Histological Response to Fluticasone Propionate in Patients With Eosinophilic Esophagitis Is Associated With Improved Functional Esophageal Mucosal Integrity

Rhijn, Bram D. van; Verheij, Joanne; Weerman, Marius A. van den Bergh; Verseijden, Caroline; Wijngaard, R.M.J.G.J. van den; Jonge, Wouter J. de; Smout, Andreas J.; Bredenoord, Albert J.

doi:10.1038/ajg.2015.247

Cited by 56 publications

(51 citation statements)

References 34 publications

(48 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[9,44] Collectively, these data support a trial of PPI for virtually any patient with oesophageal eosinophilia, regardless of the underlying mechanism. [45].…”

Section: Potential Mode Of Action Of Ppi In Eoementioning

confidence: 78%

Proton pump inhibitor-responsive oesophageal eosinophilia: an entity challenging current diagnostic criteria for eosinophilic oesophagitis

Molina–Infante

Bredenoord

Cheng

et al. 2015

Gut

Self Cite

288

216

View full text Add to dashboard Cite

Consensus diagnostic recommendations to distinguish gastro-oesophageal reflux disease (GORD) from eosinophilic oesophagitis (EoE) by response to a trial of proton pump inhibitors (PPI) unexpectedly uncovered an entity called “PPI-responsive oesophageal eosinophilia” (PPI-REE). PPI-REE refers to patients with clinical and histologic features of EoE that remit with PPI treatment. Recent and evolving evidence, mostly from adults, shows that PPI-REE and EoE patients at baseline are clinically, endoscopically and histologically indistinguishable, and have significant overlap in terms of features of Th2 immune-mediated inflammation and gene expression. Furthermore, PPI therapy restores oesophageal mucosal integrity, reduces Th2 inflammation and reverses the abnormal gene expression signature in PPI-REE patients, similar to the effects of topical steroids in EoE patients. Additionally, recent series have reported that EoE patients responsive to diet/topical steroids may also achieve remission on PPI therapy. This mounting evidence supports the concept that PPI-REE represents a continuum of the same immunologic mechanisms that underlie EoE. Accordingly, it seems counterintuitive to differentiate PPI-REE from EoE based on a differential response to PPI therapy when their phenotypic, molecular, mechanistic, and therapeutic features cannot be reliably distinguished. For patients with symptoms and histologic features of EoE, it is reasonable to consider PPI therapy not as a diagnostic test, but as a therapeutic agent. Due to its safety profile, ease of administration and high response rates (up to 50%), PPI can be considered a first-line treatment, before diet and topical steroids. The reasons why some EoE patients respond to PPI, while others do not, remain to be elucidated.

show abstract

“…[9,44] Collectively, these data support a trial of PPI for virtually any patient with oesophageal eosinophilia, regardless of the underlying mechanism. [45].…”

Section: Potential Mode Of Action Of Ppi In Eoementioning

confidence: 78%

Proton pump inhibitor-responsive oesophageal eosinophilia: an entity challenging current diagnostic criteria for eosinophilic oesophagitis

Molina–Infante

Bredenoord

Cheng

et al. 2015

Gut

Self Cite

288

216

View full text Add to dashboard Cite

show abstract

“…In one study, patients with active and treated EoE demonstrated signifi cant increase in impedance (2,574 vs. 6,618 Ω, P <0.01) corresponding to measurements made on biopsy using Ussing chambers. Th ese fi ndings suggest that histologic response to therapy in EoE results in mucosal healing and a decrease in transepithelial molecule fl ux, which is a restoration of mucosal integrity ( 96 ). A recent study confi rmed the clinical utility of direct mucosal impedance measurement in the assessment of EoE activity, with an inverse correlation between esophageal eosinophil density, dilated epithelial intercellular spaces, and mucosal impedance.…”

