ReviewOral immunotherapy for food allergy: A Spanish guideline. Immunotherapy egg and milk Spanish guide (items guide). Part I: Cow milk and egg oral immunotherapy: Introduction, methodology, rationale, current state, indications contraindications and oral immunotherapy build-up phase☆
Introduction
Cow milk (CM) and egg are the most frequent causes of food allergy in the first years of life.1 Two recent European studies conducted by the EuroPrevall group have reported an incidence of CM allergy and egg in the first two years of life of 0.54% (0.57% among the infants recruited in Spain) and 0.84% (0.78% among the infants recruited in Spain), respectively.2, 3 A study carried out in the Valencian Community (Spain), in which the diagnosis was confirmed by oral food challenge, reported an incidence of CM allergy of 0.36% in the first year of life.4
The only currently approved treatments for food allergy are avoidance and administration of emergency medications on accidental exposure.5
New treatment options have therefore been explored – the most widely studied being oral immunotherapy (OIT). Milk-OIT and egg-OIT induces changes in the immune system and favors the development of desensitization in most patients, though there is little evidence on its long-term safety and efficacy.6
Although the immunological mechanisms intervening in OIT have not been fully clarified, this type of therapy is known to induce a decrease in the activation and release of mediators from mast cells and basophils, with an increase in specific IgG4 titers, a decrease in specific IgE levels, the activation of specific regulatory T cells, and Th2-mediated response inhibition.7, 8, 9, 10Adverse reactions (AR) are frequent and can also manifest in the maintenance phase. Although such reactions are generally mild, they may prove more serious, with the need for ephinefrine administration. While sometimes associated to cofactors (e.g., exercise, infections), AR may appear unpredictably with doses that were previously well tolerated.5, 11
Desensitization is achieved in most patients, though in at least 20% of the cases OTI fails due to the appearance of AR. For this reason, new therapeutic strategies must be developed, such as for example adjuvant therapy with anti-IgE antibodies, in order to broaden the scope of application of OIT.12
The long-term outcome and time needed to achieve permanent tolerance of the causal food are not known.5, 13, 14 On the other hand, it must be taken into account that prolongation of the maintenance phase can lead to treatment adherence problems.15
These elements of uncertainty are the reason why OIT is currently still advised only in the research setting, not in clinical practice.
However, the fact is that CM and Egg-OIT has already been introduced in clinical practice and forms part of the management options of many hospitals in Spain. Different treatment protocols are being used; it is therefore necessary to define the bases for regulating the requirements, with standardization and optimization of the treatments, and particularly reduction of the risks in clinical practice.
The aim of this document is to offer a clinical guideline in the use of OIT in patients with IgE-mediated allergy to CM and egg-white proteins. By incorporating the data derived from the extensive available experience, the guide will attempt to establish the guidelines for OIT during the build-up phase and subsequent maintenance treatment, with the maximum safety guarantees.
The ultimate outcome is to improve clinical practice and to allow the professionals involved in such treatment to feel that their work is endorsed by the scientific societies SEICAP and SEAIC.
Section snippets
Methodology
Development of the guide has been based on the following elements:
- 1.
A literature search and review referred to:
- o
Studies and meta-analyses of milk and egg-OIT published between 1984 and June 2016, found in the PubMed database.
- o
Doctoral theses on milk and egg-OIT and egg published in Spain.
- o
Abstracts referred to milk and egg-OIT presented between 2010 and 2014 on occasion of the congresses of the SEICAP, SEAIC, EAACI and AAAAI.
- 2.
Opinion consensus among Spanish researchers with experience in OIT.
- 3.
Levels
The spontaneous short-term course of food allergy is not favorable in all individuals, and in some cases tends to persist indefinitely
CM and egg allergy in children is generally associated to a good prognosis. Approximately 85% of all infants with CM allergy develop tolerance by three years of age.17, 18, 19, 20 Egg-allergy persists for a longer period of time, though approximately 65% of all affected patients reach tolerance by 6 years of age.21, 22
However, more recent studies suggest a tendency toward longer persistence of milk allergy(36% of the patients do not tolerate milk at 12 years of age)23 and egg-allergy (32% of
Milk and egg-OIT: build-up phase
The build-up phase is the time between the first dose of the food and the moment at which the target dose is achieved
Depending on the protocol used, this period may last from a few days to several months.
Liquid milk in commercial containers
Packaged commercial milk is the preferred presentation because it is the way that is routinely consumed at home and requires no preparation. It is sold pasteurized, sterilized or subjected to upperization/UHT (Ultra High Temperature). No allergenic differences have been demonstrated among them.
The most frequently consumed presentation corresponds to milk subjected to upperization/UHT (5–8 s at a temperature between 150 and 200 °C, followed by rapid cooling). Depending on the brand and percentage
Conclusions
The published rush protocols have been found to be effective and less time-consuming. Their safety profile is similar to that of the published slower protocols.
Rush protocols may be useful in less severely affected patients without the described risk factors for adverse reactions.
(Level of evidence V. Grade of recommendation D: expert opinion).
Confidentiality of data
The authors declare that no patient data appear in this article.
Right to privacy and informed consent
The authors declare that no patient data appear in this article.
Protection of human and animal subjects
The authors declare that no experiments were performed on humans or animals for this study.
Conflict of interest
The authors have no conflict of interest to declare.
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Copublished in the Journal of Investigational Allergology and Clinical Immunology.