Q&A: Allergy test interpretations require caution
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Key takeaways:
- Blood tests do not require direct contact with the allergen but take longer than SPTs.
- SPTs often use allergen extracts instead of individual allergen molecules.
Allergy treatment relies on accurate diagnoses, but current methods such as skin, blood and provocation testing all offer limitations that can lead to false positives and other poor outcomes.
Allergists are encouraged to exercise care in interpreting any testing results. Healio spoke with Rasa Petraitytė-Burneikienė, PhD, research scientist at Vilnius University Life Sciences Centre, to find out more.
Healio: What options are available for allergists to use in diagnosing food allergy?
Petraitytė-Burneikienė: The diagnosis of food allergies is first based on the patient’s clinical history, eliminating a certain type of food from the diet and seeing if the symptoms disappear. To confirm the sensitization in IgE-mediated allergy, skin prick testing is carried out.
The allergen is applied to the skin, which is then poked with a needle, and it is observed whether the skin is reddened where the allergen was applied. If the skin reddens in the place where the allergen is applied, it may mean that the allergen is causing an allergy. Also, a blood test to detect specific IgE can be used to confirm an allergy.
It helps to distinguish true allergies from cross-reactivity due to the presence of similar proteins in different foods. If there are discrepancies between the patient’s clinical history and SPTs or blood tests, then provocation tests can be used to confirm the allergy diagnosis. In a provocation test, a person is given a specific food to eat to determine whether it will cause an allergic reaction. This test is usually performed under medical supervision.
Healio: Specifically, what are the advantages and disadvantages of blood tests?
Petraitytė-Burneikienė: Blood tests detect the presence of specific IgE molecules in the blood. An increased level of IgE antibodies in the blood indicates sensitization of the patient.
Blood tests are safe for patients because they do not have contact with the allergen, unlike in SPTs, where the allergen is applied to the skin, or in provocative tests, where the allergen is also administered, causing side symptoms.
The blood test is very useful if you have multiple allergies. During one test, sensitization to several hundred different allergens can be tested. It can provide quantitative measurements of IgE antibody levels, which allow an assessment of the severity of allergic sensitization.
The disadvantages are that the blood test takes longer to perform. Results are obtained the next day or later, for example. When doing a SPT, the results are obtained after about half an hour. A blood test also is more expensive. False-positive results are sometimes obtained because elevated IgE levels alone do not necessarily indicate allergy if you do not experience any allergy symptoms. This is called asymptomatic sensitization.
In case of asymptomatic sensitization, the human body produces IgE antibodies in response to the allergen. However, these patients do not have any allergy symptoms when exposed to that allergen because the body has mechanisms to regulate the immune response. In some cases, these mechanisms can suppress allergic reactions even in the presence of elevated IgE levels. Sometimes false negative results are obtained when the test may not detect an allergy.
Healio: What are the advantages and disadvantages of SPTs?
Petraitytė-Burneikienė: SPTs are cheaper, and results are obtained very quickly after about half an hour. However, the test requires the patient’s skin to be clear. If the patient has eczema, such a test cannot be performed.
Also, antihistamines should be discontinued before this test, as the results may be skewed. Moreover, during the test, the patient may experience systemic allergic reactions of varying severity. Most often, SPTs use allergen extracts instead of individual allergen molecules, so due to the use of non-standardized extracts, the tested extract may not contain the allergen, and then we will not detect an allergy using that extract.
Especially during the preparation of fruit and vegetable extracts, individual allergens in them are very unstable. They can break down, and then the commercially-prepared extract may contain very small amounts or none at all. It is also possible to obtain inaccurate results due to cross-reactions that occur.
Healio: Do provocation tests have any advantages or disadvantages?
Petraitytė-Burneikienė: The main advantage of provocative tests is their ability to accurately confirm a diagnosis when other tests, such as blood tests, SPTs or clinical history, yield inconclusive results. These tests ensure that if the patient is allergic, the symptoms will appear, thereby the diagnosis will be clarified.
However, allergen provocation tests are not useful in assessing the severity of an allergy. They can only determine an allergy is present, not the severity of an allergy. For example, a weak reaction to a provocation test at the time of examination does not mean that subsequent responses will also be mild, as they can occur when the patient is not in good health or accidentally ingesting a larger amount of allergen that can cause more serious reactions.
The main disadvantage is that systemic reactions, sometimes even severe, and even anaphylaxis are possible during this test, so such tests are performed only under medical supervision.
Healio: What kinds of consequences might result from inaccurate results from these tests?
Petraitytė-Burneikienė: The consequences are unnecessary dietary restrictions, where a person might eliminate certain foods from their diet despite being able to consume them safely. An incorrect diagnosis can also lead to inappropriate treatment that consequently can develop into more serious diseases and complications, including a risk for an anaphylactic reaction. Without a correct diagnosis, individuals also may not have essential emergency medications, increasing the risk for an unexpected reaction.
Healio: Considering these limitations, what can allergists do to ensure more accurate diagnoses?
Petraitytė-Burneikienė: In allergology, it is not possible to rely on the results of only one test. The results of blood and SPTs must be supported by a comparison of the symptoms experienced by the patient. Interpret results with caution due to the possibility of false positives or false negatives. The results of the SPT should be supplemented with a blood test, where specific IgE antibodies against allergens are tested. Molecular tests of allergen components will provide more information and help eliminate cross-reactions. If there are still uncertainties, provocation tests should be applied.
Healio: Looking ahead, what can be done to make these tests more accurate?
Petraitytė-Burneikienė: Allergen extracts used should be standardized. Standardized extracts ensure that the allergen content is the same in each batch. This consistency is essential to obtain reliable and reproducible SPT results that aid in the accurate diagnosis of allergies. Standardization allows the comparison of results from different testing centers and at different times, providing a consistent basis for interpreting allergy test results. For allergen immunotherapy, it is very important to accurately determine the dose of the allergen. Standardized extracts ensure that patients receive the correct amount of allergen, which is essential for the safety and efficacy of the treatment.
The use of allergen components in SPTs should be introduced, as they have several significant advantages over whole allergen extracts. Using specific allergen components would help to more accurately identify the specific proteins causing the allergic reaction. Specific allergen components can distinguish true sensitization from cross-reactivity. All allergen extracts may contain large amounts of protein that can cause cross-reactivity. The ingredients help reduce this by targeting only the specific proteins associated with the patient’s allergy.
Multiplex tests that can simultaneously test several allergen components and provide a complete allergy profile from one blood sample would also help to get more accurate results.
Moreover, the tests should undergo continuous research and be regularly updated to include new allergenic molecules that may not yet have been identified as allergens. New tests are being developed. Bead-based epitope assays with cellular tests, basophil activation and mast cell tests, which are promising, are not yet applied in clinical practice and are still undergoing research standardization and validation. These tests will not be limited to diagnosis, but will also include risk assessment, aiming to identify patients who may experience severe allergic reactions and determine the prognosis.
For more information:
Rasa Petraitytė-Burneikienė, PhD, can be reached at rasa.burneikiene@bti.vu.lt.