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.

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.

Frequency of allergic reactions in egg allergic patients after receiving the yellow fever vaccine.

BACKGROUND: Immunization with live attenuated viral yellow fever vaccine (YFV) grants effective immunity in most cases, and is recommended and prioritized for residents and travelers of endemic countries. YFV is seldom administered to egg-allergic patients (EAP) since it is cultivated in embryonated chicken eggs and may contain residual egg proteins, being a problem for egg-allergic residents and travelers of endemic countries. OBJECTIVE: Describe the frequency of allergic reactions after YFV administration in confirmed EAP from an allergy outpatient center in Bogotá, Colombia. METHODS: An observational, retrospective, cross-sectional, and descriptive study was conducted from January 2017 to December 2019. EAP whose allergy was confirmed with a positive Skin Prick Test (SPT) and/or egg protein-specific IgE levels who hadn't received the YFV were included. Every patient had an SPT, severe EAP, and an additional Intradermal Test (IDT) done with the vaccine. If the vaccine SPT and IDT were negative, the YFV was administered as a single dose; if either were positive, the YFV was administered in graded doses. Statistical analysis was done in Stata16MP. RESULTS: Seventy one patients were included, 24 (33.8%) of those had a history of egg anaphylaxis. All patients had negative YFV SPTs, and two of the five YVF IDTs were positive. Two patients, with previous egg-anaphylaxis, presented allergic reactions to the vaccine. CONCLUSIONS: YFV did not trigger allergic reactions in EAP without history of egg-anaphylaxis. With further research, safe single-dose vaccination to this population could be considered; however, patients with previous egg-anaphylaxis should be evaluated by an allergist before vaccination.

Effect of Maternal Egg Intake During the Early Neonatal Period and Risk of Infant Egg Allergy at 12 Months Among Breastfeeding Mothers: A Randomized Clinical Trial.

Importance: Egg introduction in infants at age 4 to 6 months is associated with a lower risk of immunoglobulin E-mediated egg allergy (EA). However, whether their risk of EA at age 12 months is affected by maternal intake of eggs at birth is unknown. Objective: To determine the effect of maternal egg intake during the early neonatal period (0-5 days) on the development of EA in breastfed infants at age 12 months. Design, Setting, and Participants: This multicenter, single-blind (outcome data evaluators), randomized clinical trial was conducted from December 18, 2017, to May 31, 2021, at 10 medical facilities in Japan. Newborns with at least 1 of 2 parents having an allergic disease were included. Neonates whose mothers had EA or were unable to consume breast milk after the age of 2 days were excluded. Data were analyzed on an intention-to-treat basis. Interventions: Newborns were randomized (1:1) to a maternal egg consumption (MEC) group, wherein the mothers consumed 1 whole egg per day during the first 5 days of the neonate's life, and a maternal egg elimination (MEE) group, wherein the mothers eliminated eggs from their diet during the same period. Main Outcomes and Measures: The primary outcome was EA at age 12 months. Egg allergy was defined as sensitization to egg white or ovomucoid plus a positive test result in an oral food challenge or an episode of obvious immediate symptoms after egg ingestion. Results: Of the 380 newborns included (198 [52.1%] female), 367 (MEC: n = 183; MEE: n = 184) were followed up for 12 months. On days 3 and 4 after delivery, the proportions of neonates with ovalbumin and ovomucoid detection in breast milk were higher in the MEC group than in the MEE group (ovalbumin: 10.7% vs 2.0%; risk ratio [RR], 5.23; 95% CI, 1.56-17.56; ovomucoid: 11.3% vs 2.0%; RR, 5.55; 95% CI, 1.66-18.55). At age 12 months, the MEC and MEE groups did not differ significantly in EA (9.3% vs 7.6%; RR, 1.22; 95% CI, 0.62-2.40) or sensitization to egg white (62.8% vs 58.7%; RR, 1.07; 95% CI, 0.91-1.26). No adverse effects were reported. Conclusions and Relevance: In this randomized clinical trial, EA development and sensitization to eggs were unaffected by MEC during the early neonatal period. Trial Registration: UMIN Clinical Trials Registry: UMIN000027593.

Frequency of Infant Egg Consumption and Risk of Maternal-Reported Egg Allergy at 6 Years.

