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).