Antonella Cianferoni

Background: Multiple routes of allergen immunotherapy (AIT) are approved for several IgE‐mediated allergic diseases; however, the use of AIT in eosinophilic esophagitis (EoE) remains controversial and is supported by limited evidence. This review, conducted within the frame of an EAACI Task Force, aims to systematically evaluate the use of AIT as a potential treatment for EoE. Methods: The protocol was registered and prepared in accordance with PRISMA guidelines. The literature search was conducted across three online databases (PubMed, Embase, and Scopus) and included studies published through January 31 ^st , 2025. Risk of Bias was assessed for each eligible study. Results: Four articles met the inclusion criteria. Three articles evaluated EPIT for milk‐induced EoE in pediatric patients, all from the SMILEE (Study of Efficacy and Safety of Viaskin Milk for milk‐induced EoE) trial and its extensions. These included a randomized, placebo‐controlled trial, its open‐label extension, and a pilot immunological study. The SMILEE trial found no statistically significant difference in tissue eosinophilia between the active (EPIT) and control (placebo) arms in the intention‐to‐treat population, while 47% of treated EoE patients tolerated milk without recurrence of esophageal eosinophilia. This finding was further supported by a subsequent open‐label study with a 2‐year follow‐up. In the third publication, the researchers found that EPIT was associated with decreased Th2‐related transcripts and increased regulatory T‐cell‐associated transcripts. Only one eligible study evaluated the use of SCIT for treating EoE. It was a retrospective case‐control study reporting that SCIT had a neutral effect and yielded inconclusive findings regarding the course of EoE. Conclusion: There is insufficient high‐quality evidence to support the effectiveness of alternative routes of AIT for the treatment of EoE, either as an add‐on or a standalone treatment.

IgE‐mediated allergies play a significant role in respiratory diseases. Given the similar mucosal epithelium of the upper and lower respiratory tracts and their shared (patho)physiological immune responses, the “unified airways” concept views these tracts as a single system. Recently, this model has been extended to include the middle ear, with studies confirming that the Eustachian tube and middle ear are both anatomically and functionally part of the upper airways. However, the relationship between allergies and middle ear disorders remains controversial, with conflicting findings regarding pathogenesis and treatment. The increasing prevalence of allergies highlights the importance of further research. In Germany, the current sensitization rate to aeroallergens is 33.6%, with similar trends across Europe, where rates commonly range up to 30%. This widespread increase underscores the urgent need for a deeper understanding of the correlation between allergies and middle ear disorders across diverse European populations. Ineffective pharmacotherapy or possibly harmful medication for acute and chronic OME, such as systemic steroids, is most likely used globally in an uninformed way, due to a lack of evidence on the connection between allergic inflammation and eustachian tube dysfunction. Further research is essential to clarify the mechanisms linking IgE‐mediated allergies to middle ear pathologies and to develop effective treatment strategies. Addressing these knowledge gaps is critical for improving patient outcomes and managing the rising burden of allergic diseases.

Standard treatments for eosinophilic esophagitis (EoE) may present adherence, tolerance, and efficacy challenges. Dupilumab 300 mg weekly is approved for the treatment of EoE in patients ≥ 1 year old, weighing ≥ 15 kg. This analysis aimed to evaluate dupilumab efficacy in patients from the LIBERTY EoE TREET trial (NCT03633617), with prior history of different EoE interventions. This analysis included patients from Parts B/B - C of LIBERTY EoE TREET. Dupilumab efficacy was analyzed according to prior swallowed budesonide or fluticasone use and in those patients with previously trialed food elimination diet, esophageal dilation, or baseline proton pump inhibitor use, as stratified by prior swallowed topical corticosteroid (STC) use or STC inadequate response/intolerance/contraindication. Dupilumab improved the proportion of patients achieving peak intraepithelial eosinophil count ≤ 6 eosinophils/high-power field, absolute change in Dysphagia Symptom Questionnaire score, and other histologic, symptomatic, and endoscopic endpoints vs. placebo at Week (W) 24, irrespective of prior swallowed budesonide/fluticasone use. Improvements were maintained at W52. Similar results were observed across the other subgroups. Dupilumab was efficacious in patients with EoE irrespective of prior treatments/interventions. www.clinicaltrials.gov identifier is NCT03633617.

Eosinophilic esophagitis (EoE) is a chronic clinical-pathologic disease characterized by eosinophilic infiltration of the esophageal epithelium with esophageal dysfunction symptoms.EoE can occur at any age and has different clinical manifestations depending on the age onset.To date, esophago-gastroduodenal endoscopy (EGD) with biopsy is the gold-standard for EoE diagnosis.According to the recent consensus guidelines, proton pump inhibitors, corticosteroids and elimination diets could be a first-line therapy option. The aim of the treatment is clinical and histological remission for preventing long-lasting untreatable fibrosis.A multidisciplinary approach (allergist, gastroenterology, dietitian, and pathologist) is recommended for managing patients affected by EoE, given the complexity of its treatment.This review will provide a practical guide to assist pediatricians treating children with EoE.Moreover, it highlights the unmet needs in diagnosis and treatment that require urgent attention from the scientific community in the aim of improving the management of patients with EoE.

Background Food anaphylaxis is commonly elicited by unintentional ingestion of foods containing the allergen above the tolerance threshold level of the individual. While labelling the 14 main allergens used as ingredients in food products is mandatory in the EU, there is no legal definition of declaring potential contaminants. Precautionary allergen labelling such as “may contain traces of” is often used. However, this is unsatisfactory for consumers as they get no information if the contamination is below their personal threshold. In discussions with the food industry and technologists, it was suggested to use a voluntary declaration indicating that all declared contaminants are below a threshold of 0.5 mg protein per 100 g of food. This concentration is known to be below the threshold of most patients, and it can be technically guaranteed in most food production. However, it was also important to assess that in case of accidental ingestion of contaminants below this threshold by highly allergic patients, no fatal anaphylactic reaction could occur. Therefore, we performed a systematic review to assess whether a fatal reaction to 5mg of protein or less has been reported, assuming that a maximum portion size of 1kg of a processed food exceeds any meal and thus gives a sufficient safety margin. Methods MEDLINE and EMBASE were searched until 24^th January 2021 for provocation studies and case reports in which one of the 14 major food allergens was reported to elicit fatal or life-threatening anaphylactic reactions and assessed if these occurred below the ingestion of 5mg of protein. A Delphi process was performed to obtain an expert consensus on the results. Results In the 210 studies included, in our search no reports of fatal anaphylactic reactions reported below 5 mg protein ingested were identified. However, in provocation studies and case reports, severe reactions below 5mg were reported for the following allergens: eggs, fish, lupin, milk, nuts, peanuts, soy, and sesame seeds. Conclusion Based on the literature studied for this review it can be stated that cross-contamination of the 14 major food allergens below 0.5 mg/100 g is likely not to endanger most food allergic patients when a standard portion of food is consumed. We propose to use the statement “this product contains the named allergens in the list of ingredients, it may contain traces of other contaminations (to be named, e.g. nut) at concentrations less than 0.5 mg per 100 g of this product” for a voluntary declaration on processed food packages. This level of avoidance of cross-contaminations can be achieved technically for most processed foods, and the statement would be a clear and helpful message to the consumers. However it is clearly acknowledged that a voluntary declaration is only a first step to a legally binding solution. For this, further research on threshold levels is encouraged.