Allergy blood testing: A practical guide for clinicians

LIMITATIONS OF THESE TESTS

A limitation of allergy blood tests is that there is no gold-standard test for many allergic conditions. (Double-blind, placebo-controlled oral food challenge testing has been proposed as the gold-standard test for food allergy, and nasal allergen provocation challenge has been proposed for allergic rhinitis.)

Also, allergy blood tests can give false-positive results because of nonspecific binding of antibody in the assay.

Of note: evidence of sensitization to a particular allergen (ie, a positive blood test result) is not synonymous with clinically relevant disease (ie, clinical sensitivity).

Conversely, these tests can give false-negative results in patients who have true IgE-mediated disease as confirmed by skin testing or allergen challenge. The sensitivity of blood allergy testing is approximately 25% to 30% lower than that of skin testing, based on comparative studies.² The blood tests are usually considered positive if the allergen-specific IgE level is greater than 0.35 kU/L; however, sensitization to certain inhalant allergens can occur at levels as low as 0.12 kU/L.¹⁴

Specific IgE levels measured by different commercial assays are not always interchangeable or equivalent, so a clinician should consistently select the same immunoassay if possible when assessing any given patient over time.¹⁵

Levels of specific IgE have been shown to depend on age, allergen specificity, total serum IgE, and, with inhalant allergens, the season of the year.^15,16

Other limitations of blood testing are its cost and a delay of several days to a week in obtaining the results.¹⁷

WHEN TO ORDER ALLERGY BLOOD TESTING

The allergy evaluation should begin with a thorough history to look for possible triggers for the patient’s symptoms.

For example, respiratory conditions such as asthma and rhinitis may be exacerbated during particular times of the year when certain pollens are commonly present. For patients with this pattern, blood testing for allergy to common inhalants, including pollens, may be appropriate. Similarly, peanut allergy evaluation is indicated for a child who has suffered an anaphylactic reaction after consuming peanut butter. Blood testing is also indicated in patients with a history of venom anaphylaxis, especially if venom skin testing was negative.

In cases in which the patient does not have a clear history of sensitization, blood testing for allergy to multiple foods may find evidence of sensitization that does not necessarily correlate with clinical disease.¹⁸

Likewise, blood tests are not likely to be clinically relevant in conditions not mediated by IgE, such as food intolerances (eg, lactose intolerance), celiac disease, the DRESS syndrome (drug rash, eosinophilia, and systemic symptoms), Stevens-Johnson syndrome, toxic epidermal necrolysis, or other types of drug hypersensitivity reactions, such as serum sickness.³

INTERPRETING COMMONLY ORDERED BLOOD TESTS FOR ALLERGY

Tests for allergy to hundreds of substances are available.

Foods

Milk, eggs, soy, wheat, peanuts, tree nuts, fish, and shellfish account for most cases of food allergy in the United States.¹⁸

IgE-mediated hypersensitivity to milk, eggs, and peanuts tends to be more common in children, whereas peanuts, tree nuts, fish, and shellfish are more commonly associated with reactions in adults.¹⁸ Children are more likely to outgrow allergy to milk, soy, wheat, and eggs than allergy to peanuts, tree nuts, fish, and shellfish—only about 20% of children outgrow peanut allergy.¹⁸

Patients with an IgE-mediated reaction to foods should be closely followed by a specialist, who can best help determine the appropriateness of additional testing (such as an oral challenge under observation), avoidance recommendations, and the introduction of foods back into the diet.¹⁹

Specific IgE tests for allergy to a variety of foods are available and can be very useful for diagnosis when used in the appropriate setting.

One caveat about these studies is that many were initially performed in children with a history of food allergy, many of whom had atopic dermatitis, and the findings have not been systematically reexamined in larger studies in more heterogeneous populations.

For example, at least eight studies tried to identify a diagnostic IgE level for cow’s milk allergy. The 95% confidence intervals varied widely, depending on the study design, the age of the study population, the prevalence of food allergy in the population, and the statistical method used for analysis.⁵ For most other foods for which blood tests are available, few studies have been performed to establish predictive values similar to those in Table 1.

Thus, slight elevations in antigen-specific IgE (> 0.35 kU/L) may correlate only with in vitro sensitization in a patient who has no clinical reactivity upon oral exposure to a particular antigen.

Broad food panels have been shown to have false-positive rates higher than 50%—ie, in more than half of cases, positive results have no clinical relevance. Therefore, these large food panels should not be used for screening.¹⁹ Instead, it is recommended that tests be limited to relevant foods based on the patient’s history when evaluating symptoms consistent with an IgE-mediated reaction to a particular food.

Food-specific IgE evaluation is also not helpful in evaluating non-IgE adverse reactions to foods (eg, intolerances).

Therefore, the patient’s history remains the most important tool for evaluation of food allergy. In cases in which the patient’s history suggests a food-associated IgE-mediated reaction and the blood test is negative, the patient should be referred to a specialist for skin testing with commercial extracts or even fresh food extracts, given the higher sensitivity of in vivo testing.²⁰