Section: Mucosal Integrity Assessed By Impedancementioning

confidence: 96%

Esophageal Impedance Monitoring: Clinical Pearls and Pitfalls

Ravi

Katzka

2016

American Journal of Gastroenterology

View full text Add to dashboard Cite

The development of intraluminal esophageal impedance monitoring has improved our ability to detect and measure gastroesophageal reflux without dependence on acid content. This ability to detect previously unrecognized weak or nonacid reflux episodes has had important clinical implications in the diagnosis and management of gastroesophageal reflux disease (GERD). In addition, with the ability to assess bolus transit within the esophageal lumen, impedance monitoring has enhanced the recognition and characterization of esophageal motility disorders in patients with nonobstructive dysphagia. The assessment of the intraluminal movement of gas and liquid has also been proven to be of diagnostic value in conditions such as rumination syndrome and excessive belching. Further, alternative applications of impedance monitoring, such as the measurement of mucosal impedance, have provided novel insights into assessing esophageal mucosal integrity changes as a consequence of inflammatory change. Future applications for esophageal impedance monitoring also hold promise in esophageal conditions other than GERD. However, despite all of the clinical benefits afforded by esophageal impedance monitoring, important clinical and technical shortcomings limit its diagnostic value and must be considered when interpreting study results. Overinterpretation of studies or application of impedance monitoring in patients can have deleterious clinical implications. This review will highlight the clinical benefits and limitations of esophageal impedance monitoring and provide clinical pearls and pitfalls associated with this technology.

show abstract

“…The barrier function of esophageal mucosa in EoE might be regulated by Th2 cytokines and filaggrin [47,48].…”

Section: Eosinophilic Esophagitis (Eoe)mentioning

confidence: 99%

Gastrointestinal mucosal barrier function and diseases

2016

View full text Add to dashboard Cite

The gastrointestinal mucosal barrier plays an essential role in the separation of the inside of the body from the outside environment. Tight junctions (TJs) are the most important component for construction of a constitutive barrier of epithelial cells, and they regulate the permeability of the barrier by tightly sealing the cell-cell junctions. TJ proteins are represented by claudins, occludin, junctional adhesion molecules, and scaffold protein zonula occludens. Among these TJ proteins, claudins are the major components of TJs and are responsible for the barrier and the polarity of the epithelial cells. Gastrointestinal diseases including reflux esophagitis, inflammatory bowel disease, functional gastrointestinal disorders, and cancers may be regulated by these molecules, and disruption of their functions leads to chronic inflammatory conditions and chronic or progressive disease. Therefore, regulation of the barrier function of epithelial cells by regulating the expression and localization of TJ proteins is a potential new target for the treatment of these diseases. Treatment strategies for these diseases might thus be largely altered if symptom generation and/or immune dysfunction could be regulated through improvement of mucosal barrier function. Since TJ proteins may also modify tumor infiltration and metastasis, other important goals include finding a good TJ biomarker of cancer progression and patient prognosis, and developing TJ protein-targeted therapies that can modify patient prognosis. This review summarizes current understanding of gastrointestinal barrier function, TJ protein expression, and the mechanisms underlying epithelial barrier dysregulation in gastrointestinal diseases.

show abstract

Histological Response to Fluticasone Propionate in Patients With Eosinophilic Esophagitis Is Associated With Improved Functional Esophageal Mucosal Integrity

Abstract: Fluticasone propionate treatment decreases eosinophilic inflammation and improves the esophageal mucosal barrier integrity in adult EoE patients. Improvement of the mucosal barrier integrity correlates with normalization of expression of desmoglein-1 and filaggrin marker genes.

Cited by 56 publications

References 34 publications

Proton pump inhibitor-responsive oesophageal eosinophilia: an entity challenging current diagnostic criteria for eosinophilic oesophagitis

Proton pump inhibitor-responsive oesophageal eosinophilia: an entity challenging current diagnostic criteria for eosinophilic oesophagitis

Esophageal Impedance Monitoring: Clinical Pearls and Pitfalls

Gastrointestinal mucosal barrier function and diseases

Contact Info

Product

Resources

About