INTRODUCTION — Nearly 90 percent of patients with systemic sclerosis (SSc) have some degree of gastrointestinal (GI) involvement, and approximately one-half are symptomatic [1,2]. Although the esophagus is the most frequently affected part of the GI tract, any part of the GI tract may be involved. Severe involvement occurs in less than 10 percent of patients and is associated with an unfavorable prognosis [3,4]. As with other major organ-based manifestations of SSc, association of severe disease with antinuclear antibody subgroups may help in stratification of patients at higher risk for GI involvement of SSc . This topic will review the management of GI disease associated with SSc. Our approach is generally consistent with clinical practice guidelines for the management of common SSc manifestations affecting the GI tract . The pathogenesis, pathology, clinical manifestations, and diagnosis of GI manifestations of SSc are discussed separately. (See "Gastrointestinal manifestations of systemic sclerosis (scleroderma)".)
OROPHARYNGEAL DISEASE — The management of oral manifestations of systemic sclerosis (SSc) is largely supportive. Regular dental hygiene is necessary to help prevent dental caries, and increased frequency of dental cleaning is recommended in the presence of significant sicca symptoms. Patients with decreased oral aperture may be able to improve gingival health using adaptive oral hygiene devices (eg, flossers, oscillating-rotating toothbrushes) combined with facial exercises to increase the oral mouth opening [7,8]. Artificial saliva may be used in patients who also have sicca syndrome. (See "Treatment of dry mouth and other non-ocular sicca symptoms in Sjögren’s disease", section on 'Inadequate benefit from salivary stimulation and water'.)
ESOPHAGEAL DISEASE — Management of esophageal disease is largely directed toward the amelioration of symptoms of heartburn and dysphagia, which may be due to esophageal dysmotility or gastroesophageal reflux disease (GERD) and its complications (eg, strictures, esophagitis).
Gastroesophageal reflux — The management of GERD in patients with systemic sclerosis (SSc) is similar to that in patients without SSc. However, patients with SSc often have more severe symptoms.
While lifestyle and dietary modification should be recommended in all patients with GERD, these measures are usually inadequate by themselves. These measures include elevation of the head of the bed and selective elimination of dietary triggers (see "Medical management of gastroesophageal reflux disease in adults", section on 'Lifestyle and dietary modification'). Calcium channel blockers and anticholinergic agents, which may be used to treat other manifestations of SSc, can potentially worsen reflux.
Proton pump inhibitors (PPIs) are the most effective drugs for the treatment of GERD in SSc and should be used in symptomatic patients. Patients who fail to respond to once-daily PPI therapy should be treated with twice-daily PPI therapy , with the goal being to eliminate symptoms as much as possible. One study in patients with SSc found that omeprazole healed esophagitis and reduced elevated hydroxyproline levels to normal, suggesting some reversal of esophageal fibrosis . Patients on long-term PPI therapy may develop adverse effects that require additional monitoring (eg, hypomagnesemia, vitamin B12 deficiency). (See "Medical management of gastroesophageal reflux disease in adults", section on 'Severe or frequent symptoms or erosive esophagitis' and "Proton pump inhibitors: Overview of use and adverse effects in the treatment of acid related disorders", section on 'Adverse effects'.)
Patients who fail to respond to twice-daily PPI therapy are considered to have refractory GERD and should be referred to a gastroenterologist. We add a H2 receptor antagonist (H2RA) at bedtime in patients who failed PPI twice daily. H2RA can reduce gastroesophageal reflux, improve symptoms, and treat mild erosive esophagitis . However, the development of tachyphylaxis limits their use as maintenance therapy for GERD, although regular short drug holidays may help reduce this problem. In addition, H2 blockers alone are less effective as compared with PPIs in treating GERD and are ineffective in patients with severe esophagitis. We therefore generally reserve H2RA to reduce nocturnal acid breakthrough in patients who are refractory to PPI therapy. Other approaches include addition of sucralfate that can provide effective symptomatic relief for some patients. (See "Medical management of gastroesophageal reflux disease in adults", section on 'PPI refractory symptoms'.)
