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.