Clinical Reviews in Allergy & Immunology

, Volume 55, Issue 2, pp 118–138 | Cite as

The Impact of Baked Egg and Baked Milk Diets on IgE- and Non-IgE-Mediated Allergy

  • Julia UptonEmail author
  • Anna Nowak-Wegrzyn


Baked milk (BM) and baked egg (BE) diets are increasingly used in the management of milk and egg allergy, rather than avoidance. Children with tolerance versus reactivity to BM and BE may have smaller skin prick test and lower specific IgE, and BM-tolerant children have less basophil reactivity and more peripheral T regulatory cells. However, most milk- and egg-allergic children tolerate BM and BE and an individual’s reactivity is unpredictable. Non-reactivity is due to conformational changes in the allergens. Significant differences in the published advice about methods of introduction exist from graded introduction at home to a medically supervised full dose. These approaches carry different risks and may have different immunological effects. Reactivity to BM is a predictor of a severe milk allergy. Therefore, medical supervision for BM and BE introduction is prudent. The baked diet allows dietary liberation. Most, but not all, BM- and BE-tolerant children continue eating the baked foods. The prognosis of children who can eat BM and BE is favorable with likely resolution of their allergy over the next few years. Murine models of BE diets demonstrate that heated egg can impart clinical protection against anaphylaxis and cause immune changes. Most observational human studies of BM and BE diets demonstrate clinical resolution of allergy and favorable immune changes versus regular care controls. However, the one randomized controlled trial for the BE diet in BE-tolerant children did not support an immune-modifying effect of the BE diet. Another study of BE immunotherapy is expected to be completed in 2018. There is currently no evidence for prevention of allergy with the baked diets. There may be a future role for BM and BE in liberating the diets of individuals with non-IgE-mediated allergy given recent studies that a subset of these patients can consume BM without a clinical reaction.


Immunotherapy Baked Heated Milk Egg Food allergy 


Compliance with Ethical Standards

Conflict of Interest

Author JU has received research funding from SickKids Foundation and the Department of Pediatrics, Hospital for Sick Children, speaker honorarium from Food Allergy Canada, research support from DBV, Aimmune, and ALLEVIATE, and is the Anaphylaxis and Food Allergy Section Chair for the Canadian Society of Allergy and Clinical Immunology. Author ANW has received research funding from NIH NIAID, FARE, DBV, Nutricia, and Nestle. She serves as the DMC chair for the trial of sublingual dust mite immunotherapy for Merck, and she is a member of the Advisory Council for the Gerber Nutrition Institute and has received honoraria from Nestle, Nutricia, and Thermo Fisher Scientific. She serves as the vice chair of the Food Allergy, Dermatitis, Drug Allergy and Anaphylaxis Section of the American Academy of Allergy, Asthma and Immunology. She is the medical chair for the International FPIES Association.


  1. 1.
    Sicherer SH, Allen K, Lack G, Taylor SL, Donovan SM, Oria M (2017) Critical issues in food allergy: a National Academies Consensus report. Pediatrics 140(2):e20170194. CrossRefGoogle Scholar
  2. 2.
    Sicherer SH, Sampson HA (2014) Food allergy: epidemiology, pathogenesis, diagnosis, and treatment. J Allergy Clin Immunol 133(2):291–307; quiz 308. CrossRefPubMedGoogle Scholar
  3. 3.
    Nwaru BI, Hickstein L, Panesar SS, Roberts G, Muraro A, Sheikh A (2014) Prevalence of common food allergies in Europe: a systematic review and meta-analysis. Allergy 69(8):992–1007. CrossRefGoogle Scholar
  4. 4.
    Bollinger ME, Dahlquist LM, Mudd K, Sonntag C, Dillinger L, McKenna K (2006) The impact of food allergy on the daily activities of children and their families. Ann Allergy Asthma Immunol 96(3):415–421. CrossRefPubMedGoogle Scholar
  5. 5.
    Indinnimeo L, Baldini L, De Vittori V, Zicari AM, De Castro G, Tancredi G, Lais G, Duse M (2013) Duration of a cow-milk exclusion diet worsens parents’ perception of quality of life in children with food allergies. BMC Pediatr 13(1):203. CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Sicherer SH, Simons FER (2017) Epinephrine for first-aid management of anaphylaxis. Pediatrics 139(3):e20164006. CrossRefPubMedGoogle Scholar
  7. 7.
    Mehta H, Groetch M, Wang J (2013) Growth and nutritional concerns in children with food allergy. Curr Opin Allergy Clin Immunol 13(3):275–279. CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Wood RA (2003) The natural history of food allergy. Pediatrics 111(6 Pt 3):1631–1637PubMedGoogle Scholar
  9. 9.
    Skripak JM, Matsui EC, Mudd K, Wood RA (2007) The natural history of IgE-mediated cow’s milk allergy. J Allergy Clin Immunol 120(5):1172–1177. CrossRefPubMedGoogle Scholar
  10. 10.
    Cantani A, Micera M (2004) Natural history of cow’s milk allergy. An eight-year follow-up study in 115 atopic children. Eur Rev Med Pharmacol Sci 8(4):153–164PubMedGoogle Scholar
  11. 11.
    Savage JH, Matsui EC, Skripak JM, Wood RA (2007) The natural history of egg allergy. J Allergy Clin Immunol 120(6):1413–1417. CrossRefPubMedGoogle Scholar
  12. 12.
    Vazquez-Ortiz M, Turner PJ (2016) Improving the safety of oral immunotherapy for food allergy. Pediatr Allergy Immunol 27(2):117–125. CrossRefPubMedGoogle Scholar
  13. 13.
