Allergen immunotherapy for IgE-mediated food allergy: a systematic review and meta-analysis.
Topic: Immunotherapy

The European Academy of Allergy and Clinical Immunology (EAACI) is developing Guidelines for Allergen Immunotherapy (AIT) for IgE-mediated Food Allergy. To inform the development of clinical recommendations, we sought to critically assess evidence on the effectiveness, safety and cost-effectiveness of AIT in the management of food allergy.

PICO
Population: Patients with IgE-mediated food allergy
Intervention: Allergen immunotherapy
Comparison: Standard care or placebo
Outcomes: Effectiveness, safety, and cost-effectiveness of AIT in the management of food allergy

Included studies:
title: Specific oral tolerance induction in children with very severe cow's milk-induced reactions.
abstract: Some children allergic to cow's milk proteins (CMPs) experience exceptionally severe reactions after ingesting only trace amounts of antigen. Avoiding the food and carrying self-injectable epinephrine are the current strategies for their management.
title: Sublingual immunotherapy for hazelnut food allergy: a randomized, double-blind, placebo-controlled study with a standardized hazelnut extract.
abstract: Food allergy may be life-threatening, and patients affected need to receive accurate diagnoses and treatment. Hazelnut has often been implicated as responsible for allergic reactions, and trace quantities can induce systemic reactions.
title: Early oral immunotherapy in peanut-allergic preschool children is safe and highly effective.
abstract: Oral immunotherapy (OIT) is an effective experimental food allergy treatment that is limited by treatment withdrawal and the frequent reversibility of desensitization if interrupted. Newly diagnosed preschool children may have clinical and immunological characteristics more amenable to treatment.
title: Peanut oral immunotherapy results in increased antigen-induced regulatory T-cell function and hypomethylation of forkhead box protein 3 (FOXP3).
abstract: The mechanisms contributing to clinical immune tolerance remain incompletely understood. This study provides evidence for specific immune mechanisms that are associated with a model of operationally defined clinical tolerance.
title: Sublingual immunotherapy for peanut allergy: a randomized, double-blind, placebo-controlled multicenter trial.
abstract: There are presently no available therapeutic options for patients with peanut allergy.
title: Oral immunotherapy for cow's milk allergy with a weekly up-dosing regimen: a randomized single-blind controlled study.
abstract: Cow's milk allergy (CMA) in children is a important problem in medical practice. Oral desensitization has been proposed as a therapeutic approach, but current protocols are time-consuming and impractical.
title: A randomized controlled study of peanut oral immunotherapy: clinical desensitization and modulation of the allergic response.
abstract: Open-label oral immunotherapy (OIT) protocols have been used to treat small numbers of patients with peanut allergy. Peanut OIT has not been evaluated in double-blind, placebo-controlled trials.
title: Sublingual immunotherapy for peanut allergy: clinical and immunologic evidence of desensitization.
abstract: There are no treatments currently available for peanut allergy. Sublingual immunotherapy (SLIT) is a novel approach to the treatment of peanut allergy.
title: Early sustained unresponsiveness after short-course egg oral immunotherapy: a randomized controlled study in egg-allergic children.
abstract: No studies have evaluated the potential of egg oral immunotherapy (egg-OIT) to induce sustained unresponsiveness after discontinuing therapy following short-term treatments.
title: Administration of a probiotic with peanut oral immunotherapy: A randomized trial.
abstract: Coadministration of a bacterial adjuvant with oral immunotherapy (OIT) has been suggested as a potential treatment for food allergy.
title: Fibrosis of skin and subcutaneous tissue following megavoltage radiotherapy.
title: Oral specific desensitization in food-allergic children.
abstract: The possibility of obtaining oral desensitization in patients with food allergy is still a matter of debate. We decided to evaluate the safety and efficacy of standardized protocols for oral desensitization with the most common food allergens. Forty-two children (ages up to 16 years) diagnosed as affected by food allergy (on the basis of clinical history, skin prick tests, measurement of specific IgE, and double-blind, placebo-controlled food challenge) underwent a sublingual-oral desensitizing treatment according to new standardized protocols. The control group consisted of 10 patients who followed an elimination diet. The treatment was successfully completed by 85.7% of the patients. Specific IgE showed a significant decrease, while specific IgG(4) showed a significant increase, in all treated patients. The immunological modifications observed in our patients lead us to hypothesize that oral tolerance may be mediated by the same mechanisms as those involved in traditional desensitizing treatments for respiratory and insect sting allergy.
title: Increased cow's milk protein-specific IgG4 levels after oral desensitization in 7- to 12-month-old infants.
abstract: Cow's milk protein (CMP)-specific IgG4 responses and the efficacy of oral desensitization in infants with cow's milk allergy (CMA) warrant more clarification.
