Egg white
Summary
Hen’s egg (Gallus gallus domesticus) is a protein-rich food source and is usually consumed as raw, cooked, or processed. Egg white is rich in proteins and is regarded as highly allergenic. The egg has been considered one of the most common food allergy sources, particularly in infants and children. Around 0.5 – 2.5 % of young children within a normal population have been found to be allergic to eggs. However, the prevalence of egg allergy in adults is less than 0.25 %. Egg sensitization, having IgE antibodies to egg, is a prerequisite for egg allergy. Egg sensitization is more prevalent than egg allergy, and the prevalence rate has been reported to be up to 6 % depending on age. The specific IgE (sIgE) test for egg white is commonly used when investigating a patient with a suspicion of egg allergy. Most egg-allergic children can develop tolerance to egg proteins over time. A patient's highest recorded egg white sIgE is significantly related to the persistence of egg allergy. A higher egg white sIgE value denotes a more extended period to develop tolerance. Egg IgE is predictive of allergy outcome and should be used in counseling patients on prognosis.
Egg white consumption may lead to allergic symptoms, such as gastrointestinal reactions, respiratory symptoms, cutaneous reactions, and anaphylaxis among egg white allergic patients. Therefore, egg-allergic individuals are usually recommended to avoid egg and egg-based food products strictly.
Moreover, egg allergy children are often falsely denied influenza or MMR vaccination as the vaccine might contain a small amount of egg protein. However, several studies and guidelines have claimed these vaccines to be safe for children with egg allergies.
An oral food challenge is considered to be the gold standard for diagnosing egg allergy. Egg sIgE testing can aid in diagnosing egg allergy, indicate when an egg challenge is safe to perform, and is predictive of egg allergy outcome. This means that the egg white test could be utilized in counseling patients on prognosis. Furthermore, egg allergy or egg white sensitization has been found to elevate the risk of developing sensitization to aeroallergens (such as grass pollens, house dust mites, cats, and dogs).
Early introduction of egg into the infants’ diet has been found to be beneficial in developing tolerance to the egg; it is presently studied as a means of primary prevention of egg allergy. Additionally, oral immunotherapy (for egg) is also performed in some countries on egg-allergic patients who fail to develop natural tolerance to the egg.
Epidemiology
Worldwide distribution
The egg has been reported as one of the common inducers of food allergy prevalent in industrialized countries. According to a study, around 0.5-2.5% of young children have been observed to be affected with egg allergy. A high prevalence of childhood egg allergy has been reported in Japan and France. According to a study conducted in Japan among 24 egg white allergic patients, 92% showed reactivity towards the egg white allergen (Gal d 1, ovomucoid). An Italy-based study involving 104 suspected egg-allergic patients (0.7-15.1 years) reported 43.5% (20/46), 52.1% (24/46), and 36.9% (17/46) of patients to exhibit allergenicity towards Gal d 1, Gal d 2, and Gal d 4, respectively. Furthermore, a US-based cohort study also detected the prevalence of egg allergy to be approximately <0.25% (from graphical representation) in 4425 adults (20-60+ years).
Sensitization to the egg white means that IgE antibodies are produced towards the egg white and is a prerequisite for an IgE-mediated egg allergy. Egg white sensitization is more prevalent than egg allergy, and IgE antibodies have been detected already in very young age groups. Tedner et al. found in a Nordic population-based birth-cohort study the prevalence of egg white sensitization among 3-month old infants to be 3.7% (41/1102). A German-based population study conducted on 14,836 children and adolescents (3-17 years) found the overall sensitization rate towards egg white was 5%. Moreover, a Japan-based cohort study found 0.8% of the children (at 9 years) to be sensitized towards egg white protein (Gal d 1). A Taiwanese study on 2256 allergic children (0.1-17.6 years) detected the positive sensitization rate for egg white was highest (53.5%) among children of age 2-4 years. Besides, egg white sensitization among the adult population has been reported in few studies. A European cohort study found an overall prevalence of egg white sensitization to be 0.4% among the adult (20-39 years) population. Furthermore, a US-based cohort study reported the prevalence of egg white sensitization in the adult population ranging between 2.1% to 3.9% among 4425 adults (20-60+ years).
