Immunoglobulin E (IgE)-mediated food allergies are reported to affect around 3.5% of children and 2.4% of adults, with symptoms varying in range and severity. While being the gold standard for diagnosis, oral food challenges are burdensome, and diagnostic tools based on specific IgE can be flawed. Furthering our understanding of the mechanisms behind food allergy onset, severity, and persistence could help reveal immune profiles associated with the disease, to ultimately aid in diagnosis. Alterations to cytokine levels and immune cell ratios have been identified, though further research is needed to fully capture the heterogenous nature of food allergy. Moreover, the existence of such immune alterations also raises the question of potential wider systemic effects. For example, recent research has emphasised the existence and impact of neuro-immune interactions and implicated behavioural and neurological changes associated with food allergy. This review will provide an overview of such food allergy-driven neuro-immune interactions, with the aim of emphasising the importance of furthering our understanding of the immune mechanisms underlying IgE-mediated food allergy.

Background. Food allergy (FA) is associated with poor quality of life and high levels of psychological distress. Psychological support is therefore extremely important but is not always available. As part of the Global Access to Psychological Services for Food Allergy (GAPS) Study, we aimed to assess distress and use of psychological services for adults with food allergy. Methods. Participants (n=1329 adults with FA) from >20 countries were recruited through patient organisations, social media adverts and online survey panels to complete an online survey. Surveys were offered in six languages. Results. A total of 67.7% of adults reported they had experienced FA-related psychological distress with the biggest issue being anxiety about having an allergic reaction (64.1%). Only 19.4% had been assessed for FA-related psychological distress; 22.9% had seen a mental health professional for treatment for their FA-related distress. There were significant differences across countries for levels of distress, screening for distress, seeing a mental health professional and being diagnosed with a FA-related mental health disorder (all p<0.001). The UK and Brazil had the highest number of adults reporting distress. The biggest barriers to seeing a mental health professional were cost, lack of insurance coverage, failure to provide a referral, and lack of practitioner in the area. Conclusions. FA-related distress is common in adults. Few have accessed the psychological care and support they need and there is significant variability across countries. Clinicians should consider routine assessment of adults for distress and easily accessible resources are needed to help support adult patients.

Background: Basophil activation test (BAT) or the mast cell activation test (MAT) are two in vitro tests that are currently being studied in food allergy as diagnostic tools as an alternative to oral food challenges (OFCs). We conducted a meta-analysis on BAT and MAT assessing their specificity and sensitivity in diagnosing peanut allergy. Methods: Six databases were searched for studies on patients suspected of having peanut allergy. Studies using BAT or MAT to peanut extract and/or component as diagnostic tools with results given in percentage of CD63 activation were included in this meta-analysis. Study quality was evaluated with the QUADAS-2 tool. Results: On the eleven studies identified, eight focused exclusively on children, while three included a mixed population of adults and children. Only one study provided data on MAT, precluding us from conducting a statistical analysis. The diagnostic accuracy of BAT was higher when stimulated with peanut extract rather than Ara h2 with a pooled specificity of 96% (95% CI: 0.89-0.98) and sensitivity of 0.86 (95% CI: 0.74-0.93). The sensitivity and specificity of BATs in discriminating between allergic and sensitized patients was studied as well with pooled analysis revealing a sensitivity of 0.86 (95% CI: 0.74; 0.93) and a specificity of 0.97 (95% CI: 0.94, 0.98). Conclusion: BATs, when stimulated with peanut extracts, exhibit a satisfactory sensitivity and specificity for the diagnosis of peanut allergy and can help to discriminate between allergic individuals and those only sensitized to peanut. More investigations on the potential for MATs diagnostic methods are warranted.

Background: The basophil activation test (BAT) has high accuracy to diagnose peanut allergy (PA) and can reduce the need for oral food challenges (OFC); however, so far it has not been incorporated in clinical practice. Methods: We compared two BAT methodologies, their performance in two separate laboratories, their diagnostic utility and impact of BAT in clinical-decision-making in a specialised centre. Results: 102 children being assessed for PA were tested on BAT (72 allergic, 30 sensitised tolerant). There was little internal variation (CV<15%) and a very strong correlation (Rs>0.95) between BAT performed across laboratories. The 2 BAT methods were correlated but not interchangeable and 19% of cases had opposite results. The in-house BAT method (IH-BAT) was superior, as demonstrated by its better diagnostic performance (area under the ROC curve 0.929/0.957 versus 0.892/0.895 for CD63/CD203c), lower number of non-responders (4% versus 14%), lower background basophil activation (4% versus 9%) and less need for oral food challenges (29/12 versus 37/20 for OFC/positive OFC). BAT was feasible and well-accepted by clinicians: no patient with positive BAT was referred for OFC; only 37% of all tested patients needed an OFC and 14% of these (5% of total) reacted during OFC, which corresponded to 72/89% decrease in OFC/positive OFC, respectively, with the integration of BAT in the diagnostic work-up for peanut allergy. Conclusions: The BAT is a robust test that can reliably be transferred between laboratories; however, different BAT methods are not interchangeable. BAT was well integrated in the clinical decision-making process in a specialised centre.