title: Oral desensitizing treatment in food allergy: clinical and immunological results.
abstract: The possibility of inducing oral desensitization in patients with food allergy is still controversial and no standardized programmes are yet available.
title: Oral desensitization as a useful treatment in 2-year-old children with cow's milk allergy.
abstract: Limited published evidence shows oral desensitization to be a potential intervention option for cow's milk protein (CMPs) allergy.
title: Specific oral tolerance induction in paediatric patients with persistent egg allergy.
abstract: Desensitisation or specific oral tolerance induction (SOTI) to food is a new topical-therapeutic approach of food allergy for those children who have not achieved tolerance spontaneously. The objective of this study is to induce clinical tolerance in children with persistent allergy using an oral desensitisation protocol with powdered pasteurised egg.
title: A new protocol for specific oral tolerance induction in children with IgE-mediated cow's milk allergy.
abstract: IgE-mediated cow's milk allergy (CMA) is a heavy burden for patients, particularly for children and their families. Allergen avoidance represents the only therapeutic option, but oral desensitization protocols have been suggested. Because of the long duration and complexity of these protocols we examined the feasibility of an oral tolerance induction protocol using a weekly up-dosing schedule. Children with IgE-mediated food allergy to milk, confirmed by a double-blind placebo-controlled food challenge, were recruited. Six of them were randomized to double-blind desensitization with milk or soy formula as placebo. Seven patients underwent the protocol in open fashion. The desensitization schedule started with one drop of whole CM diluted 1:25 every week. The dose was doubled weekly until the 18th week to achieve an intake of 200 mL in approximately 4 months. Of the 13 children enrolled, 10 children received CM and 3 control children received soy formula. Full tolerance (200 mL of milk) was achieved in 7 children; in 2 children this therapeutic approach failed, because severe reactions occurred during the procedure. One patient achieved a partial tolerance (64 mL of milk). The three control children receiving placebo still showed a positive food challenge at the end of the study. A weekly up-dosing oral tolerance induction could be a viable alternative to traditional protocols for children with IgE-mediated CMA.
title: 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.
abstract: Food allergy is treated by avoidance diets in order to prevent anaphylactic reactions and to cure chronic associated symptoms. However, the natural history is left unchanged.
title: Food allergy in children: results of a standardized protocol for oral desensitization.
abstract: Food allergy in children is still an unresolved problem that merits investigation, particularly when the food is fundamental for the child's growth. Reports in the literature that deal with the possibility of a desensitizing treatment are sporadic and often inconsistent, and no standardized protocols are yet available. In this paper we propose a standardized oral desensitization program for food allergy in children.
title: A randomized, double-blind, placebo-controlled study of milk oral immunotherapy for cow's milk allergy.
abstract: Orally administered, food-specific immunotherapy appears effective in desensitizing and potentially permanently tolerizing allergic individuals.
title: Oral food desensitization in children with IgE-mediated hen's egg allergy: a new protocol with raw hen's egg.
abstract: Hen's egg allergy affects young children and can cause severe allergic reactions. Avoidance results in dietary limitations and can affect the quality of life, especially in cases where potentially life-threatening reactions exist. Our objective was to desensitize children with moderate-severe IgE-mediated hen's egg allergy over a 6-month period, by introducing increasing and very gradual daily doses of raw hen's egg in order to enable the children to assume 25ml of this food, or to induce tolerance to the highest possible dose. The protocol foresaw the egg reintroduction in the home setting.
title: Efficacy and safety of oral desensitization in children with cow's milk allergy according to their serum specific IgE level.
abstract: Oral desensitization in children allergic to cow's milk proteins is not risk free. The analysis of factors that may influence the outcome is of utmost importance.
title: Oral Immunotherapy for Egg Allergy: A Double-Blind Placebo-Controlled Study, with Postdesensitization Follow-Up.
abstract: Oral immunotherapy (OIT) may be an effective treatment for food allergy in children. It is not clear if the OIT-induced effect is achieved by desensitization (transient state dependent on regular antigen exposure), or by tolerance (persistent condition where the ability to consume the food is retained even after a period of withdrawal).
title: Specific oral tolerance induction with raw hen's egg in children with very severe egg allergy: a randomized controlled trial.
abstract: Treatment of severe egg allergy is avoidance of hen's egg (HE) and carrying self-injectable epinephrine. Specific oral tolerance induction (SOTI) seems a promising alternative treatment. However, some aspects of SOTI are still considered experimental.
title: Clinical evaluation of the analeptic, doxapram, in dogs and cats.