Esophageal Diameter Is Decreased in Some Patients With Eosinophilic Esophagitis and Might Increase With Topical Corticosteroid Therapy

Lee, Joohee; Huprich, James E.; Kujath, Christine; Ravi, Karthik; Enders, Felicity; Smyrk, Thomas C.; Katzka, David A.; Talley, Nicholas J.; Alexander, Jeffrey A.

doi:10.1016/j.cgh.2011.12.042

Cited by 80 publications

(61 citation statements)

References 26 publications

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“…Most recently, Alexander characterized restriction of the esophageal diameter in a cohort of adults with EoE, demonstrating a reduction in both the maximum and minimum diameters compared with controls. [38] Radiologic assessment of esophageal remodeling is clinically feasible but does not assess for variations in diameter as a function of intraluminal distension forces. A small volume of barium with low intrabolus distension pressure will have a tendency to provide falsely low estimates of the diameter of an esophageal stricture since the stiffness of the esophageal wall limits the ability of the wall to expand.…”

Section: Clinical Methods To Assess Remodeling In Eoementioning

confidence: 99%

“…[9, 33, 62] In some contrast, Alexander and colleagues found improvements in esophageal lumen diameter in the subset of subjects with more restricted pre-treatment esophageal caliber following short term topical budesonide. [38] However, there were no significant improvements in luminal caliber on barium esophagram following 6 weeks of topical steroids among subjects who initially had a normal caliber esophagus. Treatment of adults with elemental formula demonstrated improvements in endoscopic features that reflect inflammation (furrows, plaques) but not in the features of rings or strictures that likely reflect long-term tissue remodeling.…”

Section: Effectiveness Of Available Therapies For Remodeling In Eoementioning

confidence: 99%

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Clinical Implications and Pathogenesis of Esophageal Remodeling in Eosinophilic Esophagitis

Hirano

Aceves

2014

Gastroenterology Clinics of North America

117

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In eosinophilic esophagitis (EoE), remodeling changes are manifest histologically in both the epithelium as well as in the subepithelium where lamina propria (LP) fibrosis, expansion of the muscularis propria and increased vascularity occur. The major clinical symptoms and complications of EoE are largely consequences of esophageal remodeling. Important mediators of the process include IL-5, IL-13, TGFβ1, mast cells, fibroblasts and eosinophils. Methods to detect remodeling effects include upper endoscopy, histopathology, barium esophagram, endoscopic ultrasonography, esophageal manometry, and functional luminal imaging. These modalities provide evidence of organ dysfunction that include focal and diffuse esophageal strictures, expansion of the mucosa and subepithelium, esophageal motor abnormalities and reduced esophageal distensibility. Complications of food impaction and perforations of the esophageal wall have been associated with reduction in esophageal caliber and increased esophageal mural stiffness. The therapeutic benefits of topical corticosteroids and elimination diet therapy in resolving mucosal eosinophilic inflammation of the esophagus are evident. Available therapies, however, have demonstrated variable ability to reverse existing remodeling changes of the esophagus. Systemic therapies that include novel, targeted biologic agents have the potential of addressing subepithelial remodeling. Esophageal dilation remains a useful, adjunctive therapeutic maneuver in symptomatic adults with esophageal stricture. As novel treatments emerge, it is essential that therapeutic endpoints account for the fundamental contributions of esophageal remodeling to overall disease activity.

