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Evidence Gaps in Oral Immunotherapy for Food Allergy

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

Abstract

Purpose of review

Purpose of review IgE-mediated food allergy (FA) is a potentially life-threatening condition with negative impact on the quality of life of patients and their family. It has been emerging as a public health priority in westernized countries in the recent two decades. The current standard approach to FA consists of the strict avoidance of the triggering food and keeping rescue medication readily available in the event an allergic reaction occurs. However, an elimination diet may be difficult and frustrating, above all for those foods (e.g., milk and egg) that are pivotal in the common diet.

Recent findings

Recent findings Oral immunotherapy (OIT) may increase the amount of food that the patient can intake without reaction, and reduce the risk of potential life-threatening allergic reactions As its enormous potential, OIT is currently considered the most promising treatment for FA. However, many gaps are still unsolved. OIT is logistically demanding, time-consuming, and most patients are affected by side effects though often mild.

Summary

Summary The aim of this review is to shed light on the main needs in OIT that are currently unmet in order to stimulate in the near future the development of longitudinal, prospective, well-designed studies with the final goal of a “precision medicine”, tailored on each single patient suffering from FA.

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References and Recommended Reading

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

  1. Gupta RS, Springston EE, Warrier MR, Smith B, Kumar R, Pongracic J, et al. The prevalence, severity, and distribution of childhood food allergy in the United States. Pediatrics. 2011;128:e9–17.

    Article  PubMed  Google Scholar 

  2. Sicherer SH, Sampson HA. Food allergy: epidemiology, pathogenesis, diagnosis, and treatment. J Allergy Clin Immunol. 2014;133:291–307.

    Article  CAS  PubMed  Google Scholar 

  3. Rona RJ, Keil T, Summers C, Gislason D, Zuidmeer L, Sodergren E, et al. The prevalence of food allergy: a meta-analysis. J Allergy Clin Immunol. 2007;120:638–46.

    Article  PubMed  Google Scholar 

  4. Cummings AJ, Knibb RC, King RM, Lucas JS. The psychosocial impact of food allergy and food hypersensitivity in children, adolescents and their families: a review. Allergy. 2010;65:933–45.

    Article  CAS  PubMed  Google Scholar 

  5. Lieberman JA, Sicherer SH. Quality of life in food allergy. Curr Opin Allergy Clin Immunol. 2011;11:236–42.

    Article  CAS  PubMed  Google Scholar 

  6. Savage JH, et al. The natural history of egg allergy. J Allergy Clin Immunol. 2007;120:1413–7.

    Article  CAS  PubMed  Google Scholar 

  7. Skripak JM, Matsui EC, Mudd K, Wood RA. The natural history of IgE-mediated cow’s milk allergy. J Allergy Clin Immunol. 2007;120:1172–7.

    Article  CAS  PubMed  Google Scholar 

  8. Wood RA, Sicherer SH, Vickery BP, Jones SM, Liu AH, Fleischer DA, et al. The natural history of milk allergy in an observational cohort. J Allergy Clin Immunol. 2013;131:805–12.

    Article  CAS  PubMed  Google Scholar 

  9. Sicherer SH, Wood RA, Vickery BP, Jones SM, Liu AH, Fleischer DM, et al. The natural history of egg allergy in an observational cohort. J Allergy Clin Immunol. 2014;133:492–9.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Keet CA, Matsui EC, Dhillon G, Lenehan P, Paterakis M, Wood RA. The natural history of wheat allergy. Ann Allergy Asthma Immunol. 2009;102:410–5.

    Article  CAS  PubMed  Google Scholar 

  11. Savage JH, Kaeding AJ, Matsui EC, Wood RA. The natural history of soy allergy. J Allergy Clin Immunol. 2010;125:683–6.

    Article  CAS  PubMed  Google Scholar 

  12. Skolnick HS, Conover-Walker MK, Koerner CB, Sampson HA, Burks W, Wood RA. The natural history of peanut allergy. J Allergy Clin Immunol. 2001;107:367–74.

    Article  CAS  PubMed  Google Scholar 

  13. Fleischer DM, Conover-Walker MK, Matsui EC, Wood RA. The natural history of tree nut allergy. J Allergy Clin Immunol. 2005;116:1087–93.

