INTRODUCTION:Real-world data on dupilumab for eosinophilic esophagitis (EoE), particularly regarding flexible dosing and fibrostenotic phenotypes, are scarce. We aimed to evaluate the effectiveness and safety of dupilumab in clinical practice using the EoE CONNECT registry. METHODS:This cross-sectional analysis included all patients prospectively recruited in the largest European multicenter EoE registry. Baseline characteristics, dosing regimens (300 mg weekly vs semiweekly), clinicohistological response, dose adjustments, and treatment tolerability were assessed. RESULTS:We analyzed 161 patients (145 adults; 16 adolescents). At baseline, 69.1% of patients displayed endoscopic fibrotic features (rings/strictures). After a median of 6.5 months, peak eosinophil count decreased from 57 ± 45 to 8 ± 19 eos/hpf, edema, rings, exudates, furrows, and strictures score declined from 3.0 ± 1.6 to 1.3 ± 1.3, and Dysphagia Symptom Score improved from 5.8 ± 3.7 to 2.5 ± 2.8 (all P < 0.001). Clinicohistological response was achieved by 86.0% of patients on 300 mg weekly and 81.2% on semiweekly dosing ( P = 0.57). Multivariate analysis identified severe atopy as the reason for starting dupilumab as the strongest predictor for semiweekly regimen choice (odds ratio: 26.9; P < 0.001), with conjunctivitis, asthma, and having 2 or more food allergies being significant. Both regimens were equally effective in reducing peak eos/hpf, symptomatology and edema, rings, exudates, furrows, and strictures. Dose tapering from weekly to semiweekly/monthly was successful in all evaluable cases (8/8), whereas dose escalation from semiweekly to weekly rescued 80% (4/5) of nonresponders. Discontinuation occurred only in 8 patients (5%), primarily because of adverse events. DISCUSSION:Dupilumab is effective and safe in real-world EoE management, with no significant differences between weekly and semiweekly induction. Efficacy was generally regained after escalation or maintained after dose tapering.

This review aims to critically summarize current evidence on the biological rationale, efficacy, safety, patient selection, and clinical positioning of mepolizumab in children and adolescents with severe eosinophilic asthma. Severe eosinophilic asthma in childhood is associated with recurrent exacerbations, impaired quality of life, healthcare utilization, and cumulative corticosteroid toxicity. Mepolizumab is a humanized monoclonal antibody targeting interleukin-5 and is approved as add-on treatment for severe eosinophilic asthma in children aged 6 years and older. Pediatric pharmacokinetic and pharmacodynamic studies demonstrate profound and sustained suppression of blood eosinophils, while randomized and real-world evidence consistently supports a reduction in severe exacerbations. Available data also suggest corticosteroid-sparing effects and reduced healthcare utilization in selected patients, whereas improvements in lung function and daily symptom control are less consistent. Pediatric studies indicate a generally favorable safety and tolerability profile, although long-term pediatric-specific data remain limited. Within the current biologic treatment landscape, mepolizumab appears particularly relevant when eosinophilic inflammation, recurrent exacerbations, and corticosteroid burden represent the dominant treatable traits. However, the pediatric evidence base remains substantially smaller than that available in adults, and no head-to-head trials have directly compared mepolizumab with other biologics. Important unresolved issues include the identification of more precise predictors of response, the optimal duration of treatment, criteria for treatment withdrawal or switching, and the potential disease-modifying effects of early biologic intervention.