Prokinetic agents have not been found to be beneficial except in patients who have GERD due to delayed gastric emptying.
Surgery for gastroesophageal reflux, such as with gastric fundoplication, is relatively contraindicated in patients with SSc because of the high incidence of postoperative dysphagia (38 to 71 percent) . Its use is generally limited to patients with severe, refractory reflux. Unfortunately, the recurrence rate with surgery is also high. In one study involving 20 SSc patients, reflux esophagitis recurred in all patients at an average of four years after surgery . A retrospective review of 23 SSc patients undergoing surgery for GERD comparing fundoplication, Roux-en-Y gastric bypass, and esophagectomy found improved control of reflux symptoms with Roux-en-Y compared with the other surgical techniques . However, surgical antireflux techniques have not been well-studied in patients with SSc and should be avoided or pursued with caution. (See "Surgical treatment of gastroesophageal reflux in adults".)
Esophageal motility disorder — Esophageal dysmotility can present as dysphagia or a sensation of food being stuck in the throat. In patients with persistent symptoms despite twice-daily PPI therapy, we suggest a trial of prokinetic drugs (eg, metoclopramide, cisapride, domperidone, prucalopride) to relieve these symptoms. These drugs act by increasing esophageal sphincter pressure, improving peristalsis, and enhancing gastric emptying [15-17]. Cisapride acts to release acetylcholine within the myenteric plexus. Although cisapride is better tolerated as compared with metoclopramide , its use has been associated with important adverse effects and has been removed from markets in the United States and other countries. Cisapride significantly lengthens the QT interval and has been associated with drug-induced torsades de pointes. The risk is further increased when cisapride is used in combination with drugs that lengthen the QT interval or in the presence of other risk factors for prolonged QT, as well as when it is taken in combination with drugs that inhibit CYP3A4 (eg, erythromycin and azole antifungals). In the United States, prescriptions for cisapride can only be filled through an investigational limited access program from the manufacturer after providing documentation as to need for cisapride and assessment of risk factors for cardiac arrhythmias in the individual patient (eg, a QTc >450 ms). Domperidone is only available in the United States under a US Food and Drug Administration (FDA) Investigational New Drug application, and may also increase the QT interval and cause fatal arrhythmias . (See "Treatment of gastroparesis", section on 'Domperidone'.)
In patients who fail to respond to metoclopramide and/or cisapride, we suggest a trial of erythromycin. Erythromycin acts as a motilin agonist which increases gastric contractions and lowers esophageal sphincter pressure [20,21]. However, erythromycin should not be given in combination with cisapride or domperidone. The latter can increase the risk of potentially fatal cisapride-induced torsade de pointes . (See "Treatment of gastroparesis", section on 'Macrolide antibiotics'.)
Stricture — Symptomatic esophageal strictures require endoscopic dilation. Following esophageal dilation, patients should be treated with PPIs to promote healing and reduce the risk of stricture recurrence. (See "Endoscopic interventions for nonmalignant esophageal strictures in adults", section on 'Procedure'.)
Infectious and medication-induced esophagitis — Esophageal candidiasis usually occurs in the setting of immunosuppression and requires systemic antifungal therapy (eg, fluconazole). Cessation of therapy is associated with a high rate of recurrence . (See "Oropharyngeal candidiasis in adults", section on 'Treatment'.)
Medication-induced esophagitis is more common in SSc due to decreased peristalsis. If possible, culprit medications should be discontinued (eg, oral bisphosphonates). If they cannot be discontinued, they should be substituted by another formulation (eg, liquid, intravenous). Patients should also implement measures to minimize the risk of recurrent medication-induced esophagitis. (See "Pill esophagitis" and "Pill esophagitis", section on 'Precautions to decrease risk'.)
GASTRIC DISEASE — The principal manifestations of gastric involvement in systemic sclerosis (SSc) are those of delayed gastric emptying and bleeding.
