OFC with half a heated whole hen's egg was 271 (98-593) IU/mL. The median specific IgE level in egg white and ovomucoid was 9.7 (3.2-21.5) and 4.4 (1.3-6.9) UA/mL, respectively. The quail egg OFC results revealed that none of the 59 patients who ate the three quail eggs completely had an allergic reaction. The SPT-positive and SPT-negative rates in raw and boiled hen and quail egg whites were both correlated. The diameters of wheals with SPT in raw hen and quail egg whites and yolks were positively correlated. CONCLUSION: Patients with an acquired tolerance to hen eggs may not be required to avoid consuming quail eggs.

An integrated calibration strategy for the development and validation of an LC-MS/MS method for accurate quantification of egg allergens (Gal d 1-6) in foods.

Accurate determination of egg allergens in food is vital for allergen management and labeling. However, quantifying egg allergens with mass spectrometry poses challenges and lacks validation methods. Here, we developed and validated an LC-MS/MS method for quantifying egg allergens (Gal d 1-6) in foods. Sample extraction, enzymatic digestion, purification, proteins/peptides selection, and calibration curves were optimized. VMVLC[+57]NR (Gal d 1) and GTDVQAWIR (Gal d 5) exhibited outstanding sensitivity and stability, serving as quantitation markers for egg white and yolk. Using a matrix-matched calibration curve with allergen ingredients as calibrants and labeled peptides as standards, we achieved highly accurate quantitation. Validation involved spiking egg protein into egg-free foods, showing excellent sensitivity (LOQ: 1-5 mg/kg), accuracy (62.4 %-88.5 %), and reproducibility (intra-/inter-day precision: 3.5 %-14.2 %/8.2 %-14.6 %). Additionally, we successfully applied this method to commercial food analysis. These findings demonstrate optimal allergen selection, peptides, and calibration strategy are crucial parameters for food allergen quantification via MS-based methods.