The Accuracy of Diagnostic Testing in Determining Tree Nut Allergy: A Systematic Review

Abstract

Background: Food allergy is most accurately diagnosed by a formal oral food challenge (OFC); however, it is time and labor intensive, risks the individual to severe reaction, and access is often a limiting step in the diagnostic process. This is compounded for tree nut allergy diagnosis as several OFCs may be required to determine allergy status to each individual tree nut. Accurate diagnosis using minimally invasive diagnostic tests in predicting clinical tree nut allergy is important to correctly identify those with potentially life-threatening reactions and to efficiently and safely tailor nut avoidance to only those nuts deemed allergic to enable less restricted diets and increased food choices for food allergic individuals.

Objective: To conduct a systematic review on the diagnostic capacity of clinical tests (skin prick test, specific IgE, component-resolved diagnostics, and basophil activation test) to determine OFC-proven or clinical tree nut allergy.

Methods: We searched 4 electronic databases (OVID Medline, Embase, Cochrane library, and PubMed) until May 2020. Eligible studies were categorized by type of tree nut and diagnostic test.

Results: A total of 27 studies assessed diagnostic accuracy to a specific tree nut. Overall, the accuracy of diagnostic testing was only reasonable, with 95% positive predictive values established in a small number of tree nuts. Cashew has 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 clinical use.

Conclusion: The systematic review highlights the limitations of our current diagnostic tools for tree nut allergy and highlights further areas for research. The unidirectionality of cross-reactivity between cashew/pistachio and walnut/pecan is described and can aid diagnosis. Using diagnostic algorithms such as those demonstrated for walnut/pecan and cashew/pistachio allergy, greater diagnostic accuracy and reduced number of OFCs may be achieved.

Keywords: Almond; Area under the curve; Basophil activation test; Brazil nut; Cashew; Component-resolved diagnostics; Diagnosis; Diagnostic accuracy; Food allergy; Hazelnut; IgE; Macadamia; Pecan; Pistachio; Positive predictive value; Sensitivity; Skin prick test; Specificity; Tree nut allergy; Walnut.