Description of the condition
The National Institute of Allergy and Infectious Diseases (NIAID) defines FA as an "adverse immune response that occurs reproducibly on exposure to a given food and is distinct from other adverse responses to food, such as food intolerance, pharmacologic reactions, and toxin-mediated reactions" (Chafen 2010). This definition encompasses immune responses that are IgE mediated (immediate), non–IgE mediated (delayed), or a combination of both, and is in agreement with other international guidelines (Burks 2012).
Food allergy (FA) is a disease on the increase, and affects around 6% of young children in US and 3 to 4% of adults in UK (Sicherer 2011). According to The National Center for Health Statistics, 3.9% of US children in 2007 reported an FA (Kim 2011; Beyer 2012), with an increase of 18% in prevalence from 1997 to 2007 (Branum 2008). There are several hypotheses for this increase, of which the 'hygiene hypothesis' has received significant attention, but does not provide a sufficient immunological explanation. Other hypotheses describe associations between environmental and genetic factors, and also include food allergens (Mousallem 2012). There is a lack of accurate data on the prevalence of FA, particularly with regard to fruits, vegetables, nuts, and other edible plants. The prevalence of allergy to fruits has been estimated to be between 0.1 to 4.3% (Zuidmeer 2008). However, if prevalence is measured only by skin tests, this figure may be closer to 1% (Dalal 2002; Rance 2005). The prevalence of allergy to fruits as diagnosed by the patient's perception, is between 0.4% to 3.5% in adults and in children under three years, can be 11.5% (Eggesbo 1999). In this latter age group, Zuidmeer 2008 found the prevalence of allergy dependant on fruit species as 8.5% to apple, and 6.8% to orange and/or lemon.
The FA treatment, for allergy, including that to fruit, is the elimination of the allergen. Unfortunately, many patients accidentally ingest allergenic foods, which can result in severe anaphylactic reactions (Bock 1989). While it is advisable to use intramuscular adrenaline as emergency treatment in cases of accidental ingestion of allergenic food (Kim 2011), allergen-specific immunotherapy has also been studied as a longer-term treatment option in cases where avoidance of allergenic foods may prove difficult (Enrique 2005).
Description of the intervention
The concept of 'allergen immunotherapy' refers to a modulation of the immune system (Krishna 2011), which is expected to perform an allergen involved hyposensitization, in this case, to a food allergen (Scott-Taylor 2005). Recently, studies have been conducted on different types of immunotherapy for the treatment of FA, including oral immunotherapy (OIT) and sublingual immunotherapy (SLIT). Oral immunotherapy involves the ingestion of small amounts of the allergen (milligrams to grams) in the form of a flour combined with a food vehicle; while sublingual immunotherapy (SLIT) involves the administration of micrograms to milligrams of allergen extract under the tongue. Despite the good results obtained with OIT, further studies are needed to consolidate these findings (Jones 2009; Clark 2009; Patriarca 2003). SLIT offers an alternative that also requires additional studies for routine use (Kim 2011).
How the intervention might work
Desensitization is defined as the ability to increase the amount of food protein required to induce a clinical reaction, while still on regular immunotherapy. 'Tolerance' is the ability to consume large amounts of the food protein after treatment cessation. Thus food allergy immunotherapy aims to establish a permanent state of tolerance. While the mechanism by which immunotherapy induces tolerance maybe unclear, immunotherapy appears to alter the T cell responses to the allergen by skewing the Th2 response to a Th1 response and via the induction of Tregs (regulatory T cells). These Tregs can be natural (thymus derived) or inducible (antigen-specific), and both can suppress the immune responses by different mechanisms, including secretion of IL-10 and transforming growth factor (TGF)-b. Tregs in turn can suppress the allergic immune response, including secretion of IL-10 and transforming growth factor (TGF)-b (Shevach 2009). Both these cytokines have been found to be important in FA (Mousallem 2012; Chehade 2005; Maggi 2010; Perez-Machado 2003).
Why it is important to do this review
OIT and SLIT seem to be the most novel approaches for treating food allergies. OIT appears to be more effective than sublingual (Scott-Taylor 2005). At the time of writing this protocol, the effectiveness and safety of these interventions are as yet unclear. This review will provide a rigorous summary of the available evidence regarding the efficacy associated with OIT and SLIT for the management of allergy to fruits.