Skip to main content

Advertisement

Log in

Safety and Efficacy Balance of Baked Milk and Egg Oral Immunotherapy

  • Food Allergy (M Fernández-Rivas, Section Editor)
  • Published:
Current Treatment Options in Allergy Aims and scope Submit manuscript

Opinion statement

Purpose of review There is a subgroup of individuals with egg or cow’s milk (CM) allergy that can tolerate heated egg or CM. Thermal processing has been shown to affect antigen allergenicity either directly by denaturation of significant epitopes, or indirectly by synergistically altering their susceptibility to the digestion process under specific pH conditions. CM and egg proteins have heat labile molecules that become hypoallergenic after thermal treatment. The allergenicity may be further reduced when the CM and egg allergens are interacting with wheat proteins, and in particular gluten, in an interplay that teleologically affects solubility and therefore bioavailability. This phenomenon is known as the food matrix effect. By exploiting these observations, it has been suggested that diets containing extensively heated CM and egg might comprise an oral immunotherapeutic approach that could alter the expected natural allergy resolution or immunomodulate to tolerance the cases with persistent allergy.

Recent findings There is evidence suggesting that most of the baked-tolerant patients can be benefited from baked CM or egg oral immunotherapy (OIT). Following this approach, these patients can be desensitized, can be promoted to a transition from baked CM/egg OIT-induced tolerance to unheated CM and egg OIT-induced tolerance, or may acquire sustained tolerance.

Summary Baked CM or egg OIT may accelerate CM or egg allergy resolution and therefore may be a new therapeutic option to etiologically and not just symptomatically treating CM and egg allergy. It remains to be appropriately studied which are the phenotypic characteristics of these patients and which will be the appropriate immunotherapeutic protocol so that OIT can be easily and safely be offered to them.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Sampson HA, Aceves S, Bock SA, James J, Jones S, Lang D, et al. Food allergy: a practice parameter update—2014. J Allergy Clin Immunol. 2014;134(5):1016–25 e43. doi:10.1016/j.jaci.2014.05.013.

    Article  PubMed  Google Scholar 

  2. Howe L, Franxman T, Teich E, Greenhawt M. What affects quality of life among caregivers of food-allergic children? Ann Allergy Asthma Immunol. 2014;113(1):69–74 e2. doi:10.1016/j.anai.2014.04.016.

    Article  PubMed  Google Scholar 

  3. Ostblom E, Egmar AC, Gardulf A, Lilja G, Wickman M. The impact of food hypersensitivity reported in 9-year-old children by their parents on health-related quality of life. Allergy. 2008;63(2):211–8. doi:10.1111/j.1398-9995.2007.01559.x.

    Article  CAS  PubMed  Google Scholar 

  4. Mehta H, Groetch M, Wang J. Growth and nutritional concerns in children with food allergy. Curr Opin Allergy Clin Immunol. 2013;13(3):275–9. doi:10.1097/ACI.0b013e328360949d.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Burbank AJ, Sood P, Vickery BP, Wood RA. Oral immunotherapy for food allergy. Immunol Allergy Clin N Am. 2016;36(1):55–69. doi:10.1016/j.iac.2015.08.007.

    Article  Google Scholar 

  6. Nurmatov U, Dhami S, Arasi S, Pajno GB, Fernandez-Rivas M, Muraro A, et al. Allergen immunotherapy for IgE-mediated food allergy: a systematic review and meta-analysis. Allergy. 2017; doi:10.1111/all.13124.

  7. Nwaru BI, Hickstein L, Panesar SS, Roberts G, Muraro A, Sheikh A, et al. Prevalence of common food allergies in Europe: a systematic review and meta-analysis. Allergy. 2014;69(8):992–1007. doi:10.1111/all.12423.

    Article  CAS  PubMed  Google Scholar 

  8. • Savage J, Sicherer S, Wood R. The natural history of food allergy. J Allergy Clin Immunol Pract. 2016;4(2):196–203; quiz 4. doi:10.1016/j.jaip.2015.11.024. A comperhensive review of the natural history of food allergy for all common allergenic foods

  9. Wood RA, Sicherer SH, Vickery BP, Jones SM, Liu AH, Fleischer DM, et al. The natural history of milk allergy in an observational cohort. J Allergy Clin Immunol. 2013;131(3):805–12. doi:10.1016/j.jaci.2012.10.060.

