Dilated Intercellular Spaces in Eosinophilic Esophagitis

Ravelli, A; Villanacci, Vincenzo; Cadei, Moris; Fuoti, Maurizio; Gennati, Giada; Salemme, Marianna

doi:10.1097/mpg.0000000000000491

Cited by 37 publications

(48 citation statements)

References 20 publications

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“…Such damage might expose epithelial cells and nerves to further acid injury. 46,47 Lastly, remodelling effects in EoE, manifested as fibrosis and increased thickness of the oesophageal wall, substantially increase oesophageal mural stiffness (reduced distensibility), as demonstrated by studies using the functional luminal imaging probe. 48,49 Alterations in oesophageal function might contribute to increased acid exposure due to impaired clearance of refluxed contents.…”

Section: Interactions Between Eoe and Gerdmentioning

confidence: 97%

Distinguishing GERD from eosinophilic oesophagitis: concepts and controversies

Kia

Hirano

2015

Nat Rev Gastroenterol Hepatol

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Over the past three decades, the detection of oesophageal mucosal eosinophils has transitioned from a biomarker of GERD to a diagnostic criterion for eosinophilic oesophagitis (EoE). In GERD, oesophageal eosinophils are considered part of the chronic inflammatory response to acid reflux, whereas the marked eosinophilia in EoE is viewed as a central feature of the immune response to ingested food and/or environmental antigen stimulation. Descriptions of a considerable subset of patients with symptomatic, endoscopic and histological findings of EoE that resolve with PPI therapy has led to confusion and controversy regarding the distinction of EoE from GERD. Study findings indicate that PPI-responsive oesophageal eosinophilia (PPI-REE) more closely resembles EoE than GERD, both from a clinical and immunological aspect. Although responsiveness to PPI therapy should not be utilized to exclude EoE, PPI therapy is effective at reducing oesophageal eosinophilia in ~40% of patients, and PPI therapy is both a safe and practical initial step in the management of patients with oesophageal eosinophilia. Ongoing studies elucidating the mechanism behind PPI-REE will improve our understanding and management of EoE. In this Review, the mechanisms and evidence that underlie the controversy in the distinction between GERD and EoE are evaluated.

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Section: Interactions Between Eoe and Gerdmentioning

confidence: 97%

Distinguishing GERD from eosinophilic oesophagitis: concepts and controversies

Kia

Hirano

2015

Nat Rev Gastroenterol Hepatol

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“…Furthermore, DIS can be reproduced without symptoms in HV by way of acid perfusion. 14 Finally, DIS can occur in healthy 15 as well as in non-reflux settings, such as eosinophilic esophagitis and esophageal Candidiasis 16,17 without concomitant heartburn, suggesting that DIS may merely be a non-specific response to epithelial inflammation rather than a cause of reflux symptoms.…”

Section: Background and Aimsmentioning

confidence: 99%

Superficial Esophageal Mucosal Afferent Nerves May Contribute to Reflux Hypersensitivity in Nonerosive Reflux Disease

et al. 2017

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“…Esophageal tissue integrity has a critical role in disease pathogenesis, 4–10 as illustrated by profound dysregulation of the epidermal differentiation complex (EDC) genes 11 and decreased expression of desmoglein 1 ( DSG1 ) in active EoE and in IL-13–stimulated esophageal epithelial cells. 4 In line with these findings, genes for structural proteins including keratin 6C, keratin 32 and the EDC gene cornulin (CRNN), are among the most highly expressed genes in the homeostatic esophagus on the basis of the Human Protein Atlas.…”

Section: Introductionmentioning

confidence: 99%

Profound loss of esophageal tissue differentiation in patients with eosinophilic esophagitis

Rochman

Travers

Miracle

et al. 2017

Journal of Allergy and Clinical Immunology

104

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Background A key question in the allergy field is to understand how tissue specific disease is manifested. Eosinophilic esophagitis (EoE) is an emerging tissue specific allergic disease whose pathogenesis remains unclear. Objective Herein, we tested the hypothesis that a defect in tissue specific esophageal genes is an integral part of EoE pathogenesis. Methods We interrogated the pattern of expression of esophagus-specific signature genes derived from the Human Protein Atlas in the EoE transcriptome and in EPC2 esophageal epithelial cells. Western blot and immunofluorescence were used for evaluating expression of esophageal proteins in control and active EoE biopsies. Whole-exome sequencing (WES) was performed to identify mutations in esophagus-specific genes. Results We found that ~39% of the esophagus-specific transcripts were altered in EoE, with ~90% being downregulated. The majority of transcriptional changes observed in esophagus-specific genes were reproduced in vitro in esophageal epithelial cells differentiated in the presence of IL-13. Functional enrichment analysis revealed keratinization and differentiation as the most affected biological processes, and identified IL-1 cytokines and serine peptidase inhibitors (SERPINs) as the most dysregulated esophagus-specific protein families in EoE. Accordingly, EoE biopsies evidenced a profound loss of tissue differentiation, decreased expression of keratin 4 and cornulin and elevated expression of keratin 5 and 14. Whole-exome sequencing of 33 unrelated EoE cases revealed 39 rare mutations in 18 esophagus-specific differentially expressed genes. Conclusions A tissue-centered analysis has revealed a profound loss of esophageal tissue differentiation (identity) as an integral and specific part of the pathophysiology of EoE, and implicated protease- and IL-1–related activities as putative central pathways in disease pathogenesis.

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Dilated Intercellular Spaces in Eosinophilic Esophagitis

Abstract: DIS are a prominent morphological feature of EoE, in which they can be significantly reduced by an appropriate non-PPI therapy.

Cited by 37 publications

References 20 publications

Distinguishing GERD from eosinophilic oesophagitis: concepts and controversies

Distinguishing GERD from eosinophilic oesophagitis: concepts and controversies

Superficial Esophageal Mucosal Afferent Nerves May Contribute to Reflux Hypersensitivity in Nonerosive Reflux Disease

Profound loss of esophageal tissue differentiation in patients with eosinophilic esophagitis

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