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image of Oral Immunotherapy with the Rush Method in Patients with Egg White Allergy: A Randomized, Double Blind, Clinical Trial

Abstract

Introduction

The sole approved treatment for egg allergy is abstaining from consuming eggs. We assessed the effectiveness of oral immunotherapy (OIT) utilizing egg-white powder to treat egg allergy in children.

Methods

This is a randomized clinical trial on patients with egg white allergy. A desensitization protocol for egg allergies involves a modify rush desensitization method with a build-up and maintenance phase. During the build-up phase, patients consume increasing doses of egg white powder mixed with mashed potatoes for 5-7 days until they can tolerate a whole egg white. During the maintenance phase, patients consume a daily intake of whole cooked egg whites for six months. After two weeks of abstinence, a food challenge test is administered to determine if the patient has developed tolerance.

Results

Thirty-two patients aged 4-7 years with egg white hypersensitivity were recruited. Sixteen participants were in the intervention group, and 16 were in the control group. The intervention group had the highest number of anaphylaxis reactions on day one. During the build-up phase, all patients in the intervention group experienced 60 responses, with skin reactions being the most common. In the maintenance phase, patients were prescribed medications to ensure the success of desensitization. After six months, the intervention group demonstrated a higher tolerance rate for egg whites compared to the control group. Before OIT, the levels of total immunoglobulin E (IgE), serum immunoglobulin G4 (IgG4), and Radioallergosorbent Test (ImmunoCAP RAST) were similar between the intervention and control groups. After OIT, the level of IgG4 increased in the intervention group and decreased in the control group. ImmunoCap RAST increased in both groups, but significantly more in the intervention group. Skin Prick Test (SPT) wheal decreased significantly in the intervention group but not in the control group. The size of the SPT flare significantly decreased in the intervention group but remained the same in the control group.

Conclusion

OIT is adequate for most children with egg allergies. It is a promising intervention for food allergies, but the mechanism underlying its efficacy remains unclear. A better understanding of risks and effective dosing schedules is needed for it to become a recommended standard of care. Long-term immune tolerance strategies are also critical.

Clinical Trial Number

(No. IRCT20190116038387N1).

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/content/journals/raiad/10.2174/0127722708380059251111100817
2026-01-22
2026-03-02
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References