    Article  CAS  PubMed  Google Scholar 

  10. Elizur A, Rajuan N, Goldberg MR, Leshno M, Cohen A, Katz Y. Natural course and risk factors for persistence of IgE-mediated cow’s milk allergy. J Pediatr. 2012;161(3):482–7 e1. doi:10.1016/j.jpeds.2012.02.028.

    Article  CAS  PubMed  Google Scholar 

  11. Savage JH, Matsui EC, Skripak JM, Wood RA. The natural history of egg allergy. J Allergy Clin Immunol. 2007;120(6):1413–7. doi:10.1016/j.jaci.2007.09.040.

    Article  CAS  PubMed  Google Scholar 

  12. Eigenmann PA. Anaphylactic reactions to raw eggs after negative challenges with cooked eggs. J Allergy Clin Immunol. 2000;105(3):587–8.

    Article  CAS  PubMed  Google Scholar 

  13. Nowak-Wegrzyn A, Bloom KA, Sicherer SH, Shreffler WG, Noone S, Wanich N, et al. Tolerance to extensively heated milk in children with cow’s milk allergy. J Allergy Clin Immunol. 2008;122(2):342–7. 7 e1-2

    Article  PubMed  Google Scholar 

  14. Urisu A, Ando H, Morita Y, Wada E, Yasaki T, Yamada K, et al. Allergenic activity of heated and ovomucoid-depleted egg white. J Allergy Clin Immunol. 1997;100(2):171–6.

    Article  CAS  PubMed  Google Scholar 

  15. • Konstantinou GN, Giavi S, Kalobatsou A, Vassilopoulou E, Douladiris N, Saxoni-Papageorgiou P, 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(2):414–5. The first study but with a retrospective design showing that incorporating baked egg on a regular basis into the diet of baked-egg tolerant but boiled milk allergic individuals may result in a more rapid clinical tolerance induction to egg.

  16. Leonard SA, Sampson HA, Sicherer SH, Noone S, Moshier EL, Godbold J, et al. Dietary baked egg accelerates resolution of egg allergy in children. J Allergy Clin Immunol. 2012;130(2):473–80 e1. doi:10.1016/j.jaci.2012.06.006.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. •• Peters RL, Dharmage SC, Gurrin LC, Koplin JJ, Ponsonby AL, Lowe AJ, et al. The natural history and clinical predictors of egg allergy in the first 2 years of life: a prospective, population-based cohort study. J Allergy Clin Immunol. 2014;133(2):485–91. doi:10.1016/j.jaci.2013.11.032.A prospective and the only until now population-based cohort study examining the natural history of egg allergy in infants with challenge confirmed raw hen’s egg allergy

  18. • Kim JS, Nowak-Wegrzyn A, Sicherer SH, Noone S, Moshier EL, Sampson HA. Dietary baked milk accelerates the resolution of cow’s milk allergy in children. J Allergy Clin Immunol. 2011;128(1):125–31 e2.The only until now published study showing with a prospective design that incorporating baked milk into the diet of baked milk tolerant but unheated milk-allergic subjects may accelerate the development of unheated milk tolerance.

  19. • Thomas K, Herouet-Guicheney C, Ladics G, Bannon G, Cockburn A, Crevel R, et al. Evaluating the effect of food processing on the potential human allergenicity of novel proteins: international workshop report. Food Chem Toxicol. 2007;45(7):1116–22. doi:10.1016/j.fct.2006.12.016.A comprehensive international workshop report reviewing the effects of food processing on the allergenicity of food proteins

  20. Besler M, Steinhart H, Paschke A. Stability of food allergens and allergenicity of processed foods. J Chromatogr B Biomed Sci Appl. 2001;756(1–2):207–28.

