Approach Considerations
The approach to the diagnosis of food allergy requires consideration of the history, the epidemiology of food allergic disease, cross-reactivity, and the degree of positivity of tests; these must be evaluated to assist in diagnosis. Simple tests for food-specific IgE antibodies are available, but the clinician must appreciate that a positive test for food-specific IgE primarily denotes sensitization and may not confirm clinical allergy. A physician-supervised oral food challenge may be required for diagnosis.
When the history of an allergic reaction to a food suggests that the onset of symptoms is delayed by hours or days following ingestion, adjust the timing and monitoring of the challenge to correspond to these characteristics.
Because specific laboratory tests for some food hypersensitivities are not available, diagnosing non–IgE-mediated food allergies (eg, cow milk–induced and soy-induced enterocolitis syndromes or allergic eosinophilic gastroenteritis) is more difficult than diagnosing IgE-mediated food allergies.
In cases of allergic eosinophilic gastroenteritis, a biopsy may need to be performed. Elimination diets with gradual reintroduction of foods and supervised oral food challenges are often needed to help identify the causative foods.
For food protein–induced enterocolitis syndrome, the oral food challenge is typically performed with 0.15-0.30 g of protein per kilogram of body weight of the implicated protein and observe the patient for several hours. Positive reactions (eg, profuse vomiting, diarrhea) are typically accompanied by a rise in the absolute neutrophil count of more than 3500 cells/mm3 (see the Absolute Neutrophil Count calculator). Because of the potential for shock, these challenges are best performed in the hospital setting.
The successful administration of oral food challenges to young children requires a great deal of preparation, patience, and creativity. Young children may refuse to ingest the challenged food. Prior planning with the family is important to choose proper vehicles (eg, juice, cereal, solid food) for disguising the challenged substance. [51]
Serum Studies
IgE antibody testing
Specific IgE antibodies to foods can be quantified by in vitro laboratory methods. The term RAST (radioallergosorbent test) is antiquated because modern methods do not use radiation.
The serum test may offer advantages over skin prick testing when skin testing is limited by dermatographism, generalized dermatitis, or a clinical history of severe anaphylactic reactions to a given food. However, although the serum test provides information similar to the skin prick test, it is more expensive and results are not immediate.
Studies have correlated the outcomes of physician-supervised oral food challenges with serum test results. While the studies have generally shown increasing risks of reaction with increasing concentrations of allergen, the specific correlations vary among studies. [52, 53] The concentration of food-specific IgE does not correlate very well with the severity of an allergy.
Studies (so far primarily using 1 brand of test system) have reported levels highly indicative of allergy (>95%). [52, 54] However, specific results have varied among studies, which is probably due to differences in patient selection, interpretation of positive outcomes, and other factors. Only a few foods have been analyzed in this manner (primarily peanuts, eggs, and milk), and predictive results are different for the different foods.
Test systems vary with regard to measurements, and similarly reported results may not be equivalent. [55] The clinician should also be aware of different reporting units that are not interchangeable with one another (eg, class vs units vs percentage).
An emerging serum test is component resolved diagnosis (CRD). Foods are composed of many proteins to which an IgE immune response may develop. IgE responses against labile proteins may carry little risk of significant allergy because these proteins presumably do not easily enter the circulation. In contrast, stable proteins are clinically relevant. With peanut, for example, the proteins Ara h 1, Ara h2, Ara h 3, and Ara h 9 are relatively stable, while Ara h 8 is a pollen related protein that is labile. In CRD, positive testing to Ara h 8 with negative results to Ara H 1-3 and 9 is typically not associated with any significant clinical allergy. These types of tests are being evaluated for improved diagnosis for many foods. [56, 57]
Peripheral serum measurements of eosinophils or total IgE concentrations
Abnormal results from these tests do not identify or confirm the diagnosis of food allergy. Likewise, normal values do not exclude diagnosis.
Basophil histamine-release assays
These tests are limited primarily to research settings and have not been shown conclusively to provide reproducible results useful for diagnostic testing in a clinical setting.
Other
Studies are underway to determine, for example, if analysis of IgE epitope binding provides additional diagnostic information. [58]
Diet Diary
This consists of keeping a chronological record of all foods eaten and any associated adverse symptoms. It is an inexpensive endeavor that documents the frequency of symptoms and their occurrence in relationship to food ingestion. In addition, it encourages the patient to focus on his or her diet.
This record is occasionally helpful for identifying the food implicated in an adverse reaction; however, it is not usually diagnostic, especially when symptoms are delayed or infrequent.
Occasionally, review of the diet diary reveals that the patient is not experiencing a reaction when eating, as an ingredient in other foods, a significant amount of a food to which he or she was thought to be allergic.
Elimination Diet
This is used for diagnostic and treatment purposes. When used as a diagnostic tool, the elimination diet requires complete avoidance of suspected foods or groups of foods for a given time period (usually 7-14d) while the patient is monitored for an associated decrease in symptoms. The trial elimination diet may be most useful to evaluate chronic symptoms.
Success depends on identifying the correct food allergen and completely eliminating it from the diet. Limitations of this method include potential effects of patient or physician biases, variable patient compliance, and the time-consuming nature of the endeavor.
If symptoms improve, confirmation of the food as causal typically requires a medically supervised oral food challenge.
When the elimination diet is used as treatment, identified food allergens are removed from the diet indefinitely unless evidence exists that the food allergy has resolved.
