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The Natural History and Clinical Predictors Of Egg Allergy In The First 2 Years Of Life: A Prospective, Population-Based, Cohort Study
Abstract
Background:
There is a paucity of data examining the natural history of and risk factors for egg allergy persistence, the most common IgE-mediated food allergy in infants.
Objective:
We aimed to assess the natural history of egg allergy and identify clinical predictors for persistent egg allergy in a population-based cohort.
Methods:
The HealthNuts study is a prospective, population-based cohort study of 5276 infants who underwent skin prick tests to 4 allergens, including egg. Infants with a detectable wheal were offered hospital-based oral food challenges (OFCs) to egg, irrespective of skin prick test wheal sizes. Infants with challenge-confirmed raw egg allergy were offered baked egg OFCs at age 1 year and follow-up at age 2 years, with repeat OFCs to raw egg.
Results:
One hundred forty infants with challenge-confirmed egg allergy at age 1 year participated in the follow-up. Egg allergy resolved in 66 (47%) infants (95% CI, 37% to 56%) by 2 years of age; however, resolution was lower in children with baked egg allergy at age 1 year compared with baked egg tolerance (13% and 56%, respectively; adjusted odds ratio, 5.27; 95% CI, 1.36-20.50; P = .02). In the subgroup of infants who were tolerant to baked egg at age 1 year, frequent ingestion of baked egg (≥5 times per month) compared with infrequent ingestion (0-4 times per month) increased the likelihood of tolerance (adjusted odds ratio, 3.52; 95% CI, 1.38-8.98; P = .009). Mutation in the filaggrin gene was not associated with the resolution of either egg allergy or egg sensitization at age 2 years.
Conclusion:
Phenotyping of egg allergy (baked egg tolerant vs allergic) should be considered in the management of this allergy because it has prognostic implications and eases dietary restrictions. Randomized controlled trials for egg oral immunotherapy should consider stratifying at baseline by the baked egg subphenotype to account for the differential rate of tolerance development.
... Baking allergens is best described for cow's milk and egg [15][16][17][18]. The terms "baked milk" (BM) and "baked egg" (BE) refer to these foods in bakery products, defined as egg or milk in a batter (also known as matrix) baked in an oven for 30 min [19][20][21][22][23][24][25][26][27][28][29][30][31]. ...
... The majority of milk-and egg-allergic children are tolerant to the baked form [20][21][22][23][24][25][26][27][29][30][31][32][33][34][35][36][37][38][39][40]. The reduced allergenicity of BM and BE appears to be related to both protein denaturation at elevated temperatures, as well as complex chemical interactions between BM and BE and other proteins, carbohydrates, and lipids in the batter [12]. Casein is the major protein in cow's milk and it is heat stable. ...
... Indeed, 42% of patients tested by OFC to be BM-tolerant were reported to tolerate regular milk after ingesting BM daily for an average of 17 months [40], and 66% of BE-tolerant children were tolerant to hardboiled eggs after ingesting BE daily for an average of 15 months [36]. Similarly, infants tolerating BE at 1 year of age who ingested BE ≥ 5 times per month were 3.5 times more likely to tolerate raw egg white than those who ingested BE ≤ 4 times monthly [22]. These observational studies do not demonstrate that consuming the baked form was therapeutic because there was no comparison group avoiding all forms of milk or egg. ...
Purpose of Review
There is an increasing awareness among clinicians that industrial and household food processing methods can increase or decrease the allergenicity of foods. Modification to allergen properties through processing can enable dietary liberations. Reduced allergenicity may also allow for lower risk immunotherapy approaches. This review will equip physicians, nurses, dieticians and other health care providers with an updated overview of the most clinically oriented research in this field. We summarize studies assessing the allergenicity of processed foods through clinically accessible means, such as oral food challenges, skin prick tests, and sIgE levels.
Recent Findings
Baking, boiling, canning, fermenting, pasteurizing, peeling, powdering, and roasting heterogenously impact the likelihood of reactivity in egg-, milk-, peanut- and other legume-, tree nut-, fruit-, and seafood-allergic patients. These variations may be due to the use of different temperatures, duration of processing, presence of a matrix, and the specific allergens involved, among other factors. Accurate prediction of tolerance to processed allergens with skin prick tests and sIgE levels remains largely elusive. Food allergy management strategies, especially with milk and egg, have capitalized on the decreased allergenicity of baking. Many milk- and egg-allergic patients tolerate baked and heated forms of these allergens, and the use of these processed foods in oral immunotherapy (OIT) continues to be extensively investigated. Heat is also well recognized to reduce allergic symptoms from some fruits and vegetables in food-pollen syndrome. Other forms of processing such as boiling, fermenting, and canning can reduce allergenicity to a diverse array of foods. Roasting, on the other hand, may increase allergenicity. The application of food processing to food allergy treatments remains largely unexplored by large clinical studies and provides a key avenue for future research.
Summary
The recognition that food allergy represents a spectrum of hypersensitivity, rather than an all-or-nothing phenomenon, has led to approaches to enable dietary liberation with processed, less-allergenic foods and their use in food allergy immunotherapies.
... Hen's egg is one of the most common causes of food allergy worldwide, with a reported prevalence of 1.6-10.1% (1). The HealthNut study reported that the prevalence of hen's egg allergy (HEA) at one year of age was 9.5%, higher than with other major food allergies such as peanut (3.1%) and cow's milk (1.5%) (2). The natural history of HEA has been reported in several studies. ...
... The rate of tolerance varies between reports, ranging from 12% to 73% by 6 years of age (1,3,4). Peters et al. (2) studied 140 infants with challenge-confirmed HEA at one year of age and reported resolution of HEA in 47% by two years of age (2). ...
... The rate of tolerance varies between reports, ranging from 12% to 73% by 6 years of age (1,3,4). Peters et al. (2) studied 140 infants with challenge-confirmed HEA at one year of age and reported resolution of HEA in 47% by two years of age (2). ...
... Although many patients outgrow their food allergies within the first few years of life, a significant subset continues to experience allergic reactions into adolescence and even adulthood. This refractory course necessitates ongoing management and vigilance to prevent and treat potential allergic reactions (5)(6)(7)(8)(9)(10). ...
... Various factors have been linked to the persistence of food allergies, including a history of anaphylaxis, the severity of reactions, the age at symptom onset, family history of atopy, specific immunoglobulin E (sIgE) levels, skin prick test wheal sizes, the presence of multiple food allergies, and the involvement of multiple systems. These factors contribute to the complexity of managing food allergies and highlight the need for tailored approaches to patient care (6,7,9). ...
... However, data on the rates of tolerance to baked forms within this period is limited. Research has primarily focused on whether tolerating baked foods impacts the resolution of allergies to their native forms (9,11). In this study, we investigate the natural history of infants admitted solely with immediate-type hypersensitivity to milk and/or egg with a specific focus on their tolerability to baked forms of these foods by the age of two in addition to their predicting factors for baked allergen tolerability at initial admission. ...
... 124 Indeed, earlier studies suggested that the regular ingestion of baked egg in egg allergic children could accelerate the development of egg tolerance. 5,125 In a small, non-randomized clinical trial, the incremental ingestion of baked egg (from 125 mg to 3.8 g of baked egg daily) was shown to induce progressive desensitization to baked egg and lightly cooked egg (cooking conditions not specified). 124 Importantly, compared to other OITs, only very few adverse events were reported. ...
... A Beyond contributing to the quality of life of egg-allergic patients, a patient classification based on responsiveness to heated eggs might be useful to anticipate patient prognostics. As mentioned, many patients will outgrow hen's egg allergy, with a resolution of approximately 50% at the age of 2.5 The ability to tolerate baked egg is predictive of the transiency of egg allergy; patients unable to tolerate baked egg are five times less likely to develop tolerance.5 In line with the characteristics distinguishing baked egg-tolerant from reactive patients, it has been proposed that patients who have higher sIgE to raw EW, that are sensitized to OVM or multiple egg allergens and that are highly reactive to linear epitopes of OVM or OVA are less ...
... A Beyond contributing to the quality of life of egg-allergic patients, a patient classification based on responsiveness to heated eggs might be useful to anticipate patient prognostics. As mentioned, many patients will outgrow hen's egg allergy, with a resolution of approximately 50% at the age of 2.5 The ability to tolerate baked egg is predictive of the transiency of egg allergy; patients unable to tolerate baked egg are five times less likely to develop tolerance.5 In line with the characteristics distinguishing baked egg-tolerant from reactive patients, it has been proposed that patients who have higher sIgE to raw EW, that are sensitized to OVM or multiple egg allergens and that are highly reactive to linear epitopes of OVM or OVA are less ...
Hen's egg allergy is the second most frequent food allergy found in children. Allergic symptoms can be caused by raw or heated egg, but a majority of egg‐allergic children can tolerate hard‐boiled or baked egg. Understanding the reasons for the tolerance towards heated egg provides clues about the molecular mechanisms involved in egg allergy, and the differential allergenicity of heated and baked egg might be exploited to prevent or treat egg allergy. In this review, we therefore discuss (i) why some patients are able to tolerate heated egg; by highlighting the structural changes of egg white (EW) proteins upon heating and their impact on immunoreactivity, as well as patient characteristics, and (ii) to what extent heated or baked EW might be useful for primary prevention strategies or oral immunotherapy. We describe that the level of immunoreactivity towards EW helps to discriminate patients tolerant or reactive to heated or baked egg. Furthermore, the use of heated or baked egg seems effective in primary prevention strategies and might limit adverse reactions. Oral immunotherapy is a promising treatment strategy, but it can sometimes cause significant adverse events. The use of heated or baked egg might limit these, but current literature is insufficient to conclude about its efficacy.
... 16,17 Challenge-confirmed egg allergy was found in 9% of infants at age 12 months, with 50% of cases resolving by age 2 years. 17,18 The HealthNuts study has now completed further follow-up of the cohort at age 6 years. The aims of the present study are to describe the natural history of food allergy across the first 6 years of life and to assess whether demographic or clinical factors present at diagnosis are predictive of the persistence or resolution of food allergy. ...
... The HealthNuts study's methods for recruitment and the age 2 years, age 4 years, and age 6 years follow-up visits have been described in detail in previous publications. [17][18][19][20] A brief overview is provided here and in Fig 1. Recruitment at age 1 year. HealthNuts is a population-based, prospective study that recruited 5276 infants (aged 11-15 months; 74% participation) from council-run immunization sessions across Melbourne from 2007 to 2011. ...
... All infants with challenge-confirmed raw egg allergy at 12 months of age who had been recruited after February 2010 (n 5 264) were invited to participate in an additional baked egg OFC at age 1 year and follow-up at age 2 years with repeat raw egg OFCs. 18 Age 4 years follow-up. At age 4 years, all enrolled participants were invited to complete a questionnaire (n 5 4291 participated). ...
Background
Prospectively collected data on the natural history of food allergy are lacking.
Objective
We examined the natural history of egg and peanut allergy in children from age 1 to 6 years and assessed whether a skin prick test (SPT) result or other clinical factors at diagnosis are associated with the persistence or resolution of food allergy in early childhood.