    Keet CA, Seopaul S, Knorr S, Narisety S, Skripak J, Wood RA (2013) Long-term follow-up of oral immunotherapy for cow’s milk allergy. J Allergy Clin Immunol 132(3):737–739 e736. CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Urisu A, Ando H, Morita Y, Wada E, Yasaki T, Yamada K, Komada K, Torii S, Goto M, Wakamatsu T (1997) Allergenic activity of heated and ovomucoid-depleted egg white. J Allergy Clin Immunol 100(2):171–176. CrossRefPubMedGoogle Scholar
  15. 15.
    Eigenmann PA (2000) Anaphylactic reactions to raw eggs after negative challenges with cooked eggs. J Allergy Clin Immunol 105(3):587–588. CrossRefPubMedGoogle Scholar
  16. 16.
    Nowak-Wegrzyn A, Bloom KA, Sicherer SH, Shreffler WG, Noone S, Wanich N, Sampson HA (2008) Tolerance to extensively heated milk in children with cow’s milk allergy. J Allergy Clin Immunol 122(2):342–347, 347 e341-342. CrossRefPubMedGoogle Scholar
  17. 17.
    Leonard SA, Caubet JC, Kim JS, Groetch M, Nowak-Wegrzyn A (2015) Baked milk- and egg-containing diet in the management of milk and egg allergy. J Allergy Clin Immunol Pract 3(1):13–23; quiz 24. CrossRefPubMedGoogle Scholar
  18. 18.
    Fiocchi A, Dahda L, Dupont C, Campoy C, Fierro V, Nieto A (2016) Cow’s milk allergy: towards an update of DRACMA guidelines. World Allergy Organ J 9(1):35. CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Leonard SA, Nowak-Wegrzyn AH (2016) Baked milk and egg diets for milk and egg allergy management. Immunol Allergy Clin N Am 36(1):147–159. CrossRefGoogle Scholar
  20. 20.
    Konstantinou GN, Kim JS (2012) Paradigm shift in the management of milk and egg allergy: baked milk and egg diet. Immunol Allergy Clin N Am 32(1):151–164. CrossRefGoogle Scholar
  21. 21.
    Allen CW, Campbell DE, Kemp AS (2009) Food allergy: is strict avoidance the only answer? Pediatr Allergy Immunol 20(5):415–422. CrossRefPubMedGoogle Scholar
  22. 22.
    Leung J, Hundal NV, Katz AJ, Shreffler WG, Yuan Q, Butterworth CA, Hesterberg PE (2013) Tolerance of baked milk in patients with cow’s milk-mediated eosinophilic esophagitis. PubMedGoogle Scholar
  23. 23.
    Uncuoglu A, Yologlu N, Simsek IE, Uyan ZS, Aydogan M (2017) Tolerance to baked and fermented cow’s milk in children with IgE-mediated and non-IgE-mediated cow’s milk allergy in patients under two years of age. Allergol Immunopathol 45(6):560–566. CrossRefGoogle Scholar
  24. 24.
    Anderson KJ, McLaughlan P, Devey ME, Coombs RR (1979) Anaphylactic sensitivity of guinea-pigs drinking different preparations of cows’ milk and infant formulae. Clin Exp Immunol 35(3):454–461PubMedPubMedCentralGoogle Scholar
  25. 25.
    Heppell LM, Cant AJ, Kilshaw PJ (1984) Reduction in the antigenicity of whey proteins by heat treatment: a possible strategy for producing a hypoallergenic infant milk formula. Br J Nutr 51(1):29–36. CrossRefPubMedGoogle Scholar
  26. 26.
    Bloom KA, Huang FR, Bencharitiwong R, Bardina L, Ross A, Sampson HA, Nowak-Wegrzyn A (2014) Effect of heat treatment on milk and egg proteins allergenicity. Pediatr Allergy Immunol 25(8):740–746. CrossRefGoogle Scholar
  27. 27.
    Nowak-Wegrzyn A, Fiocchi A (2009) Rare, medium, or well done? The effect of heating and food matrix on food protein allergenicity. Curr Opin Allergy Clin Immunol 9(3):234–237. CrossRefPubMedGoogle Scholar
  28. 28.
    Verhoeckx KC, Vissers YM, Baumert JL, Faludi R, Feys M, Flanagan S, Herouet-Guicheney C, Holzhauser T, Shimojo R, van der Bolt N, Wichers H, Kimber I (2015) Food processing and allergenicity. Food Chem Toxicol 80:223–240. CrossRefPubMedGoogle Scholar
  29. 29.
    Bu G, Luo Y, Chen F, Liu K, Zhu T (2013) Milk processing as a tool to reduce cow’s milk allergenicity: a mini-review. Dairy Sci Technol 93(3):211–223. CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Tordesillas L, Berin MC, Sampson HA (2017) Immunology of food allergy. Immunity 47(1):32–50. CrossRefPubMedGoogle Scholar
  31. 31.
    Claeys WL, Cardoen S, Daube G, De Block J, Dewettinck K, Dierick K, De Zutter L, Huyghebaert A, Imberechts H, Thiange P, Vandenplas Y, Herman L (2013) Raw or heated cow milk consumption: review of risks and benefits. Food Control 31(1):251–262. CrossRefGoogle Scholar
  32. 32.
    Chokshi NY, Sicherer SH (2015) Molecular diagnosis of egg allergy: an update. Expert Rev Mol Diagn 15(7):895–906. CrossRefPubMedGoogle Scholar
  33. 33.
