Introduction
Cow’s milk allergy (CMA) is defined as a reproducible adverse reaction to cow milk protein mediated by an immunologic mechanism, involving immunoglobulin E (IgE)-mediated, non-IgE-mediated, or mixed mechanisms[1]. IgE-mediated reactions often occur rapidly, typically beginning within minutes to 2 hours from the time of ingestion[2]. Clinical manifestations of IgE-mediated cow’s milk allergy (IMCMA) include urticaria, angioedema, rhinitis, conjunctivitis, asthma, oral allergy syndrome, gastrointestinal symptoms, and generalized anaphylaxis. Many children with CMA improve before school age, but in some cases, it persists even into adulthood[3, 4]. The current standard treatment for CMA is strict avoidance and emergency treatment of severe adverse reactions. However, because milk is ubiquitous in store-bought foods, and in-home and restaurant recipes, it is especially difficult to avoid. On the other hand, it is inevitable of accidental exposure to cow’s milk, sometimes it can be life-threatening and has a major impact on quality of life[5]. A strict avoidance has negative consequences in patients such as a risk of poor nutrition, increased levels of anxiety, and possible unjustified restrictions to further foods, with an increased immunological risk of non-acquiring tolerance[6]. So it needs to find some new treatments, such as oral immunotherapy (OIT). OIT can be proposed at different ages as an effective and safe treatment[1, 7].
OIT involves the introduction of a very small amount of cow’s milk protein and gradual increases of the dose at predetermined intervals. The global aim is to increase the reactive threshold of allergic patients, and finally enable them to ingest a target quantity of allergen without any reaction throughout the treatment (desensitization). Many studies have showed the efficacy of OIT in desensitization, and some of them in sustained unresponsiveness. However, there is an ongoing debate about the safety of OIT[7-9]. Because of the increasing interest in this topic and emerging studies, it is important to provide an up-to-date systematic review with ongoing updates. The main objective of this meta-analysis is to assess the clinical efficacy and safety of OIT in children with IMCMA as compared to a placebo treatment or milk avoidance.