Methods
The HealthNuts cohort consists of 5276 children who were recruited at age 1 year and have been followed prospectively. Children with food allergy at age 1 year (peanut [n = 156] or raw egg [n = 471] allergy ) and children who developed new sensitizations or food reactions after age 1 year were assessed for food sensitization and allergy (confirmed by oral food challenge when indicated) at the 6-year follow-up.
Results
New-onset food allergy developed by age 6 years was more common for peanut (0.7% [95% CI = 0.5%-1.1%]) than egg (0.09% [95% CI = 0.03%-0.3%]). Egg allergy resolved more commonly (89% [95% CI = 85%-92%]) than peanut allergy (29% [95% CI = 22%-38%]) by age 6 years. The overall weighted prevalence of peanut allergy at age 6 years was 3.1% (95% CI = 2.6-3.7%) and that of egg allergy was 1.2% (95% = CI 0.9%-1.6%). The factors at age 1 year associated with persistence of peanut allergy were peanut SPT result of 8 mm or larger (odds ratio [OR] = 2.35 [95% CI 1.08-5.12]), sensitization to tree nuts (adjusted OR [aOR] = 2.51 [95% CI = 1.00-6.35]), and early-onset severe eczema (aOR = 3.23, [95% CI 1.17-8.88]). Factors at age 1 associated with persistence of egg allergy at age 6 were egg SPT result of 4 mm or larger (OR = 2.98 [95% CI 1.35-6.36]), other (peanut and/or sesame) food sensitizations (aOR = 2.80 [95% CI = 1.11-7.03]), baked egg allergy (aOR = 7.41 [95% CI = 2.16-25.3]), and early-onset severe eczema (aOR = 3.77 [95% CI = 1.35-10.52]).
Conclusion
Most egg allergy and nearly one-third of peanut allergy resolves naturally by age 6 years. The prevalence of peanut allergy at age 6 years was similar to that observed at age 1 year, largely owing to new-onset food peanut allergy after age 1 year. Infants with early-onset eczema, larger SPT wheals, or multiple food sensitizations and/or allergies were less likely to acquire tolerance to either peanut or egg.
... The natural history of HE allergy (HEA) has been previously reported in various countries [7][8][9][10][11][12][13][14][15]. The rate of tolerance varies across reports, from 12% to 73% by 6 years of age. ...
... The natural history of HEA has been reported previously, including in Japan [7][8][9][10][11][12][13][14][15]. Many of those reports were based on the follow-up of patients during the first few years of their lives. ...
... Our study results showed a similar trend, with 60.5% of the patients who still had HEA at the age of 6 years acquiring HE tolerance by the age of 12 years. Our results and those of the previous studies cannot be simply compared because our study enrolled patients at a starting age of 6 years, unlike the previous studies that investigated patients at much younger ages [7][8][9][10][11][12][13][14][15]. However, our study participants and their results may be better reflections of the real world. ...
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.
... 54 However, multiple observational research studies report a beneficial effect with regular baked egg consumption. 55,56 Children who react to baked egg in their initial exposure appear to have a more severe phenotype and lower rates of natural resolution. In contrast, children with negative or low sensitization to Gal d 1 are more likely to tolerate baked/heated egg. ...
... Peters et al examined 140 infants with challengeconfirmed egg allergy at age 1 year and reported egg allergy resolution in 47%, 12 months later (at age 2). 55 Those infants who had reacted to baked egg at baseline, showed lower rates of resolution. Additionally, infants that consumed baked egg more than 5 times per month had better odds in developing tolerance. ...
... Additionally, infants that consumed baked egg more than 5 times per month had better odds in developing tolerance. 55 A similar study, which included 70 participants who regularly ate baked egg, evaluated the role of baked egg in the development of tolerance to regular egg. 56 A reported 53% of the above participants were able to tolerate regular egg after an approximately 3-year study period, compared with only 28% of the participants in the comparison group (who all adhered to strict avoidance). ...
Egg allergy occurs frequently in childhood with a reported prevalence of 1.3–1.6%. Providing optimal care to egg-allergic patients requires knowledge of the most up-to-date developments in both diagnosis and management, as well as effective communication skills, which will engage the patient in the shared decision-making process. This review aims to provide up-to-date information on egg allergy and also serve as a concise guide on optimal patient diagnosis and management. The field of food allergy has seen multiple advances in recent years, including use of component resolved diagnostics, early egg introduction into the infant diet as a way of preventing egg allergy, baked egg introduction and oral immunotherapy as a form of active therapy. Faced with a variety of options and treatment paths, it is important to ensure that patients and families taking part in the decision-making process have fully understood the potential outcomes and trade-offs and can undertake a detailed discussion of all options that are available to them. Shared decision-making remains the cornerstone of optimal patient care.
... Besides, evasion of all egg items represents a significant detriment as eggs are of high dietetic importance, giving fundamental nutrients, proteins and unsaturated fats [71]. Contrastingly, research shows that the capacity to endure cooked egg provides an expected indicator of temporary egg sensitivity, with 80% of children with a crude egg hypersensitivity able to endure the consumption of cooked types of egg [72,73]. This is essential to think about given the current administration for egg sensitivities, featuring the further requirement for precise analysis, anticipation and discrimination between egg-hypersensitivity, egg open minded and eggsharpened people. ...
... Besides, evasion of all egg items represents a significant detriment as eggs are of high dietetic importance, giving fundamental nutrients, proteins and unsaturated fats [71]. Contrastingly, research shows that the capacity to endure cooked egg provides an expected indicator of temporary egg sensitivity, with 80% of children with a crude egg hypersensitivity able to endure the consumption of cooked types of egg [72,73]. This is essential to think about given the current administration for egg sensitivities, featuring the further requirement for precise analysis, anticipation and discrimination between egg-hypersensitivity, egg open minded and egg-sharpened people. ...
Food allergies (FA) are commonly depicted as immune responses. The mechanism of allergic reactions involves immunoglobulin E (IgE) and non-immunoglobulin E (non-IgE)-related responses caused by contact with specific foods. FAs can be fatal, have negative effects and have become the subject of fanaticism in recent years. In terms of food safety, allergic compounds have become a problem. The immune response to allergens is different to that from food intolerance, pharmacological reactions, and poisoning. The most important allergenic foods are soybeans, milk, eggs, groundnuts, shellfishes, tree nuts, cereals and fish, which together are known as the “Big Eight”. This review will introduce and discuss FAs in milk, peanuts, nuts, shellfishes, eggs and wheat and their detections and potential treatments will also be provided. We believe that this review may provide important information regarding food-induced allergies for children who have allergic reactions and help them avoid the allergenic food in the future.
... The age at onset is reported to affect the prognosis of FA being related to severe reactions in anaphylaxis. 6,15,16 Elizur et al. 6 demonstrated that resolution of cow's milk allergy was significantly delayed in infants whose first reaction occurred before 1 month of age. In contrast, Topal et al. 16 showed that presentation after 6 months of age was associated with persistence of cow's milk allergy. ...
... Frequency of mite sensitivity has been reported to be higher in patients with persistent FA. 22,23 We found that sensitivity to pollen, another aeroallergen, was higher in the nontolerant group. In accordance with previous studies on FA, 13,15,16,22 multiple FIA were more frequent in the persistent group in our study (33% versus 5%). In our study, the total IgE level (p = 0.042) and highest SPT wheal size (p = 0.006) were greater in those with multiple FAs, which suggested a higher level of allergen sensitivity in those with multiple FAs, which contributes to the longer persistence. ...
Background: Food allergies are known to resolve over time, but there is little information on the natural history of food-induced anaphylaxis (FIA). Objective: This study aimed to evaluate the natural history of FIA in children and determine the factors that affect prognosis. Methods: Children with FIA who were followed up for at least 3 years, between 2010 and 2020, were included. Patients' families were contacted by telephone to question their child's tolerance status and invite them for reevaluation if uncertain. The patients were grouped as tolerant or persistent according to parent reports or reevaluation results. Logistic regression analysis was performed to determine the factors that affected persistence. Results: The study included 185 patients (62.2% boys) with 243 anaphylactic reactions to various foods. Fifty-eight patients (31%) gained tolerance within a 3-year follow-up period. Tolerance rates were higher in patients with FIA to milk (40%) and egg (43.9%) compared with to tree nuts (18.8%), legumes (5.6%), and/or seafood (11.1%) (p < 0.001). In a multivariate analysis, risk factors for persistent FIA were multiple food anaphylaxis (odds ratio [OR] 3.755 [95% confidence interval {CI}, 1.134‐12.431]; p = 0.030), total IgE > 100 kU/L (OR 5.786 [95% CI, 2.065‐16.207]; p = 0.001), and skin-prick test wheal size > 10 mm (OR 4.569 [95% CI, 1.395‐14.964]; p = 0 .012) at presentation. Conclusion: Approximately a third of the patients with FIA developed tolerance within 3 years. Clinicians should remember that children with food allergies, even anaphylaxis, may develop tolerance over time. Regular follow up and reevaluation of tolerance status are necessary to avoid unnecessary elimination.
... Management of food allergies has historically been limited to avoidance with periodic reassessment. However, there is increasing recognition that children with egg and milk allergy may tolerate baked/processed forms of milk and egg, and that ongoing ingestion of these forms may help with resolution of their food allergy [8,9]. Conformational changes in immune-activating epitopes that occur during the baking or heating processes alter the allergenicity of milk and egg and may allow for tolerance [10]. ...
... If a child is confirmed to be fully tolerant to foods on a higher step of the ladder, they need not start at Step 1; rather, they may start at the step corresponding to foods currently tolerated. Caregivers are advised that children can progress as slowly through the food ladder as tolerated and desired, as even consuming baked goods regularly (Step 1) has been shown to promote tolerance [8,9]. ...
Food ladders are clinical tools already widely used in Europe for food reintroduction in milk- and egg-allergic children. Previously developed milk and egg ladders have limited applicability to Canadian children due to dietary differences and product availability. Herein we propose a Canadian version of cow’s milk and egg food ladders and discuss the potential role that food ladders may have in the care of children with IgE-mediated allergies to cow’s milk and/or egg, as either a method of accelerating the acquisition of tolerance in those who would outgrow on their own, or as a form of modified oral immunotherapy in those with otherwise persistent allergy.
... It is cheap and easily accessible, used in many homemade dishes, and it is also widely used by the food industry in processed foods. HE allergy (HEA) is one of the most common IgE-mediated FAs in pediatric ages, with a typical onset in the first year of life [5]. ...
Hen’s egg allergy is one of the most common food allergies in the Western world, with an increase in recent years. It affects about 9.5% of the pediatric population, and the onset most often occurs before the first year of life. The occurrence of spontaneous oral tolerance acquisition varies among studies, but it is generally high by school age. Nowadays, allergen immunotherapy may represent the only therapeutic strategy able to modify the natural history of hen’s egg allergy. Specifically, many children with hen’s egg allergy may tolerate baked eggs. Food processing, specifically high temperatures, alters the allergenicity of hen’s egg proteins by causing conformational changes in allergen epitopes, which makes them less allergenic. This review aims to discuss the scientific evidence in the field of baked egg oral immunotherapy in hen’s egg-allergic children, with a meticulous examination of the pertinent literature surrounding the subject matter.
