Allergy blood testing: A practical guide for clinicians

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ABSTRACTBlood tests are available that measure levels of immunoglobulin E (IgE) against specific allergens such as foods, inhalants, medications, latex, and venoms. These tests can confirm the diagnosis of an allergic disorder, supplementing a clinical history consistent with an immediate allergic reaction. They are particularly useful when skin testing cannot or should not be performed.


  • Specific IgE levels higher than 0.35 kU/L suggest sensitization, but that is not synonymous with clinical disease.
  • Prospective studies have identified IgE levels that can predict clinical reactivity with greater than 95% certainty for certain foods, but similar studies have not been performed for most other foods, drugs, latex, or venom.
  • The likelihood of an IgE-mediated clinical reaction often increases with the level of specific IgE, but these levels do not predict severity or guarantee a reaction will occur.
  • The sensitivity of allergy blood tests ranges from 60% to 95%, and the specificity ranges from 30% to 95%.
  • In the appropriate setting, these tests can help in identifying specific allergens and assessing allergic disease.
  • Neither allergy blood testing nor skin testing should be used for screening: they may be most useful as confirmatory tests when the patient’s history is compatible with an IgE-mediated reaction.



Health care providers often need to evaluate allergic disorders such as allergic rhinoconjunctivitis, asthma, and allergies to foods, drugs, latex, and venom, both in the hospital and in the clinic.

Unfortunately, some symptoms, such as chronic nasal symptoms, can occur in both allergic and nonallergic disorders, and this overlap can confound the diagnosis and therapy. Studies suggest that when clinicians use the history and physical examination alone in evaluating possible allergic disease, the accuracy of their diagnoses rarely exceeds 50%.1

Blood tests are now available that measure immunoglobulin E (IgE) directed against specific antigens. These in vitro tests can be important tools in assessing a patient whose history suggests an allergic disease.2 However, neither allergy skin testing nor these blood tests are intended to be used for screening: they may be most useful as confirmatory diagnostic tests in cases in which the pretest clinical impression of allergic disease is high.


In susceptible people, IgE is produced by B cells in response to specific antigens such as foods, pollens, latex, and drugs. This antigen-specific (or allergen-specific) IgE circulates in the serum and binds to high-affinity IgE receptors on immune effector cells such as mast cells located throughout the body.

Upon subsequent exposure to the same allergen, IgE receptors cross-link and initiate downstream signaling events that trigger mast cell degranulation and an immediate allergic response—hence the term immediate (or Gell-Coombs type I) hypersensitivity.3

Common manifestations of type I hypersensitivity reactions include signs and symptoms that can be:

  • Cutaneous (eg, acute urticaria, angioedema)
  • Respiratory (eg, acute bronchospasm, rhinoconjunctivitis)
  • Cardiovascular (eg, tachycardia, hypotension)
  • Gastrointestinal (eg, vomiting, diarrhea)
  • Generalized (eg, anaphylactic shock). By definition, anaphylaxis is a life-threatening reaction that occurs on exposure to an allergen and involves acute respiratory distress, cardiovascular failure, or involvement of two or more organ systems.4


The blood tests for allergic disease are immunoassays that measure the level of IgE specific to a particular allergen. The tests can be used to evaluate sensitivity to various allergens, for example, to common inhalants such as dust mites and pollens and to foods, drugs, venom, and latex.

Types of immunoassays include enzyme-linked immunosorbent assays (ELISAs), fluorescent enzyme immunoassays (FEIAs), and radioallergosorbent assays (RASTs). At present, most commercial laboratories use one of three autoanalyzer systems to measure specific IgE:

  • ImmunoCAP (Phadia AB, Uppsala, Sweden)
  • Immulite (Siemens AG, Berlin, Germany)
  • HYTEC-288 (Hycor/Agilent, Garden Grove, CA).

These systems use a solid-phase polymer (cellulose or avidin) in which the antigen is embedded. The polymer also facilitates binding of IgE and, therefore, increases the sensitivity of the test.5 Specific IgE from the patient’s serum binds to the allergen embedded in the polymer, and then unbound antibodies are washed off.

Despite the term “RAST,” these systems do not use radiation. A fluorescent antibody is added that binds to the patient’s IgE, and the amount of IgE present is calculated from the amount of fluorescence.6 Results are reported in kilounits of antibody per liter (kU/L) or nanograms per milliliter (ng/mL).5–7


In general, the sensitivity of these tests ranges from 60% to 95% and their specificity from 30% to 95%, with a concordance among different immunoassays of 75% to 90%.8

Levels of IgE for a particular allergen are also divided into semiquantitative classes, from class I to class V or VI. In general, class I and class II correlate with a low level of allergen sensitization and, often, with a low likelihood of a clinical reaction. On the other hand, classes V and VI reflect higher degrees of sensitization and generally correlate with IgE-mediated clinical reactions upon allergen exposure.

The interpretation of a positive (ie, “nonzero”) test result must be individualized on the basis of clinical presentation and risk factors. A specialist can make an important contribution by helping to interpret any positive test result or a negative test result that does not correlate with the patient’s history.


Allergy blood testing is convenient, since it involves only a standard blood draw.

In theory, allergy blood testing may be safer, since it does not expose the patient to any allergens. On the other hand, many patients experience bruising from venipuncture performed for any reason: 16% in one survey.9 In another survey,10 adverse reactions of any type occurred in 0.49% of patients undergoing venipuncture but only in 0.04% of those undergoing allergy skin testing. Therefore, allergy blood testing may be most appropriate in situations in which a patient’s history suggests that he or she may be at risk of a systemic reaction from a traditional skin test or in cases in which skin testing is not possible (eg, extensive eczema).

Another advantage of allergy blood testing is that it is not affected by drugs such as antihistamines or tricyclic antidepressants that suppress the histamine response, which is a problem with skin testing.

Allergy blood testing may also be useful in patients on long-term glucocorticoid therapy, although the data conflict. Prolonged oral glucocorticoid use is associated with a decrease in mast cell density and histamine content in the skin,11,12 although in one study a corticosteroid was found not to affect the results of skin-prick testing for allergy.13 Thus, allergy blood testing can be performed in patients who have severe eczema or dermatographism or who cannot safely suspend taking antihistamines or tricyclic antidepressants.


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