    Article  CAS  PubMed  Google Scholar 

  14. Bock SA, Munoz-Furlong A, Sampson HA. Fatalities due to anaphylactic reactions to foods. J Allergy Clin Immunol. 2001;107:191–3.

    Article  CAS  PubMed  Google Scholar 

  15. Bock SA, Munoz-Furlong A, Sampson HA. Further fatalities caused by anaphylactic reactions to food, 2001–2006. J Allergy Clin Immunol. 2007;119:1016–8.

    Article  PubMed  Google Scholar 

  16. •• Muraro A, Werfel T, Hoffmann-Sommergruber K, Roberts G, Beyer K, Bindslev-Jensen C, et al., EAACI Food Allergy and Anaphylaxis Guidelines Group. EAACI food allergy and anaphylaxis guidelines: diagnosis and management of food allergy. Allergy. 2014;69:1008–25. The guidelines of the European Academy of Allergy and Clinical Immunology (EAACI) on the recognition, assessment, and management of food allergy and anaphylaxis.

    Article  CAS  PubMed  Google Scholar 

  17. 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;134:1016–25. e43.

    Article  PubMed  Google Scholar 

  18. Ford LS, Taylor SL, Pacenza R, Niemann LM, Lambrecht DM, Sicherer SH. Food allergen advisory labeling and product contamination with egg, milk, and peanut. J Allergy Clin Immunol. 2010;126:384–5.

    Article  PubMed  Google Scholar 

  19. Boyano-Martínez T, García-Ara C, Pedrosa M, Díaz-Pena JM, Quirce S. Accidental allergic reactions in children allergic to cow's milk proteins. J Allergy Clin Immunol. 2009;123:883–8.

    Article  PubMed  Google Scholar 

  20. Schofield AT. A case of egg poisoning. Lancet. 1908;1:716.

    Article  Google Scholar 

  21. •• 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. https://doi.org/10.1111/all.13124. Updated systematic review and meta-analysis conducted by EAACI and assessing the current evidence base in relation to evaluating food allergen immunotherapy for the treatment of food allergy.

  22. Caminiti L, Pajno GB, Crisafulli G, Chiera F, Collura M, Panasci G, et al. Oral immunotherapy for egg allergy: a double blind placebo controlled study, with postdesensitization follow-up. J Allergy Clin Immunol Pract. 2015;3:532–9.

    Article  PubMed  Google Scholar 

  23. Leonard SA. Baked egg and milk exposure as immunotherapy in food allergy. Curr Allergy Asthma Rep. 2016;16:32.

    Article  PubMed  Google Scholar 

  24. 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;26:509–21.

    Article  PubMed  Google Scholar 

  25. Escudero C, del Rio PR, Sanchez-Garcia S, Perez-Rangel I, Perez-Farinos N, Garcia-Fernandez C, et al. Early sustained unresponsiveness after short-course egg oral immunotherapy: a randomized controlled study in egg-allergic children. Clin Exp Allergy. 2015;45:1833–43.

    Article  CAS  PubMed  Google Scholar 

  26. Verhoeckx KC, Vissers YM, Baumert JL, Faludi R, Feys M, Flanagan S, et al. Food processing and allergenicity. Food Chem Toxicol. 2015;80:223–40.

    Article  CAS  PubMed  Google Scholar 

  27. Burks AW, Jones SM, Wood RA, Fleischer DM, Sicherer SH, Lindblad RW, et al. Oral immunotherapy for treatment of egg allergy in children. N Engl J Med. 2012;367:233–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Longo G, Barbi E, Berti I, Meneghetti R, Pittalis A, Ronfani L, et al. Specific oral tolerance induction in children with very severe cow's milk-induced reactions. J Allergy Clin Immunol. 2008;121:343–7.

    Article  CAS  PubMed  Google Scholar 

  29. Vickery BP, Berglund JP, Burk CM, Fine JP, Kim EH, Kim JI, et al. Early oral immunotherapy in peanut-allergic preschool children is safe and highly effective. J Allergy Clin Immunol. 2017;139:173–81.