... The prevalence of self-reported food allergies among Canadian children is 8.7% and is increasing. 1 After peanuts and tree nuts, egg allergy is the third most common pediatric allergy, affecting 2.1%. 1 The natural history of egg allergy is typically more favorable than that of other allergens, with resolution in half of the patients by 5 years old. [2][3][4] In 40% of patients with persistent egg allergy, tolerance to baked goods develops by 6 years of age. 4 However, owing to the ubiquity of eggs in cooking, accidental ingestions and subsequent egg-induced anaphylaxis are common. 5,6 Among a cohort of children with egg allergies, 1 study reported that 36.1% experienced an emergency department (ED) visit in the preceding 12 months for an allergic reaction and 28.1% had a history of anaphylaxis. ...
... Conversely, OM is a heat-stable and highly allergenic protein in HEW. 13 -15 Nonetheless, over 70% of children with HE allergy can reportedly tolerate extensively cooked eggs and cooked egg-containing food products; additionally, consuming extensively or adequately baked HEW may induce tolerance in children with allergies following careful evaluation by supervised oral food challenge (OFC). 16,17 Therefore, we aimed to identify the changes in HEW allergenicity using diverse cooking methods commonly used in Korean dishes and applied the results to help provide appropriate dietary consulting for developing tolerance acquisition in children with HEW allergy. ...
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.
... In Japan, hen's eggs and cow's milk are the first and second most common causes of food allergy in infancy and early childhood. 1 Most children with hen's egg and cow's milk allergies spontaneously acquire tolerance over time, [2][3][4] and for those who do not acquire tolerance, oral immunotherapy (OIT) may be administered as an experimental treatment in Japan. Although it is expected to induce desensitization to both hen's egg 5 and cow's milk, 6 OIT is accompanied by the risk of immediate allergic reactions at the intentional intake, including anaphylaxis. ...
Background:
Exercise-induced allergic reactions on desensitization (EIARDs) after successful in-hospital rush oral immunotherapy (OIT) for wheat allergy have been reported; however, the incidence rates of EIARDs after rush OIT for egg allergy and milk allergy have not been determined.
Objective:
To determine the frequency of EIARDs and associated risk factors with rush OIT for egg and milk allergy.
Methods:
This retrospective chart review, conducted in January 2020, enrolled 64 and 43 patients who underwent rush OIT for egg and milk allergy, respectively (2010-2014). Especially, 48 and 32 desensitized patients underwent exercise-provocation tests (Ex-P) after allergen administration (4,400 mg boiled egg white and 6,600 mg cow milk protein, respectively). EIARDs were determined by Ex-P or a suspicious event even after passing the Ex-P. Specific immunoglobulin E (sIgE) levels to egg white, cow milk, ovomucoid, casein, α-lactalbumin, and β-lactoglobulin were analyzed using ImmunoCAP®.
Results:
At least one episode of EIARD was observed in 10 (21%) and 17 (53%) patients with egg and milk allergy, respectively, which persisted for >5 years in one patient with egg allergy (2.1%) and 11 patients with milk allergy (34.4%) as of January 2020. We could not find background differences between the EIARD+ and EIARD- groups, except that the egg white sIgE/total IgE ratio before rush OIT was significantly higher in patients with egg allergy with EIARD than in those without.
Conclusion:
EIARDs were more frequent and common in patients with milk allergy. EIARDs to milk allergy were more likely to persist than those to egg allergy.
... Additionally, avoiding eggs can lead to nutritional deficiencies since they are a valuable source of essential vitamins, proteins, and fatty acids [211]. On the other hand, research has shown that children who can tolerate cooked eggs may not have a long-lasting allergy, with 80% of children with a raw egg allergy being able to tolerate cooked eggs [212][213][214]. This highlights the need for accurate diagnosis, prognosis, and differentiation between egg-allergic, egg-tolerant, and egg-sensitized individuals, which is crucial for effectively managing egg allergies. ...
This review article discusses advanced extraction methods to enhance the functionality of egg-derived peptides while reducing their allergenicity. While eggs are considered a nutrient-dense food, some proteins can cause allergic reactions in susceptible individuals. Therefore, various methods have been developed to reduce the allergenicity of egg-derived proteins, such as enzymatic hydrolysis, heat treatment, and glycosylation. In addition to reducing allergenicity, advanced extraction methods can enhance the functionality of egg-derived peptides. Techniques such as membrane separation, chromatography, and electrodialysis can isolate and purify specific egg-derived peptides with desired functional properties, improving their bioactivity. Further, enzymatic hydrolysis can also break down polypeptide sequences and produce bioactive peptides with various health benefits. While liquid chromatography is the most commonly used method to obtain individual proteins for developing novel food products, several challenges are associated with optimizing extraction conditions to maximize functionality and allergenicity reduction. The article also highlights the challenges and future perspectives, including optimizing extraction conditions to maximize functionality and allergenicity reduction. The review concludes by highlighting the potential for future research in this area to improve the safety and efficacy of egg-derived peptides more broadly.
... It is worth noting that the time of cooking has a greater effect on egg allergenicity than the temperature used [18] and that ovomucoid, the dominant allergen in egg white, is a heatstable protein. Although some cohort studies have suggested that the consumption of baked eggs quickly results in immune changes and tolerance acquisition to raw egg [19,20,21], others did not confirm these data [22,23]. OIT for peanut allergy OIT with peanut can be performed with defatted peanut flour [24,25], crushed roasted peanuts [26], or boiled peanuts [27]. ...
Food allergy represents a significant health issue characterized by a sizeable epidemiological burden, involving up to 5% of adults and up to 8% of children in the Western world. The elimination diet of the trigger food is the cornerstone of food allergy management. However, novel treatment options are most wanted to provide alternative strategies for this potentially fatal medical condition. Allergen immunotherapy for food allergy (FA-AIT) is considered an immunomodulatory intervention where regular exposure to increasing doses of food is performed in the context of an allergist's supervised protocol. The main objective is to decrease reactivity, attenuate life-threatening allergic episodes and reduce frequent access to the emergency department. Achieving food tolerance off-treatment is, however, the ultimate aim. In this review, we aim to summarize FA-AIT evidence and outlook.
... Similar results were also observed in a previous study covering 52 patients ranging from 3 to 114 months of age (Ahrens et al. 2012). Besides, other studies demonstrated the association between resolution or tolerance and the sIgE to wheat (Kotaniemi-Syrjanen et al. 2010;Nilsson et al. 2015), egg (Datema et al. 2019;Peters et al. 2014), peanut (Asarnoj et al. 2012;Datema et al. 2019), and pumpkin seeds (Gawryjołek et al. 2021). Therefore, CRD results (sIgE) may be potential indicators to identify patients who will best benefit from AIT (Schoos et al. 2020). ...
Food allergy (FA) is a serious public health issue afflicting millions of people globally, with an estimated prevalence ranging from 1-10%. Management of FA is challenging due to overly restrictive diets and the lack of diagnostic approaches with high accuracy and prediction. Although measurement of serum-specific antibodies combined with patient medical history and skin prick test is a useful diagnostic tool, it is still an imprecise predictor of clinical reactivity with a high false-positive rate. The double-blind placebo-controlled food challenge represents the gold standard for FA diagnosis; however, it requires large healthcare and involves the risk of acute onset of allergic reactions. Improvement in our understanding of the molecular mechanism underlying allergic disease pathology, development of omics-based methods, and advances in bioinformatics have boosted the generation of a number of robust diagnostic biomarkers of FA. In this review, we discuss how traditional diagnostic modalities guide appropriate diagnosis and management of FA in clinical practice, as well as uncover the potential of the latest biomarkers for the diagnosis, monitoring, and prediction of FA. We also raise perspectives for precise and targeted medical intervention to fill the gap in the diagnosis of FA.
... The time to acquiring tolerance to egg allergens varies. It has been found that 68% of children acquire tolerance to cooked hen's eggs by the age of 16 years old [4], while Peters et al. note that half of children develop tolerance around the age of 2 years [5]. Interestingly, patients with IgE-dependent FA are more likely to demonstrate more persistent egg allergy, similar to other forms of FA [2]. ...
Oral food challenge is the gold standard in diagnosing food allergies; however, many testing protocols are available. The present article illustrates the difficulties associated with interpreting oral challenge tests with the example of a six-year-old boy with allergy to hen's eggs. The symptoms observed on the first day of challenge indicated a negative result; however, the consumption of the cumulative dose resulted in anaphylaxis. The interpretation of the oral food challenge can be complicated. The criteria used to determine a positive or negative result are sometimes ambiguous. An accurate interpretation of the results is key to determining correct management in children with food allergy.
... First, we did not ascertain egg tolerance by double-blind, placebo-controlled food challenges. In the Australian HealthNuts study, 140 infants with challenge-confirmed raw egg allergy were followed until 2 years of age [24]. Egg allergy resolved in 66 infants (47%) in this follow-up period, and those with baked egg allergy at 1 year old was more likely to have persistent egg allergy. ...
Background:
Egg allergy is one of the most common food allergies in childhood with increasing prevalence in Hong Kong. While ample studies were published on its optimal diagnosis, there was limited data on predictors for the natural history of egg allergy in Asian populations.
Objective:
This study aimed to characterize the clinical course and outcome of children with egg allergy and identify its prognostic factors.
Methods:
All Chinese children with immediate-type egg allergy being followed since ≥3 years old in allergy clinic of our university-affiliated teaching hospital were reviewed to determine if they outgrew egg allergy at the latest follow-up. The predictive values of clinical and atopic factors for resolution of egg allergy were analyzed on Kaplan-Meier curves, and factors independently associated with persistent egg allergy was analyzed by logistic regression.
Results:
Seventy-six patients with median (interquartile range) age 8.9 years (6.3-13.0 years) were recruited. They initially presented with egg-allergic reactions at 1.0 years (0.7-1.7 years). Fifty-four children (71%) were able to tolerate egg at a median of 36 months from initial reaction. Patients with concomitant peanut allergy and those with initial reaction at ≥1 year old were more likely to have persistent egg allergy (p = 0.015 and p = 0.027 respectively). Skin prick test wheal ≥6 mm to egg yolk and egg white individually as well as to both egg yolk and egg white were predictors for egg allergy persistence (respective, p < 0.001, p = 0.001, and p = 0.001 by log-rank tests). Logistic regression showed that initial SPT ≥ 6 mm to egg yolk was the only independent predictor for persistent egg allergy (B = 2.59 ± 0.98, p = 0.008).
Conclusion:
Most Chinese children with immediate-type egg allergy can tolerate egg in long run. SPT wheal size to egg, concomitant peanut allergy and initial presentation after infancy may predict egg allergy persistence.
... Development of natural tolerance is more common to some foods, e.g., egg white, cow's milk, and wheat, compared with others, e.g., peanut. [11][12][13][14][15][16] It remains unknown why reactions to certain foods remain persistent, and few studies have investigated the mechanisms that might contribute to the development of natural tolerance in humans. [17][18][19][20][21][22][23][24][25][26] Fishbein et al. 27 showed lower egg white sIgG4/sIgE ratios in the subjects with egg white allergy compared with the subjects who were naturally tolerant. ...
Background
Food specific immunoglobulin E (sIgE) levels are associated with the development of allergic responses and are used in the clinical evaluation of food allergy. Food sIgG4 levels have been associated with tolerance or clinical nonresponsiveness, particularly in interventional studies.