Gastroparesis — The management of gastroparesis in patients with SSc is similar to other patients. Management of gastroparesis consists of dietary modification, optimization of glycemic control in patients with diabetes, hydration, and, in patients with continued symptoms, pharmacologic therapy with a prokinetic agent and antiemetics. (See "Treatment of gastroparesis".)
Gastric antral venous ectasia — The treatment of upper gastrointestinal (GI) bleeding due to telangiectasia consists of endoscopic coagulation of each lesion. Endoscopic coagulation with argon plasma coagulation (APC), heater probe, bipolar probe, laser therapy, or radiofrequency ablation (RFA) obliterates the vascular ectasia and decreases the degree of bleeding. Antrectomy prevents recurrent bleeding but is usually reserved for patients who fail multiple sessions of endoscopic therapy. There have been reports of benefit in some cases from immunosuppression that suggest that disease-modifying therapy may be helpful . However, additional studies are needed to confirm these findings. (See "Causes of upper gastrointestinal bleeding in adults", section on 'Gastric antral vascular ectasia' and "Argon plasma coagulation in the management of gastrointestinal hemorrhage".)
SMALL INTESTINAL DISEASE — The treatment of small bowel disease among patients with systemic sclerosis (SSc) largely consists of the management of malabsorption and steatorrhea, dysmotility, and recurrent pseudo-obstruction. (See "Gastrointestinal manifestations of systemic sclerosis (scleroderma)".)
Small intestinal bacterial overgrowth — The mainstay of treatment of small intestinal bacterial overgrowth (SIBO) is antibiotic therapy [25-27]. Adequate antimicrobial coverage can be achieved with several different antibiotic regimens (table 1). Bacterial culture with sensitivity testing is not helpful since various bacterial species with different antibiotic sensitivities coexist. In addition, many bacterial species in the gut cannot be grown in culture. (See "Small intestinal bacterial overgrowth: Management", section on 'Initial approach'.)
The length of therapy and degree of antibiotic rotation required for symptom remission in patients with SSc may vary depending on the degree of dysmotility. While some patients may remain asymptomatic for many months after a 7- to 10-day course of treatment, others require prolonged antibiotics for severe persistent diarrhea. Patients with SSc often have recurrent SIBO and require intermittent courses of therapy, and others need treatment on a regular basis (such as the first 5 to 10 days out of every month or every other week). Antibiotics are usually rotated (antibiotic change every four weeks with occasional "antibiotic holiday"), since continuous therapy with one agent may result in the emergence of resistant organisms and an increase in relapse rate. When diarrhea recurs in a patient still on antibiotics, metronidazole can be added for five to seven days to treat anaerobic flora. There is emerging evidence for altered gut microbiome in SSc . More data are needed before probiotics may be considered in management of bloating and diarrhea in SSc [29,30]. (See "Small intestinal bacterial overgrowth: Management", section on 'Interventions with unclear role'.)
Dysmotility and intestinal pseudo-obstruction — Prokinetics may be useful for acute and chronic therapy of intestinal pseudo-obstruction. However, their use must be balanced against the risk of reducing intestinal contractility and potentially aggravating constipation or promoting pseudo-obstruction . In addition, patients with chronic intestinal pseudo-obstruction (CIPO) require nutritional support and antibiotics for concurrent SIBO. It is also important to review medications to limit the use of drugs that may reduce gut motility, particularly opioid analgesics. The role of surgery is limited to providing access for venting and feeding. The management of chronic intestinal pseudo-obstruction is discussed in detail separately. (See "Chronic intestinal pseudo-obstruction: Management", section on 'Initial management'.)
Malnutrition — It is important to routinely assess nutritional status as part of regular medical review in patients with SSc. The Malnutrition Universal Screening Tool (MUST) questionnaire provides a simple screening method for stratifying malnutrition risk . As an adjunct to regular weight assessment to document weight loss, the MUST tool is routinely administered in clinical practice, especially when significant weight loss is documented or reported by a patient. Malnutrition in SSc patients may be due to loss of appetite, physical challenges of eating, oral symptoms, drug side effects, gastroparesis, CIPO or malabsorption secondary to bacterial overgrowth, and, rarely, pancreatic exocrine insufficiency. Referral for specialist nutritional advice should be considered in any SSc case with significant features of malnutrition or weight loss once other causes have been excluded. (See "Gastrointestinal manifestations of systemic sclerosis (scleroderma)".)