Food allergy (FA) is an immune-mediated adverse reaction to food components (mainly proteins) and represents an increasing global health problem, affecting millions of individuals and imposing substantial clinical, psychosocial, and economic burdens. Accurate diagnosis is essential to prevent life-threatening reactions while avoiding unnecessary dietary restrictions and impaired quality of life. Current diagnostic approaches rely on clinical history, skin prick tests (SPT), measurement of serum allergen-specific IgE (sIgE), and oral food challenges (OFC). However, SPT and sIgE are highly sensitive but lack specificity, frequently identifying clinically irrelevant sensitization, whereas OFC remains the diagnostic gold standard despite being resource-demanding and carrying a substantial risk of systemic reactions. In recent years, several innovative diagnostic approaches have emerged with the aim of improving diagnostic accuracy and reducing reliance on OFC. Component-resolved diagnostics (CRD) enable detailed characterization of molecular sensitization profiles, supporting improved risk stratification and identification of clinically relevant cross-reactivity patterns. Functional cellular assays, including the basophil activation test (BAT) and the mast cell activation test (MAT), offer direct assessment of IgE-mediated effector cell responses and have demonstrated higher diagnostic specificity compared with conventional testing. Epitope-specific IgE profiling and the allergen-specific IgG4/IgE ratio may additionally contribute to a better understanding of disease phenotype and evolution. Furthermore, advances in multi-omics technologies combined with artificial intelligence and machine learning are creating new opportunities for biomarker discovery and predictive modelling in FA. This narrative review summarizes current innovative diagnostic techniques in food allergy, discussing their clinical applications, limitations, and future directions toward more precise and personalized diagnostic approaches.

Eosinophilic gastrointestinal diseases (EGID) are characterized by abnormal and prominent eosinophilic inflammation of the gastrointestinal mucosa, associated with symptoms related to the segment involved, in the absence of secondary causes of eosinophilia. EGID may affect different parts of the gastrointestinal tract, causing eosinophilic oesophagitis (EoE), eosinophilic gastritis, eosinophilic enteritis and eosinophilic colitis either individually or in combination. Secondary causes of eosinophilic infiltration of the gastrointestinal tract include parasitic infections, the use of certain medications, vasculitis, allergic syndromes, haematological conditions and other inflammatory diseases. The incidence of EGID is increasing globally. EoE is the most reported form, with a prevalence of ~1 in 700 individuals. Several pathogenetic mechanisms are being investigated, in particular, the crosstalk between aeroallergens and mucosal inflammatory cell activation, which leads to a T helper 2 cell inflammatory response and disruption of epithelial barrier integrity. EGID is frequently associated with other T helper 2 cell-driven disorders, such as atopic dermatitis, allergic rhinitis and asthma. EGID is diagnosed through histological assessment, with biopsy samples of affected areas typically showing increased eosinophils, after excluding secondary causes of eosinophilia. For EoE, new treatments, including biologic therapies, are now available, whereas therapeutic options for non-EoE EGID remain limited. Patients' quality of life may be impaired owing to social and functional limitations from symptoms, such as dysphagia and food impaction in EoE, or diarrhoea and abdominal pain in eosinophilic colitis.

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 31st, 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.

PURPOSE OF REVIEW:Eosinophilic gastrointestinal disorders (EGID) are on the rise and impose a significant burden on patients. EGID other than eosinophilic esophagitis (EoE) remain diagnostically and therapeutically challenging. RECENT FINDINGS:We revised the current knowledge on primary EGID. Epithelial barrier dysfunction and type 2 inflammation are key elements in EoE pathogenesis, whereas the mechanisms underlying distal EGID are elusive. Clinical presentations of EGID vary by disease location and depth of tissue involvement. Diagnosis relies on biopsy, although eosinophilic histologic thresholds - particularly for distal forms - remain imperfect, and secondary causes must be rigorously excluded. Treatment of EoE is supported by validated clinical endpoints and includes proton pump inhibitors, topical corticosteroids, elimination diets, and the interleukin-4Rα blocker dupilumab. In contrast, management of non-EoE EGID lacks standardisation and relies predominantly on systemic corticosteroids, immunomodulators, dietary therapy, and limited emerging evidence for biologics. SUMMARY:EGID comprise a heterogeneous spectrum of primary diseases with eosinophilic infiltration of the gut. EoE is the most extensively studied among EGID, whereas non-EoE EGID-including eosinophilic gastritis, enteritis, and colitis-remain rare, understudied. The development and validation of disease-specific clinical outcome measures are awaited to design robust clinical trials and advance therapeutic options for non-EoE EGID.

