Food Allergies
Mitchell R. Lester
Diagnosing IGE Mediated Food Allergies - The History
Double-blind, placebo-controlled food challenge (DBPCFC) is the gold standard for diagnosis of FA. However even before challenge, the most important tool to identify a potential adverse reaction to food is a thorough history. A supportive history dramatically increases the sensitivity and specificity of tests for food specific IgE. There are several things to ask about every suspected hypersensitivity reaction to food.

First, what happened? Is the reaction consistent with an IgE-mediated adverse reaction? Were the signs and symptoms as one would expect with mast cell activation? If not, is the reaction consistent with another immunologic reaction, as described below?

What food triggered the suspected reaction? Cow’s milk, egg, soy, and wheat account for over 90% of new onset FA in infant and toddlers. In older children and teenagers, peanuts, tree nuts, shellfish, and finned fish account for over 90% of new onset FA. The prevalence of seed allergy has increased over the last two decades. Because other foods are far less frequently allergenic, it is reasonable to think about the most common offenders first when taking a history and testing. Diary keeping can be difficult but is essential for identifying less common allergens including herbs and spices.

Two exceptions to this paradigm of most common food allergens are the Food-Pollen and Fruit-Latex Syndromes in which patients have symptoms (often limited to the oropharynx) after ingestion of fruits and vegetables with homologous epitopes to pollen or latex, respectively.

What is the reproducibility of the reaction? That is, does the reaction occur each time a specific food is eaten? After an initial reaction many parents do not offer the food a second time, so the answer to this question is often unknown.

How long did it take from ingestion to the onset of symptoms? Did symptoms start within the expected time frame for an immediate type reaction? How much did the patient eat? If the patient had a mild reaction after eating a large amount of a food, it is reassuring but does not preclude more serious reactions with smaller ingestions. Historical details regarding the timing to onset of symptoms, their progression, treatments provided and their effectiveness, and the time to resolution are useful information for the design of food challenges in appropriate patients and for writing school management plans.

In vitro and in vivo testing for food specific IgE is useful to confirm or refute diagnostic suspicion after a detailed history. The true value of the tests comes with understanding their interpretation. A positive test does not indicate allergy. It merely reflects sensitization, the presence of specific antibody. IgE-mediated allergy is sensitization and mast cell activation with exposure; that is, there must be symptoms. When a physician orders individual tests for food specific IgE based on the history (rather than a “panel”), the statistical value (sensitivity, specificity, positive [PPV] and negative predictive values [NPV]) of the tests improves.

Radioallergosorbent tests (RASTs) are rarely used these days. Instead, in vitro tests that use the same immunologic principles but a different solid medium are preferred. The newer tests are more sensitive and specific than RASTs and in some cases the sensitivity approaches that of skin tests. There are only a few foods for which we know how to interpret ImmunoCAP® results (milk, egg white, peanut, and codfish). For those foods, if the level is low enough or high enough the NPV and PPV are known. However, interpretation of results in the grey zone between those lower and upper thresholds can be difficult. In addition, some foods can have very highly elevated levels with low PPV (e.g., soy and wheat levels of 35 kU/L have 50% PPV).

The degree of elevation does not indicate severity of allergy; it indicates greater likelihood of allergy. Only the clinical reaction itself is diagnostic of severity. In vitro tests are more expensive than skin tests and take longer to get results. Because of the range of levels reported, they can also be harder to interpret. However, they are not influenced by antihistamine use, skin disease, or behavior of patents resistant to testing.

Skin testing for foods is more specific and often easier to interpret than in vitro tests, but some of the same caveats apply. As with in vitro tests, a positive test indicates sensitization, not allergy. The foods to which we test must be driven by the history to improve the statistical value of the results. Negative skin tests have a high NPV for IgE mediated reactions, but positive tests without a supportive history have <50% PPV. Extensive testing without a supportive history is inappropriate. A larger positive skin test indicates greater likelihood of allergy, but not the severity of the allergy.

In contrast to in vitro tests, antihistamines and tricyclic antidepressants must be withheld before testing. Patients with atopic dermatitis and dermagraphism are more likely to have irrelevant or false positive tests.

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