Systematic review highlights the need for improved tree nut allergy diagnostics

Published online: May 1, 2021

Tree nut allergy is common, with a similar prevalence to peanut allergy in some countries, although the relative prevalence of allergy to different tree nuts varies throughout the world. Sensitization rates are much higher than the true rates of oral food challenge (OFC)-confirmed tree nut allergy. While the gold standard of food allergy diagnosis is an OFC, this is time and labor intensive, limited in availability and carries a risk of severe reactions. Clinically, many individuals who are peanut or tree nut allergic are sensitized on skin prick test (SPT) or serum IgE test (sIgE) but have never had oral allergen exposure. Tree nut allergy diagnosis is currently problematic - many patients may be sensitized, but due to limited capacity for OFC and limited research on the diagnostic capacity of the current clinical tests, clinicians may be forced to accept a diagnosis of ‘probable’ allergy, leading in some cases to unnecessary restrictions to diets and limited food choices.

In a recent article in The Journal of Allergy and Clinical Immunology: In Practice, Brettig et al. present the first systematic review reporting the diagnostic capacity of multiple clinical tests to determine true OFC-proven allergy for all tree nuts. Using the methods and procedures of the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines, this systematic review searched four electronic databases (OVID Medline, Embase, Cochrane Library, and PubMed) until May 2020. Studies reporting a sensitivity, specificity, positive predictive value (PPV), or negative predictive (NPV) for diagnostic tests (SPT, sIgE, Component resolved diagnostics (CRD) and Basophil activation tests (BAT)) to any of the individual tree nuts (cashew, pistachio, walnut, pecan, hazelnut, almond, macadamia, brazil nut) were included and presented.

Brettig et al identified 27 studies which met the inclusion criteria. Results were presented by individual tree nut and individual diagnostic test. Overall, the accuracy of diagnostic testing was only reasonable, with 95% PPV reported for cashew and walnut. Hazelnut has also been comprehensively studied, although no clear 95% PPV could be determined. Cashew had the best diagnostic accuracy, with the cashew component Ana o 3 being most predictive. At the other end of the spectrum, diagnostic testing of almond is poor and of limited use. Studies have included a broad range of participant populations, and also presented a wide range of optimal cut-offs, limiting the ability to pool data from individual studies.

This systematic review outlines the current strengths and limitations of the available diagnostic tests for tree nuts. This data may be used to guide clinician’s decision making when deciding on use of diagnostic testing for a patient with suspected tree nut allergy. There are clear areas where testing has not been fully evaluated, where further research could help to reduce the number of OFCs required for diagnosis. By improving diagnostic accuracy using minimally invasive tests, there will be reduced need for OFCs and potentially a reduction in rates of allergy misdiagnosis, with associated impacts on the financial and health burdens of food allergy, which is an important consideration given increasing allergy rates worldwide.

The Journal of Allergy and Clinical Immunology: In Practice is an official journal of the AAAAI, focusing on practical information for the practicing clinician.

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