    Article  CAS  PubMed  Google Scholar 

  21. Wang J, Lin J, Bardina L, Goldis M, Nowak-Wegrzyn A, Shreffler WG, et al. Correlation of IgE/IgG4 milk epitopes and affinity of milk-specific IgE antibodies with different phenotypes of clinical milk allergy. J Allergy Clin Immunol. 2010;125(3):695–702, e1- e6. doi:10.1016/j.jaci.2009.12.017.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Lewis MJ, Heppell NJ. Continuous thermal processing of foods: pasteurization and UHT sterilization. Gaithersburg: Aspen Publishers, Inc.; 2000.

    Google Scholar 

  23. Roth-Walter F, Berin MC, Arnaboldi P, Escalante CR, Dahan S, Rauch J, et al. Pasteurization of milk proteins promotes allergic sensitization by enhancing uptake through Peyer’s patches. Allergy. 2008;63(7):882–90.

    Article  CAS  PubMed  Google Scholar 

  24. Host A, Samuelsson EG. Allergic reactions to raw, pasteurized, and homogenized/pasteurized cow milk: a comparison. A double-blind placebo-controlled study in milk allergic children. Allergy. 1988;43(2):113–8.

    Article  CAS  PubMed  Google Scholar 

  25. Jost R, Monti JC, Pahud JJ. Reduction of whey protein allergenicity by processing. Adv Exp Med Biol. 1991;289:309–20.

    Article  CAS  PubMed  Google Scholar 

  26. Mine Y, Zhang JW. Comparative studies on antigenicity and allergenicity of native and denatured egg white proteins. J Agric Food Chem. 2002;50(9):2679–83.

    Article  CAS  PubMed  Google Scholar 

  27. Calvani M, Arasi S, Bianchi A, Caimmi D, Cuomo B, Dondi A, et al. Is it possible to make a diagnosis of raw, heated, and baked egg allergy in children using cutoffs? A systematic review. Pediatr Allergy Immunol. 2015;26(6):509–21. doi:10.1111/pai.12432.

    Article  PubMed  Google Scholar 

  28. Jurado-Palomo J, Fiandor-Roman AM, Bobolea ID, Sanchez-Pastor S, Pascual CY, Quirce S. Oral challenge with pasteurized egg white from Gallus domesticus. Int Arch Allergy Immunol. 2010;151(4):331–5.

    Article  PubMed  Google Scholar 

  29. 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(6):1047–59.

    Article  CAS  PubMed  Google Scholar 

  30. Yoshino K, Sakai K, Mizuha Y, Shimizuike A, Yamamoto S. Peptic digestibility of raw and heat-coagulated hen’s egg white proteins at acidic pH range. Int J Food Sci Nutr. 2004;55(8):635–40.

    Article  CAS  PubMed  Google Scholar 

  31. • Konstantinou GN, Kim JS. Paradigm shift in the management of milk and egg allergy: baked milk and egg diet. Immunol Allergy Clin N Am. 2012;32(1):151–64. doi:10.1016/j.iac.2011.11.003.A comprehensive review of the important role thermal processing has on on milk and egg proteins allergenicity and immunogenecity

  32. Kato Y, Watanabe K, Matsuda T. Decrease in ovomucoid antigenicity in the processes of breadmaking supplemented with egg white. Food Sci Technol Int Tokyo. 1997;3:362–5.

    Article  Google Scholar 

  33. Ehn BM, Ekstrand B, Bengtsson U, Ahlstedt S. Modification of IgE binding during heat processing of the cow’s milk allergen beta-lactoglobulin. J Agric Food Chem. 2004;52(5):1398–403.

    Article  CAS  PubMed  Google Scholar 

  34. Kato Y, Oozawa E, Matsuda T. Decrease in antigenic and allergenic potentials of ovomucoid by heating in the presence of wheat flour: dependence on wheat variety and intermolecular disulfide bridges. J Agric Food Chem. 2001;49(8):3661–5.