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Section: Clinical Methods To Assess Remodeling In Eoementioning

confidence: 99%

Section: Effectiveness Of Available Therapies For Remodeling In Eoementioning

confidence: 99%

Clinical Implications and Pathogenesis of Esophageal Remodeling in Eosinophilic Esophagitis

Hirano

Aceves

2014

Gastroenterology Clinics of North America

117

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“…In adult subjects treated with budesonide, the overall esophageal diameter was not improved. However, when a sub-analysis was done on those subjects who began with narrowed esophagus, there was an improvement in esophageal diameter following therapy (53). These observations are important and support the conclusions that 1- pediatric subjects likely have a disease that can be modified in terms of LP fibrosis if they are responsive to therapy, 2- adult subjects likely have fibrosis that is more difficult to reverse, 3- while the subepithelial response in children aligns with the epithelial response to therapy, in adults there can be discordance between the epithelial and subepithelial response to therapy, and 4- among both pediatric and adult EoE subjects there is heterogeneity in the ability to control subepithelial fibrosis.…”

Section: Eosinophil Associated Tissue Remodeling In Eoementioning

confidence: 99%

Remodeling and Fibrosis in Chronic Eosinophil Inflammation

Aceves

2014

Dig Dis

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Chronic eosinophilic inflammation has been associated with tissue remodeling in a number of disease states including the hypereosinophilic syndrome (HES), asthma, and, more recently, eosinophilic esophagitis (EoE). Remodeling occurs in the epithelial and subepithelial esophageal tissue, and includes basal zone hyperplasia, epithelial mesenchymal transition, fibrosis, angiogenesis, and smooth muscle hypertrophy/hyperplasia. Previously, research on the clinical impacts of tissue remodeling has been limited by a paucity of human tissue. However, in EoE, recurrent biopsies are required for diagnosis and management. As such, investigators are able to study the associations between tissue changes and clinical disease features. A number of profibrotic and proangiogenic factors are elevated in EoE, including TGF-β1, CCL-18, FGF-9, VEGF, and VCAM-1. Both eosinophils and mast cells produce a number of these factors. TGF-β1 appears to be a master regulator of end-organ dysfunction in EoE and can cause esophageal epithelial mesenchymal transition, fibrosis, and smooth muscle contraction. The requirement for eosinophils, the eosinophilopoietic interleukin, IL-5, and the canonical TGF-β1 signaling pathway for EoE-associated fibrosis, has been invoked using gene-deficient mice. The clinical consequences of eosinophil-associated tissue fibrosis can be devastating, such as endomyocardial fibrosis and heart failure in HES. In EoE, tissue remodeling appears to be the mechanism for multiple cardinal disease complications including esophageal rigidity, strictures, narrowing, and food impactions, as well as the clinical hallmark of dysphagia. Therapies that may be able to reduce or reverse EoE-associated remodeling include topical corticosteroids, anti-IL-5, and food antigen avoidance.

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“…Whether this same paradigm applies to EoE is uncertain. Additional potential targets for monitoring disease activity including biomarkers, subepithelial fibrosis and esophageal distensibility are actively being investigated [70,71].…”

Section: Potential Development Issuesmentioning

confidence: 99%

Emerging drugs for eosinophilic esophagitis

Kern

Hirano

2013

Expert Opinion on Emerging Drugs

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No FDA-approved prescription medications are currently available for EoE patients. Although a number of novel agents are being developed and tested, Phase III clinical trials are scarce. Since EoE is a newly described disease, physicians have an incomplete understanding of the disease's pathogenesis, natural history and disease manifestations. This has led to significant difficulties in determining the most appropriate endpoints of therapy. Clinical trials are hampered by the lack of an accepted, standardized disease activity measure or biomarker by which therapeutic efficacy is assessed. Effective and approved pharmaceutical therapies are eagerly awaited by both physicians and patients for this increasingly recognized and clinically important disease.

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Esophageal Diameter Is Decreased in Some Patients With Eosinophilic Esophagitis and Might Increase With Topical Corticosteroid Therapy

Cited by 80 publications

References 26 publications

Clinical Implications and Pathogenesis of Esophageal Remodeling in Eosinophilic Esophagitis

Clinical Implications and Pathogenesis of Esophageal Remodeling in Eosinophilic Esophagitis

Remodeling and Fibrosis in Chronic Eosinophil Inflammation

Emerging drugs for eosinophilic esophagitis

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