Validation of the NUT CRACKER Diagnostic Algorithm and Prediction for Cashew and Pistachio Co-Allergy

Abstract

BackgroundDue to the high cross sensitization among tree nuts, the NUT CRACKER study proposed a diagnostic algorithm to minimize the number of required oral food challenges (OFC). ObjectiveThe objective of this study was to validate the algorithm for cashew and pistachio allergy and determine markers for allergic severity. MethodsPatients (n=125) aged 7.9 (5.9-11.2) years (median (IQR)) with suspected tree nut allergy were evaluated prospectively with decision tree points based on skin prick test (SPT), basophil activation test (BAT) and knowledge of the coincidence of allergies. Validation of allergic status was determined by OFC. Markers of clinical severity were evaluated using the combined original and prospective cohort (n=187) in relationship to SPT, BAT and Ana o 3-sIgE. ResultsReactivity to cashew in SPT, BAT and Ana o 3-sIgE and the incidence of abdominal pain upon challenge were significantly higher in dual-allergic cashew/pistachio patients (n=82) vs single cashew allergy (n=18) (p=0.001). All three diagnostic tests showed significant inverse correlation with log10 reaction doses for positive cashew OFC. The algorithm reduced overall the total number of OFCs by 72.0% with a PPV and NPV of 93.0% and 99.0%, respectively. Cashew false positives were observed primarily in hazelnut allergic patients (p=0.026). In this population, Ana o 3-sIgE could diagnose cashew allergy with a sensitivity over 90%, and a specificity over 95%. ConclusionThe NUT CRACKER diagnostic algorithm was validated and reduced the number of diagnostic OFCs required. Markers for severity phenotypes may guide oral immunotherapy protocols, improving the risk/benefit ratio for patients.