Hazelnut oral immunotherapy desensitizes hazelnut but not other tree nut allergies (Nut CRACKER Study)

Background: Data on oral immunotherapy (OIT) for hazelnut allergy is limited and its potential to cross-desensitize for other nuts is unknown.

Objective: To study the efficacy and safety of hazelnut OIT in desensitizing hazelnut and additional tree nuts.

Methods: A prospective observational study of 30 hazelnut allergic patients aged ≥4 years who underwent hazelnut OIT. Full desensitization (4000 mg protein) rates were compared to 14 observational controls, and immunological changes during OIT were measured. Cross-desensitization was determined in cases of walnut and cashew co-allergy (n=12). Inhibition of IgE binding to walnut by hazelnut was evaluated in a separate set of walnut-hazelnut dual allergic patients, by ELISA.

Results: The rate of full hazelnut desensitization following OIT was 96.7% (29/30) compared to 14.3% (2/14) in controls (OR=25.7, 95% CI 3.7-178.7, p<0.001). Five patients (16.7%) were treated with injectable epinephrine for home reactions. Hazelnut SPT and sIgE to hazelnut and its main components, Cor a 9, 14 and 16, decreased while sIgG4 increased during OIT. A maintenance dose of 1200 mg hazelnut protein was sufficient to maintain full desensitization. No cross-desensitization was noted in dual hazelnut-cashew allergic patients (n=6). In dual hazelnut-walnut allergic patients, an increase in the walnut eliciting dose was observed in 2/6 (33.2%) patients (to 1200 and 4200 mg, respectively). Similarly, by cross-inhibition ELISA, hazelnut competed for IgE-binding to walnut in 5/25 (20%) hazelnut-walnut co-allergic patients.

Conclusions: Hazelnut OIT is highly effective, with a similar safety profile as OIT to other nuts. Cross-desensitization to walnut and cashew is unlikely.