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Background: Children with severe atopic status may present high risk of fatal or near fatal anaphylaxis and a highly impaired quality of life. Omalizumab has been shown to be a promising approach as monotherapy for severe allergy to multiple foods. However, very high serum total IgE levels may limit its use. Objective: To assess the efficacy of selective IgE-immunoadsorption (IgE-IA) on total IgE levels and threshold of reactivity to the culprit foods in children with history of severe anaphylaxis due to multiple foods and allergic comorbidities. Methods: In this single-center, prospective, open-label efficacy study we evaluated children with severe asthma, allergy to 2+foods and total IgE levels >2,300 kUI/L. To establish the food reactivity threshold, each patient underwent oral food challenges (OFCs) before and after IgE-IA. Results: Five patients (4 males; age, 10.9±5 years, mean±SD), underwent an average of three (range 2–5) sessions of IgE-IA. Each session reduced IgE levels by a mean of 1,958.87 kUI/L. After the IgE-IA cycle, serum total IgE dropped from 3,948±1,652.7 (mean±SD) to 360.8±71.89 kUI/L (-10.94 folds; p=0.01). The threshold of reactivity (No Observed Adverse Effect Level, NOAEL) tested at OFCs for the culprit foods (4baked-milk+2baked-egg+1lentil+2hazelnut+1wheat) increased overall from 21.51 (median, IQR 1.49-82.62) protein milligrams to 1,114.99 (837.2-4,222.8) milligrams (pConclusions: IgE-IA increased food threshold quickly. It can be considered in well-selected patients with severe food allergies and high IgE-levels especially if otherwise eligible to anti – IgE treatments.

Background. The use of eliciting doses (EDs) for food allergens is necessary to inform individual dietary advice and food allergen risk-management. The Eliciting Dose 01 (ED01) for milk and egg, calculated from populations of allergic subjects undergoing diagnostic Oral Food Challenges (OFCs), are 0.2 mg total protein. The respective Eliciting Dose 05 (ED05) are 2.4 mg for milk and 2.3 mg for egg. As about 70% children allergic to such foods may tolerate them when baked, we sought to verify the EDs of that subpopulation of milk and egg-allergic children. Methods. We retrospectively assessed consecutive diagnostic OFC for fresh milk and egg between January 2018 and December 2020 in a population of baked food-tolerant children. Results. Among 288 children (median age 56 - IQR 36-92.5 months, 67.1% male) included, 87 (30.2%) returned positive OFC results, 38 with milk and 49 with egg. The most conservative ED01 were 0.3 mg total protein (IQR 0.03-2.9) for milk and 14.4 mg total protein (IQR 3.6-56.9) for egg. The respective ED05 were 4.2 (IQR 0.9-19.6) mg for milk and 87.7 (IQR 43-179) mg for egg. Such thresholds are respectively 1.5 (milk ED01), 1.75 (milk ED05), 72 (egg ED01), and 38.35 (egg ED05) times higher than the currently used thresholds. Conclusions The subpopulation of children allergic to milk and egg, but tolerant to baked proteins, displays higher reactivity thresholds than the general population of children allergic to milk and egg. Their risk stratification, in both individual and population terms, should consider this difference. In baked milk-tolerant children, milk causes reactions at lower doses than egg in our group of egg-tolerant children. This could be associated with the relative harmlessness of egg compared to milk in the determinism of fatal anaphylactic reactions in children

BACKGROUND: Characterization of disease endotypes will open a new window for the treatment of allergic rhinitis (AR). Herein we provide the first attempt to identify specific AR phenotypes/endotypes and/or any biomarker/predictor for specific treatment response based on local biological parameters. METHODS: This observational study was carried out in 142 patients with seasonal AR and 20 non-allergic controls. Total IgE levels, specific IgE to 112 allergenic molecules and 92 proinflammatory and immunologic proteins were measured in both serum and nasal secretions (NS). RESULTS: We found increased values of MCPs and MMPs in adults both in NS and serum when compared with pediatric patients (p