Objective
We aimed to characterize food-specific antibody responses and compare responses with different foods in food allergy.
Methods
Serum sIgA, sIgG4, and sIgE to whole peanut, egg white, and wheat, along with total IgE were measured in 57 children. Children with food allergy, children with natural tolerance, and controls were studied. The Mann-Whitney test or Kruskall Wallis test with the Dunn correction were used for statistical analysis.
Results
As expected, total IgE levels were highest in the subjects with food allergy compared with the subjects who were nonallergic (p < 0.001) or the subjects who were naturally tolerant (p < 0.001). Peanut sIgE levels were higher in subjects with peanut allergy compared with the subjects who were naturally tolerant (p < 0.0001) and the control subjects (p < 0.03). Interestingly, peanut sIgG4 levels were also highest in children with peanut allergy compared with subjects who were naturally tolerant and control subjects (p = 0.28 and p < 0.001, respectively). Subjects with peanut allergy alone had comparable egg white sIgE levels to children with egg white allergy. In addition, the subjects with peanut allergy alone also had higher levels of egg white and wheat sIgE compared with the control subjects (p < 0.02 and p = 0.001, respectively). In contrast, the subjects with egg white allergy did not demonstrate elevated peanut or wheat sIgE levels.
Conclusion
These novel findings suggested that IgE production is dysregulated in patients with peanut allergy, who are much less likely to outgrow their allergy, and suggest that the mechanisms that drive more persistent forms of food allergy may be distinct from more transient forms of food allergy.
... It has long been established that 50% of cow's milk allergic children and up to 80% of hen's egg-allergic children develop tolerance by the age of 4-6 years (36)(37)(38). Moreover, recent studies showed that an increasing number of children tends to outgrow their cow's milk and egg allergies after the preschool age (37,39,40). ...
The prevalence of food allergy has increased in recent years, especially in children. Allergen avoidance, and drugs in case of an allergic reaction, remains the standard of care in food allergy. Nevertheless, increasing attention has been given to the possibility to treat food allergy, through immunotherapy, particularly oral immunotherapy (OIT). Several OIT protocols and clinical trials have been published. Most of them focus on children allergic to milk, egg, or peanut, although recent studies developed protocols for other foods, such as wheat and different nuts. OIT efficacy in randomized controlled trials is usually evaluated as the possibility for patients to achieve desensitization through the consumption of an increasing amount of a food allergen, while the issue of a possible long-term sustained unresponsiveness has not been completely addressed. Here, we evaluated current pediatric OIT knowledge, focusing on the results of clinical trials and current guidelines. Specifically, we wanted to highlight what is known in terms of OIT efficacy and effectiveness, safety, and impact on quality of life. For each aspect, we reported the pros and the cons, inferable from published literature. In conclusion, even though many protocols, reviews and meta-analysis have been published on this topic, pediatric OIT remains a controversial therapy and no definitive generalized conclusion may be drawn so far. It should be an option provided by specialized teams, when both patients and their families are prone to adhere to the proposed protocol. Efficacy, long-term effectiveness, possible role of adjuvant therapies, risk of severe reactions including anaphylaxis or eosinophilic esophagitis, and impact on the quality of life of both children and caregivers are all aspects that should be discussed before starting OIT. Future studies are needed to provide firm clinical and scientific evidence, which should also consider patient reported outcomes.
... 20 Casein Bos d 8 and ovomucoid Gal d1 specific IgE (sIgE) levels have been identified as markers of reactivity in patients with cow's milk and hen's egg allergy, respectively. 22 Dang et al. 23 described the potential role of sensitization to multiple egg allergens (i.e., Gal d 1, Gal d 2, Gal d 3, Gal d 5) as a prognostic marker for long-lasting egg allergy. With regard to peanut allergy, the absence of sIgE to Ara h2 seems to be associated with less severe reactions. ...
Background: Immunoglobulin E (IgE) mediated food allergy is a potentially life-threatening condition and represents a heavy burden for patients and their families. Identification of the most suitable way for management of each patient has currently become the primary goal for physicians. Methods: This study reviewed the current literature related to IgE-mediated food allergy. Results: The use of innovative diagnostic tools, such as allergen-specific IgG4 determination, basophil activation test, and component-resolved diagnostics, is currently available to facilitate a proper diagnosis of food allergy. After several decades of “passive clinical management” of the disease, which was based only on avoidance of the allergenic food and the use of epinephrine in the event of anaphylaxis, there has been a switch to active treatment. The most recent evidence-practice guidelines strongly recommend the use of immunotherapy as an effective therapeutic option, particularly in cases of allergy to cow's milk, egg, or peanut. The use of omalizumab, in association with immunotherapy or alone, has been tested in several studies, and results on its effectiveness seemed to be encouraging. Other biologics, such as dupilumab, reslizumab, mepolizumab, and other anticytokines therapies, are being investigated. Another interesting future treatment strategy could be the use of DNA vaccines. Conclusion: In recent years, the management of IgE-mediated food allergy has greatly improved. Knowledge of pathogenetic mechanisms, understanding of the disease course, and the introduction of novel biomarkers led to more accurate diagnoses along with the active treatment of patients.
... It has long been established that 50% of cow's milk allergic children and up to 80% of hen's eggallergic children develop tolerance by the age of 4-6 years (32)(33)(34). Moreover, recent studies showed that an increasing number of children tends to outgrow their cow's milk and egg allergies after the preschool age (33,35,36). ...
The prevalence of food allergy has increased in recent years, especially in children. Food allergen avoidance and symptomatic drugs in case of an allergic reaction remain the standard of care in food allergy. Nevertheless, increasing attention has been given to the possibility to treat food allergy, through immunotherapy, particularly oral immunotherapy (OIT). Several OIT protocols and clinical trials have been published. Most of them focus on children allergic to milk, egg, or peanuts, although recent studies developed protocols for other foods, such as wheat and different nuts. OIT efficacy in randomized controlled trials is usually evaluated as the possibility for patients to achieve desensitization, while the issue of a possible long-term sustained unresponsiveness has not been completely addressed. Here, we evaluated current OIT knowledge, focusing on the results of clinical trials and current guidelines. Specifically, we wanted to highlight what is known in terms of OIT efficacy and effectiveness, safety, and impact on quality of life. For each aspect, we reported the pros and the cons, inferable from published literature. In conclusion, even though many protocols, reviews and meta-analysis have been published on this topic, OIT remains a controversial therapy and no definitive generalized conclusion may be drawn so far. It should be an option provided by specialized teams, when both patients and their families are prone to adhere to the proposed protocol. Efficacy, long-term effectiveness, possible role of adjuvant therapies, risk of severe reactions including anaphylaxis or eosinophilic esophagitis, and impact on the quality of life of both children and caregivers are all aspects that should be discussed before starting OIT. Future studies are needed to provide firm clinical and scientific evidence, which should also consider patient reported outcomes.
Background . Food allergy (FA) is a common chronic disease. There are no official data on the prevalence of FA in Russia. The results of only a few Russian studies of FA and anaphylaxis in children have been published.
The aim of the study is to study the prevalence of sensitization to food allergens from the group of “big eight” in children with atopic phenotype living in the Moscow agglomeration.
Methods . The cross-sectional study included children aged 0 to 17 years with complaints of seasonal manifestations of allergies / diagnosed with seasonal allergic rhinitis (pollinosis); with complaints of allergic reactions when eating any food; with complaints of atopic dermatitis. The determination of sensitization to allergens was carried out using ImmunoCAP technology, ImmunoCAP ISAC / ALEX2 allergy chips.
Results . 240 children were included in the study. Sensitization to extracts of food allergens of the “big eight”, detected by the ImmunoCAP monoplex method, was determined in 1.5 (for fish) — 5 (for wheat) several times more often than with multiplex allergodiagnostics. In molecular allergodiagnosis, sensitization to hazelnut allergens was found in 57%, peanuts — in 47%, soy — in 39%, walnut — in 24%, chicken egg — in 18%, cow’s milk — in 12%, fish — in 9.7%, cashews — in 7.6%, shrimp — in 6.3%, wheat — in 4.6% of children. The frequency of food allergy symptoms, based on the assessment of the patients’ parents, was up to 7 times higher than the detected frequency of sensitization, accompanied by complaints of symptoms when eating the appropriate foods. Among the products causing symptoms in such patients, hazelnuts, cow’s milk, chicken egg and peanuts were in the lead.
Conclusion . More than half of Russian children are sensitized to the allergens of the “big eight”, while clinically significant sensitization was noted 2 times less often. Sensitization to the allergen components of the PR-10 group of hazelnuts, peanuts and soybeans was most often detected. The frequency of FA diagnosed by a doctor is significantly lower than the frequency of the disease detected by the results of a survey of patients’ parents.
More than 10 years ago, the British Society for Allergy and Clinical Immunology (BSACI) published guidelines for the management of egg allergy [1]. For the first time, these included a stepwise plan for the reintroduction of egg for egg-allergic children who could already tolerate well-cooked egg, such as cakes and cookies. Since then, various egg ladders have been developed [2, 3, 4, 5, 6, 7, 8, 9]. In the past 3 years, several studies have been published suggesting that a gradual introduction of highly processed to less processed egg containing foods contribute to the acceleration of tolerance development [2, 3, 4, 5]. However, depending on the study and egg ladder, the egg products vary in their level of processing (wheat matrix, degree, and location of heating (e.g., oven, pan, pot), egg quantity, and egg protein). In the UK, the introduction of the egg ladder is recommended at the age of 12 months or if the last reaction occurred 6 months before. The benefits of introducing egg at home include an early increase in the variety of foods, reduction of food fears, improved nutrient intake, and the avoidance of hospitalization fears in children [10]. Children with mild reactions in the past can start with small amounts of baked goods at home. Food challenges in an inpatient setting to exclude or reconfirm the allergy should be conducted if the patients have previously had severe allergic reactions, i.e., anaphylaxis, or if the smallest amounts triggered an allergic reaction or if existing asthma is poorly controlled [10, 11]. The present work includes, in addition to the evaluation of study results, a presentation of the recent studies regarding egg ladders. From these, a new egg ladder as therapeutic option for the German-speaking region has been developed. As already done for the milk ladder a detailed step-by-step plan, selection criteria, a recipe collection, and also ideas for commercial prepackaged food items can be found in the appendices [11].
Baking, especially of bread, holds special significance for many cultures. It is such a fundamental part of everyday food consumption that the children's nursery rhyme Pat-a-cake, pat-a-cake, baker's man takes baking as its subject.
This research identifies Biblical verses that mention baking and evaluates the topic of baking from a contemporary perspective.Ethnic groups have different dietary patterns based on their geographical locations and cultural influences. Food consumption patterns and eating and cooking behaviors changed dramatically in various countries.
The health effects of baking include changes in anthropometric parameters, adherence to a gluten-free diet, hypocholesterolemic effects, and the relationship between the type of mechanical ventilation and baking, the history of smoking, drug use, and baking bread. This research examines the exposure of baking products to various allergens, including egg allergies.
