INTRODUCTION
Botanically, a tree nut is a dry hard fruit that grows in trees and does not open to release its seed, such as chestnut, hazelnut, and acorn. In everyday language, the term is used to describe a variety of edible seeds of drupe fruits like walnuts, almonds, and pistachios1. The most commonly consumed tree nuts in Europe include almonds, hazelnuts, walnuts, pecan nuts, cashews, pistachio nuts, Brazil nuts, and macadamia nuts2. Peanut, although a legume, is often referred to together with tree nuts due to their similar culinary use.
Tree nuts belong to the group of the eight major allergenic foods and, along with peanuts, have been implicated in severe fatal or near-fatal allergic reactions3. However, allergic manifestations to nuts vary substantially, depending on several factors, such as the implicated nut4, the sensitization to distinct allergen components and the presence of co-factors5,6, and even the process of the nuts before consumption7. Almond, for example, rarely causes significant clinical allergy8. Furthermore, allergy to different allergen components influences the predicted severity of a reaction, ranging from benign oropharyngeal symptoms to life-threatening anaphylaxis9,10. Unlike peanut allergy, allergy to tree nuts has been under-investigated. Evidence on the prevalence, clinical manifestation, and natural history of tree nut allergy is generally sparse, as has been recently reviewed5,6,11. Recent studies12,13 suggest that allergy to tree nuts is more common than peanut, in many countries, and poses a substantial burden to patients and families. As with other food allergens, the management relies on strict avoidance of the culprit nut (and often of potentially cross-reacting foods) and symptomatic treatment of accidental consumption. Food oral immunotherapy (OIT) is actively investigated for the management of milk, egg, wheat, and peanut allergy14. FDA (U.S. Food and Drug Administration), EMA (European Medicines Agency), and NICE (U.K. National Institute for Health and Care Excellence) have recently approved peanut OIT for clinical practice. On the contrary, there is a lack of data on desensitization approaches in managing tree nut allergy. This systematic review aims to evaluate potential therapeutic options for the desensitization of patients with IgE-mediated tree nut allergy.
The primary question was, “Which are the therapeutic options for the desensitization of patients with IgE-mediated walnut or cashew or pistachio or hazelnut, or almond allergy? What is the effectiveness and safety of these options?”.