Patients with malabsorption and steatorrhea should be on a lactose-free diet that is low in dietary long-chain fatty acids (<40 g/day). Long-chain fatty acids should be substituted with medium-chain triglycerides. In patients with malnutrition despite dietary modification, an elemental diet or medium-chain triglyceride supplements should be instituted. Some patients require supplementation of fat- and water-soluble vitamins, calcium, and iron. Patients with pancreatic exocrine insufficiency require exogenous pancreatic enzymes. (See "Overview of the treatment of malabsorption in adults", section on 'Nutrient repletion and supplementation' and "Small intestinal bacterial overgrowth: Management", section on 'Interventions with unclear role'.)
In patients with significant malnutrition in whom some bowel function is preserved, percutaneous gastrostomy or jejunostomy tube can be used to administer enteral nutrition and venting for symptomatic relief. In patients with severe dysmotility and pseudo-obstruction, parenteral nutrition is often necessary. Home parenteral nutrition can be used continuously or intermittently for episodes of pseudo-obstruction or weight loss. (See "Chronic intestinal pseudo-obstruction: Management", section on 'Dietary modification'.)
Surgical resection of the involved intestinal segments should be avoided in SSc, as the disease is almost always generalized and surgery results in a prolonged ileus and increases the risk of adhesions.
Pneumatosis cystoides intestinalis and pneumoperitoneum — Unless there are clinical features suggesting an underlying acute abdominal emergency, pneumatosis cystoides intestinalis and pneumoperitoneum should be treated conservatively. The management of pneumatosis intestinalis is discussed in detail separately. (See "Pneumatosis intestinalis", section on 'Emergent management'.)
COLONIC AND ANORECTAL DISEASE — Treatment of colon and anorectal disorders in systemic sclerosis is largely aimed toward the alleviation of symptoms.
Fecal incontinence — Initial management of fecal incontinence is to reduce stool frequency and improve stool consistency with a bulking agent (eg, psyllium), antidiarrheal agents (eg, loperamide), and bile acid-binding resins (eg, cholestyramine or colestipol). Diarrhea, which is principally due to small bowel bacterial overgrowth in patients with systemic sclerosis (SSc), may contribute significantly to the development of fecal incontinence and should be treated with antibiotics. Patients who fail to respond to initial management should be referred to a gastroenterologist for additional evaluation (eg, anorectal manometry, endorectal ultrasound/magnetic resonance imaging) to detect functional and structural abnormalities causing fecal incontinence and to guide subsequent management.
In patients who fail to respond to initial management, options include biofeedback, injectable anal bulking agent, sacral nerve stimulation, and anal sphincteroplasty. Biofeedback may improve fecal incontinence in patients with manometric evidence of weakness of the external anal sphincter or decreased ability to perceive rectal distension because of nerve injury. Local injection of synthetic biopolymer may improve sphincter function in patients with passive incontinence. Sacral nerve stimulation should be reserved for refractory fecal incontinence [32-34]. Although surgical repair of the anal sphincter with posterior sphincteroplasty has been performed in patients with SSc, there is limited evidence to support surgery and anal continence declines over time . (See "Fecal incontinence in adults: Management", section on 'Refractory symptoms'.)
Constipation — The management of slow transit constipation in patients with SSc is similar to other patients with slow transit constipation and begins with an osmotic laxative (eg, polyethylene glycol) followed by secretory agents (eg, linaclotide or lubiprostone). There have been studies showing potential benefit from prucalopride in treating constipation in SSc, and it is routinely used in some centers . (See "Management of chronic constipation in adults", section on 'Osmotic agents' and "Management of chronic constipation in adults", section on 'Pharmacologic therapy'.)
Surgery to relieve outflow obstruction may have a role in SSc patients with refractory constipation when colonic transit delay is localized to the rectosigmoid colon and does not involve the remaining small intestine or colon, although disease that is localized is very uncommon and requires expert assessment . (See "Gastrointestinal manifestations of systemic sclerosis (scleroderma)", section on 'Colonic inertia'.)
LIVER AND BILIARY TREE INVOLVEMENT — Hepatic disease is rare in systemic sclerosis (SSc) but can occur in association with primary biliary cholangitis (PBC; previously referred to as primary biliary cirrhosis). Management includes treatment of the underlying PBC (eg, ursodiol) and its complications including pruritus, malabsorption, hypercholesterolemia, hypothyroidism, anemia, and deficiencies of fat-soluble vitamins. The management of PBC is discussed in detail separately. (See "Overview of the management of primary biliary cholangitis".)
PANCREATIC DISEASE — Patients with pancreatic exocrine insufficiency therapy with enzyme supplements should be initiated.
SUMMARY AND RECOMMENDATIONS
●Nearly 90 percent of patients with systemic sclerosis (SSc) have some degree of gastrointestinal (GI) involvement, and approximately one-half are symptomatic. Although the esophagus is the most frequently affected part of the GI tract, any part of the GI tract may be involved.
●We use largely supportive therapies for oral manifestations of SSc, including facial exercises for tight skin, attentive dental care, artificial saliva and other interventions for sicca symptoms. (See 'Oropharyngeal disease' above.)
●Management of esophageal disease is largely directed toward the amelioration of symptoms of heartburn and dysphagia which may be due to esophageal dysmotility or gastroesophageal reflux disease (GERD) and its complications (eg, strictures, esophagitis). (See 'Esophageal disease' above.)
●Management of gastroparesis consists of dietary modification, optimization of glycemic control in patients with diabetes, hydration, and in patients with continued symptoms, pharmacologic therapy with prokinetic and antiemetics. In patients with gastric antral venous ectasia (GAVE), endoscopic ablation may be required to decrease the degree of bleeding. (See 'Gastric disease' above.)
●Prokinetics may be useful for acute and chronic therapy of intestinal pseudo-obstruction. In addition, patients with chronic intestinal pseudo-obstruction (CIPO) require nutritional support and antibiotics for concurrent small intestinal bacterial overgrowth (SIBO). The role of surgery is limited to providing access for venting and feeding. (See 'Small intestinal disease' above.)
●Malnutrition in SSc patients may be due to loss of appetite, physical challenges of eating, oral symptoms, drug side effects, gastroparesis, CIPO or malabsorption secondary to bacterial overgrowth, and, rarely, pancreatic exocrine insufficiency. (See 'Malnutrition' above.)
●The mainstay of treatment of SIBO is antibiotic therapy. In patients with significant malnutrition in whom some bowel function is preserved, percutaneous gastrostomy or jejunostomy tube can be used to administer enteral nutrition and venting for symptomatic relief. In patients with severe dysmotility and pseudo-obstruction, parenteral nutrition is often necessary. (See 'Malnutrition' above and 'Pancreatic disease' above.)
●Pneumatosis cystoides intestinalis and pneumoperitoneum should be treated conservatively, unless there are clinical features suggesting an underlying acute abdominal emergency. (See 'Small intestinal disease' above.)
●Fecal incontinence associated with diarrhea should thus be treated with antibiotics in combination with nonspecific measures including antidiarrheal agents, and bile acid-binding resins. Patients who fail to respond to initial management should be referred to a gastroenterologist for additional evaluation. (See 'Colonic and anorectal disease' above.)
●In patients with primary biliary cholangitis (PBC; previously referred to as primary biliary cirrhosis), which may occur in patients with SSc, management includes treatment of the underlying PBC (eg, ursodiol) and its complications including pruritus, malabsorption, hypercholesterolemia, hypothyroidism, anemia and deficiencies of fat-soluble vitamins. (See "Overview of the management of primary biliary cholangitis" and 'Liver and biliary tree involvement' above.)
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