Appendix 1: Search Strategy and Study Selection.
We systematically searched PUBMED, SCOPUS and the COCHRANE LIBRARY [search terms (WALNUT OR CASHEW OR PISTACHIO OR HAZELNUT OR ALMOND OR TREENUT OR TREE NUT OR TREE NUTS OR TREENUTS) AND (ALLERGY OR HYPERSENSITIVITY OR ANAPHYLAXIS) AND (MANAGEMENT OR THERAPY OR TREATMENT OR IMMUNOTHERAPY)] for active treatments of IgE-mediated allergy to tree nuts (walnut, hazelnut, pistachio, cashew, and almond) with allergen-specific immunotherapy (AIT) using oral (OIT), sublingual (SLIT), epicutaneous (EPIT) or subcutaneous (SCIT) delivery or with other disease-modifying treatments (PROSPERO registration number: CRD42021248763). We followed the EAACI definition of allergen-specific immunotherapy, which is “repeated allergen exposure at regular intervals to modulate the immune response, to reduce symptoms and the need for medication for clinical allergies, and to prevent the development of new allergies”.
The pre-specified inclusion criteria were randomized and non-randomized comparative studies, one group non-randomized pre-post-studies, descriptive studies which include analysis of outcomes (single-subject design, case series) and case reports, of children and adults of any age, with a diagnosis of IgE-mediated allergy to one or more tree nuts (walnut, hazelnut, pistachio, cashew, almond), confirmed by IgE sensitization (SPTs or/and sIgEs) and oral food challenge or a recent (within two years) history of reactions.
The pre-specified exclusion criteria were studies in which the diagnosis of IgE-mediated tree nut allergy was based solely on IgE sensitization and/or distant (>2 years) history of reaction and studies without an exit food challenge to the culprit nut to verify tolerance or an increase in the tolerance threshold. We did not exclude studies in which the IgE-mediated allergy diagnosis was based only on a recent history reaction rather than a food challenge, because we expected that this would result in a small number of retrieved studies.
This review’s main outcome was desensitization, through the change in the threshold of the tree nut in question required to elicit an allergic reaction while on treatment, and sustained unresponsiveness, defined as the ability to consume foods containing the tree nut in question after discontinuing treatment.
The search was first performed on 10/02/2020 for PUBMED and SCOPUS databases and 09/12/2020 for COHRANE LIBRARY and repeated regularly; the last search was done on 13/07/2022.
Title and abstract screening and study selection were performed by three authors (MP, PX, EE) independently. Relevant references of included articles were also screened. Data extraction to standardized Excel forms was performed by one investigator (MP).