    Bernhisel-Broadbent J, Dintzis HM, Dintzis RZ, Sampson HA (1994) 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 93(6):1047–1059. CrossRefPubMedGoogle Scholar
  34. 34.
    Shin M, Han Y, Ahn K (2013) The influence of the time and temperature of heat treatment on the allergenicity of egg white proteins. Allergy Asthma Immunol Res 5(2):96–101. CrossRefPubMedGoogle Scholar
  35. 35.
    Escudero C, Sanchez-Garcia S, Rodriguez del Rio P, Pastor-Vargas C, Garcia-Fernandez C, Perez-Rangel I, Ramirez-Jimenez A, Ibanez MD (2013) Dehydrated egg white: an allergen source for improving efficacy and safety in the diagnosis and treatment for egg allergy. Pediatr Allergy Immunol 24(3):263–269. CrossRefPubMedGoogle Scholar
  36. 36.
    Luyt D, Ball H, Makwana N, Green MR, Bravin K, Nasser SM, Clark AT, Standards of Care Committee of the British Society for A, Clinical I (2014) BSACI guideline for the diagnosis and management of cow’s milk allergy. Clin Exp Allergy 44(5):642–672. CrossRefGoogle Scholar
  37. 37.
    Clark AT, Skypala I, Leech SC, Ewan PW, Dugue P, Brathwaite N, Huber PA, Nasser SM, British society for A, Clinical I (2010) British Society for Allergy and Clinical Immunology guidelines for the management of egg allergy. Clin Exp Allergy 40(8):1116–1129. CrossRefPubMedGoogle Scholar
  38. 38.
    Wright T, Meyer R (2009) Milk and eggs. Food hypersensitivity: diagnosing and managing food allergies and intolerance. Wiley-Blackwell, Oxford. CrossRefGoogle Scholar
  39. 39.
    Nowak-Wegrzyn AH, Strong BD, Fernandez K, Bahnson T, Sampson HA (2015) Increasing tolerance to less extensively heat-denatured (baked) milk products in milk-allergic children. J Allergy Clin Immunol 135(2):AB234. CrossRefGoogle Scholar
  40. 40.
    Shin M, Lee J, Ahn K, Lee SI, Han Y (2013) The influence of the presence of wheat flour on the antigenic activities of egg white proteins. Allergy Asthma Immunol Res 5(1):42–47. CrossRefPubMedGoogle Scholar
  41. 41.
    Lanser BJ, Faino A, Gelfand EW, Hauk PJ (2015) Influence of wheat on the outcome of oral food challenge (OFC) to baked egg. J Allergy Clin Immunol 135(2):AB25. CrossRefGoogle Scholar
  42. 42.
    Goldberg MR, Nachshon L, Appel MY, Elizur A, Levy MB, Eisenberg E, Sampson HA, Katz Y (2015) Efficacy of baked milk oral immunotherapy in baked milk-reactive allergic patients. J Allergy Clin Immunol 136(6):1601–1606. CrossRefGoogle Scholar
  43. 43.
    Nowak-Wegrzyn A, Groetch M (2012) Let them eat cake. Ann Allergy Asthma Immunol 109(5):287–288. CrossRefPubMedGoogle Scholar
  44. 44.
    Turner PJ, Mehr S, Joshi P, Tan J, Wong M, Kakakios A, Campbell DE (2013) Safety of food challenges to extensively heated egg in egg-allergic children: a prospective cohort study. Pediatr Allergy Immunol 24(5):450–455. CrossRefPubMedGoogle Scholar
  45. 45.
    Lemon-Mule H, Sampson HA, Sicherer SH, Shreffler WG, Noone S, Nowak-Wegrzyn A (2008) Immunologic changes in children with egg allergy ingesting extensively heated egg. J Allergy Clin Immunol 122(5):977–983 e971. CrossRefPubMedGoogle Scholar
  46. 46.
    Remington BC, Westerhout J, Campbell DE, Turner PJ (2017) Minimal impact of extensive heating of hen’s egg and cow’s milk in a food matrix on threshold dose-distribution curves. Allergy 72(11):1816–1819. CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Turner PJ, Gowland MH, Sharma V, Ierodiakonou D, Harper N, Garcez T, Pumphrey R, Boyle RJ (2015) Increase in anaphylaxis-related hospitalizations but no increase in fatalities: an analysis of United Kingdom national anaphylaxis data, 1992-2012. J Allergy Clin Immunol 135(4):956–963 e951. CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    Levy MB, Goldberg MR, Nachshon L, Tabachnik E, Katz Y (2012) Lessons from cases of mortality due to food allergy in Israel: cow's milk protein should be considered a potentially fatal allergen. Isr Med Assoc J 14(1):29–33PubMedGoogle Scholar
  49. 49.
    Upton J, Vadas P (2014) Biomarkers for the evaluation of severity of anaphylaxis. In: Advances in Anaphylaxis Management Future Medicine Ltd, pp 62–80.
  50. 50.
    NIAID-Sponsored Expert Panel, Boyce JA, Assa’ad A, Burks AW, Jones SM, Sampson HA, Wood RA, Plaut M, Cooper SF, Fenton MJ, Arshad SH, Bahna SL, Beck LA, Byrd-Bredbenner C, Camargo CA Jr, Eichenfield L, Furuta GT, Hanifin JM, Jones C, Kraft M, Levy BD, Lieberman P, Luccioli S, McCall KM, Schneider LC, Simon RA, Simons FE, Teach SJ, Yawn BP, Schwaninger JM (2010) Guidelines for the diagnosis and management of food allergy in the United States: report of the NIAID-sponsored expert panel. J Allergy Clin Immunol 126(6 Suppl):S1–58. CrossRefGoogle Scholar
  51. 51.
