Allergy blood testing: A practical guide for clinicians
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.
KEY POINTS
- 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.
Latex
Latex, obtained from the rubber tree Hevea brasiliensis, has 13 known polypeptides (allergens Hev b 1–13) that cause IgE-mediated reactions, particularly in health care workers and patients with spina bifida.34 Overall, the incidence of latex allergy has decreased in the United States as most medical institutions have implemented a latex-free environment.
In vitro testing is the only mode of evaluation for allergy to latex approved by the US Food and Drug Administration (FDA).35 Its sensitivity is 80% and its specificity is 95%.36
In a 2007 study, 145 people at risk for latex allergy, including 104 health care workers, 31 patients with spina bifida, and 10 patients requiring multiple surgeries, underwent latex-specific IgE analysis for sensitivity to various recombinant and native latex allergens.34 The three groups differed in their latex allergy profiles, highlighting the diversity of clinical response to latex in high-risk groups and our current inability to establish specific cutoff points for quantitative latex-specific IgE. Thus, at present, any nonzero latex-specific IgE value is considered positive.
A formal evaluation for allergy is recommended for patients who have a strong history of an IgE-mediated reaction to latex and a latex-specific IgE value of zero. Blood tests for allergy to some native or recombinant latex allergens are available; these allergens may be underrepresented in the native total latex extract.33 Skin testing for allergy to latex, although not FDA-approved or standardized, can also be useful in this setting.37
Insect venom
Type I hypersensitivity reactions can occur from the stings of Vespidae (vespids), Apidae (bees), and Formicidae (fire ants). Large localized reactions after an insect sting are not infrequent and typically do not predict anaphylactic sensitivity with future stings, even though they are considered mild IgE-mediated reactions. However, systemic reactions are considered life-threatening and warrant allergy testing.38
The level of venom-specific IgE usually increases weeks to months after a sting.39 Therefore, blood tests can be falsely negative if performed within a short time of the sting.
Patients who have suffered a systemic reaction to venom and have evidence of sensitization by either in vitro or in vivo allergy testing are candidates for venom immunotherapy.40
At present, any nonzero venom-specific IgE test is considered positive, as there is no specific value for venom-specific IgE that predicts clinical risk.
A negative blood test does not exclude the possibility of an IgE-mediated reaction.41 In cases in which a patient has a clinical history compatible with venom allergy but the blood test is negative, the patient should be referred to an allergist for further evaluation, including venom skin testing and possibly repeat blood testing at a later time.
Conversely, specific IgE testing to venom is recommended when a patient has a history consistent with venom allergy and negative skin test results.38
As mentioned previously, in vitro test performance can vary with the laboratory and testing method used, and sending samples directly to a reference laboratory could be considered.41
TESTING FOR IgG AGAINST FOODS IS UNVALIDATED AND INAPPROPRIATE
In recent years, some practitioners of alternative medicine have started testing for allergen-specific IgG or IgG4 as part of evaluations for hypersensitivity, especially in cases in which patients describe atypical gastrointestinal, neurologic, or other symptoms after eating specific foods.19
However, this testing often finds IgG or IgG4 against foods that are well tolerated. At present, allergen-specific IgG testing lacks scientific evidence to support its clinical use in the evaluation of allergic disease.5,19
