Egg allergy: Clinical features and diagnosis
- Julie Wang, MD
Julie Wang, MD
- Associate Professor of Pediatrics
- Icahn School of Medicine at Mount Sinai
Hen's egg allergy is the second most common food allergy in infants and young children (milk is the most common) . Egg allergies are immunologic responses to proteins in foods and include immunoglobulin E (IgE) antibody-mediated allergy as well as other allergic syndromes such as atopic dermatitis and eosinophilic esophagitis (EoE) . (See "Role of allergy in atopic dermatitis (eczema)" and "Clinical manifestations and diagnosis of eosinophilic esophagitis".)
The epidemiology, pathogenesis, clinical features, and diagnosis of egg allergy are presented in this topic review. Management of egg allergy is discussed separately. General discussions of food allergy are presented separately in appropriate topic reviews. The options for administration of the influenza vaccine in patients with egg allergy are also discussed separately. (See "Egg allergy: Management" and "Influenza vaccination in individuals with egg allergy".)
The prevalence of egg allergy confirmed by oral challenge was 1.6 percent of children three years of age in an unselected population in Denmark . A subsequent meta-analysis of the prevalence of food allergy estimated that egg allergy affects 0.5 to 2.5 percent of young children . There were several limitations to the meta-analysis. There was significant variability in study design that made direct comparisons difficult. The majority of studies included in the meta-analysis were based upon self-reports of food allergy, which tend to overestimate the prevalence. Some studies used skin prick test and food-specific immunoglobulin E (IgE) levels to confirm sensitization to the allergen. However, not all sensitized patients have clinical allergy, and only three studies used double-blind, placebo-controlled food challenges (DBPCFCs), the gold standard, to confirm the diagnosis of food allergy [3-5]. In these three studies of unselected populations, the prevalence of egg allergy ranged from 0.0004 percent in a cohort of German children aged 0 to 17 years , to 0.6 percent in nursery school children in Mexico , to 1.6 percent in three-year-old Danish children . New-onset egg allergy in adults is rare and is limited to case reports . (See "Oral food challenges for diagnosis and management of food allergies".)
Five major allergenic proteins from the egg of the domestic chicken (Gallus domesticus) have been identified that are responsible for immunoglobulin E (IgE)-mediated reactions; these are designated Gal d 1-5 . Most of the allergenic egg proteins are found in egg white, including ovomucoid (Gal d 1), ovalbumin (Gal d 2), ovotransferrin (Gal d 3), lysozyme (Gal d 4), and ovomucin. Ovomucoid is the dominant allergen in egg (ie, is the allergen to which the most patients are sensitized), although ovalbumin is the most abundant protein comprising hen's egg white. Two additional proteins, lipocalin-type prostaglandin D synthase and egg white cystatin, that have IgE reactivity in individuals with egg allergy have been identified . Chicken serum albumin, or alpha-livetin (Gal d 5), is the major allergen in egg yolk and is involved in the bird-egg syndrome . (See "Pathogenesis of food allergy" and "Molecular features of food allergens" and "Food allergens: Overview of clinical features and cross-reactivity".)
Egg-specific IgE molecules that identify sequential or conformational epitopes can distinguish different clinical phenotypes of egg allergy. Sequential epitopes are determined by contiguous amino acids, whereas conformational epitopes contain amino acids from different regions of the protein that are in close proximity due to the folding of the protein. Conformational epitopes can be destroyed by heating or partial hydrolysis, which alter the tertiary structure of the protein.To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:
- Rona RJ, Keil T, Summers C, et al. The prevalence of food allergy: a meta-analysis. J Allergy Clin Immunol 2007; 120:638.
- Hill DJ, Hosking CS, de Benedictis FM, et al. Confirmation of the association between high levels of immunoglobulin E food sensitization and eczema in infancy: an international study. Clin Exp Allergy 2008; 38:161.
- Osterballe M, Hansen TK, Mortz CG, et al. The prevalence of food hypersensitivity in an unselected population of children and adults. Pediatr Allergy Immunol 2005; 16:567.
- Roehr CC, Edenharter G, Reimann S, et al. Food allergy and non-allergic food hypersensitivity in children and adolescents. Clin Exp Allergy 2004; 34:1534.
- Madrigal BI, Alfaro AN, Jiménez CC, González GJ. [Adverse reactions to food in daycare children]. Rev Alerg Mex 1996; 43:41.
- Unsel M, Sin AZ, Ardeniz O, et al. New onset egg allergy in an adult. J Investig Allergol Clin Immunol 2007; 17:55.
- Heine RG, Laske N, Hill DJ. The diagnosis and management of egg allergy. Curr Allergy Asthma Rep 2006; 6:145.
- Suzuki M, Fujii H, Fujigaki H, et al. Lipocalin-type prostaglandin D synthase and egg white cystatin react with IgE antibodies from children with egg allergy. Allergol Int 2010; 59:175.
