Jonathan Michael Spergel

Background: Patients with eosinophilic oesophagitis (EoE) can present with differing disease characteristics, treatment resistance, and associated type 2 inflammatory comorbidities. We assessed the efficacy of dupilumab in subgroups of patients with EoE from the LIBERTY EoE TREET study across a range of demographics, characteristics, treatments, and comorbidities. Methods: Patients were categorised by subgroups based on weight (< 60 kg or ≥ 60 kg), body mass index (< 18.5 kg/m ² , ≥ 18.5 to < 30 kg/m ² , ≥ 30 kg/m ² ), disease duration before study entry (< 5 years, ≥ 5 to < 10 years, ≥ 10 years), history of type 2 inflammatory comorbidities (with/without asthma, allergic rhinitis, atopic dermatitis, or food allergy), history of elimination diet, concurrent elimination diet, concurrent proton pump inhibitor use, and prior oesophageal dilation. Outcomes were analysed post hoc and included the proportion of patients achieving ≤ 6 eosinophils per high‐power field (eos/hpf) and change from baseline in Dysphagia Symptom Questionnaire (DSQ) and total Endoscopic Reference Score (EREFS). Results: At Week 24, dupilumab treatment increased the proportion of patients achieving histological remission (peak eosinophil count ≤ 6 eos/hpf) versus placebo in all subgroups. At Week 52, improvements were maintained with continued dupilumab treatment. Improvements were also observed through Week 52 in patients who switched from placebo to dupilumab at Week 24. Similar results were observed for change from baseline in DSQ and EREFS. Conclusions: Dupilumab treatment improved histological, symptomatic, and endoscopic outcomes versus placebo in patients with EoE, regardless of demographics, disease characteristics, treatment history, or type 2 inflammatory disease comorbidities. Trial Registration: ClinicalTrials.gov identifier: NCT03633617

Thymic stromal lymphopoietin (TSLP) is a key upstream epithelial cytokine, and its overexpression is associated with inflammation, leading to immune dysfunction, epithelial barrier disruption, and tissue remodeling. TSLP is implicated in the pathogenesis of multiple atopic diseases, including asthma, chronic rhinosinusitis with nasal polyps, and eosinophilic esophagitis (EoE). EoE is a chronic, type 2 (T2) inflammatory disease linked to a delayed-type hypersensitivity response to food antigens and characterized by eosinophil-predominant mucosal inflammation and esophageal dysfunction. TSLP expression and TSLP-mediated T2 inflammatory activity are elevated in esophageal biopsies in patients with active EoE compared with patients with inactive EoE and healthy individuals. In phase 3 clinical trials, a monoclonal antibody against TSLP, called tezepelumab, has shown significant improvements in clinical outcomes compared with placebo in other atopic conditions that have a shared T2 inflammatory disease pathology and epithelial remodeling pathway with EoE, such as asthma and chronic rhinosinusitis with nasal polyps. In this review, we present evidence of TSLP involvement in mediating and exacerbating EoE pathology and discuss how targeting TSLP activity could be a viable therapeutic option for EoE treatment.

Eosinophilic esophagitis (EoE) is a chronic, type 2 inflammatory disease of the esophagus, characterized by infiltration of eosinophils and symptoms of esophageal dysfunction. EoE is often exacerbated by common trigger foods, such as milk, egg, soy, and wheat, and can be effectively treated by their removal from the diet without the need for life-long medication. As most patients have a single trigger food, recent studies have demonstrated comparable efficacy between the one-food elimination diet, and four- and six-food elimination diets. However, maintaining adherence to any food elimination diet can be challenging and result in reduced quality of life. Some patients seek a safe and effective treatment to allow reintroduction of trigger foods into their diet. Dupilumab is a monoclonal antibody that blocks interleukin (IL)-4 and IL-13 signaling pathways, which are key and central drivers of type 2 inflammation. In phase 3 trials, dupilumab improved histologic, endoscopic, symptomatic, and transcriptomic outcomes in patients with EoE. A recent pilot study investigated the facilitation of trigger food reintroduction with dupilumab in children with EoE, who initially received 3 months of dupilumab treatment to ensure EoE disease control, before gradually reintroducing trigger foods every 3 months with continued dupilumab treatment. Overall, 86% of instances of trigger food reintroduction were successful, without loss of histologic remission. Children were able to reintroduce trigger foods without any worsening in histologic, endoscopic, or symptomatic outcomes, or narrowing of the esophagus. While all children who completed the study were able to reintroduce at least one serving of trigger food, some lost histologic remission after an initial attempt of trigger food reintroduction but were able to successfully reintroduce trigger foods after continued dupilumab treatment. Other children were able to rapidly reintroduce trigger foods every 3 months. Further investigation is required to determine patient characteristics that may influence the rate at which trigger foods can be reintroduced. The most common adverse events were upper respiratory tract infections, followed by injection-site reactions. Dupilumab may provide an effective method to reduce dietary burden in patients with EoE. Results from an ongoing study investigating trigger food reintroduction with dupilumab in adults are anticipated.

Anaphylaxis is a rapid-onset, potentially life-threatening systemic allergic reaction that remains a significant clinical concern in pediatric practice. Food allergies are the most common trigger in children, and a substantial proportion of affected patients experience severe reactions. This review provides a practical, evidence-based framework for the diagnosis and management of IgE-mediated allergy in the pediatric setting, emphasizing recognition, treatment, and preparedness. Anaphylaxis is a clinical diagnosis based on established criteria, with age-specific presentations that may complicate recognition, particularly in infants and young children. Epinephrine is the cornerstone of treatment and the only therapy capable of reversing life-threatening respiratory and cardiovascular manifestations. Early epinephrine administration improves outcomes, yet real-world use remains suboptimal due to barriers such as needle aversion, device complexity, and access challenges. Pediatricians play a critical role in identifying at-risk patients, prescribing epinephrine, and reinforcing preparedness through education and individualized action plans across care settings. Integrating evolving therapeutic options with established best practices may help address persistent gaps in care and improve outcomes for children at risk of anaphylaxis.

Background: Eosinophilic esophagitis (EoE) is a chronic, food antigen-driven disease of the esophagus that causes considerable morbidity. Elimination of allergenic foods from a patient’s diet is a highly effective treatment. However, existing allergen testing modalities are not effective at identifying EoE-causal foods. We sought to determine the extent to which positive results for two functional T-cell assays, the EoE Milk Test and EoE Soy Test, associated with the clinical outcomes of EoE milk allergy and EoE soy allergy, respectively. Methods: Subjects were enrolled into one of two study designs: a prospective observational study or a retrospective case/control study. Additional control samples were obtained from an institutional core. The EoE Milk and Soy Tests were performed on peripheral blood samples, and the association between positive tests and clinical outcomes was determined using Receiver Operating Characteristic curves and other performance measures. Results: The EoE Milk Test maintained reliability regardless of disease activity or recent milk consumption and had 87% sensitivity and 83% specificity for EoE milk allergy in all study subjects (control and EoE). The EoE Soy Test had 90% sensitivity and 93% specificity in all subjects. Conclusions: Our evaluation of the EoE Milk and Soy Tests demonstrates that these functional T-cell assays hold promise as a predictive tool for identifying causal allergens in eosinophilic esophagitis patients.