Type 2 Inflammation in Eosinophilic Esophagitis: From Pathophysiology to Therapeutic Targets

Eosinophilic esophagitis (EoE) is a chronic immune-mediated disease of the esophagus characterized clinically by symptoms related to esophageal dysfunction and histologically by eosinophil-predominant inflammation, whose incidence is rising. It significantly affects patients’ quality of life and, if left untreated, results in fibrotic complications. Although broad consensus has been achieved on first-line therapy, a subset of patients remains non-responder to standard therapy. The pathogenesis of EoE is multifactorial and results from the complex, still mostly undefined, interaction between genetics and intrinsic factors, environment, and antigenic stimuli. A deep understanding of the pathophysiology of this disease is pivotal for the development of new therapies. This review provides a comprehensive description of the pathophysiology of EoE, starting from major pathogenic mechanisms (genetics, type 2 inflammation, epithelial barrier dysfunction, gastroesophageal reflux, allergens, infections and microbiota) and subsequently focusing on the single protagonists of type 2 inflammation (involved cells, cytokines, soluble effectors, surface proteins and transcription factors) that could represent present and future therapeutic targets, while summarizing previous therapeutic approaches in literature.

Endoscopic Ultrasonography in Children with Eosinophilic Esophagitis—A Review

Endoscopic ultrasonography (EUS) is a diagnostic endoscopy of the upper gastrointestinal tract, during which ultrasound of nearby organs is also performed. It is also possible to perform a fine needle aspiration biopsy. Currently, EUS is performed more frequently in adults. Despite some limitations, this diagnostic method is also more and more often performed in pediatric patients. Eosinophilic esophagitis (EoE) is a chronic inflammatory disease of the esophagus, which also occurs in children, and leads to irreversible fibrosis of the esophagus wall, if left untreated. Traditional methods of diagnosing and monitoring EoE treatment have significant limitations, and the use of EUS and total esophageal wall thickness (TWT) assessment may bring measurable benefits. Several studies have shown an increased thickening of TWT in EoE in children compared to pediatric patients with gastroesophageal reflux disease, and a decrease in TWT in adults who responded to EoE treatment. These results suggest that EUS and TWT measurement may become an important test in diagnostics, monitoring the effectiveness of therapy, assessing disease progression, and in individualizing the method and duration of EoE treatment also in children.

The Cellie Coping Kit for children with Eosinophilic Esophagitis: Feasibility, acceptability, and preliminary outcomes

Children with eosinophilic esophagitis (EoE) are faced with ongoing treatments that can impact their wellbeing. There are no evidence-based resources that families can implement independently to cope with EoE-related stressors. This study aimed to examine acceptability, feasibility, and preliminary outcomes of the newly developed Cellie Coping Kit for Children with EoE intervention. Forty child-caregiver dyads completed a baseline assessment (T1) and initiated the intervention; 30 (75%) child participants and 33 (82.5%) caregivers were retained to follow-up (T2). Of those who completed the T2 assessment, most reported that the intervention was easy to use (>90%) and would recommend the intervention to others (>90%). The intervention was feasible: >70% used the kit, and most indicated they would use it again (>75%). More than half of families reported learning new information and/or coping strategies. No statistically significant changes were identified in comparing T1 and T2 coping and health-related quality of life. These findings suggest that the Cellie Coping Kit for Children with EoE is a promising intervention in that it was well accepted, feasible, and helped many families learn novel strategies on how to manage EoE challenges. Future research should examine how to strengthen the intervention to achieve longer-term targeted outcomes.

The Risk of Esophageal Food Impaction In Eosinophilic Esophagitis Patients; The Role of Clinical And Socioeconomic Factors

Background: Eosinophilic esophagitis (EoE) patients present with dysphagia and often suffer from esophageal food impaction (EFI). EFI can lead to life-threatening perforation, and requires emergent endoscopic intervention. The aim of this study is to evaluate the risk factors for EFI in EoE patients.Methods: This is a retrospective study performed at a tertiary health care system. Medical records and endoscopy images of EoE cases were reviewed. Clinical characteristics and outcomes including EFIs were documented. We used Zip-code median household income as a surrogate for patients’ socioeconomic status.Results: 291 EoE cases were included, mean age was 42 years. Most patients (65%) had classic EoE endoscopic findings including linear furrows and/or concentric rings, however, a significant proportion (47%) had findings suggestive of gastroesophageal reflux disease (GERD), such as the presence of erosive-esophagitis, a hiatal hernia or Schatzki’s ring. 48 patients (16%) developed one or more esophageal food impaction (EFI). The risk of EFI was less likely in the absence of furrows and/or rings; odds ratio (OR) = .28, 95%CI (0.11, 0.72) [P = .008]. Females had less EFI risk; OR = 0.42, 95%CI (0.19, 0.95) [P = .04]. The type of medical insurance and socioeconomic status was not associated with EFI risk.Conclusion: EFI risk is higher in EoE patients with esophageal furrows and/or rings and in men. Aggressive treatment might be required in this population. GERD and EoE can coexist in many patients. Further studies are required to examine the role of the socioeconomic status in EoE complications.