    Turner PJ, Baumert JL, Beyer K, Boyle RJ, Chan CH, Clark AT, Crevel RW, DunnGalvin A, Fernandez-Rivas M, Gowland MH, Grabenhenrich L, Hardy S, Houben GF, OBH J, Muraro A, Poulsen LK, Pyrz K, Remington BC, Schnadt S, van Ree R, Venter C, Worm M, Mills EN, Roberts G, Ballmer-Weber BK (2016) Can we identify patients at risk of life-threatening allergic reactions to food? Allergy 71(9):1241–1255. CrossRefPubMedGoogle Scholar
  52. 52.
  53. 53.
    Huang F, Nowak-Wegrzyn A (2012) Extensively heated milk and egg as oral immunotherapy. Curr Opin Allergy Clin Immunol 12(3):283–292. CrossRefPubMedGoogle Scholar
  54. 54.
    Sampson HA, Gerth van Wijk R, Bindslev-Jensen C, Sicherer S, Teuber SS, Burks AW, Dubois AE, Beyer K, Eigenmann PA, Spergel JM, Werfel T, Chinchilli VM (2012) Standardizing double-blind, placebo-controlled oral food challenges: American Academy of Allergy, Asthma & Immunology-European Academy of Allergy and Clinical Immunology PRACTALL consensus report. J Allergy Clin Immunol 130(6):1260–1274. CrossRefPubMedGoogle Scholar
  55. 55.
    Nowak-Wegrzyn A, Assa’ad AH, Bahna SL, Bock SA, Sicherer SH, Teuber SS, Adverse Reactions to Food Committee of American Academy of Allergy A, Immunology (2009) Work Group report: oral food challenge testing. J Allergy Clin Immunol 123(6 Suppl):S365–S383. CrossRefGoogle Scholar
  56. 56.
    Kowalski ML, Ansotegui I, Aberer W, Al-Ahmad M, Akdis M, Ballmer-Weber BK, Beyer K, Blanca M, Brown S, Bunnag C, Hulett AC, Castells M, Chng HH, De Blay F, Ebisawa M, Fineman S, Golden DB, Haahtela T, Kaliner M, Katelaris C, Lee BW, Makowska J, Muller U, Mullol J, Oppenheimer J, Park HS, Parkerson J, Passalacqua G, Pawankar R, Renz H, Rueff F, Sanchez-Borges M, Sastre J, Scadding G, Sicherer S, Tantilipikorn P, Tracy J, van Kempen V, Bohle B, Canonica GW, Caraballo L, Gomez M, Ito K, Jensen-Jarolim E, Larche M, Melioli G, Poulsen LK, Valenta R, Zuberbier T (2016) Risk and safety requirements for diagnostic and therapeutic procedures in allergology: World Allergy Organization Statement. World Allergy Organ J 9(1):33. CrossRefPubMedPubMedCentralGoogle Scholar
  57. 57.
    Bartnikas LM, Sheehan WJ, Hoffman EB, Permaul P, Dioun AF, Friedlander J, Baxi SN, Schneider LC, Phipatanakul W (2012) Predicting food challenge outcomes for baked milk: role of specific IgE and skin prick testing. Ann Allergy Asthma Immunol 109(5):309–313 e301. CrossRefPubMedPubMedCentralGoogle Scholar
  58. 58.
    Ford LS, Bloom KA, Nowak-Wegrzyn AH, Shreffler WG, Masilamani M, Sampson HA (2013) Basophil reactivity, wheal size, and immunoglobulin levels distinguish degrees of cow's milk tolerance. J Allergy Clin Immunol 131(1):180–186 e181-183. CrossRefPubMedGoogle Scholar
  59. 59.
    Agyemang A, Feuille E, Tang J, Steinwandtner I, Sampson H, Nowak-Wegrzyn A (2017) Outcomes of 84 consecutive open food challenges to extensively heated (baked) milk in the allergy office. J Allergy Clin Immunol Pract. PubMedGoogle Scholar
  60. 60.
    Mehr S, Turner PJ, Joshi P, Wong M, Campbell DE (2014) Safety and clinical predictors of reacting to extensively heated cow’s milk challenge in cow’s milk-allergic children. Ann Allergy Asthma Immunol 113(4):425–429. CrossRefPubMedGoogle Scholar
  61. 61.
    Caubet JC, Nowak-Wegrzyn A, Moshier E, Godbold J, Wang J, Sampson HA (2013) Utility of casein-specific IgE levels in predicting reactivity to baked milk. J Allergy Clin Immunol 131(1):222–224 e221-224. CrossRefPubMedGoogle Scholar
  62. 62.
    Kwan A, Asper M, Lavi S, Lavine E, Hummel D, Upton JE (2016) Prospective evaluation of testing with baked milk to predict safe ingestion of baked milk in unheated milk-allergic children. Allergy Asthma Clin Immunol 12(1):54. CrossRefPubMedPubMedCentralGoogle Scholar
  63. 63.
    Barbosa CPG, Castro APM, Yonamine GH, Gushken AKF, Beck CML, Macedo PRC, Dorna MB, Santos CJN, Pastorino AC, Jacob CMA (2017) Baked milk tolerant patient: is there any special feature? Allergol Immunopathol 45(3):283–289. CrossRefGoogle Scholar
  64. 64.