Acute and chronic oral bicarbonate ingestion can result in metabolic alkalosis, hypernatremia, hypertension, gastric rupture, hyporeninemia, hypokalemia, hypochloremia, intravascular volume depletion, rhabdomyolysis with end-stage renal failure, hemorrhagic encephalopathy, epileptic convulsions, subdural hematoma, and urinary alkalinization. Abrupt cessation of chronic excessive bicarbonate ingestion may result in hyperkalemia, hypoaldosteronism, volume contraction, and disruption of calcium and phosphorus metabolism.
Food products can be contaminated by gluten, posing a risk for celiac patients, as well as by various microbes, fungi, and acrylamide.
It is necessary to improve and innovate various technologies to enhance the quality of baked products. The present Research also addresses the risk factors of baking products, including pterygium, of depression, increased lung cancer, work-related ill-health, allergic respiratory diseases such as bronchial asthma, irritant dermatitis and eczema.
The present research presents numerous options to improve the quality of baked goods. It covers a range of topics, including ingredient selection, proper measuring techniques, and the importance of using the right tools. Additionally, it emphasizes the significance of temperature control, both in terms of ingredient preparation and baking. Practical tips for ensuring even cooking, checking for doneness, and making necessary adjustments for different environmental conditions are provided. The Research also highlights the value of proper storage to maintain freshness and encourages continuous learning and practice to enhance baking skills. Specific advice is given for improving common baked items like bread, cakes, cookies, pies, biscuits, and pasta.
The main conclusion is that baking has accompanied humans during the long years of our existence.
Baking, especially of bread, holds special significance for many cultures. It is such a fundamental part of everyday food consumption that the children's nursery rhyme Pat-a-cake, pat-a-cake, baker's man takes baking as its subject.
This research identifies Biblical verses that mention baking and evaluates the topic of baking from a contemporary perspective. Ethnic groups have different dietary patterns based on their geographical locations and cultural influences. Food consumption patterns and eating and cooking behaviors changed dramatically in various countries.
The health effects of baking include changes in anthropometric parameters, adherence to a gluten-free diet, hypocholesterolemic effects, and the relationship between the type of mechanical ventilation and baking, the history of smoking, drug use, and baking bread. This research examines the exposure of baking products to various allergens, including egg allergies.
Acute and chronic oral bicarbonate ingestion can result in metabolic alkalosis, hypernatremia, hypertension, gastric rupture, hyporeninemia, hypokalemia, hypochloremia, intravascular volume depletion, rhabdomyolysis with end-stage renal failure, hemorrhagic encephalopathy, epileptic convulsions, subdural hematoma, and urinary alkalinization. Abrupt cessation of chronic excessive bicarbonate ingestion may result in hyperkalemia, hypoaldosteronism, volume contraction, and disruption of calcium and phosphorus metabolism.
Food products can be contaminated by gluten, posing a risk for celiac patients, as well as by various microbes, fungi, and acrylamide.
It is necessary to improve and innovate various technologies to enhance the quality of baked products. The present Research also addresses the risk factors of baking products, including pterygium, of depression, increased lung cancer, work-related ill-health, allergic respiratory diseases such as bronchial asthma, irritant dermatitis and eczema.
The present research presents numerous options to improve the quality of baked goods. It covers a range of topics, including ingredient selection, proper measuring techniques, and the importance of using the right tools. Additionally, it emphasizes the significance of temperature control, both in terms of ingredient preparation and baking. Practical tips for ensuring even cooking, checking for doneness, and making necessary adjustments for different environmental conditions are provided. The Research also highlights the value of proper storage to maintain freshness and encourages continuous learning and practice to enhance baking skills. Specific advice is given for improving common baked items like bread, cakes, cookies, pies, biscuits, and pasta.
The main conclusion is that baking has accompanied humans during the long years of our existence.
Food allergy has been increasing in prevalence in most westernised countries and poses a significant burden to patients and families; dietary and social limitations as well as psychosocial and economic burden affect daily activities, resulting in decreased quality of life. Food oral immunotherapy (food-OIT) has emerged as an active form of treatment, with multiple benefits such as increasing the threshold of reactivity to the allergenic food, decreasing reaction severity on accidental exposures, expanding dietary choices, reducing anxiety and generally improving quality of life. Risks associated with food immunotherapy mostly consist of allergic reactions during therapy. While the therapy is generally considered both safe and effective, patients and families must be informed of the aforementioned risks, understand them, and be willing to accept and hedge these risks as being worthwhile and outweighed by the anticipated benefits through a process of shared decision-making. Food-OIT is a good example of a preference-sensitive care paradigm, given candidates for this therapy must consider multiple trade-offs for what is considered an optional therapy for food allergy compared with avoidance. Additionally, clinicians who discuss OIT should remain increasingly aware of the growing impact of social media on medical decision-making and be prepared to counter misconceptions by providing clear evidence-based information during in-person encounters, on their website, and through printed information that families can take home and review.
Standard care for the management of food allergies previously centred upon allergen avoidance and treatment of adverse reactions following allergen exposure. An increase in the development of immunotherapy treatments for food allergy has occurred over the last two decades, with many centres now offering immunotherapy. Previous studies have mainly focused on school-aged children where food allergies are likely to be persistent. However, there is increasing evidence that delivering immunotherapy for food allergy in preschool age children may deliver higher rates of success, with peanut allergen immunotherapy leading the way. Conversely, the natural resolution of food allergies occurs primarily in these younger age groups, resulting in challenges in selecting patients who will ultimately benefit from these treatments. Both immunotherapy and natural history studies reveal the inherent plasticity of the immune system in early life, which may be more amenable to intervention, but this raises a delicate yet unknown balance between optimal timing of intervention versus waiting for natural resolution of the food allergy. Here we review the evidence for early food allergen immunotherapy in preschoolers, and present pro and con views for this approach, while acknowledging the important research gaps in this age group.
Food allergy is affecting 5-8% of young children and 2-4% of adults and seems to be increasing in prevalence. The cause of the increase in food allergy is largely unknown but proposed to be influenced by both environmental and lifestyle factors. Changes in intestinal barrier functions and increased uptake of dietary proteins have been suggested to have a great impact on food allergy. In this review, we aim to give an overview of the gastrointestinal digestion and intestinal barrier function and provide a more detailed description of intestinal protein uptake, including the various routes of epithelial transport, how it may be affected by both intrinsic and extrinsic factors, and the relation to food allergy. Further, we give an overview of in vitro, ex vivo and in vivo techniques available for evaluation of intestinal protein uptake and gut permeability in general.
Proteins are digested by gastric, pancreatic and integral brush border enzymes in order to allow for sufficient nutritional uptake. Absorption and transport of dietary proteins across the epithelial layer is known to be dependent on the physicochemical properties of the proteins and their digestion fragments themselves, such as size, solubility and aggregation status. It is believed, that the greater an amount of intact protein or larger peptide fragments that is transported through the epithelial layer, and thus encountered by the mucosal immune system in the gut, the greater is the risk of inducing an adverse allergic response. Proteins may be absorbed across the epithelial barrier by means of various mechanisms, and studies have shown that a transcellular facilitated transport route unique for food allergic individuals are at play for transport of allergens, and that upon mediator release from mast cells an enhanced allergen transport via the paracellular route occurs. This is in contrast to healthy individuals where transcytosis through the enterocytes is the main route of protein uptake. Thus, knowledge on factors affecting intestinal barrier functions and methods for the determination of their impact on protein uptake may be useful in future allergenicity assessments and for development of future preventive and treatment strategies.
Background
The time to acquisition of tolerance to unheated milk and regular egg after achievement of tolerance to baked goods is not known.
Objective
To determine the time to acquisition of unheated-milk–regular-egg tolerance, after the tolerance of the baked forms, in children younger than 2 years.
Methods
An initial oral food challenge with baked milk (BM) and baked egg (BE) was performed on patients who were reactive to unheated milk-regular egg, respectively. Patients who were BM-BE tolerant were offered unheated-milk–regular-egg challenges, and patients who were BM-BE reactive were offered BM-BE challenges at an average of 3-month intervals. Food-induced atopic dermatitis was included.
Results
Thirty-six children with unheated-milk allergy (median age, 7.3 months [interquartile range (IQR), 6.0-13.5]) and 65 with regular-egg allergy (median age, 7 months [IQR, 5.8-11.0]) were included. Seven of 13 children who were BM tolerant acquired unheated-milk tolerance after a median 4.0 months (IQR, 2.0-7.0). Twelve of 23 children who were BM reactive acquired unheated-milk tolerance after a median 5.0 months (IQR, 3.0-8.0) after BM tolerance. Twenty-one of 29 children who were BE tolerant acquired regular-egg tolerance after a median 3.0 months (IQR, 1.0-6.0). Sixteen of 36 children who were BE reactive acquired regular-egg tolerance after a median 4.0 months (IQR, 2.0-6.8) after BE tolerance.
Conclusion
Different tolerance rates were determined for baked products at different time points in the first 2 years of life. Unheated-milk–regular-egg allergy resolved in up to 65.5% and 75.5% of cases, respectively, in an average 4 to 5 months after acquisition of BM-BE tolerance. Baked-milk–baked-egg tolerance may be regarded as a precursor of tolerance.
Background: Food Allergy (FA) is an evolving public health concern emerging as the second wave of allergy epidemic after asthma, allergic rhinitis, and inhalant sensitization, contributing to the high economic cost of care and reduced quality of life. Screening for FA at 12 months of age can help to diagnose children with FA early, can contribute to avoiding unexpected anaphylaxis, and hence decrease in healthcare cost for FA diagnosis and management.
Objective: To assess the cost-effectiveness of screening for FA in Australian children at 12 months of age compared with non-screening, with the aim of limiting the incidence of anaphylactic events, from the Australian health system perspective.
Methods: A decision analytical model was constructed to compare the costs, outcomes and cost-effectiveness of management of FA by population-based screening compared to non-screening children over the first 4 years of age. Model inputs were sourced from the HealthNuts study for screening and LSAC database for non-screened children. Anaphylaxis incidence in the community was used as the effect measure.
Results: The screening of children for FA was seen as dominant strategy compared to non-screening since the children had less anaphylactic events compared to the non- screening and the screening strategy was less costly. The cost for FA management through screening strategy was A118.76 per child, resulting in a cost saving by A$28.97 per child. There was an average of 0.0013 anaphylactic events for screened and 0.00357 events for non-screened, resulting in the decrease in the probability of anaphylactic event of 0.00226 per child. The results were robust under a number of one-way sensitivity analyses.
Conclusion: The screening strategy is less costly and more effective than non-screening. It is likely that implementation of screening of children for FA will result in decreased government spending on FA management and medical costs associated with anaphylactic events.
Background
Studies on long-term oral immunotherapy (OIT) in children with anaphylactic egg allergy are limited.
Objective
To investigate the long-term outcomes of OIT for anaphylactic egg allergy.
Methods
Participants included children (aged ≥ 5 years) with a history of anaphylaxis to eggs and objective reactions to oral food challenge (OFC) with 250 mg egg protein. In the OIT group, the home starting dose set during 5 days of hospitalization was ingested once daily and gradually increased to 1000 mg. Over a year later, participants temporarily discontinued OIT for 2 weeks and underwent an OFC with 3100 mg annually until they passed. The historical control group was comprised of patients who did not receive OIT and repeated OFCs annually.