Irritable bowel syndrome is a common disorder associated with substantial impairment in quality of life and remains challenging to manage due to its heterogeneous and incompletely understood pathophysiology leading to high rates of treatment failure. Recent evidence supports the existence of distinct IBS endotypes, including an emerging atopic variant characterised by allergic comorbidities, type 2 inflammation, and mast cell activation and possibly response to mast cell-directed therapies. Mast cells appear to play a central role in symptom generation by modulating intestinal permeability, motility, and visceral sensitivity, and through close interactions with enteric nerves. Beyond established triggers such as stress and diet and food-related factors, growing attention has been directed towards the role of aeroallergens in influencing symptom variability. Epidemiological, clinical and translational data suggest a link between respiratory allergy and gastrointestinal symptoms. Identifying this phenotype may have important diagnostic and therapeutic implications, supporting the development of targeted treatments and more precise management strategies.

BACKGROUND & AIMS:Topical corticosteroids represent one of the effective first-line treatment options for eosinophilic esophagitis (EoE), and therapy with budesonide orodispersible tablets (BOTs) has been recently approved for the treatment of EoE and showed great efficacy in randomized-controlled clinical trials, however real-life data are lacking. Thus, we aimed to evaluate the effectiveness of treatment with BOTs in adult EoE patients in a real-life setting. METHODS:In this prospective study, clinical, histologic, endoscopic, and safety measures were assessed. Patients underwent evaluation after the induction period (12 weeks) and up 1 year of treatment with BOTs. Dysphagia Symptom Questionnaires were used for symptoms; the Adult Eosinophilic Esophagitis Quality of Life questionnaire for quality of life; the Endoscopic Reference Score for endoscopic activity; eosinophilic peaks (eosinophils per high-power field) for histologic activity. RESULTS:A total of 233 patients were enrolled and 203 completed the assessments after 12 weeks. Deep histological remission was achieved by 84% of patients, as well as clinical remission, associated with an improvement in quality of life. Eighty-six patients concluded 1 year of treatment, and 78% were still in deep remission, while 15% experienced a loss of histological response at treatment tapering. Primary nonresponders were 8%, and secondary nonresponders were 3%. No serious adverse effects were recorded. Only mild side effects related to drug assumption were reported by 28 (12%) of 233 patients, and the most common were oral symptoms. CONCLUSIONS:Our real-world data confirm that BOTs are effective in inducing clinical and histologic remission in most EoE patients. The drug has a good safety profile, with side effects occurring only in a small number of patients.

Esophageal barrier has been investigated until now on the epithelial side only. Gut vascular barrier dysfunction has been recently implicated in a number of immune-mediated gastrointestinal disorders. We here characterized the esophageal vascular barrier (EVB) in eosinophilic esophagitis (EoE). Probe-based confocal laser endomicroscopy (pCLE) was performed in two EoE and two reflux esophagitis (RE) patients. The vascular barrier marker plasmalemma vesicle-1 (PV-1) was investigated as a measure of barrier disruption, by both immunohistochemistry and qPCR, in esophageal biopsies of 16 patients with EoE, 15 with RE, and 15 healthy controls (HC). In EoE, but not RE, pCLE revealed leakage of the EVB, which was restored in one patient after dupilumab treatment. PV-1 was significantly increased in EoE in comparison to RE and HC, both in terms of protein and transcript levels, supporting vascular leakage. EVB is disrupted in active EoE. Further studies are needed to understand the diagnostic and pathogenic implications of this finding.

