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.
Inhalants
Common aeroallergens associated with allergic rhinitis, allergic conjunctivitis, and allergic asthma include dust mites, animal dander, cockroach debris, molds, trees, grasses, weeds, and ragweed. Dust mites, animal dander, and mold spores are perennial allergens and may trigger symptoms year-round. Pollen, including pollen from trees, grasses, and weeds, is generally present in a seasonal pattern in many parts of the United States.
A positive blood test for an inhalant allergen can reinforce the physician’s clinical impression in making a diagnosis of allergic rhinoconjunctivitis. Interestingly, studies have suggested a high rate of false-positives based on history alone when in vivo and in vitro allergy testing were negative for IgE-mediated respiratory disease.21
Various studies have aimed to establish threshold values of aeroallergen-specific IgE that predict the likelihood of clinically relevant disease. Unfortunately, other factors also contribute to clinical symptoms of rhinoconjunctivitis; these include concurrent inflammation, infection, physical stress, psychological stress, exposure to irritants, and hormonal changes. These factors introduce variability and make specific IgE cutoffs for inhalant allergens unreliable.22
Prospective studies have suggested that skin testing correlates better with nasal allergen challenge (the gold standard) than blood testing for the diagnosis of inhalant allergy, though more recent studies using modern technologies demonstrate reasonable concordance (67%) between skin testing and blood testing (specifically, ImmunoCAP).23,24 According to current guidelines, skin tests are the preferred method for diagnosing IgE-mediated sensitivity to inhalants.25
Compared with skin prick tests as the gold standard, the sensitivity of specific IgE immunoassays is approximately 70% to 75%.25 Nevertheless, specific IgE values greater than 0.35 kU/L are generally considered positive for aeroallergen sensitization, although lower levels of dog-specific IgE have recently been shown to correlate with clinical disease.14
Drugs, including penicillins
A variety of clinical reactions can occur in response to oral, intravenous, or topical medications.
At present, blood tests are available for the evaluation of IgE-mediated adverse reactions to only a limited number of drugs. Reactions involving other mechanisms, such as those related to the drug’s metabolism, intolerances (eg, nausea), idiosyncratic reactions (eg, Stevens-Johnson syndrome, the DRESS syndrome), or other types of reactions can be diagnosed only by history and physical examination.
The development of specific IgE tests for sensitivity to medications has been limited by incomplete characterization of metabolic products and the possibility that a single medication can have different epitopes or IgE binding sites in different individuals.26
In vitro allergy testing has been most studied for beta-lactam antibiotics (eg, penicillin) and not so much for other drugs.
Table 2 summarizes the sensitivity and specificity of blood allergy tests that are commercially available for drugs.
Penicillin, a beta-lactam antibiotic, is degraded into various metabolites known as the major determinant (penicilloyl) and the minor determinants (eg, benzylpenicilloate and benzylpenilloate), which act as haptens. Specific IgE testing is not available for all these determinants.
The sensitivity of blood tests for allergy to penicilloyl (penicillin) and amino-penicillins such as amoxicilloyl (amoxicillin) is reported as between 32% and 50%, and the specificity as 96% to 98%.29
By definition, any nonzero level of IgE specific for penicillin or its derivatives is considered a positive result and may be associated with a higher risk of IgE-mediated reaction to penicillins. However, in a situation analogous to that in people with food allergy who have a food-specific IgE titer lower than the empirically established threshold value (Table 1), low-titer values to penicillin may not predict anaphylactic sensitivity in a penicillin oral challenge.28 Further studies are needed to determine if there is a threshold level of penicillin-specific IgE above which a patient has a higher likelihood of an IgE-mediated systemic reaction.
Other drugs. Specific IgE blood tests are also available for certain neuromuscular agents, insulin, cefaclor (Ceclor), chlorhexidine (contained in various antiseptic products), and gelatin (Table 2). These substances have not been as well studied as penicillins, and the sensitivity and specificity data reported in Table 2 are limited by few studies and small study sizes.
Neuromuscular blocking agents. Tests for IgE against neuromuscular blocking agents are reported to have low sensitivity (30%–60%) using a cutoff value of 0.35 kU/L.30 In small studies, the sensitivity was higher (68% to 92%) when threshold values for rocuronium-specific IgE were lowered from 0.35 to 0.13 kU/L.29
Chlorhexidine, an antiseptic commonly used in surgery, has been linked to IgE-mediated reactions.31 Chlorhexidine-specific IgE levels greater than 0.35 kU/L are considered positive, based on very limited data.
Insulin. Blood tests for allergy to insulin are also commercially available. However, studies have shown a significant overlap in the range of insulin-specific IgE in patients with a clinical history consistent with insulin allergy and in controls. Therefore, this test has a very limited ability to distinguish people who do not have a history of a reaction to insulin.32 More research is needed to determine the clinical utility of insulin-specific IgE testing.
Gelatin. IgE-mediated reactions have occurred after exposure to gelatin (from either cows or pigs) contained in foods and vaccines, including measles-mumps-rubella and yellow fever. One study identified gelatin-specific IgE in 10 of 11 children with a history of systemic reaction to measles or mumps vaccine.33 In the same study, gelatin-specific IgE levels were negative in 24 children who had developed non-IgE-mediated reactions to the vaccine.33
Tests for IgE against bovine gelatin are commercially available; results are considered positive for values higher than 0.35 kU/L. A negative test result does not exclude the possibility of an allergic reaction to porcine gelatin, which can also be found in foods and vaccines, but tests for anti-porcine gelatin IgE are not commercially available.
