At a Glance

Patients with seasonal or chronic rhinitis, asthma, hives, or atopic dermatitis should be evaluated for possible environmental exposures. When the history suggests an environmental cause, allergic disorders are commonly considered.

A history of an anaphylactic reaction to a food, drug, venom, or other exposure is an indication for allergy testing if the cause of the anaphylactic reaction is not clear or warrants confirmatory testing.

What Tests Should I Request to Confirm My Clinical Dx? In addition, what follow-up tests might be useful?

If a history of exposure clarifies what allergens are responsible for symptoms, which is a common situation, then avoiding the responsible allergens can be both diagnostic and therapeutic. In some cases, avoidance can be supplemented by use of antihistamines or other symptomatic treatment. When identification or confirmation of an allergen is indicated, additional testing can be done.

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For atopic/allergic asthma, rhinitis, or conjunctivitis, consider testing for inhalant allergens. If the symptoms are seasonal, then tests should be driven by the allergens associated with that season (e.g., pollens in the spring). For unexplained hives or angioedema, anaphylaxis, or suspected allergic gastroenteritis, consider testing for food allergies. For suspected allergic eczema, inhalants or food allergies can be considered. For suspected latex rubber, penicillin, or venom allergies, specific tests can be ordered.

The common forms of allergy testing include in vivo allergy testing by use of skin tests (skin prick or skin puncture) or in vitro allergy testing by measuring allergen-specific IgE. The immunoglobulin IgE mediates many, but not all, allergic disorders. Generally, in vivo skin testing is a more reliable test modality than in vitro laboratory testing. Skin tests are insensitive, however, in patients taking systemic corticosteroids, antihistamines or drugs with antihistaminic effects, or other drugs that would block the in vivo effect of the allergen. In addition, skin testing should be used with caution or avoided in patients who have had life-threatening reactions, such as anaphylaxis, who have severe skin disease or who have other contraindications.

Some providers may not offer skin testing for logistic or other reasons. Another indication for in vitro testing is in the situation in which in vivo testing fails to confirm a clinical impression or explain a clinical phenomenon, since in vivo skin testing may be unreliable for some allergens (e.g., venom exposures). Allergen-specific IgE testing serves as an alternative to in vivo skin tests and a supplemental form of testing.

Measurement of allergen-specific IgE can help identify a suspected exposure implicated as the cause of a patient’s allergic condition. Finding a positive test for IgE antibodies directed against an allergen considered a possible cause lends support to that clinical consideration. However, the positive and negative predictive values of allergy testing is imperfect, thus, test results should be considered probabilistic (i.e., increasing the probability with positive test results and decreasing the probability with negative results), but not diagnostic or definitive.

The sensitivity of allergen-specific IgE assays compared with in vivo skin tests ranges from less than 50% to more than 90%, with the average approximately 75%. Allergen-specific IgE assays tend to be more predictive of clinical features when testing for pollens, foods that cause anaphylaxis, house dust mites, animal danders, and fungi and less reliable for assessing allergies to venoms, drugs, and chemicals.

Hundreds of substances have been implicated as causes of allergies. When testing for inhalant allergies (e.g., to evaluate asthma or rhinitis), knowledge of common local plants that cause allergic reactions is important to prioritize testing. Local or regional allergy panels can sometimes be helpful to initiate testing.

IgE allergen measurements are more likely associated with clinical symptoms and outcomes for some allergens than others. Very high serum levels are more likely associated with clinical food or inhalant allergies than are low levels of allergen-specific IgE response. (Table 1)

Table 1.
Cat dander IgE Dog dander IgE
25 kUA/L <0.1 kUA/L

This pattern of results suggests allergy to cats, for example.

Are There Any Factors That Might Affect the Lab Results? In particular, does your patient take any medications – OTC drugs or Herbals – that might affect the lab results?

In vitro allergy testing by measurement of IgE anti-allergens depends on the nature of the allergen used in the test. Often, allergens are prepared from biological materials (e.g., cat or dog dander, microbes, plant material, etc.), and standardization of the antigen material can be difficult. Furthermore, different patients may react to different portions of the allergens. Assays from different vendors and using different allergen sources in the assays can vary considerably, and quantitative results using one method often correlate poorly with quantitative results using another method.

Cross-reactive antibodies can lead to confusing results. For example, antibodies to wasp and hornet venoms may cross react with venoms from other species, leading to results that do not predict clinical allergies or reactions.

Very elevated levels of total serum IgE (e.g., >10,000 kU/L) can lead to false-positive results in allergen-specific IgE test results. If multiple allergen-specific IgE test results are elevated and the total IgE concentration is extremely elevated, dilutions studies or in vivo skin tests may clarify whether a particular allergen test is clinically positive. Very elevated total serum IgE concentrations can be found in patients with severe atopic backgrounds, the rare condition of IgE multiple myeloma with monoclonal IgE, allergic bronchopulmonary aspergillosis (a condition caused by bronchial colonization by Aspergillus, leading to severe recurrent asthma attacks and progressive pulmonary dysfunction), and occasionally other situations.

Very high levels of anti-allergen antibodies of another isotype (e.g., IgG or IgM) may block detection of IgE antibodies to the allergen of interest.

What Lab Results Are Absolutely Confirmatory?

No lab results are absolutely confirmatory of allergies. The lab results must always be interpreted together with history and physical findings, as well as other available information, including skin tests, challenge or provocative tests, clinical responses, etc.

What Tests Should I Request to Confirm My Clinical Dx? In addition, what follow-up tests might be useful?

After an episode of anaphylaxis, serum tryptase levels may remain elevated for several hours and can help clarify and document a diagnosis of anaphylaxis. Serum IgE levels do not change substantially during an episode of anaphylaxis.

Are There Any Factors That Might Affect the Lab Results? In particular, does your patient take any medications – OTC drugs or Herbals – that might affect the lab results?

The total serum IgE concentration must be measured when considering administration of the therapeutic anti-IgE monoclonal antibody omalizumab, since the drug dose depends, in part, on the serum IgE concentrations.

A number of drugs may cause anaphylactic reactions, including hypotension, bronchospasm, urticaria, etc., that are not due to IgE. For example, iodinated radiocontrast dye reactions and reactions to local anesthetics are rarely due to IgE antibodies. When a reaction follows exposure to a drug known to cause drug reactions not usually immunologically (IgE) mediated, such as iodinated radiology contrast dyes, then IgE allergen testing is likely not helpful in establishing a diagnosis.

Elevated serum concentrations of IgE are associated with certain primary immunodeficiency disorders, including very high concentrations associated with the hyper-IgE syndrome (formerly known as Job’s syndrome, with recurrent pyogenic infections and dermatitis). Nonspecific IgE elevations are also seen in patients with ataxia telangiectasia, Wiskott-Aldrich syndrome, and DiGeorge syndrome.

Notably, severe combined immunodeficiency (SCID) patients do not have elevated IgE, and, in fact, their IgE serum concentrations are typically undetectable. Since therapeutic preparations of gamma globulin given intravenously and subcutaneously usually do not contain IgE, the presence of IgE in serum of patients can be helpful in the differential diagnosis of immunodeficiency syndromes, even after gamma globulin administration.