- Quirce S, Marañón F, Umpiérrez A, et al. Chicken serum albumin (Gal d 5*) is a partially heat-labile inhalant and food allergen implicated in the bird-egg syndrome. Allergy 2001; 56:754.
- Des Roches A, Nguyen M, Paradis L, et al. Tolerance to cooked egg in an egg allergic population. Allergy 2006; 61:900.
- Konstantinou GN, Giavi S, Kalobatsou A, et al. Consumption of heat-treated egg by children allergic or sensitized to egg can affect the natural course of egg allergy: hypothesis-generating observations. J Allergy Clin Immunol 2008; 122:414.
- Lemon-Mulé H, Sampson HA, Sicherer SH, et al. Immunologic changes in children with egg allergy ingesting extensively heated egg. J Allergy Clin Immunol 2008; 122:977.
- Osborne NJ, Koplin JJ, Martin PE, et al. Prevalence of challenge-proven IgE-mediated food allergy using population-based sampling and predetermined challenge criteria in infants. J Allergy Clin Immunol 2011; 127:668.
- Martos G, Lopez-Exposito I, Bencharitiwong R, et al. Mechanisms underlying differential food allergy response to heated egg. J Allergy Clin Immunol 2011; 127:990.
- Bloom KA, Huang FR, Bencharitiwong R, et al. Effect of heat treatment on milk and egg proteins allergenicity. Pediatr Allergy Immunol 2014; 25:740.
- Takagi K, Teshima R, Okunuki H, et al. Kinetic analysis of pepsin digestion of chicken egg white ovomucoid and allergenic potential of pepsin fragments. Int Arch Allergy Immunol 2005; 136:23.
- Yamada K, Urisu A, Kakami M, et al. IgE-binding activity to enzyme-digested ovomucoid distinguishes between patients with contact urticaria to egg with and without overt symptoms on ingestion. Allergy 2000; 55:565.
- Vance GH, Grimshaw KE, Briggs R, et al. Serum ovalbumin-specific immunoglobulin G responses during pregnancy reflect maternal intake of dietary egg and relate to the development of allergy in early infancy. Clin Exp Allergy 2004; 34:1855.
- Palmer DJ, Gold MS, Makrides M. Effect of cooked and raw egg consumption on ovalbumin content of human milk: a randomized, double-blind, cross-over trial. Clin Exp Allergy 2005; 35:173.
- de Boissieu D, Dupont C. Natural course of sensitization to hen's egg in children not previously exposed to egg ingestion. Eur Ann Allergy Clin Immunol 2006; 38:113.
- Oyoshi MK, Murphy GF, Geha RS. Filaggrin-deficient mice exhibit TH17-dominated skin inflammation and permissiveness to epicutaneous sensitization with protein antigen. J Allergy Clin Immunol 2009; 124:485.
- Kodama M, Asano K, Oguma T, et al. Strain-specific phenotypes of airway inflammation and bronchial hyperresponsiveness induced by epicutaneous allergen sensitization in BALB/c and C57BL/6 mice. Int Arch Allergy Immunol 2010; 152 Suppl 1:67.
- Colver AF, Nevantaus H, Macdougall CF, Cant AJ. Severe food-allergic reactions in children across the UK and Ireland, 1998-2000. Acta Paediatr 2005; 94:689.
- Ross MP, Ferguson M, Street D, et al. Analysis of food-allergic and anaphylactic events in the National Electronic Injury Surveillance System. J Allergy Clin Immunol 2008; 121:166.
- Brown SG, Stone SF, Fatovich DM, et al. Anaphylaxis: clinical patterns, mediator release, and severity. J Allergy Clin Immunol 2013; 132:1141.
- Mehl A, Wahn U, Niggemann B. Anaphylactic reactions in children--a questionnaire-based survey in Germany. Allergy 2005; 60:1440.
- Macdougall CF, Cant AJ, Colver AF. How dangerous is food allergy in childhood? The incidence of severe and fatal allergic reactions across the UK and Ireland. Arch Dis Child 2002; 86:236.
- Escudero C, Quirce S, Fernández-Nieto M, et al. Egg white proteins as inhalant allergens associated with baker's asthma. Allergy 2003; 58:616.
- DeMasi JM. A unique cause of asthma in a baker. J Asthma 2006; 43:333.
- James JM, Crespo JF. Allergic reactions to foods by inhalation. Curr Allergy Asthma Rep 2007; 7:167.
- Lever R, MacDonald C, Waugh P, Aitchison T. Randomised controlled trial of advice on an egg exclusion diet in young children with atopic eczema and sensitivity to eggs. Pediatr Allergy Immunol 1998; 9:13.
- Tariq SM, Matthews SM, Hakim EA, Arshad SH. Egg allergy in infancy predicts respiratory allergic disease by 4 years of age. Pediatr Allergy Immunol 2000; 11:162.
- Kondo N, Fukutomi O, Agata H, et al. The role of T lymphocytes in patients with food-sensitive atopic dermatitis. J Allergy Clin Immunol 1993; 91:658.