  1. Sampson H.A. O’Mahony L. Burks A.W. Plaut M. Lack G. Akdis C.A. Mechanisms of food allergy. J. Allergy Clin. Immunol. 2018 141 1 11 19 10.1016/j.jaci.2017.11.005 29307410
    [Google Scholar]
  2. Nwaru B.I. Hickstein L. Panesar S.S. Roberts G. Muraro A. Sheikh A. Prevalence of common food allergies in Europe: A systematic review and meta-analysis. Allergy 2014 69 8 992 1007 10.1111/all.12423 24816523
    [Google Scholar]
  3. Savage J. Sicherer S. Wood R. The natural history of food allergy. J. Allergy Clin. Immunol. Pract. 2016 4 2 196 203 10.1016/j.jaip.2015.11.024 26968958
    [Google Scholar]
  4. Sicherer S.H. Sampson H.A. Food allergy: A review and update on epidemiology, pathogenesis, diagnosis, prevention, and management. J. Allergy Clin. Immunol. 2018 141 1 41 58 10.1016/j.jaci.2017.11.003 29157945
    [Google Scholar]
  5. Savage J. Johns C.B. Food allergy: Epidemiology and natural history. Immunol. Allergy Clin. North Am. 2015 35 1 45 59 10.1016/j.iac.2014.09.004 25459576
    [Google Scholar]
  6. Spolidoro G.C.I. Ali M.M. Amera Y.T. Prevalence estimates of eight big food allergies in Europe: Updated systematic review and meta‐analysis. Allergy 2023 78 9 2361 2417 10.1111/all.15801 37405695
    [Google Scholar]
  7. Engel M.L. Warren C.M. Herbert L.J. Pappalardo A.A. Ramos A. Gupta R.S. The psychosocial burden of pediatric food allergy in the United States: A population based survey. J. Allergy Clin. Immunol. Pract. 2025 13 3 630 638.e4 10.1016/j.jaip.2024.12.007 39701275
    [Google Scholar]
  8. Lodge C.J. Waidyatillake N. Peters R.L. Efficacy and safety of oral immunotherapy for peanut, cow’s milk, and hen’s egg allergy: A systematic review of randomized controlled trials. Clin. Transl. Allergy 2023 13 7 12268 10.1002/clt2.12268 37488726
    [Google Scholar]
  9. Pouessel G. Lezmi G. Oral immunotherapy for food allergy: Translation from studies to clinical practice? World Allergy Organ. J. 2023 16 2 100747 10.1016/j.waojou.2023.100747 36816599
    [Google Scholar]
  10. Palosuo K. Karisola P. Savinko T. Fyhrquist N. Alenius H. Mäkelä M.J. A randomized, open label trial of hen’s egg oral immunotherapy: Efficacy and humoral immune responses in 50 children. J. Allergy Clin. Immunol. Pract. 2021 9 5 1892 1901.e1 10.1016/j.jaip.2021.01.020 33529723
    [Google Scholar]
  11. Sasamoto K. Yanagida N. Nagakura K. Nishino M. Sato S. Ebisawa M. Long-term outcomes of oral immunotherapy for anaphylactic egg allergy in children. J. Allergy Clin. Immunol. Glob. 2022 1 3 138 144 10.1016/j.jacig.2022.03.005 37781271
    [Google Scholar]
  12. Barshow S. Tirumalasetty J. Sampath V. The immunobiology and treatment of food allergy. Annu. Rev. Immunol. 2024 42 1 401 425 10.1146/annurev‑immunol‑090122‑043501 38360544
    [Google Scholar]
  13. Skripak J.M. Nash S.D. Rowley H. A randomized, double-blind, placebo-controlled study of milk oral immunotherapy for cow’s milk allergy. J. Allergy Clin. Immunol. 2008 122 6 1154 1160 10.1016/j.jaci.2008.09.030 18951617
    [Google Scholar]
  14. Blumchen K. Ulbricht H. Staden U. Oral peanut immunotherapy in children with peanut anaphylaxis. J. Allergy Clin. Immunol. 2010 126 1 83 91.e1 10.1016/j.jaci.2010.04.030 20542324
    [Google Scholar]
  15. Keet C.A. Frischmeyer Guerrerio P.A. Thyagarajan A. The safety and efficacy of sublingual and oral immunotherapy for milk allergy. J. Allergy Clin. Immunol. 2012 129 2 448 455 10.1016/j.jaci.2011.10.023 22130425
    [Google Scholar]
  16. Romantsik O. Tosca M.A. Zappettini S. Calevo M.G. Oral and sublingual immunotherapy for egg allergy. Cochrane Libr. 2018 2018 4 CD010638 10.1002/14651858.CD010638.pub3 29676439
    [Google Scholar]
  17. Schulz K.F. Altman D.G. Moher D. CONSORT 2010 Statement: Updated guidelines for reporting parallel group randomised trials. BMC Med. 2010 8 1 18 10.1186/1741‑7015‑8‑18 20334633
    [Google Scholar]
  18. Burks A.W. Jones S.M. Wood R.A. Oral immunotherapy for treatment of egg allergy in children. N. Engl. J. Med. 2012 367 3 233 243 10.1056/NEJMoa1200435 22808958
    [Google Scholar]
  19. Santos A.F. Riggioni C. Agache I. EAACI guidelines on the management of IgE‐mediated food allergy. Allergy 2025 80 1 14 36 10.1111/all.16345 39473345
    [Google Scholar]
  20. Protudjer J.L.P. Davis C.M. Gupta R.S. Perry T.T. Social determinants and quality of life in food allergy management and treatment. J. Allergy Clin. Immunol. Pract. 2025 13 4 745 750 10.1016/j.jaip.2025.02.016 40043949
    [Google Scholar]
  21. Drakouli A.E. Kontele I. Poulimeneas D. Food allergies and quality of life among school-aged children and adolescents: A systematic review. Children 2023 10 3 433 10.3390/children10030433 36979991
    [Google Scholar]
  22. Özdemir P.G. Sato S. Yanagida N. Ebisawa M. Oral immunotherapy in food allergy: Where are we now? Allergy Asthma Immunol. Res. 2023 15 2 125 144 10.4168/aair.2023.15.2.125 37021501
    [Google Scholar]
  23. Bégin P. Chan E.S. Kim H. CSACI guidelines for the ethical, evidence-based and patient-oriented clinical practice of oral immunotherapy in IgE-mediated food allergy. Allergy Asthma Clin. Immunol. 2020 16 1 20 10.1186/s13223‑020‑0413‑7 32206067