BACKGROUND: Recent research suggests that early egg introduction during infancy may help to prevent egg allergy development. However, the infant egg consumption frequency that is sufficient to induce this immune tolerance remains uncertain. OBJECTIVES: We examined the associations between the infant egg consumption frequency and maternal-reported child egg allergy at 6 y. METHODS: We analyzed data of 1252 children from the Infant Feeding Practices Study II (2005-2012). Mothers reported the frequency of infant egg consumption at 2, 3, 4, 5, 6, 7, 9, 10, and 12 mo old. Mothers reported the status of their child's egg allergy at the 6-y follow-up. We used Fisher exact test, Cochran-Armitage Trend Test, and log Poisson regression models to compare 6-y egg allergy risk by the frequency of infant egg consumption. RESULTS: The risk of maternal-reported egg allergy at 6 y significantly (P-trend = 0.004) decreased with infant egg consumption frequency at 12 mo: 2.05% (11/537) for infants not consuming eggs, 0.41% (1/244) for those consuming eggs <2 times per wk, and 0.21% (1/471) for those consuming eggs ≥2 times per wk. A similar but nonsignificant trend (P-trend=0.109) was observed for egg consumption at 10 mo (1.25%, 0.85%, and 0%, respectively). After adjusting for socioeconomic confounders, breastfeeding, complementary food introduction, and infant eczema, infants who consumed eggs ≥2 times per wk at 12 mo had a significantly lower RR of maternal-reported egg allergy at 6 y (confounder-adjusted RR: 0.11; 95% CI: 0.01, 0.88; P = 0.038), whereas those who consumed <2 times per wk (confounder-adjusted RR: 0.21; 95% CI: 0.03, 1.67; P = 0.141) did not have a significantly lower risk than those who did not consume eggs at all. CONCLUSIONS: Consumption of eggs ≥2 times per wk in late infancy is associated with a reduced risk of developing egg allergy later in childhood.

Phenotyping of immediate-type food allergies based on 10 years of research: A latent class analysis.

BACKGROUND: Food allergy is a disease with a diverse and variable natural history, and some patients may react to two or more food antigens. This study aimed to classify and characterize the long-term prognosis of infantile-onset, immediate-type food allergies, focusing on three major antigens in Japan: egg, milk, and wheat. METHODS: All children who visited our hospital with food allergies, including suspected cases, were prospectively registered in our medical database. Among the children in this database, subjects registered by the age of 1 year with immediate-type symptoms or sensitization to the above three antigens were included. The course of the subjects up to the age of 6 years was analyzed. Cox regression analysis and repeated-measures latent class analysis (LCA) were performed to reveal risk factors and tolerance patterns for food allergies. RESULTS: We included 915 patients with immediate-type food allergy symptoms and 276 sensitized asymptomatic patients in this study. The number of patients with immediate-type symptoms to egg, milk, and wheat was 609, 443, and 235, respectively. The number of patients with multiple food allergies was 302. The proportion of patients with tolerance to egg, milk, and wheat at 6 years of age was 74%, 69%, and 75%, respectively. LCA revealed 7 classes of prognosis for food allergies. The largest class was transient egg allergy alone (19.6%), and there were severe cases of multiple food allergies (6.5%). CONCLUSIONS: This study demonstrated the prognosis of food allergy classes in Japan, including multiple food allergies, with 7 classes with its own characteristics.

Association of egg protein levels in dust with allergy status and related factors.

BACKGROUND: Levels of peanut protein in dust have been reported to be associated with sensitization and allergy to it, so controlling food protein in dust may help prevent food allergy. However, studies of factors associated with egg protein levels in dust are scarce. This study aimed to determine the factors contributing to egg protein levels in dust. METHODS: This cross-sectional study included 159 participants in the Sub-Cohort Study of the Japan Environment and Children's Study in Yamanashi Prefecture at a 6 year follow up. House dust at 6 years was collected and egg protein concentrations were measured for whole egg protein. Household factors, including the maternal frequency of egg consumption, were assessed by questionnaires. A linear regression model was used to analyze the effect of household environmental factors on egg protein in dust. RESULTS: In multivariate analysis, frequent maternal egg consumption (≥5 times a week) was associated with higher egg protein concentrations in house dust (ß = 0.96, P = 0.01). The egg protein load was significantly associated with a higher number of cohabitants (≥5, ß = 0.85, P = 0.02) in addition to frequent maternal egg consumption. Among the participants, 140 (88.1%) had no egg allergy, 15 (9.4%) were egg tolerant, and 4 (2.5%) had an egg allergy at 6 years old. There was no significant association between the current egg allergy status and egg protein concentrations in dust. CONCLUSIONS: The frequency of maternal egg consumption and the number of inhabitants are contributing factors to egg protein levels in dust.