Results
In the OIT group (20 children), baseline median egg white- and ovomucoid-specific immunoglobulin E (sIgE) levels were 45.5 and 38.5 kUA/L, respectively. The rate of passing OFC with 3100 mg gradually increased in the OIT group: 1 year, 20%; 2 years, 35%; 3 years, 55%, which was significantly higher than that in the historical control group at 3 years (5%; P < 0.001). In the OIT group, five anaphylaxis events (0.04%) occurred at home, and one participant required intramuscular adrenaline. Furthermore, egg white- and ovomucoid-sIgE levels decreased significantly after 3 years in both groups, whereas in the OIT group, these specific immunoglobin G and G4 levels increased significantly after a year.
Conclusion
Long-term OIT accelerated immunological changes and enabled ingestion of 3100 mg in half the participants with anaphylactic egg allergy.
Adverse reactions after food intake are commonly reported and a cause of concern and anxiety that can lead to a very strict diet. The severity of the reaction can vary depending on type of food and mechanism and it is not always easy to disentangle between different hypersensitivity diagnoses, which sometimes can exist simultaneously. After a carefully taken medical history, hypersensitivity to food can often be ruled out or suspected. The most common type of allergic reaction is IgE-mediated food allergy (prevalence 5–10 %). Symptoms vary from mild itching, stomach pain and rash to severe anaphylaxis. The definition of IgE-mediated food allergy is allergic symptoms combined with specific IgE-antibodies and therefore only IgE-antibodies to suspected allergens should be analyzed. Nowadays, methods of molecular allergology can help with the diagnostic process. The most common allergens are milk and egg in infants, peanut and tree nuts in children and fish and shellfish in adults. In young children milk/egg allergy have a good chance to remit, making it important to follow up and reintroduce the food when possible. Other diseases triggered by food are non-IgE-mediated food allergy e.g. eosinophilic esophagitis, celiac disease, food protein-induced enterocolitis syndrome, hypersensitivity to milk and biogenic amines. Some of the food hypersensitivities dominate in childhood, others are more common in adults. Interesting studies are ongoing regarding the possibility to treat food hypersensitivity, such as oral immunotherapy (OIT). The purpose of this review was to provide an overview of the most common types of food hypersensitivity reactions.
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Abstract
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.
Probiotics are health-promoting edible bacteria consumed through fermented foods and dairy foods. They alleviate lactose-intolerance and obesity, oxidative stress, have antimicrobial and anti-inflammatory activities, and optimizing gut microflora. The dysbiosis is an emerging topic in microbiology with increased attention being given to the microbiome. Dysbiosis is related with several diseases such as inflammatory bowel disease, obesity, and neurological disorders. Further, maintenance of infant health and enhancement of the quality of infant food are critical issues. Well-known diseases affecting infants are atopic eczema, asthma, rhinitis, and food allergies, which are related to immunity. These problems are closely associated to the mother because the placenta and breast milk are the first connections between infants and mothers; furthermore, infants are exposed to various environmental factors during the pre- and post-pregnancy periods. Through the modulation of immune cells, probiotics can suppress hypersensitivity responses or promote anti-inflammatory or anti-allergic cytokine expression; these activities are dependent on the health condition and immune system and the species of probiotics. Further, detection and countermeasure about Cronobacter sakazakii which is one of the most fatal pathogens in infant formula are also included. In this review, issues regarding infant formula, allergies in infants, and research on probiotics are discussed.
Twenty-five children with clinical egg hypersensitivity, confirmed by double-blind challenge, were followed for between 2 and 2 1/2 years. Clinical egg hypersensitivity was fund to have resolved in 11 children but was persistent in 14. Skin prick tests reactions to egg were initially of equivalent size in the resolved and persistent groups, but became negative or diminished in size with resolution of clinical egg hypersensitivity, while remaining positive in the group with persisting symptoms. Symptoms after egg ingestion were categorised as cutaneous, gastrointestinal, respiratory, and angioedema. The adverse reactions of the resolved group were either cutaneous or gastrointestinal symptoms. The persisting group had multisystem involvement and most of them developed angioedema and respiratory symptoms. These differences may be useful as prognostic indicators in clinical egg hypersensitivity.
The natural history of food allergy refers to the development of food sensitivities as well as the possible loss of the same food sensitivities over time. Most food allergy is acquired in the first 1 to 2 years of life, whereas the loss of food allergy is a far more variable process, depending on both the individual child and the specific food allergy. For example, whereas most milk allergy is outgrown over time, most allergies to peanuts and tree nuts are never lost. In addition, whereas some children may lose their milk allergy in a matter of months, the process may take as long as 8 or 10 years in other children. This review provides an overview of the natural history of food allergy and provides specific information on the natural course of the most common childhood food allergies.
Tuberculosis is a disease with high morbidity and mortality in children worldwide. Despite significant improvements in diagnostic methods, scientific researches and clinical trials for new regimens of treatment or prevention in adult tuberculosis, childhood tuberculosis has been relatively neglected. Children are at high risk of severe disease, and reactivation of latent infection in adulthood perpetuates the epidemic. Therefore, a policy of tuberculosis control in childhood should be emphasized to improve control in the total population. To understand the new view of childhood tuberculosis, this article describes changes in the disease's national epidemiology, new diagnostic tools and treatment strategies, and multi-drug resistance.
Abstract
BACKGROUND: Ninety-five percent positive predictive values (PPVs) provide an invaluable tool for clinicians to avoid unnecessary oral food challenges. However, 95% PPVs specific to infants, the age group most likely to present for diagnosis of food allergy, are limited.
OBJECTIVE: We sought to develop skin prick test (SPT) and allergen-specific IgE (sIgE) thresholds with 95% PPVs for challenge-confirmed food allergy in a large population-based cohort of 1-year-old infants with challenges undertaken irrespective of SPT wheal size or previous history of ingestion.
METHODS: HealthNuts is a population-based, longitudinal food allergy study with baseline recruitment of 1-year-old infants. Infants were recruited from council-run immunization sessions during which they underwent SPTs to 4 allergens: egg, peanut, sesame, and cow's milk/shrimp. Any infant with a detectable SPT response was invited to undergo oral food challenge and sIgE testing.
RESULTS: Five thousand two hundred seventy-six infants participated in the study. Peanut SPT responses of 8 mm or greater (95% CI, 7-9 mm), egg SPT responses of 4 mm or greater (95% CI, 3-5 mm), and sesame SPT responses of 8 mm or greater (95% CI, 5-9 mm) had 95% PPVs for challenge-proved food allergy. Peanut sIgE levels of 34 kUA/L or greater (95% CI, 14-48 kUA/L) and egg sIgE levels of 1.7 kUA/L or greater (95% CI, 1-3 kUA/L) had 95% PPVs for challenge-proved food allergy. Results were robust when stratified on established risk factors for food allergy. Egg SPT responses and sIgE levels were poor predictors of allergy to egg in baked goods.
CONCLUSION: These 95% PPVs, which were generated from a unique dataset, are valuable for the diagnosis of food allergy in young infants and were robust when stratified across a number of different risk factors.
Baked egg is tolerated by a majority of egg-allergic children.
To characterize immunologic changes associated with ingestion of baked egg and evaluate the role that baked egg diets play in the development of tolerance to regular egg.
Egg-allergic subjects who tolerated baked egg challenge incorporated baked egg into their diet. Immunologic parameters were measured at follow-up visits. A comparison group strictly avoiding egg was used to evaluate the natural history of the development of tolerance.
Of the 79 subjects in the intent-to-treat group followed for a median of 37.8 months, 89% now tolerate baked egg and 53% now tolerate regular egg. Of 23 initially baked egg-reactive subjects, 14 (61%) subsequently tolerated baked egg and 6 (26%) now tolerate regular egg. Within the initially baked egg-reactive group, subjects with persistent reactivity to baked egg had higher median baseline egg white (EW)-specific IgE levels (13.5 kU(A)/L) than those who subsequently tolerated baked egg (4.4 kU(A)/L; P= .04) and regular egg (3.1 kU(A)/L; P= .05). In subjects ingesting baked egg, EW-induced skin prick test wheal diameter and EW-, ovalbumin-, and ovomucoid-specific IgE levels decreased significantly, while ovalbumin- and ovomucoid-specific IgG(4) levels increased significantly. Subjects in the per-protocol group were 14.6 times more likely than subjects in the comparison group (P< .0001) to develop regular egg tolerance, and they developed tolerance earlier (median 50.0 vs 78.7 months; P< .0001).
Initiation of a baked egg diet accelerates the development of regular egg tolerance compared with strict avoidance. Higher serum EW-specific IgE level is associated with persistent baked and regular egg reactivity, while initial baked egg reactivity is not.
Background:
The incidence of hospital admissions for food allergy-related anaphylaxis in Australia has increased, in line with world-wide trends. However, a valid measure of food allergy prevalence and risk factor data from a population-based study is still lacking.
Objective:
To describe the study design and methods used to recruit infants from a population for skin prick testing and oral food challenges, and the use of preliminary data to investigate the extent to which the study sample is representative of the target population.
Methods:
The study sampling frame design comprises 12-month-old infants presenting for routine scheduled vaccination at immunization clinics in Melbourne, Australia. We compared demographic features of participating families to population summary statistics from the Victorian Perinatal census database, and administered a survey to those non-responders who chose not to participate in the study.
Results:
Study design proved acceptable to the community with good uptake (response rate 73.4%), with 2171 participants recruited. Demographic information on the study population mirrored the Victorian population with most the population parameters measured falling within our confidence intervals (CI). Use of a non-responder questionnaire revealed that a higher proportion of infants who declined to participate (non-responders) were already eating and tolerating peanuts, than those agreeing to participate (54.4%; 95% CI 50.8, 58.0 vs. 27.4%; 95% CI 25.5, 29.3 among participants).
Conclusion:
A high proportion of individuals approached in a community setting participated in a food allergy study. The study population differed from the eligible sample in relation to family history of allergy and prior consumption and peanut tolerance, providing some insights into the internal validity of the sample. The study exhibited external validity on general demographics to all births in Victoria.
Heat treatment of several foods, including all types of cooking, has been mainly used to minimize the number of viable microbes, reduce pathogenicity, and destroy the undesirable enzymes, maintaining food quality. In addition, food processing improves sensory, nutritional, and physical properties of the foods, due to food protein denaturation. Heat-induced alterations of food proteins can attenuate allergenicity. In this article, the authors review the important role of thermal processing on milk and egg proteins, which comprise the commonest food allergies in infancy and early childhood.
Using clearly defined inclusion/exclusion criteria and predetermined cessation criteria, we describe outcomes from over 1000 oral food challenges in 12 month old population-recruited infants that will help to inform future standardization of food challenges.
Egg allergy is common and although resolution to uncooked egg has been demonstrated, there is lack of evidence to guide reintroduction of well-cooked egg.
To examine the rate of resolution to well-cooked, compared with uncooked egg in children, and safety of egg challenges.
A longitudinal study of egg-allergic children from 2004 to 2010, who underwent challenge with well-cooked and if negative, uncooked egg. Participants underwent repeat annual challenges and egg-specific IgE measurement.