    Wang J, Lin J, Bardina L, Goldis M, Nowak-Wegrzyn A, Shreffler WG, Sampson HA (2010) Correlation of IgE/IgG4 milk epitopes and affinity of milk-specific IgE antibodies with different phenotypes of clinical milk allergy. J Allergy Clin Immunol 125(3):695–702, 702 e691-702 e696. CrossRefPubMedPubMedCentralGoogle Scholar
  65. 65.
    Bartuzi Z, Cocco RR, Muraro A, Nowak-Wegrzyn A (2017) Contribution of molecular allergen analysis in diagnosis of milk allergy. Curr Allergy Asthma Rep 17(7):46. CrossRefPubMedGoogle Scholar
  66. 66.
    Wanich N, Nowak-Wegrzyn A, Sampson HA, Shreffler WG (2009) Allergen-specific basophil suppression associated with clinical tolerance in patients with milk allergy. J Allergy Clin Immunol 123(4):789–794 e720. CrossRefPubMedPubMedCentralGoogle Scholar
  67. 67.
    Shreffler WG, Wanich N, Moloney M, Nowak-Wegrzyn A, Sampson HA (2009) Association of allergen-specific regulatory T cells with the onset of clinical tolerance to milk protein. J Allergy Clin Immunol 123(1):43–52 e47. CrossRefPubMedGoogle Scholar
  68. 68.
    Faraj Z, Kim HL (2012) Skin prick testing with extensively heated milk or egg products helps predict the outcome of an oral food challenge: a retrospective analysis. Allergy Asthma Clin Immunol 8(1):5. CrossRefPubMedPubMedCentralGoogle Scholar
  69. 69.
    Cortot CF, Sheehan WJ, Permaul P, Friedlander JL, Baxi SN, Gaffin JM, Dioun AF, Hoffman EB, Schneider LC, Phipatanakul W (2012) Role of specific IgE and skin-prick testing in predicting food challenge results to baked egg. Allergy Asthma Proc 33(3):275–281. CrossRefPubMedPubMedCentralGoogle Scholar
  70. 70.
    Bartnikas LM, Sheehan WJ, Larabee KS, Petty C, Schneider LC, Phipatanakul W (2013) Ovomucoid is not superior to egg white testing in predicting tolerance to baked egg. J Allergy Clin Immunol Pract 1(4):354–360. CrossRefPubMedPubMedCentralGoogle Scholar
  71. 71.
    Lieberman JA, Huang FR, Sampson HA, Nowak-Wegrzyn A (2012) Outcomes of 100 consecutive open, baked-egg oral food challenges in the allergy office. In: J Allergy Clin Immunol, vol 129. vol 6. United States, pp 1682-1684.e1682. CrossRefGoogle Scholar
  72. 72.
    Vazquez-Ortiz M, Pascal M, Jimenez-Feijoo R, Lozano J, Giner MT, Alsina L, Martin-Mateos MA, Plaza AM (2014) Ovalbumin-specific IgE/IgG4 ratio might improve the prediction of cooked and uncooked egg tolerance development in egg-allergic children. Clin Exp Allergy 44(4):579–588. CrossRefPubMedGoogle Scholar
  73. 73.
    Caubet JC, Bencharitiwong R, Moshier E, Godbold JH, Sampson HA, Nowak-Wegrzyn A (2012) Significance of ovomucoid- and ovalbumin-specific IgE/IgG(4) ratios in egg allergy. J Allergy Clin Immunol 129(3):739–747. CrossRefGoogle Scholar
  74. 74.
    Tan JWL, Campbell DE, Turner PJ, Kakakios A, Wong M, Mehr S, Joshi P (2013) Baked egg food challenges—clinical utility of skin test to baked egg and ovomucoid in children with egg allergy. Clin Exp Allergy 43(10):1189–1195. CrossRefPubMedGoogle Scholar
  75. 75.
    Des Roches A, Nguyen M, Paradis L, Primeau MN, Singer S (2006) Tolerance to cooked egg in an egg allergic population. Allergy 61(7):900–901. CrossRefPubMedGoogle Scholar
  76. 76.
    Clark A, Islam S, King Y, Deighton J, Szun S, Anagnostou K, Ewan P (2011) A longitudinal study of resolution of allergy to well-cooked and uncooked egg. Clin Exp Allergy 41(5):706–712. CrossRefPubMedGoogle Scholar
  77. 77.
    Ando H, Moverare R, Kondo Y, Tsuge I, Tanaka A, Borres MP (2008) Utility of ovomucoid-specific IgE concentrations in predicting symptomatic egg allergy. J Allergy Clin Immunol 122(3):583–588. CrossRefPubMedGoogle Scholar
  78. 78.
    Kim JS, Nowak-Wegrzyn A, Sicherer SH, Noone S, Moshier EL, Sampson HA (2011) Dietary baked milk accelerates the resolution of cow’s milk allergy in children. J Allergy Clin Immunol 128(1):125–131 e122. CrossRefPubMedPubMedCentralGoogle Scholar
  79. 79.
    Netting M, Gold M, Quinn P, El-Merhibi A, Penttila I, Makrides M (2017) Randomised controlled trial of a baked egg intervention in young children allergic to raw egg but not baked egg. World Allergy Org J 10(1):22. CrossRefGoogle Scholar
  80. 80.
    Lee E, Mehr S, Turner PJ, Joshi P, Campbell DE (2015) Adherence to extensively heated egg and cow’s milk after successful oral food challenge. J Allergy Clin Immunol Pract 3 (1):125–127 e124. Google Scholar
  81. 81.