    Article  CAS  PubMed  Google Scholar 

  35. • Miceli Sopo S, Greco M, Monaco S, Bianchi A, Cuomo B, Liotti L, et al. Matrix effect on baked milk tolerance in children with IgE cow milk allergy. Allergol Immunopathol. 2016;44(6):517–23. doi:10.1016/j.aller.2016.03.005.A study showing that thermally processed milk may be well tolerated from unheated milk intolerant individuals independently of the wheat matrix effect

  36. • Miceli Sopo S, Greco M, Cuomo B, Bianchi A, Liotti L, Monaco S, et al. Matrix effect on baked egg tolerance in children with IgE-mediated hen’s egg allergy. Pediatr Allergy Immunol. 2016;27(5):465–70. doi:10.1111/pai.12570.A study showing that thermally processed egg may be well tolerated from regular egg intolerant individuals independently of the wheat matrix effect.

  37. Finger A, Pfannenstiel C, Schonfelder A, Frank F, Buderus S, Lange L. Improvement of quality of life in children with milk and egg allergy after proof of tolerance to baked products. Allergy. 2012;67(s96):87.

    Google Scholar 

  38. Turner PJ, Mehr S, Joshi P, Tan J, Wong M, Kakakios A, et al. Safety of food challenges to extensively heated egg in egg-allergic children: a prospective cohort study. Pediatr Allergy Immunol. 2013;24(5):450–5. doi:10.1111/pai.12093.

    Article  PubMed  Google Scholar 

  39. Lieberman JA, Huang FR, Sampson HA, Nowak-Wegrzyn A. Outcomes of 100 consecutive open, baked-egg oral food challenges in the allergy office. J Allergy Clin Immunol. 2012;129(6):1682–4 e2. doi:10.1016/j.jaci.2012.04.007.

    Article  PubMed  Google Scholar 

  40. Cortot CF, Sheehan WJ, Permaul P, Friedlander JL, Baxi SN, Gaffin JM, et al. Role of specific IgE and skin-prick testing in predicting food challenge results to baked egg. Allergy Asthma Proc. 2012;33(3):275–81. doi:10.2500/aap.2012.33.3544.

    Article  PubMed  PubMed Central  Google Scholar 

  41. Bartnikas LM, Sheehan WJ, Hoffman EB, Permaul P, Dioun AF, Friedlander J, et al. Predicting food challenge outcomes for baked milk: role of specific IgE and skin prick testing. Ann Allergy Asthma Immunol. 2012;109(5):309–13 e1. doi:10.1016/j.anai.2012.07.026.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Peters RL, Allen KJ, Dharmage SC, Tang ML, Koplin JJ, Ponsonby AL, 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(4):874–80. doi:10.1016/j.jaci.2013.05.038.

    Article  CAS  PubMed  Google Scholar 

  43. Turner PJ, Kumar K, Fox AT. Skin testing with raw egg does not predict tolerance to baked egg in egg-allergic children. Pediatr Allergy Immunol. 2014;25(7):657–61. doi:10.1111/pai.12291.

    Article  CAS  PubMed  Google Scholar 

  44. Buelow BJ, Lee C, Zafra HT, Dasgupta M, Hoffmann RG, Vasudev M. Egg baked in product open oral food challenges are safe in selected egg-allergic patients. Allergy Rhinol. 2014;5(2):110–2. doi:10.2500/ar.2014.5.0092.

    Article  Google Scholar 

  45. Caubet JC, Nowak-Wegrzyn A, Moshier E, Godbold J, Wang J, Sampson HA. Utility of casein-specific IgE levels in predicting reactivity to baked milk. J Allergy Clin Immunol. 2013;131(1):222–224 e1–4. doi:10.1016/j.jaci.2012.06.049.

    Article  CAS  PubMed  Google Scholar 

  46. Mehr S, Turner PJ, Joshi P, Wong M, Campbell DE. Safety and clinical predictors of reacting to extensively heated cow’s milk challenge in cow’s milk-allergic children. Ann Allergy Asthma Immunol. 2014;113(4):425–9. doi:10.1016/j.anai.2014.06.023.

    Article  CAS  PubMed  Google Scholar 

  47. Ford LS, Bloom KA, Nowak-Wegrzyn AH, Shreffler WG, Masilamani M, Sampson HA. Basophil reactivity, wheal size, and immunoglobulin levels distinguish degrees of cow’s milk tolerance. J Allergy Clin Immunol. 2013;131(1):180–186 e1-3. doi:10.1016/j.jaci.2012.06.003.