Outcomes of eosinophilic esophagitis in patients managed in a multidisciplinary clinic

Background: Eosinophilic esophagitis is a complex disease with an increasing prevalence. Multidisciplinary teams are often needed to manage this difficult-to-treat condition. Objective: To observe the clinical and histologic outcomes of patients with eosinophilic esophagitis after management in a multidisciplinary clinic. Methods: An observational, retrospective chart review was conducted to include all patients referred to the Walter Reed National Military Medical Center multidisciplinary eosinophilic esophagitis clinic between August 2012 and February 2021. Only patients who had at least one esophagogastroduodenoscopy before referral, one or more visits and endoscopy after multidisciplinary management, and documented clinical symptoms were included. Statistical analysis was performed by using McNemar and Wilcoxon tests. Results: A total of 103 patients were included in the study, with a mean age at diagnosis of 17.9 years. Management in the multidisciplinary clinic was associated with a reduction in solid-food dysphagia by 70.9%, poor growth by 70.8%, and emesis or regurgitation by 87.5%. We observed that 48.5% and 62.1% had histologic remission (<15 eosinophils/hpf) on the initial and any post-multidisciplinary endoscopy, respectively. Only seven patients (5.8%) with two or more visits and endoscopies did not achieve histologic remission. More than two-thirds of the patients (68.9%) required combination therapy to achieve remission. Conclusion: Although an observational study, these findings may suggest that the management of patients with eosinophilic esophagitis in a multidisciplinary clinic may improve the likelihood of clinical and histologic remission. Targeted management with a multidisciplinary approach may reduce overall morbidity and slow disease progression; however, more research is needed.

Eosinophilic esophagitis in children: Updates and practical aspects of management for allergists in a non‐tertiary care private practice setup

Background: Eosinophilic esophagitis (EoE) is a chronic immune and/or antigen-mediated disease characterized by eosinophilic infiltration of mucosa (≥15 eosinophils per high power field) without any secondary etiology. Non‐immunoglobulin E mediated mechanisms predominate in EoE. Objective: This review concentrated on a stepwise approach for the allergist working in non‐tertiary care private practice. Methods: A medical literature search that focused on several areas of the latest developments in the diagnosis and management of EoE was conducted. Results: There has been a steady increase in the prevalence and incidence of EoE. Clinical symptoms can vary from dysphagia to failure to thrive, depending on the age at presentation; some children develop adaptive behaviors to compensate for dysphagia, such as food preferences and slow eating. The diagnosis is based on a high index of clinical suspicion and is confirmed with endoscopy with biopsies after ruling out other causes of esophageal eosinophilia. Treatment options may include dietary therapy, pharmacologic therapies, or combination therapy. Therapeutic options may also include endoscopic dilation for stricturing disease. Conclusion: Providers should be aware of recent recommendation changes in the diagnostic workup, the role of skin-prick testing, and role of the proton-pump inhibitor as first-line therapy for EoE. Also, clinicians should be aware of the emerging role of empiric dietary therapy as a preferable therapeutic option when compared with the testing-directed diet and the elemental diet. Furthermore, topical glucocorticoid therapies are available, and new developing therapies are being investigated. Reevaluation of esophageal mucosa with biopsies is required approximately 2 months after therapy for a response and after a change in therapies to confirm continued resolution.

Acute Herpes Simplex Esophagitis in an Immunocompetent Adult with Eosinophilic Esophagitis

Herpes simplex esophagitis (HSE) represents a rare entity in immunocompetent patients and has infrequently been described in association with eosinophilic esophagitis (EoE). Causality in this rare association remains a debated topic. We present a case of HSE occurring in an immunocompetent adult with EoE and review the literature in support of EoE induced mucosal disruption predisposing to increased risk of HSE.

Is Fractionated exhaled nitric oxide (FeNO) useful as a biomarker in eosinophilic esophagitis?

FeNO levels are not useful either for diagnosis or for evaluating response to treatment. Although, subjects without asthma with FeNO-l ≥ 30 ppb have probability to EoE,