The natural history of egg white allergy
Food allergy during childhood could be a transitory condition, although it can be a persistent one in some cases. Hen’s egg has been reported to be one of the frequent food allergens affecting children during the first 10 years of life. Egg allergy has been claimed to get resolved naturally with aging (2-6 years). A study conducted on 226 egg allergic children (<6 years) reported tolerance development in 30% (66/226) of children by the age of 3 years, while in 73% (164/226) of children by 6 years. Savage et al. examined the relationship between the peak egg white IgE level and the development of tolerance while studying the natural history of egg allergy. The tolerance development rate was found to be inversely proportional to the peak level of egg IgE (P < 0.0001). The fastest rate of tolerance development was found in children with a peak egg IgE <2 kU/L, whereas tolerance development rate was slower in children with peak IgE between 2 and 49.9. Nonetheless, the majority of the children with the peak IgE ranging between 2 to 49.9 kU/L developed tolerance towards egg subsequently. The tolerance rate was slowest among children with peak egg IgE ≥50 kU/L. These children mostly developed tolerance, not before 18 years (the end of the study period). For instance, the tolerance development among the study population was found to be 46% (peak egg IgE <2 kU/L), 32% (peak IgE 2 to.4.9 kU/L), 17% (IgE peak level between 5 to 9.9 kU/L), 16% (peak level of 10 to 19.9 kU/L), 14% (peak IgE 20 to 49.9 kU/L), and 11% (peak sIgE level ≥50 kU/L) by 8 years of age. The authors concluded egg IgE to be a predictor of the outcome of allergy and, therefore, should be utilized in patients’ counselling on prognosis.
Moreover, according to some studies, the majority of the egg-allergic children showing reactions to lightly cooked regular egg preparations (scrambled eggs or French toast) were found to be tolerant towards baked egg products (muffin, waffle, cakes, etc.). This tolerance towards baked egg products was indicative of the immunological shift towards the development of tolerance for regular eggs.
Risk factors
Egg allergy is associated with atopic dermatitis (AD), asthma, rhinitis, and other food allergies (such as peanut). Clinical allergy towards eggs has been found to be associated with risk factors like male gender, young age, ethnicity/race, and family history. Moreover, the presence of specific IgE (sIgE) towards all four egg allergens (Gal d 1, 2, 3, or 5) has been reported to elevate the risk of developing persistent raw egg allergy.
Children with egg allergy are often denied influenza vaccination because the vaccine contains a small amount of egg protein. However, recent studies have demonstrated that children with even severe egg allergy can safely receive the vaccine. Therefore, based on this outcome, the current guidelines recommend routine immunization (influenza vaccination) of such egg-allergic patients without undergoing any testing or special considerations. Moreover, as per the recommendations of vaccination-specific guidelines, the influenza vaccine can be received under usual clinical settings. A study conducted on egg-allergic patients immunized with live attenuated influenza vaccine reported no systemic reactions (allergic) or anaphylaxis among these patients post-immunization.
National Advisory Committee on Immunization (NACI) has deemed patients with egg allergy suitable for receiving the Measles Mumps Rubella (MMR) vaccination. According to this guideline, the immunization may be administered without prior testing but under proper guidance and adequate facility.
Pediatric issues
A significant correlation exists between sensitization towards outdoor/indoor aeroallergens (like grass pollens, house dust mites, cat, dog) and egg allergy during infancy. Additionally, the coexistence of egg allergy and eczema at infancy has also been reported as a predictive indicator of aeroallergen sensitization and respiratory allergies among children (4 years).
Route Of Exposure
Main
The route of exposure is through consumption of egg-white.
Clinical Relevance
Egg allergy has been claimed as one of the most frequent food allergies prevalent in children. Egg white consumption may lead to allergic symptoms, such as gastrointestinal (GI) reactions, respiratory symptoms, cutaneous reactions, and anaphylaxis in individuals allergic to egg white.
Anaphylaxis
An elevated egg white sIgE level has been reported to be correlated with anaphylaxis. As per a study, serum sIgE level towards egg white has been found to be higher (84.8%; 28/33) in patients with a history of anaphylaxis post-consumption of egg or egg derivatives. An OFC study on 374 egg white-allergic patients reported anaphylaxis among 2% (8/374) of the patients. Moreover, a Japanese study reported anaphylaxis in 8% (3/38) of the patients allergic to both heated and raw egg white.