    Article  CAS  PubMed  Google Scholar 

  48. 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):977–83 e1.

    Article  CAS  PubMed  Google Scholar 

  49. Matricardi PM, Kleine-Tebbe J, Hoffmann HJ, Valenta R, Hilger C, Hofmaier S, et al. EAACI molecular allergology user’s guide. Pediatr Allergy Immunol. 2016;27(Suppl 23):1–250. doi:10.1111/pai.12563.

    Article  PubMed  Google Scholar 

  50. Feldman MF, Bird JA. Oral immunotherapy for food allergy, ready for prime time? Heated egg and milk. Curr Allergy Asthma Rep. 2014;14(5):436. doi:10.1007/s11882-014-0436-6.

    Article  PubMed  Google Scholar 

  51. •• Goldberg MR, Nachshon L, Appel MY, Elizur A, Levy MB, Eisenberg E, et al. Efficacy of baked milk oral immunotherapy in baked milk-reactive allergic patients. J Allergy Clin Immunol. 2015;136(6):1601–6. doi:10.1016/j.jaci.2015.05.040.A prospective cohort study utilizing baked milk as oral immunotherapy in a baked milk reactive patients showing baked milk oral immunotherapy as a promising therapeutic approach in carrefully selected patients

  52. Lucendo AJ, Arias A, Tenias JM. Relation between eosinophilic esophagitis and oral immunotherapy for food allergy: a systematic review with meta-analysis. Ann Allergy Asthma Immunol. 2014;113(6):624–9. doi:10.1016/j.anai.2014.08.004.

    Article  PubMed  Google Scholar 

  53. Babaie D, Mesdaghi M, Nishino M, Mansouri M, Ebisawa M. Oral and sublingual immunotherapy: potential causes for eosinophilic gastrointestinal disorders? Int Arch Allergy Immunol. 2017;172(2):89–98. doi:10.1159/000457796.

    Article  PubMed  Google Scholar 

  54. • Lee E, Mehr S, Turner PJ, Joshi P, Campbell DE. Adherence to extensively heated egg and cow’s milk after successful oral food challenge. J Allergy Clin Immunol Pract. 2015;3(1):125–7 e4. doi:10.1016/j.jaip.2014.08.013.A study evaluating adherence to baked milk and egg diets in chalenge proved baked tolerant patients highlighting that allergic-like symptoms to baked milk or egg regular consumption may occur resulting even to cessation of consumption.

  55. • Leung J, Hundal NV, Katz AJ, Shreffler WG, Yuan Q, Butterworth CA, et al. Tolerance of baked milk in patients with cow’s milk-mediated eosinophilic esophagitis. J Allergy Clin Immunol. 2013;132(5):1215–6 e1. doi:10.1016/j.jaci.2013.08.017.A retrospective study showing that baked milk is well tolerated in most of the patient with cow's milk induced eosinophilic esophagitis suggesting that baked cow's milk oral immunotherapy is expected to be a very rare complication

  56. • Lambert R, Grimshaw KEC, Ellis B, Jaitly J, Roberts G. Evidence that eating baked egg or milk influences egg or milk allergy resolution: a systematic review. Clin Exp Allergy. 2017;47(6):829–37. doi:10.1111/cea.12940.A systematic review of the evidence that the regular ingestion of heated forms of hen's egg and cow’s milk from baked-tolerant patients in the context of oral immunotherapy may influence egg or milk allergy resolution

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to George N. Konstantinou MD, PhD, MSc, MC (army), FAAAAI.

Ethics declarations

Conflict of Interest

George N Konstantinou declares that he has no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

This article is part of the Topical Collection on Food Allergy

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Konstantinou, G.N. Safety and Efficacy Balance of Baked Milk and Egg Oral Immunotherapy. Curr Treat Options Allergy 4, 370–382 (2017). https://doi.org/10.1007/s40521-017-0143-3

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40521-017-0143-3

Keywords

Navigation