Oral immunotherapy (OIT) is a promising investigational therapy for food allergy. Clinical trials in peanut, milk, egg, and wheat allergy provide evidence that OIT can effectively desensitize a majority of individuals to a food allergen. While a portion of subjects demonstrate sustained unresponsiveness, the majority regain sensitivity with allergen avoidance. The safety and tolerability of OIT continue to limit its use in some patients. Virtually all studies report adverse reactions that are more frequent during dose escalation but may also occur during maintenance therapy. Recent studies have identified adjunctive therapies (such as omalizumab) which may mitigate adverse effects. There is a paucity of data on the long-term safety and efficacy of OIT. Further study is required before OIT is ready for routine clinical practice. This review is intended to provide the reader with an up-to-date understanding of OIT, including its mechanisms, efficacy, safety profile, and potential utility in clinical practice.

1.
Nwaru BI, et al: Prevalence of common food allergies in Europe: a systematic review and meta-analysis. Allergy 2014;69:992-1007.
2.
Sicherer SH, Wood RA: Advances in diagnosing peanut allergy. J Allergy Clin Immunol Pract 2013;1:1-13; quiz 14.
3.
Lieberman JA, Sicherer SH: Quality of life in food allergy. Curr Opin Allergy Clin Immunol 2011;11:236-242.
4.
Versluis A, et al: Frequency, severity and causes of unexpected allergic reactions to food: a systematic literature review. Clin Exp Allergy 2015;45:347-367.
5.
Nowak-Wegrzyn A, Albin S: Oral immunotherapy for food allergy: mechanisms and role in management. Clin Exp Allergy 2015;45:368-383.
6.
Oppenheimer JJ, et al: Treatment of peanut allergy with rush immunotherapy. J Allergy Clin Immunol 1992;90:256-262.
7.
Patriarca G, et al: Oral rush desensitization in peanut allergy: a case report. Dig Dis Sci 2006;51:471-473.
8.
Mansfield L: Successful oral desensitization for systemic peanut allergy. Ann Allergy Asthma Immunol 2006;97:266-267.
9.
Jones SM, et al: Clinical efficacy and immune regulation with peanut oral immunotherapy. J Allergy Clin Immunol 2009;124:292-300, 300 e1-e97.
10.
Vickery BP, et al: SUSU to peanut in subjects who have completed peanut oral immunotherapy. J Allergy Clin Immunol 2014;133:468-475.
11.
Burks AW, et al: Oral immunotherapy for treatment of egg allergy in children. N Engl J Med 2012;367:233-243.
12.
Syed A, 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;133:500-510.
13.
Thyagarajan A, et al: Evidence of pathway-specific basophil anergy induced by peanut oral immunotherapy in peanut-allergic children. Clin Exp Allergy 2012;42:1197-1205.
14.
Vickery BP, et al: Peanut oral immunotherapy modifies IgE and IgG4 responses to major peanut allergens. J Allergy Clin Immunol 2013;131:128-134.e1-e3.
15.
Gorelik M, et al: Suppression of the immunologic response to peanut during immunotherapy is often transient. J Allergy Clin Immunol 2015;135:1283-1292.
16.
Jones JC, et al: Incidence and risk factors associated with meniscal injuries among active-duty US military service members. J Athl Train 2012;47:67-73.
17.
Karlsson MR, Rugtveit J, Brandtzaeg P: Allergen-responsive CD4+CD25+ regulatory T cells in children who have outgrown cow's milk allergy. J Exp Med 2004;199:1679-1688.
18.
Shreffler WG, et al: Association of allergen-specific regulatory T cells with the onset of clinical tolerance to milk protein. J Allergy Clin Immunol 2009;123:43-52.
19.
Smaldini PL, et al: Orally-induced intestinal CD4+ CD25+ FoxP3+ Treg controlled undesired responses towards oral antigens and effectively dampened food allergic reactions. PLoS One 2015;10:e0141116.
20.
Begin P, Nadeau KC: Changes in peanut-specific T-cell clonotype with oral immunotherapy. J Allergy Clin Immunol 2015;135:1636-1638.
21.
Patil SU, et al: Peanut oral immunotherapy transiently expands circulating Ara h 2-specific B cells with a homologous repertoire in unrelated subjects. J Allergy Clin Immunol 2015;136:125-134.e12.
22.