    Article  CAS  PubMed  Google Scholar 

  30. Barbi E, Longo G, Berti I, Neri E, Saccari A, Rubert L, et al. Adverse effects during specific oral tolerance induction: in-hospital "rush" phase. Eur Ann Allergy Clin Immunol. 2012;44:18–25.

    CAS  PubMed  Google Scholar 

  31. Pajno GB, Caminiti L, Salzano G, Crisafulli G, Aversa T, Messina MF, et al. Comparison between two maintenance feeding regimens after successful cow's milk oral desensitization. Pediatr Allergy Immunol. 2013;24:376–81.

    Article  PubMed  Google Scholar 

  32. Anagnostou K, Islam S, King Y, Foley L, Pasea L, Bond S, et al. Assessing the efficacy of oral immunotherapy for the desensitisation of peanut allergy in children (STOP II): a phase 2 randomised controlled trial. Lancet. 2014;383:1297–304.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Tang MLK, Ponsonby AL, Orsini F, Tey D, Robinson M, Su EL, et al. Administration of a probiotic with peanut oral immunotherapy: a randomized trial. J Allergy Clin Immunol. 2015;135:737–44.

    Article  CAS  PubMed  Google Scholar 

  34. Varshney P, Jones SM, Scurlock AM, Perry TT, Kemper A, Steele P, et al. A randomized controlled study of peanut oral immunotherapy: clinical desensitization and modulation of the allergic response. J Allergy Clin Immunol. 2011;127:654–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Narisety SD, Frischmeyer-Guerrerio PA, Keet CA, Gorelik M, Schroeder J, Hamilton RG, et al. A randomized, double-blind, placebo-controlled pilot study of sublingual versus oral immunotherapy for the treatment of peanut allergy. J Allergy Clin Immunol. 2015;135:1275–82.e1-6.

    Article  CAS  PubMed  Google Scholar 

  36. 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;62:1261–9.

    Article  CAS  PubMed  Google Scholar 

  37. Vickery BP, Scurlock AM, Kulis M, Steele PH, Kamilaris J, Berglund JP, et al. Sustained unresponsiveness to peanut in subjects who have completed peanut oral immunotherapy. J Allergy Clin Immunol. 2014;133:468–75.

    Article  CAS  PubMed  Google Scholar 

  38. Jones SM, Burks AW, Keet C, Vickery BP, Scurlock AM, Wood RA, et al. Long-term treatment with egg oral immunotherapy enhances sustained unresponsiveness that persists after cessation of therapy. J Allergy Clin Immunol. 2016;137:1117–27.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. • Pajno GB, Nadeau KC, Passalacqua G, Caminiti L, Hobson B, Jay DC, et al. The evolution of allergen and non-specific immunotherapy: past achievements, current applications and future outlook. Expert Rev Clin Immunol. 2015;11:141–54. This is a detailed report describing the evolution of allergen and non-specific immunotherapy over time, looking at the future perspectives in the treatment of allergic diseases.

    Article  CAS  PubMed  Google Scholar 

  40. Pajno GB, Caminiti L, Chiera F, Crisafulli G, Salzano G, Arasi S, et al. Safety profile of oral immunotherapy with cow's milk and hen egg: a 10-year experience in controlled trials. Allergy Asthma Proc. 2016;37:400–3.

    Article  PubMed  Google Scholar 

  41. Vázquez-Ortiz M, Alvaro-Lozano M, Alsina L, Garcia-Paba MB, Piquer-Gibert M, Giner-Muñoz MT, et al. Safety and predictors of adverse events during oral immunotherapy for milk allergy: severity of reaction at oral challenge, specific IgE and prick test. Clin Exp Allergy. 2013;43:92–102.

    Article  PubMed  Google Scholar 

  42. Wood RA, Kim JS, Lindblad R, Nadeau K, Henning AK, Dawson P, et al. A randomized, double-blind, placebo-controlled study of omalizumab combined with oral immunotherapy for the treatment of cow's milk allergy. J Allergy Clin Immunol. 2016;137:1103–10.

    Article  CAS  PubMed  Google Scholar 

  43. MacGinnitie AJ, Rachid R, Gragg H, Little SV, Lakin P, Cianferoni A, et al. Omalizumab facilitates rapid oral desensitization for peanut allergy. J Allergy Clin Immunol. 2016;137(2):AB194.

