Background: Peanut allergy prevalence is reported at 3% and consumes a significant volume of oral food challenges (OFC) in the diagnosis of food allergy. Compared to skin prick test (SPT) or sIgE to whole peanut, sIgE to peanut component ara h 2 has greater diagnostic accuracy. Two-step algorithms involving both SPT and ara h 2 sIgE demonstrate increased accuracy in diagnosis in modelled studies, resulting in fewer OFCs. We aimed to determine whether there is a similar reduction in OFCs in a clinical uptake of this two-step diagnostic algorithm compared to using peanut SPT alone and perform a cost comparison between these two approaches. Methods: In 2015, The Royal Children’s Hospital, Australia (RCH) implemented a clinical guideline using peanut SPT followed by sIgE to ara h 2 if the SPT was between 3 and 8mm and clinician is considering an OFC for a patient with suspected peanut allergy. We performed an audit of patients presenting to RCH allergy outpatient clinics for assessment of peanut allergy to determine the outcomes and potential reduction in need for OFC using the two-step algorithm. We used modelled data of the same patient cohort to estimate the number of OFCs that were avoided as a result of a high (≥1.0kUA/L) ara h 2 sIgE. A cost comparison was performed comparing the two-step algorithm to using peanut SPT alone. Costs were constructed based on unit prices from hospital admissions, medicare data and individual data on allergic reaction types, applying a health system perspective. Results: 8826 patients presented to RCH for peanut allergy assessment between May 2016 and August 2020. Of these, 9.2% proceeded to an OFC, with positive results seen in 20.1% and anaphylaxis in 1.1%. 42.0% (364/867) of patients with a SPT between 3-8mm followed the diagnostic algorithm appropriately. Of those who followed the diagnostic algorithm, there was a reduction of 27.8% in OFCs as a result of an elevated (>1.0kUA/L) ara h 2 result. The diagnostic algorithm pathway resulted in a 32.05% cost reduction compared to the modelled SPT-only pathway. Sensitivity analysis demonstrated that the number of patients proceeding to OFC gives greatest impact to the overall cost of diagnosis, rather than the cost of the OFC or ara h 2 itself. Conclusions: A combined algorithm incorporating peanut SPT followed by sIgE to ara h 2 resulted in a reduction in patients requiring oral food challenges. There is also a cost saving for this approach. There is a large proportion of patients that did not follow the algorithm, and this may relate to clinical history.

Abstract: Background: The European Academy of Allergy and Clinical Immunology’s (EAACI) is updating the Guidelines on Food Allergy Diagnosis. We aimed to undertake a systematic review of the literature with meta-analyses to assess the accuracy of diagnostic tests for IgE-mediated food allergy. Methods: We searched three databases (Cochrane CENTRAL (Trials), MEDLINE (OVID) and Embase (OVID)) for diagnostic test accuracy studies published between 1 st October 2012 and 30 th June 2021 according to a previously published protocol (CRD42021259186). We independently screened abstracts, extracted data from full-texts, and assessed risk of bias with QUADRAS 2 tool in duplicate. Meta analyses were undertaken for food-test combination where 3 or more studies were available. Results: 149 studies comprising 24,489 patients met the inclusion criteria and were generally heterogeneous. 60.4% of studies were in children ≤12 years of age, 54.3% undertaken in Europe, ≥95% conducted in a specialized pediatric or allergy clinical setting and all included oral food challenge in at least a percentage of enrolled patients, in 21.5% DBPCFC. Skin prick test (SPT) with fresh cow’s milk and raw egg had high sensitivity (90% and 94%) for milk and cooked egg allergies. Specific IgE to individual components had high specificity: Ara h 2 had 92%, Cor a 14 95%, Ana o 3 94%, casein 93%, ovomucoid 92/91% for the diagnosis of peanut, hazelnut, cashew, cow’s milk and raw/cooked egg allergies, respectively. BAT was highly specific for the diagnosis of peanut (90%) and sesame (93%) allergies. Conclusions: SPT and specific IgE to extracts had high sensitivity whereas specific IgE to components and BAT had high specificity to support the diagnosis of individual food allergies. PROSPERO registration: CRD42021259186 Funding: European Academy of Allergy (EAACI).

Introduction: Children with peanut allergy are at increased risk of developing tree nut allergies, which can be severe and for most lifelong. Introduction of peanut in the first year of life can reduce the risk of peanut allergy, however, prevention strategies for tree nut allergies have not been established. We aimed to test the efficacy and safety of a novel strategy, a supervised multi-nut oral food challenge (OFC) compared to standard care for tree nut allergy prevention in infants at high risk of developing tree nut allergy, TreEAT. Methods and analysis: TreEAT is a 2-armed, open-label, randomised, controlled trial (RCT). Infants (n=212) aged 4-11months with peanut allergy will be randomised 1:1 at peanut allergy diagnosis to either a hospital-based multi-tree nut (almond, cashew, hazelnut and walnut) OFC using multi-nut butter or standard care (home introduction of individual tree nuts). All infants will be assessed at age 18months, with questionnaires and SPT to peanut and tree nuts. Peanut and tree nut OFCs will be performed as required to determine allergy status for each nut. The primary outcome is tree nut allergy at age 18 months. Secondary outcomes include peanut allergy resolution, proportion and severity of adverse events related to tree nut ingestion, number and frequency of tree nuts ingested, quality of life and parental anxiety and allergy related healthcare visits from randomisation to 18 months of age. Analyses will be performed on an intention-to-treat basis. Ethics and dissemination TreEAT was approved by the Royal Children’s Hospital Human Research Ethics Committee (#70489). Outcomes will be presented at scientific conferences and disseminated through publication. Trial registration number: ClinicalTrials.gov ID: NCT04801823

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Background: The European Academy of Allergy and Clinical Immunology (EAACI) is in the process of updating the guidelines on the diagnosis and management of food allergy. The existing guidelines are based on a systematic review of the literature until 30th September 2012. Therefore, a new systematic review must be undertaken to inform the new guidelines. This systematic review aims to assess the accuracy of index tests to support the diagnosis of IgE-mediated food allergy. Methods: The databases Cochrane CENTRAL (Trials), MEDLINE (OVID) and Embase (OVID) will be searched for diagnostic test accuracy studies from 1st October 2012 to 30th June 2021. Inclusion and exclusion criteria will be used to select appropriate studies. Data from these studies will be extracted and tabulated, and then reviewed for risk of bias and applicability using the QUADAS-2 tool. All evaluation will be done in duplicate. Studies with a high risk of bias and low applicability will be excluded. Meta-analysis will be performed if there are three or more studies of the same index test and food. Results: A protocol for the systematic review and meta-analyses is presented and was registered using Prospero prior to commencing the literature search. Discussion: Oral food challenges are the reference standard for diagnosis but involve considerable risks and resources. This protocol for systematic review aims to assess the accuracy of various tests to diagnose food allergy, which can be useful in both clinical and research settings.

Food allergy is a major public health issue with growing prevalence in the urbanized world and significant impact on the lives of allergic patients and their families. Research into the risk factors that have contributed to this increase and their underlying immune mechanisms could lead us to definitive ways for treatment and prevention of food allergy. For the time being, introduction of peanut and other allergenic foods in the diet at the time of weaning seems to be an effective way to prevent the development of food allergy. Improved diagnosis and appropriate management and support of food allergic patients are central to patient care with food immunotherapy and biologicals making the transition to clinical practice. With the new available treatments it is becoming increasingly important to include patient's and family preferences to provide a management plan tailored to their needs.