Summary

Hen’s egg (Gallus gallus domesticus) is a protein-rich food source and is usually consumed as raw, cooked, or processed. Both egg white and egg yolk are rich in proteins, but egg white is regarded as more 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. Most egg-allergic children have the ability to develop tolerance to egg proteins over time. A patient's highest recorded egg sIgE is significantly related to the persistence of egg allergy. A higher egg sIgE value denotes a more extended period to develop tolerance. Clinical manifestations of egg allergy include mild to severe reactions like skin reactions (erythema, urticaria, angioedema), gastrointestinal symptoms (vomiting, abdominal pain), respiratory conditions (rhinitis, conjunctivitis, cough, bronchospasm, breathing difficulty), and anaphylaxis. 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 usually considered the gold standard for diagnosing egg allergy. Egg sIgE testing can also aid in diagnosing egg allergy and is predictive of allergy outcome; therefore, it should be utilized in counseling patients on prognosis. Furthermore, egg allergy or 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 Norway-based birth cohort study reported the prevalence of egg allergy among children (2½ years) to be 1.6%. In another recent study (EuroPrevall), self-reported hen’s egg allergy was observed in 9.9% of 16,935 children (7-10 years). According to a population-based study in the US, the overall prevalence of egg allergy among children (0-17 years) was found to be 0.8% (304/38,480). Moreover, an Australian population study identified the prevalence of raw egg allergy among 12-month old infants to be 9.0%. Additionally, in Japan, hen’s egg has been reported to be the most frequent cause of food allergy. 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 means that IgE antibodies are produced towards the egg proteins and are a prerequisite for an IgE-mediated egg allergy. Egg 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 sensitization among 3-month old infants to be 3.7% (41/1102). Another cohort study in Sweden on 2336 children (4 years) claimed the prevalence of egg sensitization as 5% (112/2336). Moreover, a German-based cohort study confirmed the highest sensitization towards hen’s egg (around 6%) in infants at 1 year of age. Another German-based population study conducted on 14,836 children and adolescents (3-17 years) found the overall sensitization rate towards egg white was 5%. Additionally, a European cohort study found an overall prevalence of egg sensitization to be 0.4% among the adult (20-39 years) population. Furthermore, a US-based cohort study reported the prevalence of egg sensitization in the adult population to be ranging between 2.1% to 3.9% among 4425 adults (20-60+ years).

Natural History of Egg Allergy

Food allergy during childhood could be a transitory condition, although in some cases, it is found to be a persistent one. Hen’s egg has been reported to be one of the frequent food allergens affecting children during the first ten years of life. As per the American Academy of Allergy, Asthma & Immunology (AAAAI) guidelines, egg allergy has been claimed to get resolved naturally with aging. Moreover, the egg sIgE level has been regarded as one of the crucial predictive factors for the resolution of egg allergy.

A study conducted on 881 egg-allergic patients (10-23 months old) reported the development of tolerance towards eggs by the age of 4 years in 4% cases and by 16 years in 68% cases. A gradual decline in egg sIgE level was evident with aging among patients with persistent egg-allergy; in contrast, a sharp decline in egg sIgE was found in egg-allergy resolved (tolerant) patients from this study. Similarly, another 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. Furthermore, as per another study, the probability of developing egg tolerance (based on the level of sIgE) in children (<4 years) was found to be 0.52 with a 50% reduction and 0.95 with a 99% reduction in sIgE level (for 12 months).

Risk factors

Egg allergy is associated with atopic dermatitis, 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.

Children with egg allergy are often denied influenza vaccination because the vaccine may contain a small amount of egg protein. However, recent studies have demonstrated that children with even severe egg allergy can safely receive the influenza 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 also Sdeemed 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 the ingestion (consumption) of eggs or products containing eggs.

