Background
The global prevalence of food allergy is about 10% with an increase in its incidence in the last 20-30 years1,2. Evidence suggests that allergies to food are more common in Westernized countries, affecting children more than adults3. Any food can be a potential allergen; however, a large proportion of food allergies worldwide can be accounted for by nuts, milk, eggs, shellfish and wheat4. Different foods act as the most common allergens in different countries; while peanut allergies are relatively common in the UK, USA, Canada and Australia, they are very rarely seen in Asia, excluding Japan. Overall, milk and eggs appear to be the most common allergens in young children in the UK and most parts of Europe, USA, Canada, Asia and Australia5.
Food allergies can be classified as immunoglobulin E (IgE) mediated and non-IgE mediated, with the former being the most common and the focus of this systematic review. IgE mediated food allergies usually induce immediate reactions, i.e. reactions that occur up to 2 hours (usually a few minutes) after exposure to the allergen, and these can be severe, and sometimes life threatening. By contrast, non-IgE mediated allergies prompt a delayed response, with symptoms taking up to two days to evolve, or manifest chronically6. Clinical manifestations of food allergy include skin, gastrointestinal (GI) and respiratory reactions, with skin reactions being the most prevalent and presenting as urticaria, angioedema and erythema4,7. GI symptoms include abdominal pain, diarrhoea, nausea and vomiting. Rhinorrhoea, nasal obstruction, bronchospasms and oedema of the larynx are possible respiratory symptoms2. Allergic reactions can vary in severity, ranging from local reactions such as tingling in the mouth to anaphylaxis, a severe life-threatening allergic reaction affecting breathing or circulation4,8.
The diagnosis of IgE-mediated food allergy is usually based on the clinical presentation and evidence of IgE sensitisation to the specific allergen, as documented by a positive skin prick test (SPT) or serum specific IgE9. The reference standard is the oral food challenge (OFC), in which the suspected allergen is administered orally in gradually increasing doses until either a reaction occurs or all doses are tolerated. OFC are resource intensive as they must be conducted in a medical setting due to the risk of anaphylaxis. The results can subsequently be used to confirm the diagnosis, to assess tolerability in people with a confirmed allergy, or to detect the reaction threshold. In cases with a recent history of an allergic reaction, detectable IgE specific to the culprit allergen can be enough to confirm the diagnosis, dispensing oral food challenge.
Several tests have been suggested as alternatives for OFC. While SPT and sIgE confirm presence of IgE antibodies to a particular food (sensitisation) they do not necessarily correlate to a clinical reaction, with approximately half of children sensitised able to tolerate the food without reaction. These routine tests therefore generally have high sensitivity but poor specificity to clinical food allergy. Increasing magnitude of these tests are associated with increased risk of clinical reaction, and thresholds with high probability of food allergy have been identified for some foods (e.g. for peanut: SPT >=8mm or sIgE >=15 have 95%PPV) which negate the need for OFC in some settings. Reported thresholds vary in the literature, likely due to differences in study design and patient characteristics. Component-resolved diagnosis (CRD) refers to the determination of specific IgE levels to specific proteins in food10. Additional tests include the basophil activation test (BAT) and the mast cell activation test (MAT); however these are currently not used in routine clinical settings. CRD, BAT and MAT are emerging tests with early studies suggesting that they offer an improvement on sensitivity and specificity than traditional SPT or sIgE tests.
The European Academy of Allergy and Clinical Immunology is currently in the process of updating their food allergy guidelines. Thus, a systematic review of existing literature will be carried out to inform the new guidelines. The systematic review aims to assess the diagnostic accuracy measured by sensitivity and specificity of index tests for IgE-mediated food allergy compared to the standard OFC. Furthermore, comparison among index tests will be conducted if sufficient evidence is available.