A detailed medical history and physical examination are the cornerstones in the diagnosis of FA.
Diagnostic tests should be selected based on medical history provided by the patient. The tests used should aim to identify the culprit allergen as suggested by history and not randomly test for a large panel of foods. The history can help the clinician understand the underlying mechanism for the allergic reaction (ie, IgE-mediated or non–IgE-mediated) and then select the diagnostic test.
Skin prick/puncture tests. Skin prick/puncture tests (SPT) are the most commonly used tests to evaluate a patient with food allergy.24 When the patient history suggests an IgE-mediated mechanism, SPT can be done to identify the culprit food. A positive SPT result suggests the presence of food sIgE present on the surface of cutaneous mast cells. Usually, the size of the response correlates with the extent of clinical reactivity to that particular food. In a patient with confirmed FA, the SPT helps in identifying the food(s) responsible for IgE-mediated FA.
Occasionally, SPTs can be negative in patients with IgE-mediated FA. In such patients, other mechanisms such as locally secreted IgE may be responsible for the allergic reactions. In such patients in whom history is significant, diagnosis should be confirmed by tests such as physician-supervised oral food challenge.
There are some pitfalls associated with SPT in patients with food allergy. SPTs tend to have low specificity and positive predictive value as compared with oral food challenges. Also, the reagents and methods used for SPTs are not standardized. SPTs effectively detect the presence of sIgE; however, many patients have sIgE in the absence of clinical symptoms of FA. Thus, use of SPTs alone in the clinical setting is not diagnostic of FA and may result in overdiagnosis.25
Allergen-specific serum immunoglobulin E. Allergen-specific sIgE tests aim at detecting the presence of sIgE antibodies in the serum, which represents allergic sensitization rather than clinical reactivity. Specified cut-off levels are suggestive of clinical reactivity (usually defined as 95% predictive values) and are predictive of clinical reactivity.26 Originally, radioallergosorbent tests were used to measure sIgE, but now more sensitive fluorescence enzyme-labeled assays are available that have sensitivity comparable to that of SPTs. sIgE levels may correlate directly with the probability of a clinical reaction. Thus, high levels of sIgE may suggest ingestion of the food in question will lead to an allergic reaction.26
Different laboratories or different assay systems are available to measure IgE;27 however, results are not comparable between different laboratories. Different forms of antigens are used by each system (eg, skim milk vs freeze-dried milk vs whole milk). Different measurements of sIgE are provided by each system for the same serum samples. Thus, the predictive values for one assay test cannot be applied to other test methods.27
Occasionally sIgE levels may be undetectable in patients with IgE-mediated FA. Thus, confirmatory tests such as oral food challenge must be done if the history is highly suggestive of food allergy.
Atopy patch test. An atopy patch test (APT) is generally used when history is suggestive of delayed or non–IgE-mediated mechanism for the reaction. APT is an investigational tool for diagnosing FA and there are no standardized reagents available for patch testing. The sensitivity and specificity of APTs are highly variable as compared with oral food challenges. APT may be helpful for diagnosing FA in some cases such as patients with AD and EoE.
Use of skin prick tests, sIgE tests, and atopy patch tests in combination. There is no significant benefit in using all three tests (SPTs, sIgE tests, and APTs) for the evaluation of FA rather than using SPTs or sIgE tests alone. Using these tests in combination may provide higher positive and negative predictive values but may not be clinically relevant. Moreover, this may be time-consuming for the patient and families and thus inconvenient; however, using two tests may sometimes be more helpful for identifying the culprit food allergen.
Food elimination diets. In some patients, omitting one or more foods as suggested by their medical history may be useful in the diagnosis of FA. This is shown to be helpful in diagnosing some non–IgE-mediated food-induced allergic disorders such as food protein-induced enterocolitis syndrome, and some mixed IgE- and non–IgE-mediated food reactions such as EoE.28 However, this can result in nutritional deficiencies, especially when multiple foods are omitted from the diet.28
Oral food challenges. The gold standard for diagnosing FA is an oral food challenge. The double-blind, placebo-controlled food challenge reduces bias and is the most specific challenge; however, it is often time consuming. Single-blind or open-food challenges are often done to diagnose food allergy. The food challenge is negative if the patient does not develop any symptoms, and this helps to rule out FA. A definitive diagnosis of FA can be made when the challenge is positive (patient develops objective symptoms during the challenge) and results correlate with medical history and laboratory tests.
