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 to hazelnut and additional tree nuts. Methods: This was a prospective observational study of 30 hazelnut-allergic patients aged 4 years or older who underwent hazelnut OIT. Full desensitization (4,000 mg protein) rates were compared with those of 14 observational controls, and immunologic changes during OIT were measured. We determined cross-desensitization in cases of walnut and cashew co-allergy (n = 12). Inhibition of IgE binding to walnut by hazelnut was evaluated by ELISA in a separate set of dual walnut-hazelnut allergic patients. Results: The rate of full hazelnut desensitization following OIT was 96.7% (29 of 30 patients) compared with 14.3% (two of 14) in controls (odds ratio = 25.7; 95% CI, 3.7-178.7; P < .001). Five patients (16.7%) were treated with injectable epinephrine for home reactions. Hazelnut skin prick test and specific IgE to hazelnut and its main components, Cor a 9, 14 and 16, decreased whereas specific IgG4 increased during OIT. A maintenance dose of 1,200 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 two of six patients (33.2%) (to 1,200 and 4,200 mg, respectively). Similarly, by cross-inhibition ELISA, hazelnut competed for IgE-binding to walnut in five of 25 (20%) hazelnut-walnut co-allergic patients (20%). Conclusions: Hazelnut OIT is highly effective, with a safety profile similar to that of OIT to other nuts. Cross-desensitization to walnut and cashew is unlikely.