Oral and sublingual immunotherapy (giving people small amounts of things they are allergic to via their mouth or under their tongue) for fruit allergy

Review question and background

We reviewed the evidence about the effect of oral and sublingual immunotherapy in people with a food allergy to fruit. Food allergy is an abnormal response to a food, usually after eating it. The main treatment for food allergy is to avoid the food, but in people with food allergy, accidentally eating the food can cause severe reactions.

Immunotherapy is a possible long-term treatment for food allergy, including for food allergy to fruit. Immunotherapy is a process where increasing doses of the thing someone is allergic to (the allergen) are given over a period of time to help the person be less sensitive to the allergen. In oral immunotherapy, a small amount of the allergen is given to someone to eat. In sublingual immunotherapy, an extract from the allergen is put under the tongue.

Study characteristics

We found two studies with 89 participants in total. One looked at oral immunotherapy in people with an allergy to apple, comparing it to no treatment, and one looked at sublingual immunotherapy in people with an allergy to peach, comparing it to a placebo. Both studies were in adults. The evidence is current to July 2015.

Key results

The study of oral immunotherapy for apple allergy found participants who received the intervention were less sensitive to apple than people who did not receive the intervention at eight months. The study of sublingual immunotherapy for peach allergy did not find a difference between the groups in terms of sensitivity at six months. In both studies, there were more side effects in people receiving the treatment, but these were not serious. Overall, the quality of evidence is very low because both studies were small, results were not similar between studies, and there were issues with study design. More research is needed before we can tell if oral and sublingual therapy works for food allergy to fruits.

Authors' conclusions: 

There is insufficient evidence for using OIT or SLIT to treat allergy to fruit, specifically related to peach and apple. Mild or moderate adverse reactions were reported more frequently in people receiving OIT or SLIT. However, these reactions could be treated successfully with medications.

Read the full abstract...

Food allergy is an abnormal immunological response following exposure (usually ingestion) to a food. Elimination of the allergen is the principle treatment for food allergy, including allergy to fruit. Accidental ingestion of allergenic foods can result in severe anaphylactic reactions. Allergen-specific immunotherapy (SIT) is a specific treatment, when the avoidance of allergenic foods is problematic. Recently, studies have been conducted on different types of immunotherapy for the treatment of food allergy, including oral (OIT) and sublingual immunotherapy (SLIT).


To determine the efficacy and safety of oral and sublingual immunotherapy in children and adults with food allergy to fruits, when compared with placebo or an elimination strategy.

Search strategy: 

The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL, and AMED were searched for published results along with trial registries and the Journal of Negative Results in BioMedicine for grey literature. The date of the most recent search was July 2015.

Selection criteria: 

Randomised controlled trials (RCTs) comparing OIT or SLIT with placebo or an elimination diet were included. Participants were children or adults diagnosed with food allergy who presented immediate fruit reactions.

Data collection and analysis: 

We used standard methodological procedures expected by the Cochrane Collaboration. We assessed treatment effect through risk ratios (RRs) for dichotomous outcomes.

Main results: 

We identified two RCTs (N=89) eligible for inclusion. These RCTs addressed oral or sublingual immunotherapy, both in adults, with an allergy to apple or peach respectively. Both studies enrolled a small number of participants and used different methods to provide these differing types of immunotherapy. Both studies were judged to be at high risk of bias in at least one domain. Overall, the quality of evidence was judged to be very low due to the small number of studies and participants and possible bias. The studies were clinically heterogeneous and hence we did not pool the results. A study comparing SLIT with placebo for allergy to peach did not detect a significant difference between the number of patients desensitised at six months following a double-blind placebo-controlled food challenge (RR 1.16, 95% confidence interval (CI) 0.49 to 2.74). The second study, comparing OIT versus no treatment for apple allergy, found an effect on desensitisation in favour of the intervention using an oral provocation test at eight months, but results were imprecise (RR 17.50, 95% CI 1.13 to 270.19). Neither study reported data on evidence of immunologic tolerance. In both studies, the incidence of mild and moderate adverse events was higher in the intervention groups than in the controls. In the study comparing SLIT with placebo, patients in the intervention group experienced significantly more local adverse reactions than participants in the control group (RR 3.21, 95% CI 1.51 to 6.82), though there was not a significant difference in the number of participants experiencing systemic adverse reactions (RR 0.81, 95% CI 0.22 to 3.02). In the study of OIT, two of the 25 participants in the intervention group reported relevant side effects, whereas no participants in the control group reported relevant side effects.