clinical topic updates

Current and Future Diagnostic Tools for Food Allergy

by Robert A. Wood, MD

Overview

There are several areas of opportunity in allergy testing that may lead to future advancements. Techniques such as component-resolved diagnostics allow for greater confidence in allergy testing results. The oral food challenge (OFC) is expected to retain its current role when the diagnosis is unclear.

Expert Commentary

Robert A. Wood, MD

Julie and Neil Reinhard Professor of Pediatric Allergy and Immunology
Professor of Pediatrics and International Health
Director, Eudowood Division of Allergy, Immunology and Rheumatology
Director, Pediatric Clinical Research Unit
Deputy Director, Institute for Clinical and Translational Research
Johns Hopkins University School of Medicine
Baltimore, MD

“There are reasons to be optimistic that diagnostic testing will improve in the future. Nonetheless, we will still have to take a good history and utilize the OFC when the diagnosis is unclear.”

Robert A. Wood, MD

The current diagnostic approach to food allergy involves 2 commonly used tests: (1) skin tests, which are used mainly by the allergy specialists, and (2) immunoglobulin E (IgE) blood tests, which are available in a wide variety of practices and clinical settings. A recognition of the limitations of these tests is crucial. A negative skin test is usually accurate, but a positive test is about as likely to be wrong as it is to be right, underscoring the importance of the role of a careful history and OFCs to confirm an uncertain diagnosis in the setting of a positive test. 

An awareness of the likelihood of false-positive tests is extremely important for both skin and blood testing. Without it, one risks implementing unnecessary dietary restrictions, which can be associated with nutritional risks, added burdens in finding “safe” foods, and, potentially, allergic risks. For instance, if you test 25 foods in a pediatric patient with allergies, that child may be “positive” for 15 items yet able to eat most of the identified foods. Unnecessary food restrictions may increase the risk of one developing an allergy. 

Component-resolved diagnostics represent an advance in allergy testing. The components are recombinant proteins, as opposed to the crude extracts that are used in skin tests and most IgE testing, and such testing has real value. Commercial labs often offer peanut IgE testing with the reflex testing of peanut components (eg, specific Ara h proteins). Component tests are automatically run if the peanut IgE is positive. For some of the Ara h proteins, a positive result is quite consistent with a true peanut allergy, whereas others will be positive because of cross-reactivity (eg, to a tree pollen). Unfortunately, reflex testing incurs additional expense, as component testing is not always needed, but peanut is a good example of a component-resolved diagnostic that is very useful in helping to make an accurate diagnosis. 

The basophil activation test (BAT) involves the direct activation of basophils with antigen. This test makes it possible to obtain greater specificity as to the likelihood that the patient is truly allergic to a particular food. Although the BAT is currently used as only a research tool, it will hopefully start being integrated into the clinic more over time. 

There are several opportunities for the further development of our testing capabilities. We would like to be able to better predict the natural history of food allergy in individual patients. We would also like to be able to answer the following very basic, very commonly asked questions for parents: What exactly will my child’s next reaction look like, and will my child react to a trace exposure? If we had a test that could answer these questions, that would be key. Many people with peanut allergy will never react to the low levels of exposure that occur via cross-contamination, for instance; however, there are other patients who can react to trace amounts of peanut, so we need to be vigilant.

For now, the emphasis is on appropriate testing and obtaining a good history to make an accurate diagnosis. When that is not sufficient, the OFC is needed. Component-resolved diagnostics have improved our ability to determine which patients are truly peanut allergic, reducing the number of required food challenges. The BAT can further reduce the number of challenges needed for peanuts and other foods. There are reasons to be optimistic that diagnostic testing will improve in the future. Nonetheless, we will still have to take a good history and utilize the OFC when the diagnosis is unclear.

References

Barocci F, Amici MDE, Marseglia GL. Molecular evolution in food allergy diagnosis. Minerva Pediatr. 2016;68(5):374-381.

Goodman RE, Chapman MD, Slater JE. The allergen: sources, extracts, and molecules for diagnosis of allergic disease. J Allergy Clin Immunol Pract. 2020;8(8):2506-2514. doi:10.1016/j.jaip.2020.06.043

Greenhawt M, Chan ES, Fleischer DM, et al. Caregiver and expecting caregiver support for early peanut introduction guidelines. Ann Allergy Asthma Immunol. 2018;120(6):620-625. doi:10.1016/j.anai.2018.03.001

Gupta RS, Warren CM, Smith BM, et al. The public health impact of parent-reported childhood food allergies in the United States. Pediatrics. 2018;142(6):e20181235. doi:10.1542/peds.2018-1235

Manea I, Ailenei E, Deleanu D. Overview of food allergy diagnosis. Clujul Med. 2016;89(1):5-10. doi:10.15386/cjmed-513

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