Background Biological therapies relieve symptoms in allergic and inflammatory diseases so may also benefit people with IgE-mediated food allergy. We systematically reviewed the highest quality published evidence to inform forthcoming GA LEN guidelines. Methods We searched six bibliographic databases from 1946 to 30 September 2021 for randomised controlled trials, controlled clinical trials and quasi-randomised trials about biological monotherapy in people with IgE-mediated food allergy confirmed by oral food challenge. We found 3 trials with 118 participants. We used the GRADE approach. We summarised the findings narratively because studies were too heterogeneous to conduct meta-analysis. Results We included one randomised trial about etokimab, one about omalizumab and one about the discontinued TNX-901. All were in people with peanut allergy in the USA, mostly aged 13+ years. There were trends towards improved tolerance of peanut during treatment, with no increase in adverse events compared to placebo. However, we have very low certainty about the evidence. No trial reported on quality of life or cost-effectiveness. Conclusions Our review of the highest quality research found that there is not yet enough certainty of evidence to support offering etokimab or omalizumab widely for food allergy. Clinicians may consider the merits for individuals, but large randomised trials with standardised measures need to confirm the safety and efficacy and the most suitable candidates, doses and durations of treatment.

Background: Although well described in adults, there are scarce and heterogeneous data on the diagnosis and management of chronic urticaria (CU) in children (0-18 years) throughout Europe. Our aim was to explore country differences and identify the extent to which the EAACI/GA²LEN/EDF/WAO guideline recommendations for paediatric urticaria are implemented. Methods: The EAACI Taskforce for paediatric CU disseminated an online clinical survey among EAACI paediatric section members. Members were asked to answer 35 multiple choice questions on current practices in their respective centres. Results: The survey was sent to 2,773 physicians of whom 358 (13.8%) responded, mainly paediatric allergists (80%) and paediatricians (49.7%), working in 69 countries. For diagnosis, Southern European countries used significantly more routine tests (e.g., autoimmune testing, allergological tests, and parasitic investigation) than Northern European countries. Most respondents (60.3%) used a 2nd generation antihistamine as first- line treatment of whom 64.8% up dosed as a second- line. Omalizumab, was used as a second line treatment by 1.7% and third-line by 20.7% of respondents. Most clinicians (65%) follow EAACI/WAO/GA2LEN/EDF guidelines when diagnosing CU, and only 7.3% follow no specific guidelines. Some clinicians prefer to follow national guidelines (18.4%, mainly Northern European) or the AAAAI practice parameter (1.7%). Conclusions: Even though most members of the Paediatric Section of EAACI are familiar with the EAACI/WAO/GA2LEN/EDF guidelines, a significant number do not follow them. Also, the large variation in diagnosis and treatment strengthens the need to re-evaluate, update and standardize guidelines on the diagnosis and management of CU in children.

Background: Allergen immunotherapy(AIT) is the only disease-modifying treatment with long-term effects in patients with seasonal allergic rhinoconjunctivitis(SAR). Its efficacy depends on the precise identification of the pollen triggering symptoms. However, a diagnostic approach based on retrospective clinical history and sensitization to extracts often does not lead to unequivocal results. Objectives: To assess the usability and impact of a recently established algorithm for a potential clinical decision support system (@IT.2020-DSS) for pollen allergy and its diagnostic steps (including anamnesis, SPT, component resolved diagnosis, CRD, and real-time digital symptom recording, eDiary) on doctor’s AIT prescription decisions. Methods: After a concise educational training on the @IT.2020-DSS algorithm, 46 doctors (18allergy specialists, AS, and 28general practitioners, GP) expressed their hypothetical AIT prescription for 10 clinical index cases. Decisions were recorded repeatedly based on different steps of the support algorithm. The usability and perceived impact of the algorithm on individual clinical performance were evaluated. Results: The combined use of CRD and an eDiary increased the hypothetical AIT prescriptions, both among AS and GP (p