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.

Utility of Gal d 1-Specific IgE Levels in Predicting Reactivity to Boiled Egg in Chinese Children.

BACKGROUND: Many researchers have reported predicting the outcome of oral food challenges (OFCs) on the basis of specific IgE (sIgE) levels. However, the clinical usefulness of the determination of IgE antibodies to egg allergen components in Chinese children with suspected boiled egg allergy is not well studied. OBJECTIVE: Our objective was to assess the diagnostic performance of sIgE to egg white and Gal d 1, 2, 3, and 5 based on the open challenge outcome for boiled egg. METHODS: A total of 48 child patients with a suspect of boiled egg allergy were included. Serum egg white and Gal d 1, 2, 3, and 5 sIgE were measured by ImmunoCAP. Diagnostic value was assessed by area under the receiver operating characteristic curves (AUC). RESULTS: Using the OFC results as the reference parameter, Gal d 1 sIgE had the highest AUC (0.84) compared with egg white (0.77) and other investigated components (ranging from 0.51 to 0.71). The clinical sensitivity and specificity for the sIgE to Gal d 1 at optimal cutoff (6.15 kUA/L) were 73.7% and 96.7%, respectively. Sensitization to Gal d 1 with a cutoff value of >7.48 kUA/L indicated a 90% probability of positive challenge. CONCLUSION: Quantitative measurements of Gal d 1 sIgE antibodies using ImmunoCAP are useful in the management of boiled egg allergy in Chinese children.

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.

Early Introduction of Food Allergens and Risk of Developing Food Allergy.

There is increasing evidence that early introduction of allergenic foods may decrease the risk of developing IgE-mediated food allergy. Patterns of food introduction before the 2015 publication of the Learning Early about Peanut Allergy (LEAP) trial are not well-studied, but are important as a baseline for evaluating subsequent changes in infant feeding practices and potentially food allergy. We performed a retrospective longitudinal study using data from a multicenter cohort of infants hospitalized with bronchiolitis between 2011-2014. The primary outcomes were IgE-mediated egg or peanut allergy by age 3 years. Of 770 participants included in the analysis, 635 (82%) introduced egg, and 221 (27%) introduced peanut by age 12 months per parent report. Four participants had likely egg allergy, and eight participants had likely peanut allergy by age 3 years. Regular infant egg consumption was associated with less egg allergy. The association was suggestive for infant peanut consumption with zero peanut allergy cases. Overall, our results suggest that early introduction of peanut was uncommon before 2015. Although limited by the small number of allergy cases, our results suggest that early introduction of egg and peanut are associated with a decreased risk of developing food allergy, and support recent changes in practice guidelines.

Factors associated with outcome of egg allergy 1 year after oral food challenge: A good baseline quality of life may be beneficial.

BACKGROUND: Safely liberalizing the diet to include an allergenic food may accelerate resolution of food allergy. The outcome of liberalization, however, varies among patients. METHODS: We conducted a prospective observational study to identify factors associated with outcome for egg allergy 1 year after oral food challenge (OFC). We enrolled children <72 months old who had egg allergy and underwent OFC for determination of the safe intake quantity of egg allergen. Each child's baseline clinical background was recorded. Caregivers used the Food Allergy Quality of Life Questionnaire-Parent Form (FAQLQ-PF) to assess their children's QoL. Dietary advice based on the OFC result was provided to support safe egg consumption. At 1 year after OFC, the quantity of egg each child safely consumed in daily life was surveyed. We classified the outcome as Successful (Group S) if the quantity increased during the 1 year, or as Unsuccessful (Group U) if it did not. Factors associated with the outcome were investigated by multivariate logistic regression analysis. RESULTS: A total of 93 children were enrolled, and after 1 year, 57 finished in Group S and 36 in Group U. The mean FAQLQ-PF score at baseline was significantly lower (ie, a better QoL) in Group S than in Group U. Multivariate logistic regression analysis identified a good QoL and absence of comorbid asthma or atopic dermatitis as factors predicting a favorable outcome. CONCLUSION: QoL may affect food allergy outcome. Intervention focusing on the QoL may promote outgrowing of food allergies.

