Smart Testing

Serum allergen-specific IgE testing: How much is too much?

Author and Disclosure Information



A 25-year-old man is evaluated for angioedema (swelling of lips and tongue) after eating paella at a Spanish restaurant. He has no history of allergies, but he says he had never eaten such a large variety of seafood before, especially shellfish.

He suspects that he is allergic to shellfish and asks the attending physician to order blood tests for seafood allergies, as he heard from a friend that blood tests are superior to other types of tests for allergy. The physician requests a serum immunoglobulin E (IgE) food panel test for this patient.


Many methods of testing for allergy are available, including the skin-prick test, double-blind and single-blind placebo-controlled food challenges, open food challenges, inhalant challenges, drug challenges, and serum IgE tests. In clinical practice, these tests are often used in combination because when used individually, few of them are both highly sensitive and specific (Table 1).1–6

Skin-prick testing is generally the method of choice for the preliminary evaluation of IgE-mediated allergies because it is more sensitive and requires less time to get a result.1 But it is not the preferred test if the patient is at risk of a systemic reaction or has widespread dermatitis, nor is it useful if the patient is taking drugs that suppress the histamine response, such as antihistamines or tricyclic antidepressants.6 Moreover, skin-prick testing is more invasive and time-consuming than serum IgE testing.

Serum IgE testing is an attractive alternative, and it is more convenient because it requires only a single blood draw and poses a lower risk of adverse effects.


As serum IgE testing has gained popularity, researchers have tried to improve its diagnostic power (ie, maximize its sensitivity and specificity) by determining the best cutoff values for IgE against specific antigens. Unfortunately, these values are difficult to determine because of confounding factors such as the lack of a reference standard, population diversity, patient atopy, and the overwhelming number of allergens that must be examined.

In addition, some researchers have used positive and negative predictive values to evaluate diagnostic cutoffs for serum antigen-specific IgE values. But these are not the most suitable performance measure to evaluate because they depend on disease prevalence and population characteristics.

Despite these efforts, results are still conflicting, and serum antigen-specific IgE testing is not a reliable diagnostic tool.

Figure 1. Sum of sensitivity and specificity of serum antigen-specific IgE tests of different ImmunoCAP allergens. A sum of 170 or greater (dashed line) is considered clinically relevant; tests with IgE cutoffs greater than 0.35 kU/L are noted with an asterisk.

In an effort to gain insight from the available research data, we evaluated the clinical usefulness of 89 antigen-specific IgE tests, using an approach of summing their sensitivity and specificity. Previously, Wians7 proposed that a test is likely to be clinically useful if the sum of its sensitivity and specificity is equal to or greater than 170. Figure 1 shows the 89 tests, grouped into categories, and their summed sensitivities and specificities. The dashed line indicates a cutoff of 170; any bar that touches or crosses that line indicates that the test may be clinically useful, according to Wians.7

Only 7 of the 89 tests (cow, buckwheat, hazelnut, latex, Alternaria alternata, honey bee venom, and Johnson grass) satisfied this criterion. This suggests that a significant number of serum antigen-specific IgE tests perform suboptimally, and we are left with the question of why they are so commonly ordered.

Inappropriate use can lead to false-positive results, a situation in which patients may be subjected to unnecessary food avoidance that can result in nutritional deficiencies and decreased quality of life. It can also lead to false-negative results, when life-threatening diagnoses are missed and further excessive downstream testing is required—all leading; to negative outcomes for both patients and healthcare providers.


The Choosing Wisely campaign in the United States has partnered with the American Academy of Allergy, Asthma, and Immunology to advocate against indiscriminate IgE testing in evaluating allergy.8 Allergy diagnosis and evaluation should be based on a combination of clinical history and judicious ordering of specific IgE tests, whether through skin or blood testing. Ordering of serum allergen-specific IgE tests for food allergies should be consistent with a clinical history of potential IgE-mediated food allergy8 and not food intolerance (Table 2).4,5

Some jurisdictions in Canada have followed suit by restricting the number of serum IgE tests each physician is allowed to order per patient, to encourage more responsible ordering and to lower the number of potential false-positive results, which can lead to increased downstream costs as well as unnecessary patient worry and lifestyle modification.

Next Article:

Approach to asymptomatic creatine kinase elevation

Related Articles