    Weinbrand-Goichberg J, Benor S, Rottem M, Shacham N, Mandelberg A, Levine A, Sade K, Kivity S, Dalal I (2017) Long-term outcomes following baked milk-containing diet for IgE-mediated milk allergy. J Allergy Clin Immunol Pract 5(6):1776–1778.e1. CrossRefPubMedGoogle Scholar
  82. 82.
    Leonard SA, Sampson HA, Sicherer SH, Noone S, Moshier EL, Godbold J, Nowak-Wegrzyn A (2012) Dietary baked egg accelerates resolution of egg allergy in children. J Allergy Clin Immunol 130(2):473–480.e471. CrossRefPubMedPubMedCentralGoogle Scholar
  83. 83.
    Yee CS, Rachid R (2016) The heterogeneity of oral immunotherapy clinical trials: implications and future directions. Curr Allergy Asthma Rep 16(4):25. CrossRefPubMedGoogle Scholar
  84. 84.
    Martorell Calatayud C, Muriel Garcia A, Martorell Aragones A, De La Hoz Caballer B (2014) Safety and efficacy profile and immunological changes associated with oral immunotherapy for IgE-mediated cow's milk allergy in children: systematic review and meta-analysis. J Investig Allergol Clin Immunol 24(5):298–307PubMedGoogle Scholar
  85. 85.
    Skripak JM, Nash SD, Rowley H, Brereton NH, Oh S, Hamilton RG, Matsui EC, Burks AW, Wood RA (2008) A randomized, double-blind, placebo-controlled study of milk oral immunotherapy for cow’s milk allergy. J Allergy Clin Immunol 122(6):1154–1160. CrossRefPubMedPubMedCentralGoogle Scholar
  86. 86.
    Ibanez MD, Escudero C, Sanchez-Garcia S, Rodriguez del Rio P (2015) Comprehensive review of current knowledge on egg oral immunotherapy. J Investig Allergol Clin Immunol 25(5):316–328 quiz 312 p following 328PubMedGoogle Scholar
  87. 87.
    Romantsik O, Bruschettini M, Tosca MA, Zappettini S, Della Casa Alberighi O, Calevo MG (2014) Oral and sublingual immunotherapy for egg allergy. Cochrane Database Syst Rev 11:Cd010638. CrossRefGoogle Scholar
  88. 88.
    Graham F, Tardio N, Paradis L, Des Roches A, Begin P (2017) Update on oral immunotherapy for egg allergy. Hum Vaccin Immunother 13(10):2452–2461. CrossRefPubMedPubMedCentralGoogle Scholar
  89. 89.
    Morisset M, Moneret-Vautrin DA, Guenard L, Cuny JM, Frentz P, Hatahet R, Hanss C, Beaudouin E, Petit N, Kanny G (2007) Oral desensitization in children with milk and egg allergies obtains recovery in a significant proportion of cases. A randomized study in 60 children with cow's milk allergy and 90 children with egg allergy. Eur Ann Allergy Clin Immunol 39(1):12–19PubMedGoogle Scholar
  90. 90.
    Giavi S, Vissers YM, Muraro A, Lauener R, Konstantinopoulos AP, Mercenier A, Wermeille A, Lazzarotto F, Frei R, Bonaguro R, Summermatter S, Nutten S, Papadopoulos NG (2016) Oral immunotherapy with low allergenic hydrolysed egg in egg allergic children. Allergy 71(11):1575–1584. CrossRefPubMedGoogle Scholar
  91. 91.
    Moran TP, Burks AW (2015) Is clinical tolerance possible after allergen immunotherapy? Curr Allergy Asthma Rep 15(5):23. CrossRefPubMedPubMedCentralGoogle Scholar
  92. 92.
    Staden U, Rolinck-Werninghaus C, Brewe F, Wahn U, Niggemann B, Beyer K (2007) Specific oral tolerance induction in food allergy in children: efficacy and clinical patterns of reaction. Allergy 62(11):1261–1269. CrossRefPubMedGoogle Scholar
  93. 93.
    Buchanan AD, Green TD, Jones SM, Scurlock AM, Christie L, Althage KA, Steele PH, Pons L, Helm RM, Lee LA, Burks AW (2007) Egg oral immunotherapy in nonanaphylactic children with egg allergy. J Allergy Clin Immunol 119(1):199–205. CrossRefPubMedGoogle Scholar
  94. 94.
    Vickery BP, Pons L, Kulis M, Steele P, Jones SM, Burks AW (2010) Individualized IgE-based dosing of egg oral immunotherapy and the development of tolerance. Ann Allergy Asthma Immunol 105(6):444–450. CrossRefPubMedPubMedCentralGoogle Scholar
  95. 95.
    Liu T, Navarro S, Lopata AL (2016) Current advances of murine models for food allergy. Mol Immunol 70:104–117. CrossRefPubMedGoogle Scholar
  96. 96.
    Nowak-Wegrzyn AH, Strong BD, Ananos D, Sampson HA (2014) Long term follow up of children who incorporated extensively heated (baked milk) in the diet. J Allergy Clin Immunol 133(2):AB107. CrossRefGoogle Scholar
  97. 97.
    Amat F, Kouche C, Gaspard W, Lemoine A, Guiddir T, Lambert N, Zakariya M, Ridray C, Nemni A, Saint-Pierre P, Deschildre A, Couderc R, Just J (2017) Is a slow-progression baked milk protocol of oral immunotherapy always a safe option for children with cow’s milk allergy? A randomized controlled trial. Clin Exp Allergy 47(11):1491–1496. CrossRefPubMedGoogle Scholar
  98. 98.