Skin Testing
Prick and puncture tests are the most common screening tests for food allergy and can even be performed on infants in the first few months of life. However, the reliability of the results depends on multiple factors, including use of the appropriate extracts and testing technique, accurate interpretation of the results, and avoidance of medications that might interfere with testing (eg, antihistamines). [59, 60]
When used in conjunction with a standard criterion of interpretation and appropriate controls (eg, histamine: positive; saline: negative), these tests provide useful and reproducible clinical information in a short period (ie, 15-20 min), with minimal expense and negligible risk to the patient.
This is a reliable method of excluding IgE-mediated food allergies. The negative predictive accuracy is generally greater than 90%; however, the positive predictive accuracy is generally less than 50%, which limits clinical interpretation of positive skin test results. Similar to in vitro testing, interpretation of the test results must consider the clinical history (to assess prior probability) and other factors, such as the likelihood, from epidemiologic observations, of the food being an allergy trigger.
The larger the skin test wheal size, the more likely that a clinical allergy exists. [61, 62] Positive skin test results, in addition to the suggestion of clinical reactivity based on the patient’s history, must often be confirmed by an oral food challenge unless the patient has a convincing history of significant food allergy.
Food Challenge Confirmation of Food Allergy
A physician-supervised (medically supervised) oral food challenge involves gradually feeding the patient the food suspected to be causing an allergy, with careful assessment for any symptoms. If symptoms occur, the feeding is discontinued and medications are administered. [63]
Food challenges are typically preceded by a period of elimination of the suspected food. They are conducted when the patient is at a stable clinical baseline and not taking medications that could interfere with the observation of symptoms (eg, antihistamines).
Of these procedures, the double-blind, placebo-controlled food challenge (DBPCFC) is the most reliable method to help diagnose and confirm food allergy and other adverse food reactions, because it eliminates patient and observer bias. However, in a clinical setting where minimal bias is suspected, open food challenges may be preferable, because blinding of the food is often not required.
Conduct any food challenge in a clinic or hospital setting with the personnel and equipment necessary to treat a systemic allergic reaction available at all times. Patients undergoing a food challenge should not be taking beta-blocker medications or any medication that might interfere with the treatment of anaphylaxis. If indicated by risk assessment, obtaining intravenous access may be prudent.
Clinically indicated oral food challenges are not generally performed when the history and test results already support a current diagnosis of allergy to the target food.
The decision to proceed to an oral food challenge must consider many factors, including the likelihood of a reaction, the severity of a reaction if one were to occur, the need to obtain a definitive diagnosis, and social and nutritional factors, among others.
When performing oral food challenges, be prepared to recognize and treat adverse clinical symptoms immediately. Appropriately trained personnel and the necessary equipment for the treatment of anaphylactic shock must be available prior to and throughout the entire oral food challenge and observation period because of the risk of triggering an allergic reaction. Patients should never be instructed to perform a food challenge at home.
Confirm negative results from a double-blind, placebo-controlled food challenge (DBPCFC) using an open feeding (open food challenge) of the food in question in its usual form and quantity before giving final advice on dietary restrictions.
Open food challenge
This test involves the patient ingesting the suspected food, prepared in its customary fashion (ie, the challenge food is not disguised in any way). The patient and the observer (eg, physician, nurse) are aware of the food being ingested. The open food challenge is best used in clinical practice when the patient and physician bias is minimal.
Whenever the results are equivocal, perform a blinded challenge. Patients with a history of a previous reaction should never perform an open food challenge at home, even if the chance that they will develop severe symptoms is remote.
Single-blind food challenge
This challenge involves the patient ingesting the suspected food disguised in a challenge food so that the patient is unaware of the contents.
This type of challenge, which is suitable for clinical practice and some research investigations, is designed to reduce patient bias during the procedure. However, subjective attitudes regarding the outcome of the challenge cannot be completely eliminated.
Double-blind, placebo-controlled food challenge
DBPCFC involves supervised, gradual ingestion of the suspected food disguised in another food (or hidden in capsules). A food similar in taste and appearance, but without the allergen, is used as a placebo control. The feeding (potential allergen vs placebo) is randomized so that the patient and the observer are unaware of the contents of the challenge at the time of the feeding and observation. Feeding of the allergen and placebo may be separated by hours or days. [64]
This type of challenge is designed to reduce patient and observer bias and subjective attitudes during the procedure. DBPCFC is considered the criterion standard for diagnosing food allergies and is particularly used in research investigations. Currently, it is the only completely objective method for determining the validity of the history of an adverse reaction to a food.
Allergy Testing
Intradermal skin testing
The risk of inducing a systemic reaction with this type of testing is increased in comparison with the prick or puncture method; as a result, intradermal skin testing for food allergies should be avoided. In addition, the results obtained by using this method are less specific than are those obtained by using prick or puncture testing.
Patch tests
Patch tests are performed by exposing the skin to the food allergen for 24 hours under occlusion and then evaluating the area for erythema and papules in the subsequent 24-72 hours.
The test has been evaluated for diagnosis of food allergy in eosinophilic esophagitis, [65] enterocolitis, [66] and atopic dermatitis. [67] Some studies show promise for this technique, but additional studies are needed to better characterize the utility of the results. [68]
Peripheral serum measurements of eosinophils or total IgE concentrations
Results from these tests support but do not confirm the diagnosis of food allergy. Likewise, normal values do not exclude diagnosis.
Basophil histamine-release assays
These tests are limited primarily to research settings and have not been shown conclusively to provide reproducible results useful for diagnostic testing in a clinical setting.
Other
The diagnostic value of performing the following tests is not currently supported by objective scientific evidence:
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Food-specific IgG or IgG-subclass antibody concentration testing
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Testing for food antigen-antibody complexes
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Leukocyte cytotoxic tests
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Provocation and neutralization testing
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Kinesiology-based testing