An oral food challenge should begin with a dose that is lower than the dose required to elicit a reaction.29 The dose is gradually increased during the challenge while monitoring for any allergic symptoms until target dose is reached. The food challenge should be performed only under supervision of medical personnel who have experience in carrying out a food challenge so that immediate treatment can be administered in case of allergic reaction or anaphylaxis.
Molecular or component-resolved diagnostic tests. These tests aim at identifying IgE against specific proteins in a food and can provide more specific diagnostic information. For example, Ara h 2 is a major peanut protein that is associated with clinical reactions, whereas Ara h 8 is a birch tree pollen (Bet v 1 allergen) homolog and is usually not associated with significant clinical reactions. Ara h 1, 2, 3, and 9 are stable proteins whereas Ara h 8 is labile. Thus, a patient with undetectable Ara h 1, 2, 3, and 9 but positive Ara h 8 would be more likely to develop tolerance.30 On the contrary, increasing concentrations of sIgE to Ara h 2 signify increasing risk of reaction to peanut. Many component-resolved diagnostic tests have become commercially available and have been considered promising in the diagnosis of food allergy.
Routine FA testing should not be done prior to the introduction of highly allergenic foods (such as milk, egg, and peanut) in children who are at high risk of reacting to such foods.1 These include children who have severe allergies and/or significant family history of FA. Widespread testing for large panels of foods has poor predictive value and is not recommended. False-positive results are common and result in unnecessary dietary restrictions. There are no advantages in testing for FA prior to introduction of highly allergenic foods, especially when there is no personal history of allergies or family history
FA evaluation may be helpful prior to introduction of foods in some cases. An oral food challenge can be done in some people with certain risk factors, such as having a sibling who has peanut allergy or having another coexisting FA (eg, testing for tree nut allergy in a child with peanut allergy).31
Patients with FA should undergo follow-up testing to reevaluate if the food allergies are outgrown. Patients who are allergic to milk, egg, soy, and wheat can be tested annually, whereas patients who are allergic to peanut, tree nut, fish, and shellfish can be evaluated every 2 to 3 years. However, in the event of a recent FA reaction, repeat testing can be deferred for several years.
Vaccinations in Patients with Egg Allergy
Administration of vaccines containing egg protein is associated with risk of anaphylaxis in patients who have IgE-mediated egg allergy.
Influenza vaccine. Egg-based inactivated influenza vaccine has been shown to be safe in people with egg allergy.32 US allergy guidelines from the American Academy of Allergy, Asthma, and Immunology/American College of Allergy, Asthma, and Immunology Joint Task Force on Practice Parameters state that influenza vaccines can be safely administered to people with egg allergy of any severity and that no special precautions are required.33 The guidelines suggest that screening questionnaires do not need to ask about the egg allergy prior to administration of influenza vaccine.33 Live-attenuated influenza vaccine can also be safely administered to patients with egg allergy of any severity.34 Similar recommendations have been approved by American Academy of Pediatrics, the United States Centers for Disease Control and Prevention Advisory Committee on Immunization Practices, and the National Institute of Allergy and Infectious Diseases.35
Measles, mumps, rubella (MMR) vaccine and varicella vaccine (MMRV). These vaccines can be safely administered to children with egg allergy of any severity.36
Yellow fever vaccine. This vaccine is contraindicated in patients who are allergic to eggs; however, it can be safely administered if allergy evaluation and testing is done with the vaccine.37
Rabies vaccines. This vaccine is contraindicated in patients who are allergic to eggs; however, it can be safely administered if allergy evaluation and testing is done with the vaccine.37