Food allergy testing: serum IgE vs intradermal

The food allergy testing is one of the most commonly requested, most commonly misunderstood, and most commonly misapplied interventions in veterinary dermatology. The owner who is told that the dog has a "food allergy" based on a single serum test result is the owner who has received a diagnostic test that has a high false-positive rate, that does not differentiate between exposure and clinical allergy, and that often leads to inappropriate dietary changes that do not address the actual problem. The owner who is told that the dog has a "food allergy" based on a properly performed intradermal test is the owner who has received a more reliable diagnostic, but the test still requires the elimination trial confirmation, and the test result is not the final word. The food allergy testing is a useful tool in the right context, and the food allergy testing is a misleading tool in the wrong context.

This article is going to walk you through the practical comparison of the two main food allergy testing methods — the serum IgE testing (the blood test) and the intradermal testing (the skin test) — with the right use of each, the interpretation, the limitations, the relationship to the elimination trial, and the four mistakes that turn a useful tool into a confusing one. I am a board-certified veterinary dermatologist, and the food allergy testing is one of the most common topics of my consultations. The cases that go well share a common feature: the owner has understood the difference between the two tests, has used the right test for the right context, and has confirmed the test result with the elimination trial. The cases that go poorly share a different common feature: the owner has used the wrong test for the wrong context, has interpreted the result incorrectly, or has not confirmed the result with the elimination trial.

I want to be clear at the start: neither food allergy test is a definitive diagnostic for food allergy. The only definitive diagnostic is the elimination trial with the rechallenge, as I described in an earlier article. The food allergy tests (the serum and the intradermal) are screening tests that are most useful for the prioritization of the ingredients to test in the elimination trial, and the food allergy tests are most useful for the specific case where the elimination trial has been difficult to interpret or has been impractical to perform. The food allergy tests are not a replacement for the elimination trial.

The serum IgE test: what it is, what it measures, what it does not

The serum IgE test (often called the "food allergy blood test" or the "food sensitivity test") measures the IgE antibodies in the dog's blood that are specific to a panel of food antigens (typically chicken, beef, lamb, fish, dairy, egg, wheat, soy, corn, and a few other ingredients, depending on the lab). The test is performed on a blood sample, the sample is sent to a specialty lab, and the result is a report listing each ingredient tested and indicating whether the result is "negative," "equivocal," or "positive" for IgE antibodies to that ingredient.

What the serum IgE test actually measures. The serum IgE test measures the IgE antibodies that are circulating in the blood at the time of the sample. The IgE antibodies can be present for two reasons:

• True clinical allergy. The dog has been exposed to the ingredient, the dog's immune system has produced IgE antibodies to the ingredient, and the IgE antibodies are the cause of the clinical signs. This is the scenario the test is designed to detect.

• Sensitization without clinical allergy. The dog has been exposed to the ingredient, the dog's immune system has produced IgE antibodies to the ingredient, but the IgE antibodies are not causing clinical signs. The IgE is present because the immune system has "seen" the ingredient, but the immune system is not reacting to the ingredient in a clinically meaningful way. This is the much more common scenario, and it is the source of the false-positive results.

The problem with the false positives. The published literature consistently shows that the serum IgE test for food allergy has a high false-positive rate, with estimates ranging from 30% to 60% depending on the lab, the ingredient, and the population. The high false-positive rate means that the test is much more likely to identify a "positive" result that is not clinically meaningful than a "negative" result that is truly negative. The owner who receives a serum IgE test that shows 6 "positives" out of 10 ingredients is the owner who is now confused about which ingredients to avoid (the test says 6 are problems, but the test is wrong about most of them), and the owner is now faced with a confusing and unnecessarily restricted diet.

The right use of the serum IgE test. The serum IgE test is most useful for:

• The owner who is unable to perform a traditional elimination trial (the owner who has a multi-pet household, the owner who is unable to control the pet's diet, the owner who has a pet that refuses the elimination diet).

• The owner who has already performed an elimination trial and the trial was inconclusive (the trial was incomplete, the trial was not strict enough, the pet was on a medication that confounded the trial).