Urbanization poses significant challenges to ecosystems, resources, and human well-being, necessitating sustainable planning. Urban vegetation, particularly trees, provides critical ecosystem services such as carbon sequestration, air quality improvement, and biodiversity conservation. Traditional tree assessments are resource-intensive and time-consuming. Recent advances in remote sensing, especially high-resolution multispectral imagery and object-based image analysis (OBIA), offer efficient alternatives for mapping urban vegetation. This study evaluates and compares the efficacy of Sentinel-2 and Pléiades satellite imagery in classifying tree species within historic urban parks in Rome—Villa Borghese, Villa Ada Savoia, and Villa Doria Pamphilj. Pléiades imagery demonstrated superior classification accuracy, achieving an overall accuracy (OA) of 89% and a Kappa index of 0.84 in Villa Ada Savoia, compared to Sentinel-2’s OA of 66% and Kappa index of 0.47. Specific tree species, such as Pinus pinea (Stone Pine), reached a user accuracy (UA) of 84% with Pléiades versus 53% with Sentinel-2. These insights underscore the potential of integrating high-resolution remote sensing data into urban forestry practices to support sustainable urban management and planning.

The European Academy of Allergy and Clinical Immunology (EAACI) established a Task Force to assess the existing data on the relationship between eosinophilic esophagitis (EoE) and allergen immunotherapy (AIT). This systematic review and meta-analysis aimed to study the incidence of confirmed EoE, developing as a side effect of AIT to food or airborne allergens, following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) 2020 guidelines. The literature search was performed in three databases (PubMed, Embase and Scopus). Databases were searched from inception to March 31st, 2023. A total of 17 studies met the criteria for inclusion in the review. Fifteen studies, comprising 3,302 patients, were on food desensitization, and the overall estimate of EoE incidence, combining the results of these individual studies, was 2.31% (95% CI 1.45, 3.36). Registered data reported de novo cases of eosinophilic esophagitis, and its diagnosis was usually made during the maintenance phase of food desensitization. With the adopted searching strategy, only two studies on sublingual immunotherapy with aeroallergens meeting the inclusion criteria were retrieved, comprising 1,436 patients and not reporting cases of EoE. The meta-analysis showed that the development of EoE is a common adverse effect of oral immunotherapy with food allergens, whereas it is uncommon during sublingual immunotherapy with aeroallergens. Trial Registration: PROSPERO: CRD42023425917.

Background:Pollen allergy may influence irritable bowel syndrome (IBS) symptoms; however, available data are scant. Aims:This study aims to assess symptom variability in atopic IBS patients. Methods:We retrospectively analysed consecutive adult IBS patients evaluated between 2021 and 2024. Patients from the overall IBS cohort and the IBS-diarrhoea (IBS-D) subgroup were classified according to their sensitisation into grass-positive, house dust mite (HDM)-positive, or unsensitised. Symptom burden was assessed using the gastrointestinal symptom rating scale (GSRS) and a visual analogue scale for abdominal pain/distension, both outside the season period (T0) and during the pollination season (T1). Results:A total of 61 IBS patients were recruited (median age 34 years, IQR 25-50, F:M ratio 3.6:1), including 38 patients (62.8%) with IBS-D (median age 30 years, IQR 28-47, F:M ratio 2.8:1). Atopy was common in the IBS-D subgroup, particularly with respiratory manifestations. The mean GSRS significantly (p < 0.01) increased at T1 (variance of 3.4 points) only in grass-sensitised patients as opposed to those sensitised to HDM or unsensitised ones; this effect was present only in the IBS-D subgroup, while no significant variation was observed in the overall cohort. Conclusions:Pollination season influences symptoms in IBS-D patients sensitised to seasonal allergens.

