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).

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.

Although there is a considerable body of knowledge about allergen immunotherapy (AIT), there is a lack of data on the reliability of real-world evidence (RWE) in AIT and consequently, a lack of information on how AIT effectively works in real life. To address the current unmet need for an appraisal of the quality of RWE in AIT, the European Academy of Allergy and Clinical Immunology Methodology Committee recently initiated a systematic review of observational studies of AIT, which will use the RELEVANT tool and the Grading of Recommendations Assessment, Development and Evaluation approach (GRADE) to rate the quality of the evidence base as a whole. The next step will be to develop a broadly applicable, pragmatic “real-world” database using systematic data collection. Based on the current RWE base, and perspectives and recommendations of authorities and scientific societies, a hierarchy of RWE in AIT is proposed, which places pragmatic trials and registry data at the positions of highest level of evidence. There is a need to establish more AIT registries that collect data in a cohesive way, using standardised protocols. This will provide an essential source of real-world data that can be easily shared, promoting evidence-based research and quality improvement in study design and clinical decision-making.