    Lambert R, Grimshaw KEC, Ellis B, Jaitly J, Roberts G (2017) Evidence that eating baked egg or milk influences egg or milk allergy resolution: a systematic review. Clin Exp Allergy 47(6):829–837. CrossRefPubMedGoogle Scholar
  99. 99.
    Martos G, Lopez-Exposito I, Bencharitiwong R, Berin MC, Nowak-Wegrzyn A (2011) Mechanisms underlying differential food allergy response to heated egg. J Allergy Clin Immunol 127(4):990–997.e991-992. CrossRefPubMedPubMedCentralGoogle Scholar
  100. 100.
    Leonard SA, Martos G, Wang W, Nowak-Wegrzyn A, Berin MC (2012) Oral immunotherapy induces local protective mechanisms in the gastrointestinal mucosa. J Allergy Clin Immunol 129(6):1579–1587.e1. CrossRefPubMedPubMedCentralGoogle Scholar
  101. 101.
    Jimenez-Saiz R, Rupa P, Mine Y (2011) Immunomodulatory effects of heated ovomucoid-depleted egg white in a BALB/c mouse model of egg allergy. J Agric Food Chem 59(24):13195–13202. CrossRefPubMedGoogle Scholar
  102. 102.
    Konstantinou GN, Giavi S, Kalobatsou A, Vassilopoulou E, Douladiris N, Saxoni-Papageorgiou P, Papadopoulos NG (2008) Consumption of heat-treated egg by children allergic or sensitized to egg can affect the natural course of egg allergy: hypothesis-generating observations. In: J Allergy Clin Immunol, vol 122 vol 2 United States, pp 414–415. CrossRefGoogle Scholar
  103. 103.
    Allen CW, Kemp AS, Campbell DE (2009) Dietary advice, dietary adherence and the acquisition of tolerance in egg-allergic children: a 5-yr follow-up. Pediatr Allergy Immunol 20(3):213–218. CrossRefPubMedGoogle Scholar
  104. 104.
    Tey D, Dharmage SC, Robinson MN, Allen KJ, Gurrin LC, Tang ML (2012) Frequent baked egg ingestion was not associated with change in rate of decline in egg skin prick test in children with challenge confirmed egg allergy. Clin Exp Allergy 42(12):1782–1790. CrossRefPubMedGoogle Scholar
  105. 105.
    Peters RL, Dharmage SC, Gurrin LC, Koplin JJ, Ponsonby AL, Lowe AJ, Tang ML, Tey D, Robinson M, Hill D, Czech H, Thiele L, Osborne NJ, Allen KJ (2014) 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 133(2):485–491. CrossRefPubMedPubMedCentralGoogle Scholar
  106. 106.
    Saifi M, Clark A, Arneson A, Feldman M, Bird JA (2015) Baked egg oral immunotherapy (OIT) for baked egg (BE) allergic children. J Allergy Clin Immunol 135(2):AB26. CrossRefGoogle Scholar
  107. 107.
    Dorman SM, Clark A, Bird JA (2016) Baked egg oral immunotherapy (OIT) accelerates desensitization to unbaked egg (UBE) in severely egg allergic children. J Allergy Clin Immunol 137(2):AB142. CrossRefGoogle Scholar
  108. 108.
    Bravin K, Luyt D (2016) Home-based oral immunotherapy with a baked egg protocol. J Investig Allergol Clin Immunol 26(1):61–63PubMedGoogle Scholar
  109. 109.
    Urisu A, Yamada K, Tokuda R, Ando H, Wada E, Kondo Y, Morita Y (1999) Clinical significance of IgE-binding activity to enzymatic digests of ovomucoid in the diagnosis and the prediction of the outgrowing of egg white hypersensitivity. Int Arch Allergy Immunol 120(3):192–198CrossRefGoogle Scholar
  110. 110.
    Jarvinen KM, Beyer K, Vila L, Bardina L, Mishoe M, Sampson HA (2007) Specificity of IgE antibodies to sequential epitopes of hen’s egg ovomucoid as a marker for persistence of egg allergy. Allergy 62(7):758–765. CrossRefPubMedGoogle Scholar
  111. 111.
    Cooke SK, Sampson HA (1997) Allergenic properties of ovomucoid in man. J Immunol 159(4):2026–2032PubMedGoogle Scholar
  112. 112.
    David TJ (1984) Anaphylactic shock during elimination diets for severe atopic eczema. Arch Dis Child 59(10):983–986. CrossRefPubMedPubMedCentralGoogle Scholar
  113. 113.
    Flinterman AE, Knulst AC, Meijer Y, Bruijnzeel-Koomen CA, Pasmans SG (2006) Acute allergic reactions in children with AEDS after prolonged cow’s milk elimination diets. Allergy 61(3):370–374. CrossRefPubMedGoogle Scholar
  114. 114.
    Barbi E, Gerarduzzi T, Longo G, Ventura A (2004) Fatal allergy as a possible consequence of long-term elimination diet. Allergy 59(6):668–669. CrossRefPubMedGoogle Scholar
  115. 115.
    Chang A, Robison R, Cai M, Singh AM (2016) Natural history of food-triggered atopic dermatitis and development of immediate reactions in children. J Allergy Clin Immunol Pract 4(2):229–236 e221. CrossRefPubMedGoogle Scholar
  116. 116.
    Du Toit G, Roberts G, Sayre PH, Bahnson HT, Radulovic S, Santos AF, Brough HA, Phippard D, Basting M, Feeney M, Turcanu V, Sever ML, Gomez Lorenzo M, Plaut M, Lack G, Team LS (2015) Randomized trial of peanut consumption in infants at risk for peanut allergy. N Engl J Med 372(9):803–813. CrossRefPubMedPubMedCentralGoogle Scholar
  117. 117.
