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Smart Testing

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

Cheryl K. Lau, PhD and Christopher Naugler, MD, CCFP, FCFP, FRCPC
Cleveland Clinic Journal of Medicine January 2016, 83 (1) 21-24; DOI: https://doi.org/10.3949/ccjm.83a.14125
Cheryl K. Lau
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Christopher Naugler
Division Head, General Pathology, Department of Pathology and Laboratory Medicine, Department of Family Medicine, Associate Professor, University of Calgary, Alberta, Canada
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A 25-year-old man is evaluated for angio-edema (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.

SERUM ALLERGEN-SPECIFIC IgE TESTING

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

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TABLE 1

Suggested evaluations for the five major allergen groups

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.

NOT A RELIABLE DIAGNOSTIC TOOL

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.

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

FIGURE 1
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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.

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 sub-optimally, 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.

CHOOSING WISELY

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

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TABLE 2

IgE-mediated vs non–IgE-mediated food allergy

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.

CLINICAL BOTTOM LINE

Ordering diagnostic tests that have little clinical utility has long-term detrimental effects on both patient safety and healthcare sustainability.

In the case of the 25-year-old evaluated for shellfish allergy, the clinician should first explain that the swelling of the lips and tongue (angioedema) does suggest an IgE-mediated allergic reaction and not a non–IgE-mediated allergic reaction or a food intolerance. Non–IgE-mediated food allergies and food intolerances are marked by symptoms relating mainly to nonimmune aspects of the digestive system, whereas IgE-mediated food allergies affect the immune system and can involve a multitude of organs, including the skin and the respiratory and digestive systems (Table 2).

However, clinicians should avoid indiscriminately ordering food allergen IgE panels and instead should focus on foods likely to be the culprits based on the clinical history.9 In discriminate testing can lead to false-positive results and unnecessary food avoidance.

Since the patient developed symptoms of angioedema when he was exposed to his allergen, he may be apprehensive about a skin-prick test and the possibility of being subjected to the same discomfort. Therefore, in this situation, it may be best to perform serum IgE tests, but on a few targeted seafoods rather than the food panel the physician had ordered. A patient can be sensitized to an allergen (possess IgE antibodies) but not experience symptoms when exposed to it (ie, have tolerance).5 Also, false-negative results may occur, so a negative serum allergen-specific IgE test should likewise be interpreted in light of the pretest probability of allergy to a specific antigen.

If the history and the results of testing are not clear and congruent, the patient should be referred to an allergist for diagnosis or for management. The allergist can provide management techniques and periodic assessment as to the progression and resolution of the allergy. Table 2 highlights symptoms that differentiate an IgE-mediated from a non–IgE-mediated food allergy.10,11 Table 1 presents clinical indications and suggested diagnostic methods to the five most common allergen groups and the diagnostically invalid tests.1–6

The bottom line is that we must consider the poor performance of serum allergen-specific IgE tests when diagnosing and treating suspected type I allergies and avoid ordering food allergen IgE panels whenever possible.

Footnotes

  • ↵* Dr. Naugler has disclosed performing informatics consulting for Abbott Laboratories.

  • Copyright © 2016 The Cleveland Clinic Foundation. All Rights Reserved.

REFERENCES

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    1. Bernstein IL,
    2. Li JT,
    3. Bernstein DI,
    4. et al
    5. American Academy of Allergy, Asthma and Immunology
    6. American College of Allergy, Asthma and Immunology
    . Allergy diagnostic testing: an updated practice parameter. Ann Allergy Asthma Immunol 2008; 100(suppl 3):S1–S148.
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    1. Bird JA,
    2. Crain M,
    3. Varshney P
    . Food allergen panel testing often results in misdiagnosis of food allergy. J Pediatr 2015; 166:97–100.
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    1. Kattan JD,
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    . Optimizing the diagnosis of food allergy. Immunol Allergy Clin North Am 2015; 35:61–76.
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    1. Sampson HA,
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    . Food allergy: epidemiology, pathogenesis, diagnosis, and treatment. J Allergy Clin Immunol 2014; 133:291–308.
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    1. Siles RI,
    2. Hsieh FH
    . Allergy blood testing: a practical guide for clinicians. Cleve Clin J Med 2011; 78:585–592.
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    1. Wians FH Jr.
    . Clinical laboratory tests: which, why, and what do the results mean? Lab Medicine 2009; 40:105–113.
    OpenUrlCrossRef
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    1. Choosing Wisely
    . American Academy of Allergy, Asthma & Immunology. Ten Things Physicians and Patients Should Question. www.choosingwisely.org/doctor-patient-lists/american-academy-of-allergy-asthma-immunology/. Accessed December 3, 2015.
  7. ↵
    1. Fleischer DM,
    2. Burks AW
    . Pitfalls in food allergy diagnosis: serum IgE testing. J Pediatr 2015; 166: 8–10.
    OpenUrl
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    1. Boyce JA,
    2. Assaad A,
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    5. NIAID-Sponsored Expert Panel
    . Guidelines for the diagnosis and management of food allergy in the United States: summary of the NIAID-sponsored expert panel report. J Allergy Clin Immunol 2010; 126:1105–1118.
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    1. Stiefel G,
    2. Roberts G
    . How to use serum-specific IgE measurements in diagnosing and monitoring food allergy. Arch Dis Child Educ Pract Ed 2012; 97:29–36.
    OpenUrlFREE Full Text
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Serum allergen-specific IgE testing: How much is too much?
Cheryl K. Lau, Christopher Naugler
Cleveland Clinic Journal of Medicine Jan 2016, 83 (1) 21-24; DOI: 10.3949/ccjm.83a.14125

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Serum allergen-specific IgE testing: How much is too much?
Cheryl K. Lau, Christopher Naugler
Cleveland Clinic Journal of Medicine Jan 2016, 83 (1) 21-24; DOI: 10.3949/ccjm.83a.14125
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