Splenectomy or congenital asplenia is associated with severe reduction of memory B cells and increased risk of fulminant sepsis by encapsulated bacteria. Current guidelines recommend vaccinations against these pathogens before or after splenectomy, but the longevity of immunity acquired after splenectomy has not been determined. The impact of splenectomy on innate immune cells is unknown. We analyzed frequency, differentiation stage, and function of innate and adaptive immunity in the peripheral blood of adult (n = 41) and pediatric (n = 14) patients splenectomized or born asplenic and in spleens of solid organ donors. The absence of the spleen impacts the B-cell compartment, causing a significant increase of circulating immature transitional and depletion of memory B cells. Using SARS-CoV-2 vaccination as a model, we show that 1 year after the last immunization, despite normal levels of neutralizing antibodies, memory B and T cells were significantly reduced. Analysis of post-pandemic spleens shows that spike-specific memory B and T cells homed to the spleen. We also show a previously unrecognized role of the spleen in the homeostasis of innate NK and Vδ2 T cells. These populations showed altered phenotype and impaired function in the adults, but not in children, suggesting that other tissues may support innate cell development during early life. The reduced function of innate lymphocytes must be considered as an additional immune impairment and risk factor. These findings emphasize the spleen's irreplaceable role in maintaining immune memory across all ages and suggest that its absence contributes to dysfunctions of innate and adaptive immunity in adults.

Background/Objectives: Hypersensitivity reactions (HSRs) to iodinated contrast media (ICM), both immediate and non-immediate, pose clinical challenges despite using low-osmolality agents. This review aims to summarize current diagnostic approaches, cross-reactivity patterns, and the debated role of premedication. Methods: A narrative review was conducted using PubMed (2014–2024), selecting studies on ICM-related HSRs, focusing on skin and in vitro testing, drug provocation tests (DPTs), cross-reactivity, and premedication. Results: Skin tests show limited sensitivity, especially for non-immediate reactions. Cross-reactivity among ICMs is common but unpredictable. DPTs are the diagnostic gold standard but lack standardized protocols. Premedication is frequently used, though its efficacy remains uncertain. Conclusions: The management of ICM hypersensitivity is limited by diagnostic gaps and insufficient evidence on premedication. Standardized protocols and prospective studies are needed to improve patient safety and guide clinical decisions.

Eosinophilic oesophagitis (EoE) is a chronic, immune-mediated condition characterised by eosinophilic infiltration of the oesophagus, leading to significant morbidity due to oesophageal dysfunction. The pathogenic course of EoE begins with tissue injury, marked by the intricate interplay of oesophageal barrier dysfunction and T helper 2-mediated inflammation. In response to tissue damage, a subsequent phase of tissue remodelling features a complex interaction between epithelial cells and stromal cells, aimed at tissue repair. The persistence of inflammation drives these mechanisms towards oesophageal fibrostenosis, mainly through the transforming growth factor-dependent, myofibroblast-driven accumulation of the extracellular matrix. Currently, treatment options for EoE are limited, with dietary intervention, proton pump inhibitors and oral steroids serving as first-line therapies. Dupilumab, an antiinterleukin (IL) 4/IL-13 agent, is the only biologic that has been approved by European and American regulatory authorities. However, emerging OMIC technologies significantly advance our understanding of EoE pathogenesis, revealing novel cellular and molecular mechanisms driving the disease. This progress has accelerated the identification of new therapeutic targets and agents, some already under clinical investigation, potentially expanding our therapeutic arsenal and paving the way for more personalised approaches. In this evolving landscape, artificial intelligence (AI) has shown great potential to further elaborate on the complexities of EoE heterogeneity, offering standardised tools for diagnosis, disease phenotyping, and prediction of treatment response. Though still in their early stages, integrating OMICs and AI marks a pivotal step towards precision medicine in EoE.

Over the past decade, chronic rhinosinusitis (CRS) management has undergone substantial transformation, shifting from conventional symptom-focused treatments to precision medicine strategies grounded on molecular insights. The introduction of biologic agents has significantly changed the therapeutic landscape for CRS with nasal polyps (CRSwNP), directly addressing key inflammatory pathways and leading to marked reductions in nasal polyp burden, overall disease impact, and corticosteroid use. Concerns regarding long-term effectiveness, financial burden, and accessibility remain unresolved. Advances in the understanding of the mechanisms underlying CRS are paving the way for the development of novel therapeutic strategies, with increasing attention now also being directed toward the phenotype without nasal polyps (CRSsNP), which currently lacks targeted therapies. Despite progress in pharmacologic therapies, surgery remains a fundamental treatment option, with ongoing efforts to standardize surgical approaches and evaluate novel techniques. Optimizing the integration of surgical and medical therapies while expanding access to novel treatments represents a key future goal in CRS care. This review aims to guide researchers and clinicians through the evolving landscape of CRS management, covering the latest evidence on established and emerging therapies, offering practical insights into endotyping, and highlighting important considerations for the management of severe or refractory cases.