Prevalence of allergic disorders and risk factors associated with food allergy in Turkish preschoolers

BACKGROUND: The prevalence of allergic disorders is on the rise, affecting about 10% of the population. In this retrospective cohort, we investigated prevalence of allergic disorders, associated risk factors, and the outcome of food allergies. MATERIAL AND METHODS: We analyzed data from birth cohorts of two university hospitals' well-child outpatient clinics. Factors related to onset and type of allergic diseases were assessed from demographic, socioeconomic, and clinical data. RESULTS: Analyses were performed on 949 (431F/518M) infants at a mean current age of 28 ± 6 months. Any allergic disease was established among 177 cases (22%); atopic dermatitis in 123 (12.8%), respiratory allergies in 55 (5.7%), and food allergy in 41 (4.3%). The risk for allergic disorders was found to be significantly increased for male gender (OR: 2.31, 95% CI; 1.54-3.46), and positive parental atopy (OR: 1.94, 95% CI; 1.31-2.86). The risk of food allergies was significantly higher in the male gender (OR: 2.47, 95% CI; 1.21-5.02), who consumed egg-white between 6 and 12 months (OR: 2.34, 95% CI; 1.22-4.48), and who were formula-fed before 6 months (OR: 2.16, 95% CI; 1.14-4.10). We found no significant association between the rate of food allergy outgrowth or food induced-anaphylaxis with regards to the timing of introducing egg-white into the diet. CONCLUSIONS: Although the introduction of egg-white into infant diet at 6-12 months of life appeared as an independent risk for any food allergy, none of the patients developed anaphylaxis. Age at symptom onset and outgrowing food allergy were similar compared to those introduced egg-white after 12 months. We recommend promoting exclusive breastfeeding during the first 6 months of life, and avoidance of prolonged restrictive diets for children with food allergy

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Efficacy, safety, and parental anxiety in a randomized trial of two dietary instruction methods for children with suspected hen's egg allergy.

BACKGROUND: Little has been reported on how to introduce hen's egg into the diet of children with suspected egg allergy. We compared the efficacy, safety, and parental anxiety of two different dietary instruction methods to introduce egg. METHODS: Eligible participants were children aged 1-4 years who were positive for egg white IgE, and ovomucoid IgE <3.5 kUA/L. Participants were either naïve in egg consumption or had a history of an immediate, but non-anaphylactic, allergic reaction to egg. After a negative result of baseline 2 g boiled egg white oral food challenge (OFC), participants were randomly assigned to the step-up OFC testing (SOFT) or home incrementing group. The primary outcome was the proportion of participants who were able to ingest 20 g of boiled egg white 6 months after initiation. This study is registered with the University Hospital Medical Information Network clinical trial registry (UMIN000024192). RESULTS: Between September 2016 and August 2018, we randomly allocated 55 participants to the SOFT (n = 33 [60%]) and home incrementing (n = 22 [40%]) groups and analyzed 51 patients. Four patients were excluded because they were lost to follow-up. Thirty-one (96.9%) of 32 participants in the SOFT and 12 (63.2%) of 19 in the home incrementing group achieved the primary outcome (p = 0.003). No serious adverse reactions were observed in either group. Parental anxiety significantly improved during treatment in both groups. CONCLUSIONS: The SOFT method was more effective than home incrementing as dietary instruction to introduce egg in children with suspected egg allergy.

Association between sites and severity of eczema and the onset of cow's milk and egg allergy in children.

BACKGROUND: Cow's milk allergy (CMA) and egg allergy (EA) are common and can reduce quality of life in children. Infantile eczema is a well-established risk factor for the onset of food allergy via transdermal sensitization; however, various types of infantile eczema have not yet been evaluated. Therefore, we assessed the association between CMA and EA and the sites and the severity of infantile eczema. METHODS: This retrospective study was based on data from patients aged 2-19 years with atopic disease who were treated between July 2015 and March 2019 in a pediatric allergy clinic in Japan. Data regarding the history of IgE-mediated symptoms, eczema in the first year of life, parental history of atopic diseases, and infantile nutrition were collected. RESULTS: A total of 289 patients were included in the study, of which 81 and 111 children had IgE-mediated CMA and EA, respectively. The rates of CMA and EA were higher in the children with infantile eczema than in those without (30% vs. 9% and 42% vs. 21%). The rate of CMA was also higher in children with eczema on the face. Significant differences were noted in the rate of CMA among children with facial eczema of exudation (adjusted odds ratio 2.398; P = 0.017) and papules (adjusted odds ratio 2.787; P = 0.008), using multivariate analysis. CONCLUSION: The rate of IgE-mediated CMA was high among children with atopic disease having severe facial eczema during infancy.