Eosinophilic Esophagitis

Cheng, Edaire; Souza, Rhonda F.; Spechler, Stuart J.

doi:10.1016/j.gtc.2014.02.004

Cited by 47 publications

(24 citation statements)

References 104 publications

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“…This could be the mechanism by which PPIs block components of allergic inflammation. 94, 95 Future studies are needed to identify the genetic and environmental factors that contribute to PPI-REE, as well as its mechanisms of induction and progression—especially in comparison to EoE.…”

Section: Discussionmentioning

confidence: 99%

Molecular, Genetic, and Cellular Bases for Treating Eosinophilic Esophagitis

2015

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Eosinophilic esophagitis (EoE) was historically distinguished from gastroesophageal reflux disease on the basis of histology and lack of responsiveness to acid suppressive therapy, but it is now appreciated that esophageal eosinophilia can respond to proton pump inhibitors. Genetic and environmental factors contribute to risk for EoE—particularly early-life events. Disease pathogenesis involves activation of epithelial inflammatory pathways (production of eotaxin-3 [encoded by CCL26]), impaired barrier function (mediated by loss of desmoglein-1), increased production and/or activity of transforming growth factor-β, and induction of allergic inflammation by eosinophils and mast cells. Susceptibility has been associated with variants at 5q22 (TSLP) and 2p23 (CAPN14), indicating roles for allergic sensitization and esophageal specific protease pathways. We propose that EoE is a unique disease characterized by food hypersensitivity, strong hereditability influenced by early-life exposures and esophageal specific genetic risk variants, and allergic inflammation and that the disease is remitted by disrupting inflammatory and T-helper type 2 cytokine–mediated responses and through dietary elimination therapy.

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Section: Discussionmentioning

confidence: 99%

Molecular, Genetic, and Cellular Bases for Treating Eosinophilic Esophagitis

2015

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“…It is less well known that PPIs have anti-inflammatory actions (independent of antisecretory effects) that also might contribute to healing oesophagitis. 38 PPIs have antioxidant properties, inhibit immune cell functions, decrease adhesion molecule expression by endothelial cells and reduce inflammatory cytokine expression by epithelial cells. 39 PPIs also have anti-inflammatory effects that might be especially pertinent to the allergen-driven eosinophilia of EoE.…”

Section: Potential Mode Of Action Of Ppis In Eoementioning

confidence: 99%

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

Molina–Infante

Bredenoord

Cheng

et al. 2015

Gut

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290

216

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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.

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“…Early authorities deemed it crucial to distinguish this disorder from GERD [2]. However, GERD and EoE are not mutually exclusive disorders [3]. First, GERD, in the absence of EoE, can have mild esophageal eosinophilia.…”

Section: Eoe Ppi-responsive Esophageal Eosinophilia and Gerdmentioning

confidence: 99%

“…There are multiple plausible mechanisms whereby EoE patients benefit from PPI-induced acid suppression [3]. Reducing acid exposure might decrease acid injury-related cytokines, pain, and esophageal permeability.…”

Section: Ppi As a Therapeutic Option For Eoementioning

confidence: 99%

“…After PPI therapy, eotaxin-3 expression decreased in the proximal esophagus where reflux is unlikely to occur suggesting that anti-inflammatory effects rather than acid suppression are the reason for the decrease [17]. PPIs can also exhibit anti-oxidant properties, inhibit certain functions of immune cells, and decrease expression of adhesion molecules and inflammatory cytokines [3]. Lastly, the timely transcriptome analysis of PPI-REE patients showed reversion of classic allergic inflammation gene expression including eosinophilia, mastocytosis, tissue remodeling, and impaired barrier function after PPI therapy providing compelling evidence that PPIs have therapeutic properties directed at allergic inflammation [13].…”

Section: Ppi As a Therapeutic Option For Eoementioning

confidence: 99%

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Translating New Developments in Eosinophilic Esophagitis Pathogenesis into Clinical Practice

Cheng

2015

Curr Treat Options Gastro

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Opinion Statement New developments in eosinophilic esophagitis pathogenesis are shaping our current therapeutic and management strategies. EoE is a chronic allergic inflammatory disease with progression to fibrostenotic disease. The disease warrants early diagnosis and long-term maintenance therapy. The diagnosis of EoE should be based on the concept of an allergy-mediated disease with esophageal dysfunction and esophageal eosinophilia. Recent findings suggest PPI-REE is likely a continuum of EoE or similar Th2-mediated allergic process. PPIs have therapeutic properties that can benefit both GERD and EoE. Therefore, PPIs should not be considered a diagnostic tool, but rather a therapeutic option for EoE. If patients are PPI-nonresponsive, then dietary therapy or steroid therapy should be considered. Dilation can be reserved as adjuvant therapy for severe fibrostenotic lesions.

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Eosinophilic Esophagitis

Cited by 47 publications

References 104 publications

Molecular, Genetic, and Cellular Bases for Treating Eosinophilic Esophagitis

Molecular, Genetic, and Cellular Bases for Treating Eosinophilic Esophagitis

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

Translating New Developments in Eosinophilic Esophagitis Pathogenesis into Clinical Practice

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