Gastrointestinal Manifestations of Systemic Sclerosis

Abstract

Systemic sclerosis is a chronic disorder of connective tissue that affects the gastrointestinal tract in more than 80% of patients. Changes in neuromuscular function with progressive fibrosis of smooth muscle within the muscularis propria impair normal motor function, which may secondarily alter transit and nutrient absorption. Esophageal manifestations with gastroesophageal reflux and dysphagia are the most common visceral manifestation of the disease, often requiring more intense acid-suppressive medication. Gastric involvement may lead to gastroparesis, which can be found in up to 50% of patients. Severe small bowel disease can present as chronic intestinal pseudo-obstruction with distended loops of small intestine, bacterial overgrowth, impaired absorption and progressive development of nutritional deficiencies. While not studied as extensively, systemic sclerosis often also affects colorectal function resulting in constipation, diarrhea or fecal incontinence. Nutritional support and prokinetics have been used with some success to manage gastric and small or large bowel involvement in patients with systemic sclerosis. Despite advances in management, significant gastrointestinal manifestations of systemic sclerosis still carry a poor prognosis with a five-year mortality exceeding 50%.

Immunoglobulins from scleroderma patients inhibit the muscarinic receptor activation in internal anal sphincter smooth muscle cells

“…The present data provide direct support to the hypothesis that autoantibodies targeting GI structures (neuronal and/or smooth muscle) contribute to the clinical manifestations of SSc (14). The exact mechanism of this M 3 -R inactivation is not known.…”

“…systemic sclerosis; rectoanal function; muscarinic receptor; autoantibodies SYSTEMIC SCLEROSIS (scleroderma; SSc) is a systemic connective tissue disease characterized by extensive collagen deposition and sclerosis of the microvasculature and is accompanied by prominent alterations of the autonomic nervous system (14). As many as 90% of SSc patients have gastrointestinal (GI) symptoms (9,13), usually involving the esophagus, and 50 -70% may involve anorectum (21,44).…”

“…The exact mechanism of neuropathic dysfunction is still unknown. Numerous autoantibodies have been found in the sera of SSc patients (14,25).…”

Gastrointestinal manifestation of systemic sclerosis—thickening of the upper gastrointestinal wall detected by endoscopic ultrasound is a valid sign

“…SSc is characterized by vascular lesions due to endothelial cell damage and variable degrees of extracellular matrix accumulation causing fibrotic degenerative changes in organs by proliferation of subendothelial connective tissue [1,2].…”

Achalasia and thyroid disease: possible autoimmune connection?

“…A cluster consisting of varied autoimmune diseases has been linked to achalasia: myasthenia gravis, polymyositis, autoimmune thyroid disease, among others, contributing to the argument that autoimmunity may be a cause for some idiopathic achalasia (17)(18)(19). A further achalasia candidate gene selected based on its involvement in autoimmunity is the protein of tyrosine phosphatase N22 gene (PTPN22) on chromosome 1p13 (20).…”