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Inclusion Criteria:

• - Written informed consent from adult participants or parent/guardian for children.

Written assent from participants above the age of 12 years.

• - Male or female participants aged 5 through 40 years, in a good general health condition according to the participant's medical history and the clinical examination and no chronic diseases, except: - Allergic rhinitis.

• - Asthma controlled with therapy steps 1-3 according to Global Initiative for Asthma (GINA) 2017.

• - Well-controlled atopic dermatitis.

• - SPT to tree nut's extract and/or the natural tree nut (Prick-to-Prick) ≥ 3 mm (the largest diameter of the wheal) and serum IgE to tree nut of ≥ 0.35 kUA/L.

• - sIgE > 0.1 kUA/L to at least one seed storage protein of the offending tree nut, except for pistachio, where Ana o 3 will serve as a sensitization marker.

• - Positive baseline OFC, at any dose but the final, conducted following PRACTALL (Practical Issues in Allergology, Joint United States/European Union Initiative) / iFAAM (Integrated Approaches to Food Allergen and Allergy Risk Management) guidelines.

• - Exclusion of active co-allergy to walnut, almond or pistachio, unless they are introduced to the diet simultaneously, by a negative open OFC or a recent (within the last two months) history of uneventful digestion, except for pistachio introduction in participants who are co-allergic to cashew.

• - Forced Expiratory Volume at 1 second (FEV1) or Peak Expiratory Flow Rate (PEFR) ≥ 80% of predictive.

• - The participant and/or the legal custodian should agree to comply with the study procedures.

Exclusion Criteria:

• - History of systematic anaphylaxis GRADE 5 according to Sampson (loss of bowel control, respiratory arrest, severe bradycardia and/or hypotension or cardiac arrest, loss of consciousness) or/and during OFC.

• - Recent (within 12 months) initiation of immunotherapy to any allergen.

• - Past or present eosinophilic esophagitis (EoE).

• - Chronic urticaria.

• - Severe or uncontrolled atopic dermatitis.

• - Uncontrolled asthma of any severity or asthma controlled with therapy steps 4-5 according to GINA 2017.

• - Concurrent or within 6 months therapy with omalizumab or another monoclonal antibody.

• - Systematically used corticosteroids: - Daily for more than a month during the last year, - Courses of corticosteroids during the last 3 months.

• - >2 Courses of corticosteroids lasting ≥1 week during the last year.

• - Inability to discontinue antihistamines 4 days before skin prick testing or OFC.

• - Severe immune disease, severe cardiovascular disease, malignancy, chronic infection, poor compliance, and severe psychiatric disorders.

• - Any important clinical condition that can affect the safety of the participant or the results of the study, including but not limited to cardiovascular diseases, malignancies, diseases of the liver and/or the kidneys, hematologic diseases, physiologic, immunologic and endocrinologic diseases.

• - Use of beta-blockers, angiotensin-converting enzyme (ACE) inhibitors or angiotensin-receptor blockers (ARB).

• - Pregnancy or lactation.

• - History of alcohol or drug abuse.

This is a multi-centered observational study comparing the safety and compliance of different procedures for introducing tree nuts into the diet of patients with IgE-mediated allergy to nuts. The effectiveness of tree nuts' introduction in respect to tolerance induction compared to the standard care (strict avoidance of tree nuts) will also be evaluated. The study will be contacted in the Department of Allergy and Clinical Immunology, 2nd University Pediatric Clinic of "Panagiotis & Aglaia Kyriakou" Children's Hospital, Athens, Greece, in collaboration with the Allergy Unit "Dimitrios Kalogeromitros, 2nd University Clinic of Dermatology and Venereology, "Attikon" University Hospital, University of Athens, Greece and the Allergology Department of "Laiko" General Hospital, Athens, Greece. The study will include participants with persistent IgE mediated allergy to tree nuts (including at least walnut or pistachio) who are willing to follow one of the two induction procedures (A: at home, B: at the hospital) and voluntarily provide written consent in the procedures and the goals of the study. Participants will adhere to one of the two induction procedures according to their preferences. Groups will be matched in respect to the number of participants. Participants who have already followed one of the two procedures can participate following written informed consent. The control group consists of participants who do not wish to introduce tree nuts into their diet but will consent to provide their medical data and the results of their allergology work-up for research purposes. The target ratio between active and control groups will be 3:1. Introduction of Tree Nuts consists of: Baseline Assessment (Screening period): In all participants, active and control, IgE-mediated allergy is evaluated by Skin Prick Tests (SPTs), serum specific IgE (sIgE) to tree nuts, serum sIgE to tree nuts' components and Basophile Activation Test (BAT) to the implicated tree nut and is confirmed by oral food challenges (OFC) with the nut. Additionally, total IgE and tryptase levels are assessed. Tree Nuts' Introduction Phase: Commercially available drinks of the respective tree nut, in suitable dilutions, are used for the introduction. First day of introduction: Participants in both active groups (procedures A and B) receive the first dose of the drink in the hospital under specialized medical observation. Escalation period: Drinks in suitable dilutions are given daily to participants. Dose escalation is performed at weekly intervals at home (procedure A) or every 2 months at the hospital (procedure B) until reaching maintenance dose or patient's maximum tolerated dose. The escalation period is estimated at 64 weeks (16 months). The up-dosing scheme and maintenance dose and duration will be adjusted in case of adverse allergic reactions. Maintenance Phase: The maintenance starts when participants reach the maintenance dose or their maximum tolerated dose, and lasts for at least 4 weeks. Participants in the control group are instructed to strictly avoid offending tree nuts, as per standard care. During Tree Nuts' Introduction Phase all participants, active and control, will be followed up periodically in two months intervals. Final Assessment: After completing at least 4 weeks at maintenance phase all participants will undergo an open oral food challenge with the offending nut(s) to assess tolerance. SPTs, total IgE, serum sIgE to tree nuts, serum sIgE to tree nuts' components and Basophile Activation Test (BAT) to each tree nut the participant is allergic will be re-evaluated.

Arms

: At home group

Participants with allergy to tree nuts who follow the introduction procedure A (at home)

: At the hospital group

Participants with allergy to tree nuts who follow the introduction procedure B (at the hospital)

: Control group

Participants with allergy to tree nuts who follow strict avoidance of the offending nuts.

Interventions

Other: - Procedure A

Up-dosing nut drink at home

Other: - Procedure B

Up-dosing nut drink at the hospital

Other: - Control group

Strict avoidance of tree nut consumption