Hazelnut OIT is effective but does not cross-desensitize to additional tree-nuts

Published online January 10, 2025

Tree nuts in general, and hazelnuts in particular, are among the most frequent causes of food allergies worldwide, with low resolution rates and potential to trigger severe and even fatal reactions in allergic individuals. For these reasons, tree nut allergies comprise a major target for oral immunotherapy (OIT). In addition, cross-reactivity between certain pairs of tree nuts and the potential for cross-desensitization to additional tree nuts following OIT to a single nut, renders tree nut OIT even more appealing. The NUT-CRACKER (Nut Co Reactivity – Acquiring Knowledge for Elimination Recommendations) study previously demonstrated that walnut OIT cross-desensitizes for pecan, and that cashew OIT cross-desensitizes for pistachio with rare exceptions. Moreover, walnut OIT has the potential to cross-desensitize for hazelnut in most dual allergic patients. Data on hazelnut OIT, however, is limited.

In a prospective cohort study published in The Journal of Allergy and Clinical Immunology: In Practice, Elizur et al. examined 30 hazelnut allergic patients aged ≥4 years who underwent hazelnut OIT. Full desensitization (ability to consume 4000 mg protein = ~16 hazelnuts) rates were compared to 14 observational controls. The potential of a dose of 1200 mg protein (~5 hazelnuts) to induce and maintain full desensitization was examined. Cross-desensitization was determined in cases of patients who had additional walnut or cashew co-allergy (n=12). Serum immunological changes during OIT were measured. Additionally, in an independent group of walnut-hazelnut dual allergic patients, the potential of hazelnut to inhibit the binding of serum IgE to walnut was examined.

Twenty-nine out of 30 patients (96.7%) were fully desensitized to hazelnut following OIT, in contrast to only 2 of the 14 controls (14.3%, Odds Ratio=25.7, p<0.001).  Five patients (16.7%) experienced home reactions that were treated with injectable epinephrine. Serum markers, obtained before and following OIT, showed immunological desensitization. A maintenance dose of 1200 mg hazelnut protein was sufficient to induce and maintain full desensitization. No cross-desensitization was noted in dual hazelnut-cashew allergic patients (n=6). A significant increase in the walnut eliciting dose was observed in only 2/6 (33.2%) dual hazelnut-walnut allergic patients, but no cross-desensitization was noted in the remaining four. Similarly, in a separate group of hazelnut-walnut co-allergic patients, hazelnut inhibited IgE-binding to walnut in only 5/25 (20%) patients. Thus, limited cross-desensitization to other tree-nuts can be expected following hazelnut OIT.

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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