    [Google Scholar]
  24. Kim S. Ahn K. Kim J. Practical issues of oral immunotherapy for egg or milk allergy. Clin. Exp. Pediatr. 2024 67 3 140 148 10.3345/cep.2023.00234 37350169
    [Google Scholar]
  25. Golden D.B.K. Wang J. Waserman S. Anaphylaxis: A 2023 practice parameter update. Ann. Allergy Asthma Immunol. 2024 132 2 124 176 10.1016/j.anai.2023.09.015 38108678
    [Google Scholar]
  26. McHenry M. Bégin P. Chan E.S. Latrous M. Kim H. Food oral immunotherapy. Allergy Asthma Clin. Immunol. 2025 20 S3 82 10.1186/s13223‑025‑00948‑5 39940042
    [Google Scholar]
  27. Virkud Y.V. Burks A.W. Steele P.H. Novel baseline predictors of adverse events during oral immunotherapy in children with peanut allergy. J. Allergy Clin. Immunol. 2017 139 3 882 888.e5 10.1016/j.jaci.2016.07.030 27609653
    [Google Scholar]
  28. Hofmann A.M. Scurlock A.M. Jones S.M. Safety of a peanut oral immunotherapy protocol in children with peanut allergy. J. Allergy Clin. Immunol. 2009 124 2 286 291 10.1016/j.jaci.2009.03.045 19477496
    [Google Scholar]
  29. Yamashita K. Nakamura T. Imai T. Optimal period for achieving sustained unresponsiveness in peanut oral immunotherapy. Asia Pac. Allergy 2023 13 3 97 104 10.5415/apallergy.0000000000000110 37744963
    [Google Scholar]
  30. Nachshon L. Goldberg M.R. Levy M.B. Epstein-Rigbi N. Koren Y. Elizur A. Home epinephrine-treated reactions in food allergy oral immunotherapy. Ann. Allergy Asthma Immunol. 2021 127 4 451 455.e1 10.1016/j.anai.2021.05.008 34010698
    [Google Scholar]
  31. Khayatzadeh A. Gharaghozlou M. Ebisawa M. Shokouhi Shoormasti R. Movahedi M. A safe and effective method for wheat oral immunotherapy. Iran. J. Allergy Asthma Immunol. 2016 15 6 525 535 28129685
    [Google Scholar]
  32. Vickery B.P. Scurlock A.M. Steele P. Early and persistent gastrointestinal side effects predict withdrawal from peanut oral immunotherapy (OIT). J. Allergy Clin. Immunol. 2011 127 2 AB26 10.1016/j.jaci.2010.12.114
    [Google Scholar]
  33. Nadeau K.C. Schneider L.C. Hoyte L. Borras I. Umetsu D.T. Rapid oral desensitization in combination with omalizumab therapy in patients with cow’s milk allergy. J. Allergy Clin. Immunol. 2011 127 6 1622 1624 10.1016/j.jaci.2011.04.009 21546071
    [Google Scholar]
  34. Keswani T. LaHood N.A. Marini Rapoport O. Neutralizing IgG4 antibodies are a biomarker of sustained efficacy after peanut oral immunotherapy. J. Allergy Clin. Immunol. 2024 153 6 1611 1620.e7 10.1016/j.jaci.2024.02.017 38460677
    [Google Scholar]
  35. LaHood N.A. Min J. Keswani T. Immunotherapy-induced neutralizing antibodies disrupt allergen binding and sustain allergen tolerance in peanut allergy. J. Clin. Invest. 2023 133 2 164501 10.1172/JCI164501 36647835
    [Google Scholar]
  36. Bourgoin-Heck M. Wolff-Goldnadel V. Chantran Y. Molecular allergen sensitization drives phenotypes of severe asthma in children: Evidence from a megacity cohort (SAMP). Pediatr. Allergy Immunol. 2024 35 12 70014 10.1111/pai.70014 39636251
    [Google Scholar]
  37. Martín-Cruz L. Benito-Villalvilla C. Sirvent S. Angelina A. Palomares O. The role of regulatory T cells in allergic diseases: Collegium Internationale Allergologicum (CIA) update 2024. Int. Arch. Allergy Immunol. 2024 185 5 503 518 10.1159/000536335 38408438
    [Google Scholar]
  38. Conrad M.L. Barrientos G. Cai X. Regulatory T cells and their role in allergic disease. Allergy 2025 80 1 77 93 10.1111/all.16326 40497455
    [Google Scholar]
  39. Garcia-Carmona Y. Curotto de Lafaille M.A. Advances in food allergy immunotherapy: Current strategies and role of antibodies isotypes. Cells 2025 14 12 900 10.3390/cells14120900 40558527
    [Google Scholar]
  40. Barshow S.M. Kulis M.D. Burks A.W. Kim E.H. Mechanisms of oral immunotherapy. Clin. Exp. Allergy 2021 51 4 527 535 10.1111/cea.13824 33417257
    [Google Scholar]
  41. Staden U. Rolinck-Werninghaus C. Brewe F. Wahn U. Niggemann B. Beyer K. Specific oral tolerance induction in food allergy in children: Efficacy and clinical patterns of reaction. Allergy 2007 62 11 1261 1269 10.1111/j.1398‑9995.2007.01501.x 17919140
    [Google Scholar]
  42. Ebrahimi M. Gharagozlou M. Khalili A. Magaji Hamid K. Azizi G. Movahedi M. Induction of tolerance by oral immunotherapy in patients with cow’s milk allergy. J. Investig. Allergol. Clin. Immunol. 2016 26 5 341 343 10.18176/jiaci.0094 27763871
    [Google Scholar]
  43. Khalili A. Khayatzadeh A. Ebrahimi M. Rafiemanesh H. Azizi G. Movahedi M. Evaluation of tolerance in patients with type-1 hypersensitivity reaction to wheat after oral immunotherapy. J. Investig. Allergol. Clin. Immunol. 2016 26 5 339 340 10.18176/jiaci.0093 27763870
    [Google Scholar]
  44. Jr A. Bochner B. Burks A.W. Middleton’s Allergy: Principles and Practice. Elsevier 2013
    [Google Scholar]
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  • Article Type:
    Research Article
Keywords: egg ; Oral immunotherapy ; hypersensitivity ; allergy ; immunoglobulin ; skin prick test (SPT)
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