Clinical Usefulness and Influence on Esophageal Motility of Pyridostigmine for Dysphagia in Systemic Sclerosis

Overview

Systemic sclerosis is characterized by progressive fibrosis of different organ systems. With a longer duration, the risk of gastrointestinal involvement increases. There is a high prevalence of gastro-esophageal reflux disease (GERD) secondary to a severe insufficiency of the lower esophageal sphincter (LES), resulting in severe reflux esophagitis when left untreated. On the long run, this is associated with an elevated risk of esophageal bleeding, peptic stenosis, Barrett esophagus and associated risk of esophageal cancer. Apart from the insufficiency of the LES, esophageal aperistalsis is frequently observed. This results in prolonged esophageal contact with the refluxate due to insufficient clearance by the absence of adequate peristalsis. As a consequence of impaired peristalsis, patients with esophageal involvement in systemic sclerosis often experience dysphagia for solids, causing weight loss and malnu-trition, and reducing in quality of life. To control reflux disease, high dose proton pump inhibitor therapy is part of the advocated treatment for esophageal involvement in systemic sclerosis. This therapy is highly effective in reducing acidic reflux, but has no influence on the esophageal motility disorder, leaving the dysphagia untreated. Because of the lack of a specific treatment targeting dysphagia, most patients eventually are advised to take conservative measures such as eating while sitting up straight, chewing well and flushing every food bolus with fluids. While current treatment targets the acidic reflux, there is no accepted treatment to improve esophageal motility. In the presence of dysphagia patients are advocated to follow conservative measures like sitting upright when eating and drinking water to help passage of the bolus. A cholinesterase inhibitor, pyridostigmine prevents the degradation of acetyl choline at the neuromuscular junction, prolonging its excitatory action. A recent uncontrolled study in patients suffering from systemic sclerosis identified a beneficial effect on gastro-intestinal symptoms, especially constipation. In healthy volunteers intake of pyridostigmine enhanced esophageal contractility as revealed by an increased amplitude of distal esophageal con-tractions. Despite this beneficial influence on esophageal motility there are no data on the possible therapeutic effects in patients with systemic sclerosis and esophageal involvement. This study aims at evaluating the effects of pyridostigmine on symptoms of dysphagia. Additionally improvement of GERD symptoms and quality of life will be recorded. Improvement of parameters of esophageal motility as well as baseline esophageal impedance during esophageal contraction will also be assessed.