Burton OT, et al: Oral immunotherapy induces IgG antibodies that act through FcγRIIb to suppress IgE-mediated hypersensitivity. J Allergy Clin Immunol 2014;134:1310-1317.e6.
23.
Frischmeyer-Guerrerio PA, et al: Modulation of dendritic cell innate and adaptive immune functions by oral and sublingual immunotherapy. Clin Immunol 2014;155:47-59.
24.
Perezabad L, et al: Clinical efficacy and immunological changes subjacent to egg oral immunotherapy. Ann Allergy Asthma Immunol 2015;114:504-509.
25.
Blumchen K, et al: Oral peanut immunotherapy in children with peanut anaphylaxis. J Allergy Clin Immunol 2010;126:83-91.
26.
Varshney P, et al: A randomized controlled study of peanut oral immunotherapy: clinical desensitization and modulation of the allergic response. J Allergy Clin Immunol 2011;127:654-660.
27.
Anagnostou K, 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;383:1297-1304.
28.
Narisety SD, 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;135:1275-1282.e1-e6.
29.
Tang ML, et al: Administration of a probiotic with peanut oral immunotherapy: a randomized trial. J Allergy Clin Immunol 2015;135:737-744 e8.
30.
Patriarca G, et al: Food allergy in children: results of a standardized protocol for oral desensitization. Hepatogastroenterology 1998;45:52-58.
31.
Patriarca G, et al: Oral desensitizing treatment in food allergy: clinical and immunological results. Aliment Pharmacol Ther 2003;17:459-465.
32.
Buchanan AD, et al: Egg oral immunotherapy in nonanaphylactic children with egg allergy. J Allergy Clin Immunol 2007;119:199-205.
33.
Vickery BP, et al: Individualized IgE-based dosing of egg oral immunotherapy and the development of tolerance. Ann Allergy Asthma Immunol 2010;105:444-450.
34.
Staden U, et al: Specific oral tolerance induction in food allergy in children: efficacy and clinical patterns of reaction. Allergy 2007;62:1261-1269.
35.
Morisset M, et al: 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 (Paris) 2007;39:12-19.
36.
Caminiti L, et al: Oral immunotherapy for egg allergy: a double-blind placebo-controlled study, with postdesensitization follow-up. J Allergy Clin Immunol Pract 2015;3:532-539.
37.
Escudero C, et al: Early SUSU after short-course egg oral immunotherapy: a randomized controlled study in egg-allergic children. Clin Exp Allergy 2015;45:1833-1843.
38.
Meglio P, et al: A protocol for oral desensitization in children with IgE-mediated cow's milk allergy. Allergy 2004;59:980-987.
39.
Meglio P, et al: Oral desensitization in children with immunoglobulin E-mediated cow's milk allergy - follow-up at 4 years and 8 months. Pediatr Allergy Immunol 2008;19:412-419.
40.
Skripak JM, et al: A randomized, double-blind, placebo-controlled study of milk oral immunotherapy for cow's milk allergy. J Allergy Clin Immunol 2008;122:1154-1160.
41.
Narisety SD, et al: Open-label maintenance after milk oral immunotherapy for IgE-mediated cow's milk allergy. J Allergy Clin Immunol 2009;124:610-612.
42.
Longo G, et al: Specific oral tolerance induction in children with very severe cow's milk-induced reactions. J Allergy Clin Immunol 2008;121:343-347.
43.
Martorell A, et al: Oral desensitization as a useful treatment in 2-year-old children with cow's milk allergy. Clin Exp Allergy 2011;41:1297-1304.
44.
Salmivesi S, et al: Milk oral immunotherapy is effective in school-aged children. Acta Paediatr 2013;102:172-176.
45.
Pajno GB, et al: Comparison between two maintenance feeding regimens after successful cow's milk oral desensitization. Pediatr Allergy Immunol 2013;24:376-381.
46.
Keet CA, et al: The safety and efficacy of sublingual and oral immunotherapy for milk allergy. J Allergy Clin Immunol 2012;129:448-455, 455.e1-e5.
47.
Rodriguez del Rio P, et al: Oral immunotherapy in children with IgE-mediated wheat allergy: outcome and molecular changes. J Investig Allergol Clin Immunol 2014;24:240-248.
48.
Sato S, et al: Wheat oral immunotherapy for wheat-induced anaphylaxis. J Allergy Clin Immunol 2015;136:1131-1133.e7.
