Esophageal Motor Disorders in Adults with Eosinophilic Esophagitis

Moawad, Fouad J.; Maydonovitch, Corinne; Veerappan, Ganesh R.; Bassett, John T.; Lake, Jason M.; Wong, Roy K.H.

doi:10.1007/s10620-011-1655-5

Cited by 40 publications

(41 citation statements)

References 20 publications

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“…However, motility studies are normal in the majority of EoE patients. 22 Moreover, food impaction, the hallmark symptom of EoE, is not common in patients with esophageal motility disorders. 23 With the rapid response of dysphagia to steroids, one might postulate that a product of eosinophil secretion may alter esophageal compliance or promote adhesiveness, which in turn may account for the symptom of dysphagia.…”

Section: Discussionmentioning

confidence: 99%

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

Lee

Huprich

Kujath

et al. 2012

Clinical Gastroenterology and Hepatology

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Section: Discussionmentioning

confidence: 99%

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

Lee

Huprich

Kujath

et al. 2012

Clinical Gastroenterology and Hepatology

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“…For example, pediatric EoE subjects have dysphagia and impactions but rarely have esophageal narrowing (1, 17). Patterns of dysmotility in EoE include increased contraction amplitude, nutcracker esophagus, achalasia, and ineffective, uncoupled contractions (13, 15, 16, 19–22). However, despite these multiple clinical observations, the molecular mechanisms driving esophageal smooth muscle remodeling and dysfunction in EoE remain largely undefined.…”

Section: Introductionmentioning

confidence: 99%

TGF-β1–induced phospholamban expression alters esophageal smooth muscle cell contraction in patients with eosinophilic esophagitis

Beppu

Anilkumar

Newbury

et al. 2014

Journal of Allergy and Clinical Immunology

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Background Eosinophilic esophagitis (EoE) is a chronic antigen mediated disease characterized by esophageal eosinophilia, remodeling, and fibrosis. TGFβ1 is a central regulator of EoE remodeling and increases esophageal smooth muscle cell contraction. Objective In this study, we aimed to understand the molecular mechanisms by which TGFβ1 could induce esophageal smooth muscle cell contraction. Methods We used primary human esophageal smooth muscle (ESM) cells and EoE myofibroblasts (EMF) to assess the mechanisms of TGFβ1-induced contraction. We analyzed the expression, phosphorylation, and function of phospholamban (PLN), a sarcoendoplasmic reticulum regulatory protein which was induced by TGFβ1. Expression of PLN, phospho-PLN, and its regulatory pathway was analyzed in the esophageal smooth muscle of EoE and control biopsies. Gene silencing in EoE EMFs was utilized to understand the role of PLN in contraction. Results TGFβ1 induced and phosphorylated PLN in primary human ESM and EoE EMFs. PLN and phospho-PLN were elevated in EoE as compared to control subject smooth muscle in vivo. PLN inhibition significantly diminished TGFβ1 induced EoE EMF contraction. PLN expression and ESM/EMF contraction depended on TGFβ receptor I signals. Conclusion We describe a previously unrecognized mechanism for esophageal smooth muscle cell contraction that depends on TGFβ1, its receptors, and PLN. Since PLN is elevated in EoE smooth muscle and PLN silencing diminishes contraction, we provide a novel potential mechanistic framework and therapeutic target for esophageal smooth muscle dysfunction in EoE.

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“…Dysmotility may be present in up to 60% of cases, and may only be transient, explaining the intermittent nature of symptoms in many patients. Manometric improvement mirrors symptomatic, histological and endoscopic resolution following treatment of the underlying oesophagitis 14 15…”

Section: Discussionmentioning

confidence: 92%

A hard act to swallow: modern management of eosinophilic oesophagitis

Louis-Auguste

Hoare

2012

Frontline Gastroenterol

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Eosinophilic oesophagitis (EO) is now established as an important cause of oesophageal symptoms. It is presumed to result from eosinophilic activation to dietary antigens, which is limited to the oesophagus. Inflammatory strictures and secondary dysmotility are common and contribute to symptomatology. Current management involves food exclusion diets and swallowed topical steroid. Strictures may require endoscopic dilatation. Relapse is common but strategies for maintaining remission are not well described. Here we describe a patient with severe stricturing EO, whose symptoms were significantly exacerbated by secondary oesophageal spasm. His symptoms were refractory to dietary, endoscopic and medical therapy including parenteral corticosteroid but responded dramatically to diltiazem. Remission was eventually achieved and maintained with azathioprine, and he was able to discontinue the other therapies and relax his dietary restrictions. We discuss the evidence for dietetic, endoscopic and pharmacological interventions for this disease. CASE REPORTA 36-year-old male professional musician presented to the emergency department with a 3-week history of progressive dysphagia to solids more than liquids, localised to the mid-sternum. There was associated severe odynophagia, chest pain and marked weight loss (5.5 kg or 7% of baseline body weight). Further questioning revealed that he had needed to eat slowly since childhood, but had grown accustomed to this.Past medical history was significant for atopy (seasonal allergic rhinitis, mild predominantly seasonal asthma and oral allergy syndrome). He was otherwise fit and well and on Salbutamol inhalers only.Oesophagogastroduodenoscopy (OGD) showed features suggestive of EO with longitudinal furrowing, concentric ridged folds and micro-abscesses (figure 1). A smooth impassable mid-oesophageal stricture was also noted. Oesophageal and stricture biopsies were consistent with EO, with spongiotic squamous epithelium and >25 eosinophils per high power field.A water-soluble contrast swallow showed a smooth 3.5 cm long midoesophageal stricture that was causing mild narrowing only, which was not causing any hold-up. Motility could not be assessed as the patient was reluctant to take adequate mouthfuls.He was started on swallowed fluticasone (500 mcg twice daily) and high dose proton pump inhibitor (PPI). His symptoms and oral intake failed to improve and he was admitted 2 weeks later with complete dysphagia for nutritional support and further investigation and management.On admission, he was started on oral corticosteroid ( prednisolone 40 mg once daily) and a six food elimination diet (SFED: cow's milk protein, soya, wheat, egg, nuts and seafood) after being assessed by a dietician. Skin prick testing was negative for all common food groups and specific immunoglobulin (Ig)E was positive for wheat only. He was given supplementary elemental feeding by nasogastric tube to meet his daily nutritional requirements. These interventions resulted in only mild symptomatic improvement...

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Esophageal Motor Disorders in Adults with Eosinophilic Esophagitis

Cited by 40 publications

References 20 publications

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

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

TGF-β1–induced phospholamban expression alters esophageal smooth muscle cell contraction in patients with eosinophilic esophagitis

A hard act to swallow: modern management of eosinophilic oesophagitis

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