Clinical Relevance

Egg-allergic patients might experience a range of symptoms or reactions after consumption of egg or egg-based products. Based on the severity, these reactions can be further categorized as mild reactions (vomiting, cough, conjunctivitis, rhinitis, localized urticaria, erythema), moderate reactions (mild bronchospasm, facial angioedema, generalized urticaria), and severe reactions (anaphylactic shock, hypotension, breathing difficulty, severe bronchospasm).

Anaphylaxis

Egg-allergic patients with asthma are at high risk of manifesting anaphylaxis on egg exposure. An oral food challenge (OFC) study on 374 egg white-allergic patients reported anaphylaxis among 2% (8/374) of the patients. Another study in Korea on 363 infants (0 – 2 years old) with anaphylaxis found hen’s egg as a common food allergen, affecting 21.9% (74/338) of the infants. Additionally, anaphylaxis was claimed to be higher among children with prolonged egg allergy.

Gastrointestinal (GI) symptoms

GI symptoms are mostly seen as immediate hypersensitivity reactions in egg-allergic individuals. According to a study, 21% (78/881) of the patients showed GI reactions (like abdominal pain, bloody stool, diarrhea, vomiting) as initial symptoms of egg allergy. As per another OFC study, 9% (34 out of 374) of egg white-allergic children exhibited GI reactions.

Skin reactions and Atopic dermatitis (AD)

Skin reactions like urticaria or angioedema are reported as IgE-mediated common allergic reactions prevalent in children (within minutes to a few hours) post-consumption of eggs. A study conducted on 881 egg-allergic patients exhibited skin reactions (like a non-eczematous rash, angioedema, and urticaria) as initial egg allergy symptoms in 58% (219/881) of the patients. Additionally, eczema was also observed in 18% (69/881) of the egg-allergic patients. Another study (OFC with egg white) found cutaneous reactions in 98% (368/374) of patients.

A higher prevalence of AD has been found among egg sensitized children compared to children not sensitized. Moreover, an OFC study reported a positive clinical reaction towards hen’s egg in 62% (19/64) of children with AD.

Asthma

A study reported egg as one of the typical food allergens prevalent in 185 of the 365 asthmatic children with food allergy.

Lower respiratory symptoms and mucous membrane reactions were observed in 6% (21 out of 374) and 2% (7 out of 374) of egg white-sensitized children in an OFC study.

Diagnostics

Challenge tests

OFC is considered the gold standard for diagnosing egg allergy. However, this mode of diagnosis is often regarded as time extensive, resource-consuming, and potentially risky.

In vitro diagnostics

Egg 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.

Periodic monitoring of the absolute values of egg sIgE antibody level combined with the clinical history of egg allergy can accurately diagnose egg allergy.

Prevention And Therapy

Allergen immunotherapy

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.

An exploratory study was conducted to identify the reason for maintaining egg intake in patients post achieving desensitization through OIT. The study involved three groups, which included the non-egg-allergic group, pre-/post-egg OIT group, and naturally egg-allergy outgrown group. Higher sIgE levels were evident in post-egg OIT participants compared to the naturally egg-allergy outgrown group. Therefore, the study recommended egg intake in patients post-OIT to maintain desensitization.

Prevention strategies

Complete avoidance of egg and egg-based products from the diet is considered the possible treatment option for egg allergy; however, this could be challenging as chances of accidental intake of egg or egg-based products are usually quite high.

Patients allergic to heat-labile egg protein (like ovalbumin) might be tolerant towards cooked, boiled, or fried form of eggs. Therefore, differential avoidance is typically recommended for egg-allergic patients based on their reactivity towards raw or cooked eggs. 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 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.

Cross-Reactivity

Hen’s egg exhibited high cross-reactivity with egg white from turkey, duck, goose, and seagull. Moreover, the presence of various avian serum albumins could be responsible for cross-reactivity between bird feathers and egg yolk, according to a study. Furthermore, livetin (allergenic protein) mediated cross-reactivity between hen’s egg proteins and bird dander has also been reported.