49.
Bloom KA, et al: Effect of heat treatment on milk and egg proteins allergenicity. Pediatr Allergy Immunol 2014;25:740-746.
50.
Chatchatee P, et al: Identification of IgE- and IgG-binding epitopes on alpha(s1)-casein: differences in patients with persistent and transient cow's milk allergy. J Allergy Clin Immunol 2001;107:379-383.
51.
Cooke SK, Sampson HA: Allergenic properties of ovomucoid in man. J Immunol 1997;159:2026-2032.
52.
Martos G, et al: Mechanisms underlying differential food allergy response to heated egg. J Allergy Clin Immunol 2011;127:990-997.
53.
Kim JS, et al: Dietary baked milk accelerates the resolution of cow's milk allergy in children. J Allergy Clin Immunol 2011;128:125-131.
54.
Leonard SA, et al: Dietary baked egg accelerates resolution of egg allergy in children. J Allergy Clin Immunol 2012;130:473-480.e1.
55.
Goldberg MR, et al: Efficacy of baked milk oral immunotherapy in baked milk-reactive allergic patients. J Allergy Clin Immunol 2015;136:1601-1606.
56.
Leonard SA, Nowak-Wegrzyn A: Food protein-induced enterocolitis syndrome: an update on natural history and review of management. Ann Allergy Asthma Immunol 2011;107:95-101.
57.
Nadeau KC, et al: Rapid oral desensitization in combination with omalizumab therapy in patients with cow's milk allergy. J Allergy Clin Immunol 2011;127:1622-1624.
58.
Schneider LC, et al: A pilot study of omalizumab to facilitate rapid oral desensitization in high-risk peanut-allergic patients. J Allergy Clin Immunol 2013;132:1368-1374.
59.
Wood RA, 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;137:1103-1110.e11.
60.
Begin P, et al: Safety and feasibility of oral immunotherapy to multiple allergens for food allergy. Allergy Asthma Clin Immunol 2014;10:1.
61.
Begin P, 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.
62.
Savilahti EM, et al: Use of IgE and IgG4 epitope binding to predict the outcome of oral immunotherapy in cow's milk allergy. Pediatr Allergy Immunol 2014;25:227-235.
63.
Hofmann AM, et al: Safety of a peanut oral immunotherapy protocol in children with peanut allergy. J Allergy Clin Immunol 2009;124:286-291, 291.
64.
Varshney P, et al: Adverse reactions during peanut oral immunotherapy home dosing. J Allergy Clin Immunol 2009;124:1351-1352.
65.
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;113:624-629.
66.
Keet CA, et al: Long-term follow-up of oral immunotherapy for cow's milk allergy. J Allergy Clin Immunol 2013;132:737-739 e6.
67.
Elizur A, et al: Clinical and laboratory 2-year outcome of oral immunotherapy in patients with cow's milk allergy. Allergy 2016;71:275-278.
68.
Paassilta M, et al: Children who were treated with oral immunotherapy for cows' milk allergy showed long-term desensitisation seven years later. Acta Paediatr 2016;105:215-219.
69.
Otani IM, et al: Multiple-allergen oral immunotherapy improves quality of life in caregivers of food-allergic pediatric subjects. Allergy Asthma Clin Immunol 2014;10:25.
70.
Epstein Rigbi N, et al: Patient quality of life following induction of oral immunotherapy for food allergy. Pediatr Allergy Immunol 2015;27:263-268.
71.
Greenhawt MJ, Vickery BP: Allergist-reported trends in the practice of food allergen oral immunotherapy. J Allergy Clin Immunol Pract 2015;3:33-38.
72.
Wasserman RL, et al: Oral immunotherapy for peanut allergy: multipractice experience with epinephrine-treated reactions. J Allergy Clin Immunol Pract 2014;2:91-96.
73.
Sampson HA: Peanut oral immunotherapy: is it ready for clinical practice? J Allergy Clin Immunol Pract 2013;1:15-21.
74.
Nurmatov U, et al: Effectiveness and safety of orally administered immunotherapy for food allergies: a systematic review and meta-analysis. Br J Nutr 2014;111:12-22.
75.
Sampson HA, et al: Food allergy: a practice parameter update-2014. J Allergy Clin Immunol 2014;134:1016-1025.e43.
You do not currently have access to this content.