    Article  Google Scholar 

  44. Bégin P, Dominguez T, Wilson SP, Bacal L, Mehrotra A, Kausch B, et al. Phase 1 results of safety and tolerability in a rush oral immunotherapy protocol to multiple foods using omalizumab. Allergy Asthma Clin Immunol. 2014;10:7.

    Article  PubMed  PubMed Central  Google Scholar 

  45. Wood RA, Sicherer SH, Burks AW, Grishin A, Henning AK, Lindblad R, et al. A phase 1 study of heat/phenol-killed, E. coli-encapsulated, recombinant modified peanut proteins Ara h 1, Ara h 2, and Ara h 3 (EMP-123) for the treatment of peanut allergy. Allergy. 2013;68:803–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Gupta RS, Springston EE, Smith B, Kim JS, Pongracic JA, Wang X, et al. Food allergy knowledge, attitudes, and beliefs of parents with food-allergic children in the United States. Pediatr Allergy Immunol. 2010;21:927–34.

    Article  PubMed  Google Scholar 

  47. Gupta R, Holdford D, Bilaver L, Dyer A, Holl JL, Meltzer D. The economic impact of childhood food allergy in the United States. JAMA Pediatr. 2013;167:1026–31.

    Article  PubMed  Google Scholar 

  48. Arasi S, Otani IM, Klingbeil E, Bégin P, Kearney C, Dominguez TL, et al. Two year effects of food allergen immunotherapy on quality of life in caregivers of children with food allergies. Allergy Asthma Clin Immunol. 2014;10:57.

    Article  PubMed  PubMed Central  Google Scholar 

  49. Keet CA, Frischmeyer-Guerrerio PA, Thyagarajan A, Schroeder JT, Hamilton RG, Boden S, et al. The safety and efficacy of sublingual and oral immunotherapy for milk allergy. J Allergy Clin Immunol. 2012;129:448–55. 55, e1–5

  50. Syed A, Garcia MA, Lyu SC, Bucayu R, Kohli A, Ishida S, et al. Peanut oral immunotherapy results in increased antigen-induced regulatory T-cell function and hypomethylation of forkhead box protein 3 (FOXP3). J Allergy Clin Immunol. 2014;133:500–10. e11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Jones SM, Pons L, Roberts JL, Scurlock AM, Perry TT, Kulis M, et al. Clinical efficacy and immune regulation with peanut oral immunotherapy. J Allergy Clin Immunol. 2009;124:292–300. e1-97

  52. Akdis M, Verhagen J, Taylor A, Karamloo F, Karagiannidis C, Crameri R, et al. Immune responses in healthy and allergic individuals are characterized by a fine balance between allergen-specific T regulatory 1 and T helper 2 cells. J Exp Med. 2004;199:1567–75.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Smaldini PL, Delgado MLO, Fossati CA, Docena GH. Orally-induced intestinal CD4+ CD25+ FoxP3+ Treg controlled undesired responses towards oral antigens and effectively dampened food allergic reactions. PLoS One. 2015;10:e0141116.

    Article  PubMed  PubMed Central  Google Scholar 

  54. Aslam A, Chan H, Warrell DA, Misbah S, Ogg GS. Tracking antigen-specific T-cells during clinical tolerance induction in humans. PLoS One. 2010;5:e11028.

    Article  PubMed  PubMed Central  Google Scholar 

  55. Vickery BP, Lin J, Kulis M, Fu Z, Steele PH, Jones SM, et al. Peanut oral immunotherapy modifies IgE and IgG 4 responses to major peanut allergens. J Allergy Clin Immunol. 2013;131:128–34. e3.

    Article  CAS  PubMed  Google Scholar 

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Correspondence to Stefania Arasi MD, PhD.

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Stefania Arasi declares that she has no conflict of interest.

Giovanni Pajno declares that he has no conflict of interest.

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

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This article is part of the Topical Collection on Food Allergy

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Arasi, S., Pajno, G.B. Evidence Gaps in Oral Immunotherapy for Food Allergy. Curr Treat Options Allergy 4, 458–467 (2017). https://doi.org/10.1007/s40521-017-0146-0

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