Gastrointestinal (GI) reactions
GI symptoms are mostly seen as immediate hypersensitivity reactions in egg-allergic individuals. As per an OFC study, 9% (34 out of 374) of egg white-allergic children exhibited GI reactions. In another OFC study, 84% (104/124) of patients (egg-sensitized; 1-19 years) showing positive response towards heated egg white challenge reported GI symptoms.
Skin reactions and Atopic dermatitis
Cutaneous reactions due to egg white allergy usually include urticaria, erythema, angioedema, and oral allergy syndrome (OAS). In an OFC study (with cooked and raw egg white), 95% (37/39) of children with positive challenge showed cutaneous reactions such as urticaria (28/37), erythema (4/37), OAS (4/37), and angioedema (2/37). Another OFC study (with egg white) found cutaneous reactions in 98% (368/374) of egg-white allergic patients. Additionally, as per an OFC study, 41% (51/124) and 48% (59/124) of patients (egg-sensitized; 1-19 years) showing positive response towards heated egg white challenge reported skin symptoms and OAS, respectively.
Children with AD have been commonly found to show sensitization towards hen’s egg. A study reported AD in 87% (33/38) of the patients allergic to both heated and raw egg white.
Diagnostics
Challenge test
Oral food challenge is considered the gold standard for diagnosing egg allergy. However, this diagnosis mode is often regarded as time extensive, resource-consuming, and potentially risky.
In-vitro diagnostics
Egg white sIgE testing is used as an aid in diagnosing egg allergy and to monitor the disease development. The sIgE diagnostic values have been reported to be beneficial for physicians in deciding the necessity of an egg challenge while estimating its potential risk on the patients’ health. Furthermore, an age-specific correlation has been observed between egg sIgE levels and OFC outcome; younger children usually exhibit reactivity to even at low egg sIgE levels in contrast to the older children. Therefore, periodic monitoring of the absolute values of egg specific-IgE antibody level combined with a clinical history of egg allergy and physical examination can accurately help diagnose egg allergy as well as indicate when an egg challenge should be performed. A prospective study conducted on 81 children (<2years; suspected of egg allergy) diagnosed (utilizing cooked and raw egg white) egg allergy among 79% (56/81) of these children, and egg white sIgE testing has been reported to show high diagnostic efficacy.
Prevention And Therapy
Prevention strategies
Complete avoidance of egg and egg-based products from the diet is the recommended treatment for egg allergy; however, this could be challenging as egg is a common ingredient of many food and accidental intake of egg or egg-based products are usually quite common.
Patients allergic to heat-labile egg protein (like ovalbumin) might be tolerant towards cooked, boiled, or fried form of eggs. Hence, differential avoidance is typically recommended for egg-allergic patients based on their reactivity towards raw or cooked eggs. Here, component resolved diagnosis (CRD) with egg components can be helpful in giving personalized avoidance advice. Moreover, reactivity towards raw or slightly cooked eggs has been found to be more prevalent compared to extensively processed egg-based food.
Early introduction of eggs into the diet has been found to be potentially beneficial in the prevention of egg allergy. In a study conducted on 231 infants allergic to egg, early introduction of egg (4-6 months age) was found to be correlated with a reduced risk of egg allergy. In contrast, late introduction of an egg-based diet (at 10 months) might increase the risk of developing egg allergy. In general, guidelines recommend the necessity of more studies before early introduction of egg into the diet of an infant.
Allergen immunotherapy
Currently, allergen immunotherapy has been attempted to treat egg-allergic patients in addition to induction of oral tolerance. A study was conducted on 30 egg-allergic children (≥4 years) to estimate the efficacy of oral immunotherapy (OIT)-egg desensitization and evaluate the maintenance of tolerance. All the patients (n=16) attained desensitization towards egg after 4 months of therapy, while 31% were reported to retain tolerance towards egg even after 3 months of avoiding egg consumption.
Cross-Reactivity
A study reported cross-reactivity of the majority of allergens found in hen’s egg white with egg white proteins from turkey, duck, goose, and seagull. Moreover, egg white protein (Gal d 1) has been found to exhibit cross-reactivity with proteins present in egg yolk (Gal d 5 and Gal d 6).
Furthermore, an immunoreactive allergen (66 kDa) isolated from the bird’s nest is claimed to be homologous with ovoinhibitor protein found in hen’s egg white, resulting in cross-reactivity between the two allergenic proteins. Additionally, livetin (allergenic protein) mediated cross-reactivity between hen’s egg proteins and bird dander has also been reported.
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