Cashew cross-reactivity and diagnosis: a difficult nut to crack

Published: February 19, 2024

Tree nut allergies are an increasing concern, as they often manifest with severe anaphylactic reactions. Accurate diagnosis of tree nut allergies is complicated due to the occurrence of cross-reactivity between different tree nuts, and with pollen. Thus, patients often demonstrate sensitivity to multiple tree nuts (by skin prick test (SPT), for example), which may or may not reflect true clinical allergy. As is the case for food allergies in general, oral food challenges (OFC) remain the gold standard for diagnosis of tree nut allergies. While determinative, OFC require time and the expertise of healthcare personnel and pose a risk of anaphylaxis. Therefore, there is a need for diagnostic approaches for tree nut allergies that reduce the reliance on OFC. Although individual allergy testing methods vary in their diagnostic performance for different tree nut allergies, approaches integrating multiple testing methods may yield improved accuracy. The NUTCRACKER study (Elizur et al, Allergy 2018;73:593-601.) described algorithms for tree nut allergy diagnosis in an Israeli cohort, integrating SPT and basophil activation testing (BAT) to optimize diagnostic accuracy, and reduce the reliance on OFC. Importantly, the study found tree nut allergies manifest within botanical groups, with pistachio allergy being almost invariably coincident with cashew allergy.

Continuing the NUTCRACKER study, Goldberg et al. present a prospective evaluation of the cashew/pistachio diagnostic algorithm in a recent article published in The Journal of Allergy and Clinical Immunology: In Practice. Furthermore, the authors evaluate the performance of specific IgE (sIgE), to the cashew protein Ana o 3 for diagnosis of cashew allergy, and investigate the association of the various diagnostic tests with reaction severity in cashew/pistachio allergic patients

The current prospective study validated the NUTCRACKER cashew/pistachio allergy algorithm, with an accuracy of over 95% (235 correct diagnoses out of 246 evaluations), and an OFC required in fewer than 30% of cases. While not integrated into the algorithm, sIgE to Ana o 3 was shown to be a robust predictor of both cashew and pistachio allergies, with an especially strong utility among those patients with a hazelnut allergic background. For cashew allergic patients, all three-allergy tests, SPT, BAT and sIgE to Ana o 3, inversely correlated with the cashew protein reactive dose, suggesting their utility in predicting allergic sensitivity. The study by Goldberg et al. thereby provides a strategy to navigate testing for cashew and pistachio allergy, while also suggesting that background knowledge of other tree nut allergies, such as hazelnut, may help to further optimize allergy testing schemes. Adoption of the NUTCRACKER algorithms into the mainstay of allergy diagnostic practice will require its further validation in different clinical settings, across different ethnic groups, patient ages, and geographic locations.

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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