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Cow’s milk and Hen’s Eggs

Learning objectives

After this chapter, participants will be able to:

  • describe cross-reactivities related to cow’s milk and hen’s eggs components
  • explain how component-resolved diagnostics can be applied in the diagnosis of cow’s milk and hen’s egg allergies.

Cow’s milk and hen’s egg allergies

  • Cow’s milk and hen’s egg (hereafter referred to as milk and egg, respectively) are staple ingredients in cuisines worldwide.
  • Both milk and egg can induce allergy in individuals, particularly in infants and young children.1,2 However, resolution of these allergies may occur over time.3,4
  • In children under the age of two:
    • The incidence of milk allergy was highest in the UK (1.26%) and lowest in Greece (0.00%).5
    • The incidence of egg allergy was also highest in the UK (~2%) and lowest in Greece (0.11%).6
  • Exposure to aerosolised egg particles can also lead to occupational egg allergies in adults – this has been reported in bakera7 and individuals working in embryological research facilities.8
  • Exposure to heat such as baking may reduce the allergenicity of milk and egg, making it tolerable in patients with clinically relevant allergies.9

Allergen components in egg and milk10

  • Several allergen components have been identified in egg and milk:

Key allergen components in eggs

  • Although Gal d 2 is the most abundant protein in egg whites,9 Gal d 1 is considered to be the dominant major allergen.13
  • Sensitisation to egg lysozyme (Gal d 4), often used as a bacteriolytic preservative in food, has been shown to be of potential clinical relevance.14
  • Egg allergies in adulthood can be due to the manifestation of “bird-egg syndrome, a cross-reactivity caused by shared IgE epitopes of budgerigar feathers, hen feathers and egg yolk alpha-livetin.15

Key allergen components in milk

*less stable than casein proteins
Table adapted from Refs 10,16

  • The αS1-caseins and αS2-caseins from cow, goat and sheep share high amino acid sequence identities (87–98%) and cross-reactivities in the laboratory.17 In patients with cow’s milk allergies, over 90% were also positive for goat’s milk allergy.18
  • Although rare, individuals with persistent milk allergies can also react to serum albumin proteins in different mammalian meats. For example, bovine serum albumin (Bos d 6) has been shown to be involved in the co-sensitisation to milk and beef.19

Component-resolved diagnosis (CRD) in egg allergies

  • Current routine diagnostics for egg allergies use specific IgE blood tests or skin-prick testing.10 However, the utility of CRD in elucidating the specific allergens that are eliciting a reaction has been investigated:
    • CRD using Gal d 1 (ovomucoid) has been shown to predict clinically relevant egg allergy.20,21
    • CRD for Gal d 4 may be a useful tool to detect specific IgE against lysozyme in egg-allergic patients.14,16
    • Multiplex CRD for Gal d 1 in children residing in Italy showed that those who were negative for Gal d 1 had a high frequency of tolerance to boiled egg, whereas Gal d 1 – positive children showed a high frequency of raw egg allergy.22

CRD can be used to support allergy diagnosis; a definitive conclusion on clinical relevance should be drawn from an indicative medical history, diagnostic tests and, if necessary, an open or double-blind, placebo-controlled challenge with cooked or raw egg forms.8,16

CRD may be useful in distinguishing patients with raw egg or cooked egg allergies.

CRD in milk allergies

  • Current routine testing is via specific IgE blood tests and skin prick tests using complete milk extracts.10 However, the utility of CRD in elucidating the specific allergens that are eliciting a reaction has been investigated:
    • One study in Northern China showed that specific IgE against Bos d 12 had the highest diagnostic performance for milk allergies, whilst specific IgE against Bos d 4 showed the weakest performance. Milk allergy diagnosis improved in accuracy using combinations of milk allergen components, for example Bos d 5 + Bos d 12.23
    • High IgE levels to three milk components (α-lactalbumin, Bos d 4; β-lactoglobulin, Bos d 5 and casein, Bos d 8) in patients before oral immunotherapy were associated with a less successful outcome of therapy. Therefore, CRD may be useful in the selection of patients with cow’s milk allergy for immunotherapy.24
    • CRD measuring casein (Bos d 8) – specific IgE provided a significantly greater accuracy for predicting baked milk reactivity compared to the β-lactoglobulin component and the more traditional diagnostic tests measuring specific IgE to cow’s milk extract.25

CRD may be useful in predicting which patients are more likely either to respond to oral immunotherapy or to tolerate baked milk goods.

Can component-resolved diagnostics replace oral food challenges in milk and egg allergy?


  • CRD can be used to distinguish primary sensitisations from cross-reactions in patients with cow’s milk and hen’s egg allergy, directing appropriate management.
  • CRD may be useful in determining whether patients are able to tolerate baked or cooked milk or egg.
  • CRD may be useful in predicting whether patients might respond to oral immunotherapy.


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  2. Savage JH et al. J Allergy Clin Immunol. 2007;120(6):1413–7.
  3. Sicherer SH et al. J Allergy Clin Immunol. 2014;133(2):492–9.
  4. Wood RA et al. J Allergy Clin Immunol. 2013;131(3):805–12.
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  10. Matricardi PM et al. (Editors). Molecular Allergology User’s Guide. 2016. Zurich: European Academy of Allergy and Clinical Immunology.
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  16. Kleine-Tebbe J, Jakob T. (Editors). Molecular Allergy Diagnostics. 2015. Cham: Springer International Publishing.
  17. Walter SP et al. Allergy. 1997;52(3):293–8.
  18. Bellioni-Businco B et al. J Allergy Clin Immunol. 1999;103(6):1191–4.
  19. Martelli A et al. Ann Allergy Asthma Immunol. 2002;89(Suppl):38–43.
  20. D’Urbano LE et al. Clinical & Experimental Allergy. 2010;40(10):1561–70.
  21. Haneda Y et al. J Allergy Clin Immunol. 2012;129(6):1681–2.
  22. Alessandri C et al. Clinical & Experimental Allergy. 2012;42(3):441–50.
  23. Li J et al. International Immunopharmacology. 2018;61:126–31.
  24. Kuitunen M et al. Allergy. 2015;70(8):955–62.
  25. Caubet J-C et al. J Allergy Clin Immunol. 2013;131(1):222–4.


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