    Gupta M, Sicherer SH (2017) Timing of food introduction and atopy prevention. Clin Dermatol 35(4):398–405. CrossRefPubMedGoogle Scholar
  118. 118.
    Ierodiakonou D, Garcia-Larsen V, Logan A, Groome A, Cunha S, Chivinge J, Robinson Z, Geoghegan N, Jarrold K, Reeves T, Tagiyeva-Milne N, Nurmatov U, Trivella M, Leonardi-Bee J, Boyle RJ (2016) Timing of allergenic food introduction to the infant diet and risk of allergic or autoimmune disease: a systematic review and meta-analysis. JAMA 316(11):1181–1192. CrossRefPubMedGoogle Scholar
  119. 119.
    Palmer DJ, Metcalfe J, Makrides M, Gold MS, Quinn P, West CE, Loh R, Prescott SL (2013) Early regular egg exposure in infants with eczema: a randomized controlled trial. J Allergy Clin Immunol 132(2):387–392 e381. CrossRefPubMedGoogle Scholar
  120. 120.
    Koplin JJ, Osborne NJ, Wake M, Martin PE, Gurrin LC, Robinson MN, Tey D, Slaa M, Thiele L, Miles L, Anderson D, Tan T, Dang TD, Hill DJ, Lowe AJ, Matheson MC, Ponsonby AL, Tang ML, Dharmage SC, Allen KJ (2010) Can early introduction of egg prevent egg allergy in infants? A population-based study. J Allergy Clin Immunol 126(4):807–813. CrossRefPubMedGoogle Scholar
  121. 121.
    Natsume O, Kabashima S, Nakazato J, Yamamoto-Hanada K, Narita M, Kondo M, Saito M, Kishino A, Takimoto T, Inoue E, Tang J, Kido H, Wong GW, Matsumoto K, Saito H, Ohya Y, Team PS (2017) Two-step egg introduction for prevention of egg allergy in high-risk infants with eczema (PETIT): a randomised, double-blind, placebo-controlled trial. Lancet (London, England) 389(10066):276–286. CrossRefGoogle Scholar
  122. 122.
    Molina-Infante J, Gonzalez-Cordero PL, Arias A, Lucendo AJ (2017) Update on dietary therapy for eosinophilic esophagitis in children and adults. Expert Rev Gastroenterol Hepatol 11(2):115–123. CrossRefPubMedGoogle Scholar
  123. 123.
    Dellon ES, Gonsalves N, Hirano I, Furuta GT, Liacouras CA, Katzka DA, American College of G (2013) ACG clinical guideline: evidenced based approach to the diagnosis and management of esophageal eosinophilia and eosinophilic esophagitis (EoE). Am J Gastroenterol 108(5):679–692; quiz 693. CrossRefPubMedGoogle Scholar
  124. 124.
    Hill DA, Shuker M, Cianferoni A, Wong T, Ruchelli E, Spergel JM, Brown-Whitehorn TF (2015) The development of IgE-mediated immediate hypersensitivity after the diagnosis of eosinophilic esophagitis to the same food. J Allergy Clin Immunol Pract 3(1):123–124. CrossRefPubMedGoogle Scholar
  125. 125.
    Alsalamah M, Makhija M, Somers G, Marcon M, Hummel D, Upton J (2016) Anaphylaxis to milk after elimination diet for eosinophilic gastrointestinal disease. Am J Gastroenterol 111(5):752–753. CrossRefGoogle Scholar
  126. 126.
    Soller L, Mill C, Avinashi V, Teoh T, Chan ES (2017) Development of anaphylactic cow’s milk allergy following cow’s milk elimination for eosinophilic esophagitis in a teenager. J Allergy Clin Immunol Pract 5(5):1413–1414. CrossRefPubMedGoogle Scholar
  127. 127.
    Fiocchi A, Brozek J, Schunemann H, Bahna SL, von Berg A, Beyer K, Bozzola M, Bradsher J, Compalati E, Ebisawa M, Guzman MA, Li H, Heine RG, Keith P, Lack G, Landi M, Martelli A, Rance F, Sampson H, Stein A, Terracciano L, Vieths S, World Allergy Organization Special Committee on Food A (2010) World Allergy Organization (WAO) Diagnosis and Rationale for Action against Cow’s Milk Allergy (DRACMA) guidelines. Pediatr Allergy Immunol 21(Suppl 21):1–125. CrossRefPubMedGoogle Scholar
  128. 128.
    Jarvinen KM, Nowak-Wegrzyn A (2013) Food protein-induced enterocolitis syndrome (FPIES): current management strategies and review of the literature. J Allergy Clin Immunol Pract 1(4):317–322. CrossRefPubMedGoogle Scholar
  129. 129.
    Caubet JC, Ford LS, Sickles L, Jarvinen KM, Sicherer SH, Sampson HA, Nowak-Wegrzyn A (2014) Clinical features and resolution of food protein-induced enterocolitis syndrome: 10-year experience. J Allergy Clin Immunol 134(2):382–389. CrossRefPubMedGoogle Scholar

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© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Division of Clinical Immunology and Allergy, Department of Pediatrics, Hospital for Sick ChildrenUniversity of TorontoTorontoCanada
  2. 2.Jaffe Food Allergy Institute, Department of Pediatrics, Division of Allergy and ImmunologyIcahn School of Medicine at Mount SinaiNew YorkUSA

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