Introduction
Scleroderma refers to a group of rare chronic autoimmune diseases marked by fibrosis involving the skin and internal organs where hardening and thickening of tissues occurs due to overproduction of collagen. Scleroderma affects about 300,000 Americans, usually between the ages of 30-50. It is more prevalent in women. Two main subtypes are localized scleroderma confined to the skin and systemic sclerosis, with extensive internal organ involvement. Up to 90 percent of scleroderma patients develop gastro-intestinal (GI) complications. These symptoms considerably impact the quality of life and contribute to morbidity and mortality.
What Is the Root Cause of GI Disease in Scleroderma?
The hallmark features of scleroderma, abnormal fibroblast activity, and collagen overproduction extend to the gastro-intestinal (GI) tract. Excessive collagen is deposited in the smooth muscle layers of the intestinal tract, leading to muscle atrophy and weakness. This impairs normal peristaltic contractions and motility. Inflammatory cells and auto-antibodies also drive injury to the GI muscular layers. Antibodies may directly bind and inhibit intestinal smooth muscle cells. Chronic inflammation also damages the enteric nervous system. Fibrosis and strictures develop in the gastric and intestinal blood vessels, restricting blood flow. All these processes result in abnormal gut motility and function.
What Is the Pathophysiology of Gastrointestinal Involvement in Scleroderma?
The pathogenesis of scleroderma begins with endothelial cell injury and activation of the immune system. This stimulates collagen production and other extracellular matrix components by activating fibroblasts. In the gastrointestinal tract, this fibrotic process affects the smooth muscle layers, leading to their atrophy and hypocontractility. Loss of intestinal peristalsis impairs motility, while fibrosis of the sphincters causes loss of barrier function.
Chronic inflammation also damages the intestinal muscularis layers. Autoantibodies are implicated in the GI manifestations of scleroderma. Anti-ribonucleic acid (RNA) polymerases and anti-topoisomerase I antibodies correlate with overall GI involvement, while anti-centromere antibodies are associated with intestinal pseudo-obstruction. Antibodies targeting muscarinic receptors directly inhibit intestinal smooth muscle contraction. Local ischemia from fibrotic changes in the gastric and intestinal vasculature also contributes to GI dysmotility and strictures.
The impaired motility leads to bacterial overgrowth, particularly in the small intestine. The migrating motor complex propels intestinal contents regularly to prevent excessive bacterial growth. When this cleansing action is disrupted due to hypomotility, bacteria proliferate and cause chronic inflammation, diarrhea, malabsorption, and malnutrition. Bacterial overgrowth also increases the risk of sepsis when bacteria translocate across damaged intestinal barriers.
How Does Scleroderma Manifest in Different Parts of the GI Tract?
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Esophagus:
Up to 90 percent of patients develop esophageal dysmotility with a weakened lower esophageal sphincter and poor peristalsis. This leads to chronic acid reflux, heartburn, and strictures. Dysphagia occurs from stricturing. Esophageal dilatation and Barrett's esophagus raise cancer risk.
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Stomach:
Gastroparesis arises from gastric fibrosis and impaired motility. It causes nausea, bloating, and early satiation. Delayed gastric emptying leads to malnutrition.
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Small Intestine:
Fibrosis causes pseudo-obstruction, mimicking mechanical obstruction but without a physical blockage. Symptoms include pain, bloating, and diarrhea, especially after meals when peristalsis is increased. Bacterial overgrowth is common.
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Large Intestine:
Constipation results from colonic dysmotility. Diarrhea and incontinence occur from bacterial overgrowth or rectal prolapse. Delayed colonic transit raises the risk of perforation from endoscopic procedures.
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Anorectal:
Hemorrhoids and anal fissures are common, impairing quality of life. Fecal incontinence occurs.
How to Diagnose GI Issues in Scleroderma?
Since many GI symptoms are nonspecific, objective testing is useful to characterize involvement. A barium swallow evaluates esophageal anatomy, motility, and stricture severity. Gastric emptying scintigraphy quantifies delays. Wireless motility capsules assess small intestinal transit times. Breath testing detects bacterial overgrowth.
Colonic transit studies utilize radiopaque markers. Computed tomography (CT) and magnetic resonance imaging (MRI) enterography visualize intestinal dilation, thickening, and stricture location and degree. Nutritional blood tests identify deficiencies resulting from malabsorption. Upper endoscopy screens for esophagitis, gastritis, bleeding, and malignancy. Colonoscopy visualizes pseudo-obstruction and excludes colorectal cancer. Early diagnosis guides appropriate symptom management.
What Are the Goals of Treating GI Issues in Scleroderma?
As no disease-modifying therapy for scleroderma exists, treatment aims to control symptoms, maintain nutrition, and prevent complications. Acid suppression, prokinetics, antibiotics, and laxatives help alleviate symptoms and promote GI healing. Nutritional support is key to correcting weight loss and deficiencies. Surgery may be required for recalcitrant strictures or severely impaired motility that is not responsive to medications. Treating physicians should screen for and promptly manage malnutrition, bacterial overgrowth, and bleeding when warranted. Multidisciplinary treatment approaches optimize outcomes.
How Do GI Issues in Scleroderma Impact the Quality of Life and Survival?
GI disease negatively impacts the quality of life of most scleroderma patients. Pain, bloating, malnutrition, and weight loss are common. Social activities revolve around food, so patients often withdraw and become isolated. Esophageal reflux causes sleep disturbances. Diarrhea is socially disabling. Anemia may result from bleeding or iron deficiency.
Small intestinal bacterial overgrowth increases sepsis risk in immunocompromised scleroderma patients, contributing to mortality. Despite treatments, GI function often deteriorates over time. Supportive nutritional and psychosocial counseling is key. With comprehensive management, some patients achieve stabilization of GI issues. Overall, gastrointestinal involvement in scleroderma predicts a poorer prognosis and reduced survival.
What Are the Complications of GI Involvement in Scleroderma?
Gastrointestinal involvement worsens the quality of life in scleroderma patients and leads to undernutrition, weight loss, and vitamin deficiencies. Esophageal dysmotility increases the risk of aspiration pneumonia and esophageal adenocarcinoma. Intestinal pseudo-obstruction can cause bowel perforation, a life-threatening emergency. Bacterial overgrowth leads to sepsis in immunocompromised scleroderma patients, a leading cause of mortality. Bleeding from gastric antral vascular ectasia (GAVE) worsens anemia and requires multiple blood transfusions in some cases.
How Is the Prognosis of GI Involvement in Scleroderma?
Patients with certain scleroderma antibodies, like anti-RNA polymerase III, have higher rates of GI involvement. Even with optimal medical management, progressive malnutrition and cachexia are not uncommon. Small intestinal bacterial overgrowth portends a worse prognosis overall. Some patients develop severe GI dysmotility within three to five years of Raynaud's phenomenon onset. The 10-year survival rate for patients with systemic sclerosis is estimated to be around 70 percent. Thus, the gastrointestinal manifestations of scleroderma significantly impact morbidity, mortality, and quality of life.
Conclusion
In summary, gastrointestinal disease affects most scleroderma patients and contributes greatly to poor outcomes. Impaired motility throughout the digestive tract leads to reflux, gastroparesis, malabsorption, bacterial overgrowth, and pseudo-obstruction. These derangements result in debilitating symptoms, undernutrition, anemia, and increased infections.
Diagnostic testing helps characterize the degree of involvement while monitoring nutritional status and progression. Therapies target alleviating fibrostenosis and inflammation, improving motility, eradicating bacteria, and providing nutrition. However, GI disease remains a major determinant of disability and prognosis in scleroderma. Further elucidation of pathologic mechanisms and treatment advances are needed to optimize the management of the gastrointestinal complications of this challenging autoimmune disease.