Background: Various biomarkers are used to define peanut allergy (PA). We aimed to observe changes in PA resolution and persistence over time comparing biomarkers in PA and peanut sensitised but tolerant (PS) children in a population-based cohort. Methods: Participants were recruited from the EAT and EAT-On studies, conducted across England and Wales and were generally well exclusively breastfed babies recruited at 3 months old and followed up until 11 years old. Clinical characteristics, skin prick test (SPT), sIgE to peanut and peanut components and mast cell activation tests (MAT) were assessed at 12m, 36m and 7-11y. Results: The prevalence of PA was 2.1% with only 1 child having PA resolution at 7-11y. PA children had larger SPT size, higher peanut-sIgE, Ara h 2-sIgE and MAT (all p<0.001) compared to PS children at 36m and 7-11y. SPT, peanut-sIgE, Ara h 2-sIgE and MAT between children with persistent PA, new PA, outgrown PA and PS were statistically significant at both 36m and 7-11y (p<0.001). Those with persistent PA had SPT, peanut-sIgE and Ara h 2-sIgE that increased over time and MAT which was highest at 36m. New PA children had increased SPT and peanut-sIgE from 36m to 7-11y, but MAT remained low. PS children had low biomarkers across time. Conclusions: In this cohort, few children outgrow or develop new PA between 36m and 7-11y. Children with PA have significantly higher SPT, peanut-sIgE, Ara h 2-sIgE and MAT compared to PS children, evident from 12-36m of age.

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).

We report for the first time the case of allergy to egusi seeds in an atopic child of Nigerian origin with allergy to other seeds and nuts. This case highlights the need to know and explore less common foods as potential allergens, the importance of modified skin prick testing and the basophil activation test to support the diagnosis of rare food allergies and of awareness about world cuisine and exotic foods as potential allergens.

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 (FA) is now one of the most common chronic diseases of childhood often lasting throughout life and leading to significant worldwide healthcare burden. The precise mechanisms responsible for the development of this inflammatory condition are largely unknown; however, a multifactorial aetiology involving both environmental and genetic contributions is well accepted. A precise understanding of the pathogenesis of FA is an essential first step to developing comprehensive prevention strategies that could mitigate this epidemic. As it is frequently preceded by atopic dermatitis and can be prevented by early antigen introduction, the development of FA is likely facilitated by the improper initial presentation of antigen to the developing immune system. Primary oral exposure of antigens allowing for presentation via a well-developed mucosal immune system, rather than through a disrupted skin epidermal barrier, is essential to prevent FA. In this review, we present the data supporting the necessity of 1) an intact epidermal barrier to prevent epicutaneous antigen presentation, 2) the presence of specific commensal bacteria to maintain an intact mucosal immune system and 3) maternal/infant diet diversity, including vitamins and minerals, and appropriately timed allergenic food introduction to prevent FA.

Immune modulation is a key therapeutic tool for allergic diseases and asthma. It can be achieved in an antigen-specific way via allergen immunotherapy (AIT) or in endotype-driven approach using biologicals that target the major pathways of the type 2 (T2) immune response: IgE, IL-5 and IL-4/IL-13. COVID-19 vaccine provides an excellent opportunity to tackle the global pandemics and is currently being applied in an accelerated rhythm worldwide. It works as well through immune modulation. Thus, as there is an obvious interference between these treatment modalities recommendations on how they should be applied in sequence are expected. The European Academy of Allergy and Clinical Immunology (EAACI) gathered an outstanding expert panel under its Research and Outreach Committee (ROC). This expert panel was called to evaluate the evidence and formulate recommendation on the administration of COVID-19 vaccine in patients with allergic diseases and asthma receiving AIT or biologicals. The panel also formulated recommendations for COVID-19 vaccine in association with biologicals targeting the type 1 or type 3 immune response. In formulating recommendations, the panel evaluated the mechanisms of COVID-19 infection, of COVID-19 vaccine, of AIT and of biologicals and considered the data published for other anti-infectious vaccines administered concurrently with AIT or biologicals.

Food Allergy (FA) is now one of the most common chronic diseases of childhood often lasting throughout life and leading to significant worldwide healthcare burden. The precise mechanisms responsible for the development of this inflammatory condition are largely unknown; however, a multifactorial aetiology involving both environmental and genetic contributions is well accepted. A precise understanding of the pathogenesis of FA is an essential first step to developing comprehensive prevention strategies that could mitigate this epidemic. As it is frequently preceded by atopic dermatitis and can be prevented by early antigen introduction, the development of FA is likely facilitated by the improper initial presentation of antigen to the developing immune system. Primary oral exposure of antigens allowing for presentation via a well-developed mucosal immune system, rather than through a disrupted skin epidermal barrier, is essential to prevent FA. In this review, we present the data supporting the necessity of 1) an intact epidermal barrier to prevent epicutaneous antigen presentation, 2) the presence of specific commensal bacteria to maintain an intact mucosal immune system and 3) maternal/infant diet diversity, including vitamins and minerals, and appropriately timed allergenic food introduction to prevent FA.

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.