i. Main findings
We identify three main strategies addressing the modification of tree nut allergy: the sublingual immunotherapy, the oral immunotherapy, single or multiple, with or without omalizumab, and the use of monoclonal antibodies interfering with allergic responses.
Sublingual immunotherapy was investigated in a small number of patients with LTP hazelnut allergy, with moderate efficacy but a favorable safety profile19,22,28. Single OIT was investigated for hazelnut, walnut and cashew allergy. Efficacy and safety varied according to protocol, population, and tree nut tested23,24,30,31,33. Multi-OIT studies included participants with variable tree nut allergy profile17,18,20,21,25,26. Multi-OIT was not significantly more or less effective than single-nut OIT21. The use of omalizumab appeared to allow for faster desensitization with fewer adverse reactions, especially during the build-up phase, and does not affect efficacy17. Overall, the efficacy and the safety of tree nut OIT was found to be similar to that demonstrated by peanut OIT trials34,35. Omalizumab and dupilumab were investigated in a case report and two small cohort studies of multi-food allergic children and adults, with favorable outcomes27,29,32.
Cross-desensitization between cashew and pistachio, or walnut and pecan, was described17,18,20,23,24, attributed to the close phylogenetic affinity of the respective nuts36. Interestingly, cross desensitization to distant phylogenetic nuts through walnut and cashew OIT was also documented23,24. Linear and structural homologies of vicilin, legumin, and 2S albumin epitopes of tree nuts belonging to different botanical families36 could contribute to the observed cross-desensitization, which, additionally to multi-OIT results, straightly affects the management options for multi-nut allergic patients.
Sustained unresponsiveness depended on the length of avoidance, with fewer participants maintaining their desensitization over time18,33.
Managing tree nut allergy had a positive effect on the quality of life of patients and families, especially when desensitization to more nuts was achieved24,27,29.