• The case where the elimination trial is being planned, and the test results can be used to prioritize the ingredients to include or exclude in the trial.

The serum IgE test is NOT useful for:

• The first-time diagnosis of food allergy. The first-time diagnosis should be the elimination trial, not the serum IgE test.

• The case where the test result will be used as the sole basis for the dietary change. The test result should always be confirmed (or refuted) with the elimination trial.

The intradermal food allergy test: what it is, what it measures, what it does not

The intradermal food allergy test is performed by a board-certified veterinary dermatologist, and the test involves the injection of a panel of food antigens into the skin (typically the lateral thorax or the abdomen, with the area shaved), with the reactions measured at 15–20 minutes after the injection. A positive reaction (a wheal at the injection site) indicates that the skin contains IgE antibodies specific to that ingredient, which suggests a clinical allergy to the ingredient.

What the intradermal test actually measures. The intradermal test measures the IgE antibodies that are bound to the mast cells in the skin. The IgE on the mast cells is the IgE that is responsible for the immediate (Type I) hypersensitivity reaction, and the IgE is the most clinically relevant IgE for the food allergy. The intradermal test is, in principle, a more direct measure of the clinically relevant IgE than the serum test (which measures the circulating IgE, not the cell-bound IgE).

The advantages of the intradermal test over the serum test.

• The intradermal test measures the cell-bound IgE, which is the more clinically relevant IgE.

• The intradermal test is more sensitive (the test detects lower levels of IgE than the serum test) and more specific (the test has fewer false positives).

• The intradermal test is performed by a board-certified dermatologist, which means the test is interpreted in the context of the clinical exam and the history.

The limitations of the intradermal test.

• The intradermal test requires sedation (the test requires multiple injections and the waiting period for the reaction).

• The intradermal test requires the pet to be off steroids for 2–4 weeks prior (the steroids suppress the skin reactivity, and the test is unreliable in the presence of the steroids).

• The intradermal test is more expensive than the serum test.

• The intradermal test is performed only by specialists (which may require travel and a referral).

• The intradermal test still requires the elimination trial confirmation. The intradermal test is more reliable than the serum test, but the intradermal test is not a definitive diagnostic.

The right use of the intradermal test. The intradermal test is most useful for:

• The case where the elimination trial has been inconclusive or impractical.

• The case where the owner wants the most reliable test result before committing to a long-term dietary change.

• The case where the pet is also being tested for environmental allergies (the intradermal test can be combined with the environmental allergy test, often with the same sedation event).

The interpretation of the test results

The interpretation of the food allergy test results, regardless of the test type, requires the same framework:

The result is a "screen," not a "diagnosis." The result is a list of ingredients to consider for the elimination trial, not a list of ingredients to avoid for the rest of the pet's life. The result must be confirmed (or refuted) by the elimination trial.

The "negative" result does not rule out the food allergy. The false-negative rate of both tests is non-zero, and the dog or cat that has a clinical food allergy may have a negative test result. The "negative" result is a useful data point, but the "negative" result is not a definitive exclusion of the food allergy.

The "positive" result does not confirm the food allergy. The false-positive rate of both tests is significant, and the dog or cat that has a positive test result may not have a clinical food allergy. The "positive" result is a useful data point for prioritizing the elimination trial, but the "positive" result is not a definitive confirmation of the food allergy.

The rechallenge is the final word. The elimination trial with the rechallenge is the only definitive diagnostic, and the rechallenge is the test that confirms or refutes the test result. The pet that has a positive serum IgE test for chicken and a positive intradermal test for chicken, and that improves on a chicken-free diet, and that relapses on the chicken rechallenge, is the pet that has a confirmed chicken allergy. The pet that has a positive serum IgE test for chicken but that does not relapse on the chicken rechallenge is the pet that has a sensitization, not a clinical allergy.

The relationship to the elimination trial

The food allergy test, whether the serum or the intradermal, is most useful when used in conjunction with the elimination trial, not as a replacement for the trial. The framework:

Step 1: Consider the elimination trial first. The pet with the suspected food allergy should be started on the elimination trial, with the trial being the first-line intervention. The trial is the most reliable diagnostic, and the trial produces the most actionable information.