- Liacouras CA, Spergel JM, Ruchelli E, et al. Eosinophilic esophagitis: a 10-year experience in 381 children. Clin Gastroenterol Hepatol 2005; 3:1198.
- Spergel JM, Beausoleil JL, Mascarenhas M, Liacouras CA. The use of skin prick tests and patch tests to identify causative foods in eosinophilic esophagitis. J Allergy Clin Immunol 2002; 109:363.
- Noel RJ, Putnam PE, Rothenberg ME. Eosinophilic esophagitis. N Engl J Med 2004; 351:940.
- Spergel JM, Brown-Whitehorn TF, Beausoleil JL, et al. 14 years of eosinophilic esophagitis: clinical features and prognosis. J Pediatr Gastroenterol Nutr 2009; 48:30.
- Ruffner MA, Ruymann K, Barni S, et al. Food protein-induced enterocolitis syndrome: insights from review of a large referral population. J Allergy Clin Immunol Pract 2013; 1:343.
- Zubrinich C, Hew M, O'Hehir R. Egg provoked food protein-induced enterocolitis-like syndrome in an adult. Clin Case Rep 2016; 4:899.
- Kondo M, Fukao T, Omoya K, et al. Protein-losing enteropathy associated with egg allergy in a 5-month-old boy. J Investig Allergol Clin Immunol 2008; 18:63.
- Sicherer SH, Wood RA, Vickery BP, et al. The natural history of egg allergy in an observational cohort. J Allergy Clin Immunol 2014; 133:492.
- Savage JH, Matsui EC, Skripak JM, Wood RA. The natural history of egg allergy. J Allergy Clin Immunol 2007; 120:1413.
- Järvinen KM, Beyer K, Vila L, et al. Specificity of IgE antibodies to sequential epitopes of hen's egg ovomucoid as a marker for persistence of egg allergy. Allergy 2007; 62:758.
- Gradman J, Mortz CG, Eller E, Bindslev-Jensen C. Relationship between specific IgE to egg components and natural history of egg allergy in Danish children. Pediatr Allergy Immunol 2016; 27:825.
- Bernhisel-Broadbent J, Dintzis HM, Dintzis RZ, Sampson HA. Allergenicity and antigenicity of chicken egg ovomucoid (Gal d III) compared with ovalbumin (Gal d I) in children with egg allergy and in mice. J Allergy Clin Immunol 1994; 93:1047.
- Shek LP, Soderstrom L, Ahlstedt S, et al. Determination of food specific IgE levels over time can predict the development of tolerance in cow's milk and hen's egg allergy. J Allergy Clin Immunol 2004; 114:387.
- Boyano-Martínez T, García-Ara C, Díaz-Pena JM, Martín-Esteban M. Prediction of tolerance on the basis of quantification of egg white-specific IgE antibodies in children with egg allergy. J Allergy Clin Immunol 2002; 110:304.
- Clark A, Islam S, King Y, et al. A longitudinal study of resolution of allergy to well-cooked and uncooked egg. Clin Exp Allergy 2011; 41:706.
- Sampson HA. Utility of food-specific IgE concentrations in predicting symptomatic food allergy. J Allergy Clin Immunol 2001; 107:891.
- Perry TT, Matsui EC, Kay Conover-Walker M, Wood RA. The relationship of allergen-specific IgE levels and oral food challenge outcome. J Allergy Clin Immunol 2004; 114:144.
- Boyano Martínez T, García-Ara C, Díaz-Pena JM, et al. Validity of specific IgE antibodies in children with egg allergy. Clin Exp Allergy 2001; 31:1464.
- Peters RL, Allen KJ, Dharmage SC, et al. Skin prick test responses and allergen-specific IgE levels as predictors of peanut, egg, and sesame allergy in infants. J Allergy Clin Immunol 2013; 132:874.
- Hill DJ, Heine RG, Hosking CS. The diagnostic value of skin prick testing in children with food allergy. Pediatr Allergy Immunol 2004; 15:435.
- Knight AK, Shreffler WG, Sampson HA, et al. Skin prick test to egg white provides additional diagnostic utility to serum egg white-specific IgE antibody concentration in children. J Allergy Clin Immunol 2006; 117:842.
- Sampson HA, Aceves S, Bock SA, et al. Food allergy: a practice parameter update-2014. J Allergy Clin Immunol 2014; 134:1016.
- Caffarelli C, Cavagni G, Giordano S, et al. Relationship between oral challenges with previously uningested egg and egg-specific IgE antibodies and skin prick tests in infants with food allergy. J Allergy Clin Immunol 1995; 95:1215.
- CLINICAL FEATURES
- Immunoglobulin E (IgE)-mediated reactions
- Mixed and non-IgE-mediated reactions
- - Atopic dermatitis
- - Gastrointestinal reactions
- Natural course
- IgE-mediated reactions
- - Asthma
- Other reactions
- Diagnostic pitfalls
- DIFFERENTIAL DIAGNOSIS
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS