# Improving Safety in Food Allergen-Specific Oral Immunotherapy
## 1 Introduction  
With a prevalence of around 1.6-5.6% in children across Europe, food allergies represent a significant burden for the pediatric population. In Europe, the prevalence of food allergies confirmed by double-blind, placebo-controlled food challenges ranges from 0.4% to 4.6% among children aged four to ten years. The most commonly reported symptoms of allergic reactions are cutaneous manifestations (up to 70%) and gastrointestinal symptoms (up to 40%). Among the most prevalent food allergens in almost all European centers are cow's milk, hen's eggs, and peanuts [1]. The quality of life of these patients is affected by the impairment of social activities, the fear of accidentally eating the suspect food and the risk of life-threatening anaphylaxis, leading to emotional stress and anxiety. Therefore, an active approach to ameliorate these difficulties is sought in contrast to the elimination diet and the application of medicines in emergencies.  
Oral immunotherapy (OIT) for food allergies has proven to be a promising intervention that offers several benefits to patients: reducing the risk of allergic reactions due to contaminated foods, reducing the severity of reactions when foods are accidentallyconsumed, improving quality of life by minimizing dietary and social restrictions and alleviating anxiety, and allowing some patients to consume small amounts of allergenic food safely [2]. Although the first report of OIT dates back to 1908, when [PERSON] successfully desensitized a 13-year-old boy with a history of anaphylactic reactions to eggs through the oral intake of gradually increasing amounts of egg, OIT was neglected for most of the 20 th century [3].  
Food oral immunotherapy (F-OIT) consists of the oral ingestion of small, gradually increasing amounts of the culprit food to reach the maintenance dose, which is taken over a prolonged period [4]. Despite different OIT protocols, most protocols start with an initial escalation day to determine the tolerance threshold, followed by a build-up period over several months to years until the final target maintenance dose is achieved [4]. For some patients, F-OIT may protect them from accidental exposure, while others may achieve food intake [5].  
As the treatment consists of ingesting allergenic foods, it is clear that it carries some risk. During OIT, the majority of children experience mild to moderate reactions, while severe reactions occur in about 5-10% of cases [6].  
The most common adverse reactions (ARs) during OIT are mild to moderate and include gastrointestinal symptoms, skin reactions, and respiratory symptoms. However, there is a risk of severe reactions, including anaphylaxis [5]. The frequency of ARs tends to be higher during the initial escalation phase and decreases once the maintenance dose is reached [2]. Since there are no standardized F-OIT protocols, the goal of this review is to identify the differences between published F-OIT protocols in (a) milk OIT, (b) egg OIT and (c) peanut OIT in children, focusing on safety. The additional goal is to evaluate the adjuvant methods in improving safety in F-OIT protocols.