Step 2: Consider the test if the trial is inconclusive or impractical. The pet that has been through a proper elimination trial that did not produce a clear result, or the pet for whom the trial is impractical (the multi-pet household, the pet that refuses the diet), is the pet for whom the test is most useful.

Step 3: Use the test result to prioritize the rechallenge. The pet that has a positive test result for several ingredients is the pet for whom the rechallenge can be prioritized (the most "positive" ingredients are tested first in the rechallenge, the less "positive" ingredients are tested second). The test result is a prioritization tool, not a dietary prescription.

Step 4: Confirm the test result with the rechallenge. The ingredient that is "positive" on the test should be introduced in the rechallenge, and the rechallenge should confirm or refute the clinical allergy. The "positive" test result that is not confirmed by the rechallenge is a sensitization, not a clinical allergy.

The four mistakes that turn a useful tool into a confusing one

Mistake 1: Using the serum IgE test as the first-line diagnostic. The most common mistake. The owner has a dog with chronic skin signs, the vet runs the serum IgE test, the test shows 5 "positives," and the owner is now restricting the diet based on the test. The 5 "positives" are mostly false positives, the dietary restriction is unnecessary, and the dog's actual food allergy (or the actual atopic dermatitis, or the actual flea allergy) is not being addressed. The fix is the elimination trial first, the test second.

Mistake 2: Skipping the rechallenge. The second mistake. The pet has a "positive" test result, the pet is put on a restricted diet, the pet improves, the owner concludes that the food allergy is confirmed. The improvement on the restricted diet may be due to the elimination of an actual allergen, or the improvement may be due to the change in the food (the new food may be more digestible, the new food may have a different nutrient profile, the improvement may be due to the placebo effect of the owner). The only way to confirm the food allergy is the rechallenge. The fix is the rechallenge.

Mistake 3: Using the test result as a permanent dietary prescription. The third mistake. The pet has a "positive" test result for several ingredients, the owner is told to avoid those ingredients for the rest of the pet's life, and the pet is on a restricted diet that may not be necessary. The test result is a screening result, not a permanent prescription. The fix is the elimination trial, the rechallenge, and the long-term dietary management based on the confirmed results.

Mistake 4: Ignoring the test result because of the "false positive" risk. The fourth mistake. The owner has heard that the test is unreliable, the owner dismisses the test result entirely, and the owner misses the opportunity to prioritize the rechallenge. The test result, when used appropriately, is a useful prioritization tool, and the test result should not be ignored. The fix is the appropriate use of the test (the elimination trial first, the test to prioritize, the rechallenge to confirm).

The bottom line

The food allergy testing is a useful tool when used in the right context, and the food allergy testing is a misleading tool when used in the wrong context. The serum IgE test is the more accessible but the less reliable test. The intradermal test is the more reliable but the less accessible test. The elimination trial with the rechallenge is the definitive diagnostic, and the rechallenge is the test that the food allergy test cannot replace.

The owner who understands the difference between the two tests, who uses the test appropriately, and who confirms the test result with the rechallenge is the owner who has a pet that is correctly diagnosed. The owner who uses the test as a replacement for the elimination trial is the owner who has a pet that is incorrectly diagnosed. The difference is the appropriate use. The appropriate use is the framework above. The framework, applied with discipline, is the right prevention.

The pet with the correctly diagnosed food allergy is a pet that is on the right long-term diet, that is comfortable, and that is not on unnecessary restrictions. The pet with the incorrectly diagnosed food allergy is a pet that is on the wrong diet, that is still symptomatic, or that is on unnecessary restrictions. The difference is the diagnosis. The diagnosis is the framework above. The framework, applied with discipline, is the right prevention.

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About the author

Hannah Kim, DVM, DACVD, is a board-certified veterinary dermatologist and internal-medicine consultant with a focus on food allergy, environmental allergy, and the differentiation of the two. She has a particular interest in the appropriate use of allergy testing, the elimination trial as the gold standard diagnostic, and the practical management of food-allergic pets. She runs a busy referral practice in the Pacific Northwest and writes regularly on the practical interface between diagnostic rigor and clinical reality in veterinary dermatology.