This post is a sidebar to the CLP May 2014 feature, “The Food-Sensitization Dilemma.”

milk_eggsBy Robert W. Reinhardt, MD

Protein stability may affect a person’s ability to tolerate different foods and influence the severity of clinical reactions. Some food allergens may cause reactions when they are consumed raw or have not been fully cooked, but those same allergens may no longer be allergenic after they have been thoroughly cooked. Some allergens will give rise to clinical reactions ranging from mild or moderate to severe, whereas others will cause sensitization without a clinical reaction.1 One caveat applies: The ingested dose of allergen affects outcome. Even rather labile proteins have the potential to give rise to systemic reactions if the quantities are sufficient.

Cow’s milk allergy usually starts in infancy. It occurs in 19.9% of young American children, and is second only to peanut in prevalence among food allergies.2 High levels of cow’s milk IgE suggest the likelihood of sensitivity, but cannot predict reactions to baked milk (in bakery items or pizza, for example) or how long symptoms might persist.3 Casein and whey proteins can act as allergens, with casein comprising 80% and whey 20% of the total milk proteins.4 The component Bos d 8 (casein) is resistant to heat denaturation,5 and is associated with a higher anaphylactic risk in milk-allergic children. Bos d 4 (?-lactalbumin) and Bos d 5 (?-lactoglobulin) sensitivities are generally mild and are likely to be outgrown. Because Bos d 4 and Bos d 5 are susceptible to heat denaturation, 75% of children with cow’s milk allergy can tolerate baked milk even though they are at high risk of reacting to fresh milk.5

Egg-specific IgE antibodies are among the earliest detected in children who develop allergies. Indeed, sensitivity to egg white at 6 months of age is highly predictive of developing allergy to perennial inhalant allergens, such as house dust mites, during the first 5 years of life.6 Two egg components are of particular interest: ovalbumin (Gal d 2) and ovomucoid (Gal d 1). Sensitivity to the first predicts a high risk of reaction to raw egg but a low risk of reaction to well-baked egg, because ovalbumin is denatured by heat.7,8Ovalbumin sensitization may be transferred via breast milk. Current recommendations suggest that mothers with infants who have egg allergy should take caution when breast-feeding.9

In situations where the patient is mono-sensitized to only ovalbumin, an OFC with cooked egg may be appropriate. Children with sole ovalbumin sensitivity are also likely to outgrow their egg allergy.10 The other component of interest, ovomucoid, is resistant to heat denaturation and poses a high risk of reaction to all forms of egg.7 Patients with high s-IgE levels to ovomucoid are unlikely to outgrow their egg allergy. Still, some 70% of children with egg allergy can tolerate cooked egg,11 so clinicians may consider conducting component testing biennially during childhood to determine if tolerance has developed.


1. Sastre J. Molecular diagnosis in allergy. Clin Exper Allergy. 2010:1–19.

2. Warren CM, Jhaveri S, Warrier MR, Smith B, Gupta RS. The epidemiology of milk allergy in US children. Ann Allergy Asthma Immunol. 2013;110(5):370–374.

3. Shek LP, Bardina L, Castro R, Sampson HA, Beyer K. Humoral cellular responses to cow milk proteins in patients with milk-induced IgE-mediated and non IgE-mediated disorders. Allergy. 2005;60(7):912–919.

4. Ahn K. The usefulness of component-resolved diagnostics in food allergy. Allergy Asthma Immunol Res. 2014;6(2):103–104.

5. Nowak-Wegrzyn A, Bloom KA, Sicherer SH, et al. Tolerance to extensively heated milk in children with cow’s milk allergy. J Allergy Clin Immunol. 2008;122(2):342–347.

6. Sasai K, Furukawa S, Muto T, Baba M, Yabuta K, Fukiwatari Y. Early detection of specific IgE antibody against house dust mite in children at risk of allergic disease. J Pediatr. 1996;128(6):834–840.

7. Ando H, Moverare R, Kondo Y, et al. Utility of ovomucoid-specific IgE concentrations in predicting symptomatic egg allergy. J Allergy Clin Immunol. 2008;122(3):583–588.

8. Shin M, Han Y, Ahn K. The influence of the time and temperature of heat on the allergenicity of egg white proteins. Allergy Asthma Immunol Res. 2013;5(2):96–101.

9. Clark AT, Skypala I, Leech LC, et al. British Society for Allergy and Clinical Immunology guidelines for the management of egg allergy. Clin Exp Allergy. 2010;40(8):1116–1129.

10. Tomicic S, Norrman G, Faith-Magnuson K, Jenmalm MC, Devenney I, Bottcher MF. High levels of IgG4 IgE antibodies to foods during infancy are associated with tolerance to corresponding foods later in life. Pediatr Allergy Immunol. 2009;20(1):35–41.

11. Lemon-Mule H, Sampson HA, Sicherer SH, Shreffler WG, Noone S, Nowak-Wegrzyn A. Immunologic changes in children with egg allergy ingesting extensively heated egg. J Allergy Clin Immunol. 2008;122(5):977–983.