One hundred and eighty-one open egg challenges were performed in 95 children whose median age of allergy onset was 12 months. Fifty-three of 95 (56%) had at least one annual repeat challenge. Pre-study historical reactions occurred to baked egg in five (5%), lightly cooked in 58 (61%) and uncooked in nine (9%); respiratory reactions occurred in 11 (12%) and seven (7%) had anaphylaxis; adrenaline was used during five reactions. There were 77 well-cooked and 104 uncooked egg challenges. Tolerance was gained twice as rapidly to well-cooked than uncooked egg (median 5.6 vs. 10.3 years; P<0.0001) and continued to 13 years; hazard ratio 2.23 (95% confidence interval 1.6-3.9). Nearly 1/3 had resolved allergy to well-cooked egg at 3 years and 2/3 at 6 years. Of 28/77 (37%) positive well-cooked egg challenges, 65% had cutaneous symptoms, 68% gastrointestinal and 39% rhinitis, with no other respiratory reactions. Adrenaline was not required. CONCLUSIONS AND CLINICAL RELEVANCE RESOLUTION: of egg allergy takes place over many years, with children outgrowing allergy to well-cooked egg approximately twice as quickly as they outgrow allergy to uncooked egg. There were no severe reactions to well-cooked egg challenge, and adrenaline was not required. Our data support initiation of home reintroduction of well-cooked egg from 2 to 3 years of age in children with previous mild reactions and no asthma. Resolution continues to occur in older children, so that despite an earlier positive challenge, attempts at reintroduction should be continued.
Several indicators suggest that food allergy in infants is common and possibly increasing. Few studies have used oral food challenge to measure this phenomenon at the population level.
To measure the prevalence of common IgE-mediated childhood food allergies in a population-based sample of 12-month-old infants by using predetermined food challenge criteria to measure outcomes.
A sampling frame was used to select recruitment areas to attain a representative population base. Recruitment occurred at childhood immunization sessions in Melbourne, Australia. Infants underwent skin prick testing, and those with any sensitization (wheal size ≥ 1 mm) to 1 or more foods (raw egg, peanut, sesame, shellfish, or cow's milk) were invited to attend an allergy research clinic. Those who registered a wheal size ≥ 1 mm to raw egg, peanut, or sesame underwent oral food challenge.
Amongst 2848 infants (73% participation rate), the prevalence of any sensitization to peanut was 8.9% (95% CI, 7.9-10.0); raw egg white, 16.5% (95% CI, 15.1-17.9); sesame, 2.5% (95% CI, 2.0-3.1); cow's milk, 5.6% (95% CI, 3.2-8.0); and shellfish, 0.9% (95% CI, 0.6-1.5). The prevalence of challenge-proven peanut allergy was 3.0% (95% CI, 2.4-3.8); raw egg allergy, 8.9% (95% CI, 7.8-10.0); and sesame allergy, 0.8% (95% CI, 0.5-1.1). Oral food challenges to cow's milk and shellfish were not performed. Of those with raw egg allergy, 80.3% could tolerate baked egg.
More than 10% of 1-year-old infants had challenge-proven IgE-mediated food allergy to one of the common allergenic foods of infancy. The high prevalence of allergic disease in Australia requires further investigation and may be related to modifiable environmental factors.
The national prevalence and patterns of food allergy (FA) in the United States are not well understood.
We developed nationally representative estimates of the prevalence of and demographic risk factors for FA and investigated associations of FA with asthma, hay fever, and eczema.
A total of 8203 participants in the National Health and Nutrition Examination Survey 2005-2006 had food-specific serum IgE measured to peanut, cow's milk, egg white, and shrimp. Food-specific IgE and age-based criteria were used to define likely FA (LFA), possible FA, and unlikely FA and to develop estimates of clinical FA. Self-reported data were used to evaluate demographic risk factors and associations with asthma and related conditions.
In the United States, the estimated prevalence of clinical FA was 2.5% (peanut, 1.3%; milk, 0.4%; egg, 0.2%; shrimp, 1.0%; not mutually exclusive). Risk of possible FA/LFA was increased in non-Hispanic blacks (odds ratio, 3.06; 95% CI, 2.14-4.36), males (1.87; 1.32-2.66), and children (2.04; 1.42-2.93). Study participants with doctor-diagnosed asthma (vs no asthma) exhibited increased risk of all measures of food sensitization. Moreover, in those with LFA, the adjusted odds ratio for current asthma (3.8; 1.5-10.7) and an emergency department visit for asthma in the past year (6.9; 2.4-19.7) were both notably increased.
Population-based serologic data on 4 foods indicate an estimated 2.5% of the US population has FA, and increased risk was found for black subjects, male subjects, and children. In addition, FA could be an under-recognized risk factor for problematic asthma.
Montesinos E, Martorell A, Félix R, Cerdá JC. Egg white specific IgE levels in serum as clinical reactivity predictors in the course of egg allergy follow-up. Pediatr Allergy Immunol 2010: 21: 634–639. © 2009 John Wiley & Sons A/S
It is thought that the natural evolution of egg allergy has a good tolerance prognosis. However, there are few follow-up studies that determine the exact probability of tolerance. The aim of this study was to determine the likelihood that children younger than 2,5 years of age with allergy to egg would eventually have tolerance to it and to analyze if monitoring egg white–specific IgE level over time could be used as a predictor for determining when patients develop clinical tolerance. We performed a retrospective study of our last 42 patients diagnosed with egg allergy. Annual follow-up comprised prick testing, specific IgE (sIgE) and provocation testing with egg white (EW), allowing the prediction of tolerance at that timepoint with a probability of ≥95%. Median survival time was 48 months. The mean initial and final levels of EW sIgE were lower in the patients that reached tolerance (p<0.05). EW sIgE levels of 1.52, 1.35, and 2.59 KUA/l, respectively predicted clinical reactivity (PPV > 95%) at the different follow-up timepoints analyzed (25-36, 37-48 and 49-60 months. Quantification of egg whitespecific IgE levels is a useful test for diagnosing symptomatic allergy to egg white in the pediatric population and could eliminate the need to perform oral challenges tests in a significant number of children.
The aim of this study was to understand the natural course of egg allergy and to identify the prognostic factors for tolerance. A retrospective study that included 106 children with atopic dermatitis and egg allergy diagnosed at less than 2 years of age was conducted using medical records and parental telephone interviews. Tolerance was defined as the absence of an allergic reaction in response to the parental introduction of cooked eggs to the diet of children whose egg white specific IgE level had decreased to less than 1.5 kU(A)/l. The median age of tolerance to egg allergy was 4 years. Kaplan-Meier analysis predicted that 41% of children had developed tolerance to egg allergy by age 3, while 60% of children had developed tolerance by age 5. The age at the diagnosis of egg allergy was the only significant prognostic factor of egg allergy tolerance identified by the Cox proportional regression model.
Better knowledge of the accuracy of a skin prick test (SPT) and specific IgE (sIgE) levels to egg allergens would help to identify persistent egg-allergic children, avoiding unnecessary risky challenges. This study was designed to assess the accuracy of a SPT and sIgE levels to egg allergens in order to determine persistent egg allergy in IgE-mediated allergic children after an egg-free diet.
Children below 16 years were prospectively and consecutively recruited. Inclusion criteria were: allergy to egg proteins (children with a positive clinical case of IgE-mediated egg allergy and a positive SPT to egg allergens and/or positive sIgE levels), and strict egg avoidance diet followed for at least 6 months. Clinical histories were recorded and all patients underwent SPTs, sIgE levels to egg allergens and the gold standard -a double-blind placebo-controlled egg challenge (DBPCFG). DBPCFG was interpreted without knowledge of the results of the other tests and vice-versa. A SPT and sIgE levels' ROC curves analysis was performed to compare the diagnostic performance of the different tests.
Finally, 157 children were included in the study. One hundred out of these 157 children (63.7%) had a positive oral challenge. Ninety-six were male (61%), and the median age was 2.5 years. One hundred and three (66.9%) had atopic dermatitis. A 7 mm egg white prick test had a positive likelihood ratio (+LR) of 6.7, and a level of 1.3 KU/L egg white-sIgE had a +LR of 5.1. A 7 mm egg white SPT had a positive predictive value of 92.3% (95% CI 85.1-99.5), and for a 9 mm egg white SPT this value was 95.6% (95% CI 87.3-100.0). For egg white-sIgE, 1.5 KU/L had a positive predictive value of 90.4% (95% CI 82.4-98.4) and for 25 KU/L it was 100.0% (95% CI 100.0-100.0). SPTs with ovotransferrin and lysozyme showed the lowest accuracy, followed by yolk and ovalbumin SPTs.
This study is the first to evaluate both tests (SPT and sIgE levels) and all egg allergens to determine the persistence of egg allergy in IgE-mediated allergic children. Measuring the SPT and sIgE levels is useful to predict persistent allergy in these children, especially with the egg white complete extract. An oral challenge should not be performed in egg allergic paediatric patients with either an egg white prick test above 7 mm or a white egg-sIgE determination above 1.3 KU/L, because there is a 90% probability of remaining allergic.
To review recent advances in the area of food allergen processing and the effect on protein allergenicity.
Heating generally decreases protein allergenicity by destroying conformational epitopes. In peanut and shrimp, heat-induced Maillard reaction (glycation) may increase allergenicity. The majority of milk and egg-allergic children tolerate extensively heated (baked with wheat matrix) milk and egg. Introduction of extensively heated milk and egg proteins is associated with decreasing sizes of skin prick test wheals and increasing serum food-specific IgG4 levels.
Heating and other methods of food processing have different effects on food allergens, even those contained in the same complex food. Structural homology does not reliably predict the effect of processing on allergenicity, and individual food allergens have to be tested. Interactions with other proteins, fat, and carbohydrates in the food matrix are complex and poorly understood. Introduction of extensively heated milk and egg proteins into the diet of allergic children may represent an alternative approach to oral tolerance induction. Better characterization of these aspects of food allergy is critical for elucidation of food protein interactions with the gut-associated lymphoid tissue, the ability to induce IgE sensitization, the potential to trigger hypersensitivity reactions, and different clinical phenotypes of food allergy with regard to severity and persistence.
Prior studies have suggested that heated egg might be tolerated by some children with egg allergy.
We sought to confirm tolerance of heated egg in a subset of children with egg allergy, to evaluate clinical and immunologic predictors of heated egg tolerance, to characterize immunologic changes associated with continued ingestion of heated egg, and to determine whether a diet incorporating heated egg is well tolerated.
Subjects with documented IgE-mediated egg allergy underwent physician-supervised oral food challenges to extensively heated egg (in the form of a muffin and a waffle), with tolerant subjects also undergoing regular egg challenges (in a form of scrambled egg or French toast). Heated egg-tolerant subjects incorporated heated egg into their diets. Skin prick test wheal diameters and egg white, ovalbumin, and ovomucoid IgE levels, as well as ovalbumin and ovomucoid IgG4 levels, were measured at baseline for all subjects and at 3, 6, and 12 months for those tolerant of heated egg.