Purpose of review Eosinophilic esophagitis is a chronic and commonly evolving condition leading to relevant and potentially irreversible burden in terms of tissue damage and related functional impairment, thus significantly impacting on quality of life. The aim of the present review is to summarize the recent advances in terms of diagnostic work-up and pharmacological and nonpharmacological management of the disease, under the broader perspective of type 2 inflammation. Recent findings Two major novelties have prompted an innovative approach to EoE. In terms of diagnosis, it has been proposed to dissect the disease heterogeneity in three endotypes, independent from tissue eosinophil number: EoEe1, characterized by normal appearing oesophagus; EoEe2, associated with type 2 inflammation and steroid-refractoriness; EoEe3, whose features include adult onset, a more fibro-stenotic aspect and loss of epithelial gene expression. Concerning treatment, two recently licensed drugs for EoE, oro-dispersible budesonide and dupilumab represent the first treatment options specifically developed for EoE and addressing EoE-related peculiar pathobiological features. Summary In the era of precision medicine, managing EoE according to a phenotype-driven approach might be helpful in defining the best treatment options in the different disease forms or stages. In addition, exploring the coexistence or the previous occurrence of other type 2 conditions may suggest the opportunity to specifically target type 2 inflammation through biologic therapy. The complex EoE pathobiology combining inflammatory and functional features, both at organ and systemic level, requires a multidimensional approach relying on the strict integration of gastroenterologists and allergist-immunologists.

To the Editor, omega-5 gliadin (O5G), Tri a 19, allergy is usually responsible for wheat-dependent exercised-induced anaphylaxis (WDEIA) (1-4) but not all episodes are characterised by a systemic anaphylactic reaction (5) and factors modulating the reaction severity are elusive (6).We evaluated the prevalence and clinical/laboratory features of O5G in patients presenting with recurrent acute urticaria in a retrospective study in an Italian tertiary referral centre.We enrolled all consecutive adult patients referred in 2021-2023 for recurrent acute urticaria (3), i.e., >1 episode of acute urticaria over 6 months, not induced by physical factors and not present daily and continuously for >6 weeks (7).Patients underwent skin prick tests for aero-and food-allergens (Lofarma, Italy) according to clinical history and specific IgE (FEIA, ImmunoCAP®, Thermo fischer, Sweden), to wheat, O5G, gluten/gliadin were systematically performed.Patients underwent screening for H.

Purpose of review The connection between eosinophilic esophagitis (EoE) and food and airborne allergens is complex. Exposure to allergens (mainly food) is often the trigger for EoE flares. The development of EoE has been described as a side effect of allergen immunotherapy, especially oral immunotherapy (OIT, with food allergens), while isolated cases of EoE have been reported during sublingual immunotherapy (SLIT, with extracts of aeroallergens). Recent findings EoE is currently recognized as a common side effect of OIT, while a solid correlation between SLIT and EoE is missing. Animal models have been developed to study the pathophysiological link between sensitization to aeroallergens and the induction of EoE and will probably provide an interpretation of why there are cases of EoE developed during SLIT. Recent findings in animal models suggest a genetic connection to EoE development after sensitization and re-exposure to airborne allergens. Subcutaneous allergen immunotherapy does not have a causative effect on EoE; on the contrary, a beneficial effect on EoE has been reported. Moreover, epicutaneous immunotherapy with a vector containing milk has also been used to treat children with milk-induced EoE. Summary Discovering the immune links between allergens and EoE will further guide the proper use of allergen immunotherapy and help define future strategies for the management of EoE.