Sixty-four of 117 subjects tolerated heated egg, 23 tolerated regular egg, and 27 reacted to heated egg. Heated egg-reactive subjects had larger skin test wheals and greater egg white-specific, ovalbumin-specific, and ovomucoid-specific IgE levels compared with heated egg- and egg-tolerant subjects. Continued ingestion of heated egg was associated with decreased skin test wheal diameters and ovalbumin-specific IgE levels and increased ovalbumin-specific and ovomucoid-specific IgG4 levels.
The majority of subjects with egg allergy were tolerant of heated egg. Continued ingestion of heated egg was well tolerated and associated with immunologic changes that paralleled the changes observed with the development of clinical tolerance to regular egg.
Skin tests represent a major tool in the diagnosis of reaginic allergy; however, their interpretation does not appear to be without difficulty in children under the age of 3 yr. Seventy-eight infants from birth to 24 mo were prick tested and compared with 30 nonallergic adult subjects. Skin tests were performed without bleeding by use of two strengths of histamine hydrochloride (1 and 10 mg/ml), a mast cell degranulating agent (codeine phosphate, 50 mg/ml), and allergenic extracts. Negative control solution elicited a small wheal (less than 1.5 mm) in two infants who were excluded from further results. A clear and significant (p less than 0.001) hyporeactivity to both histamine and codeine phosphate was observed in infancy, especially before the age of 6 mo. Six infants were allergic and presented positive prick tests to either food or inhalant allergens. These tests were confirmed by serum specific IgE and a suggestive clinical history. The size of the allergen-induced prick test wheal ranged from 2 to 5 mm in diameter, suggesting that prick test wheals may be smaller in infants. This study confirms that prick tests can be performed and interpreted without difficulty in infants, keeping in mind the small wheal size induced by both positive control solutions and allergen-induced prick tests.
The skin test reactivity to allergen and histamine differs according to the age of the patients, but complete data from infancy to old age are still lacking. Three hundred sixty-five subjects (1 to 85 years of age, 33.9% atopic, and 50.1% male patients) were prick tested with threefold dilutions of histamine hydrochloride (1 to 243 mg/ml). There was a significant (p less than 0.0001; F test) main effect of age on the skin reactivity to histamine. Age groups were defined and statistical analysis were performed by means of parallel line bioassay. All dose-response curves were linear and parallel. There is a significant increase in the mean wheal size between 4 to 5 and 6 to 9 years of age, 10 to 14 and 15 to 20 years. There was almost no difference between 15 to 20 and 21 to 50 years. No difference was observed between 21 to 30, 31 to 40, and 41 to 50 years, and then, the mean wheal sizes decreased significantly to reach a plateau after the age of 60 years. There was no sex difference, and skin tests with histamine were similar in atopic and nonatopic individuals.
The effect of wheat gluten, soybean protein and milk casein on the heat-induced in solubilization of egg white ovomucoid was investigated by using ELISA inhibition and immunoblotting analysis. Heat treatment at 180 degree C for 10 min of egg white mixed with wheat gluten specifically accelerated the heat-induced change in ovomucoid. Such an effect was weakly brought about by soybean protein, but not by casein.
The demonstration of specific IgE antibodies to egg supports the existence of allergy to this food, but a correct diagnosis can only be obtained after a challenge test. Several studies have assessed different cut-off points in the level of these antibodies as predictors of clinical reactivity.
Validation of the specific IgE antibodies measured by the CAP System Fluorescence enzyme immunoassay (FEIA) technique in the diagnosis of egg allergy in children under 2 years of age.
A prospective study of 81 children with suspected egg allergy was performed. Specific IgE antibodies was quantified for egg white, egg yolk, ovoalbumin and ovomucoid. The diagnostic challenge test was carried out following the previously established criteria. The validity of the specific IgE antibodies was analysed using children with a negative diagnostic challenge test as control group.
The prevalence of egg allergy in the group studied was 79% and egg white was the allergen that showed the greatest diagnostic efficacy. The sensitivity and positive predictive value of the prick test and of the CAP to egg white were excellent and the specificity and the negative predictive value had lower values. A level of > or = 0.35 KU(A)/L for specific IgE antibodies to egg white predicted the existence of reaction in 94% of the cases.
Quantification of the specific IgE antibodies to egg white is useful in the diagnosis of egg allergy. In children under 2 years of age with a background of immediate hypersensitivity after egg ingestion and presence of specific IgE antibodies to egg white of > or = 0.35 KU(A)/L, diagnostic challenge test is not necessary to establish the diagnosis of allergy to this food.
It is thought that the natural evolution of food allergy has a good tolerance prognosis. However, there are few follow-up studies that determine the exact probability of tolerance to a given food or that analyze prognostic factors that can help us to understand the evolution of a child who begins life with a food allergy.
We sought to determine the likelihood that children younger than 2 years of age with allergy to egg would eventually have tolerance to it and to analyze several prognostic predictors using egg white-specific IgE level as the main variable.
We performed a prospective study of 58 children younger than 2 years of age with egg allergy, who were studied periodically until tolerance developed or until the end of the study. During the follow-up period, open challenge tests were carried out according to previously established criteria to verify tolerance to egg. Factors such as egg white-specific IgE level, serum total IgE level, symptoms after egg ingestion, size of skin prick test reactions to egg white, atopic dermatitis, and sex were analyzed as prognostic markers. Kaplan-Meier survival curves were used to calculate cumulative tolerance probability. Predictor influence and relative prognostic importance were estimated with the Cox proportional regression model.
The median time from the appearance of the first symptoms to tolerance was 35 months. Cumulative tolerance probability was 16% at 12 months of follow-up, 28% at 24 months, 52% at 36 months, 57% at 48 months, and 66% at 60 months. The relative weight of prognostic factors, expressed as the hazard ratio, was 50.95 for symptoms and 3.74 for the size of skin prick test reactions, with both being independent effects. The hazard ratio was 1.173 for every 0.1-unit decrease in the concentration log (decimal logarithm) of specific IgE level, with this effect being associated with tolerance only in children with cutaneous symptoms.
Half of the children younger than 2 years of age with egg allergy will tolerate the food at 35 months of follow-up, and the proportion could be 66% after 5 years. At that age, the main predictors were the symptoms experienced after egg ingestion, followed by the size of skin prick test reactions. In addition, the specific IgE antibody level is an important prognostic marker in children who only had cutaneous symptoms.
The natural history of food allergy refers to the development of food sensitivities as well as the possible loss of the same food sensitivities over time. Most food allergy is acquired in the first 1 to 2 years of life, whereas the loss of food allergy is a far more variable process, depending on both the individual child and the specific food allergy. For example, whereas most milk allergy is outgrown over time, most allergies to peanuts and tree nuts are never lost. In addition, whereas some children may lose their milk allergy in a matter of months, the process may take as long as 8 or 10 years in other children. This review provides an overview of the natural history of food allergy and provides specific information on the natural course of the most common childhood food allergies.
The majority of children with cow's milk and hen's egg allergy develop clinical tolerance with time. However, there are no good indices to predict when and in whom this occurs.
The aim of this study was to determine if monitoring food specific IgE levels over time could be used as a predictor for determining when patients develop clinical tolerance.
Eighty-eight patients with hen's egg and 49 patients with cow's milk allergy who underwent repeated double-blind, placebo-controlled food challenges were included in the study. Using the Pharmacia CAP-System FEIA, specific IgE (sIgE) levels to cow's milk and hen's egg were retrospectively determined from stored serum samples obtained at the time of the food challenges. Logistic regression was used to evaluate the relationship between tolerance development and the decrease in sIgE levels over a specific time period between the two challenges.
Twenty-eight of the 66 egg-allergic and 16 of the 33 milk-allergic patients lost their allergy over time. For egg, the decrease in sIgE levels (P=.0014) was significantly related to the probability of developing clinical tolerance, with the duration between challenges having an influence (P=.06). For milk there also was a significant relationship between the decrease in sIgE levels (P=.0175) and the probability of developing tolerance to milk but no significant contribution with regard to time. Stratification into 2 age groups, those below 4 years of age and those above 4 years of age at time of first challenge, had an effect, with the younger age group being more likely to develop clinical tolerance in relation to the rate of decrease in sIgE. The median food sIgE level at diagnosis was significantly less for the group developing "tolerance" to egg (P <.001), and a similar trend was seen for milk allergy (P=.06). Using these results, we developed a model for predicting the likelihood of developing tolerance in milk and egg allergy based on the decrease in food sIgE over time.
We found that the rate of decrease in food sIgE levels over time was predictive for the likelihood of developing tolerance in milk and egg allergy. Using the likelihood estimates from this study could aid clinicians in providing prognostic information and in timing subsequent food challenges, thereby decreasing the number of premature and unnecessary double-blind, placebo-controlled food challenges.
Prevalence and incidence of food hypersensitivity (FHS) and its trends in early childhood are unclear.
A birth cohort born on the Isle of Wight (UK) between 2001 and 2002 was followed-up prospectively. Children were clinically examined and skin prick tested at set times and invited for food challenges when indicated.
Nine hundred and sixty-nine children were recruited and 92.9%, 88.5% and 91.9% of them respectively were assessed at 1, 2 and 3 years of age. Prevalence of sensitization to foods was 2.2%, 3.8% and 4.5% respectively at these ages. Cumulatively, 5.3% [95% confidence interval (CI): 3.9-7.1] children were sensitized to a food. Using open food challenge and a good clinical history, the cumulative incidence of FHS was 6.0% (58/969, 95% CI: 4.6-7.7). Based on double-blinded, placebo-controlled, food challenge (DBPCFC) and a good clinical history, the cumulative incidence was 5.0% (48/969, 95% CI: 3.7-6.5). There is no evidence to suggest that the incidence of FHS has increased, comparing these results with previous studies. Overall, 33.7% of parents reported a food-related problem and of these, 16.1% were diagnosed with FHS by open challenge and history and 12.9% by DBPCFC and history. Main foods implicated were milk, egg and peanut.
By the age of 3 years, 5-6% of children suffer from FHS based on food challenges and a good clinical history. There were large discrepancies between reported and diagnosed FHS. Comparing our data with a study performed in the USA more than 20 years ago, there were no significant differences in the cumulative incidence of FHS.
Egg allergy is very common, affecting 1% to 2% of children. It is generally thought that the majority of children with egg allergy develop tolerance in early childhood; however, this has not been examined in a large cohort with egg allergy.
The purpose of the study was to estimate the proportion of children with egg allergy who develop egg tolerance and to identify predictors of tolerance development.
Retrospective chart review of patients with egg allergy seen in a tertiary referral clinic. Patients were considered to have developed egg tolerance if they tolerated concentrated egg.
Kaplan-Meier analysis predicted resolution in 4% of patients with egg allergy by age 4 years, 12% by age 6 years, 37% by age 10 years, and 68% by age 16 years. Patients with persistent egg allergy had higher egg IgE levels at all ages to age 18 years. A patient's highest recorded egg IgE, presence of other atopic disease, and presence of other food allergy were significantly related to egg allergy persistence.
A majority of patients with egg allergy will develop egg tolerance, although the rate of tolerance development is slower than described previously. Egg IgE is predictive of allergy outcome and should be used in counseling patients on prognosis.
Most patients with egg allergy are likely to develop egg tolerance by late childhood, with the exception of patients with an egg IgE greater than 50 kU/L, who are unlikely to develop egg tolerance.
