What Is the Incidence of Large Bowel Involvement in Systemic Sclerosis?

Robert Fox, MD


August 16, 2005


What is the incidence of large bowel involvement in systemic sclerosis (SSc) in comparison to esophageal and small bowel, and can large bowel involvement occur without upper GI involvement? Is bosentan indicated for ulcers of the finger in SSc?

JoAnne Sickeri, MD

Response from Robert Fox, MD

Esophageal dysfunction as detected by motility testing has been found in as many as 90% of patients with scleroderma.[1] However, many of these patients are asymptomatic. Thus, large bowel involvement may appear to be present on clinical history in the absence of upper bowel involvement. The most important manifestations of oropharyngeal dysphagia occur in up to 25% of patients with SSc.[2] Abnormal small bowel function has been reported in 20% to 60% of patients with scleroderma, and more than one half have a histologic abnormality at post-mortem.[3] Colonic disease occurs in 10% to 50% of patients with scleroderma, with the anorectum being the most frequently affected area.[4] A recent study, for example, found that the colon is almost as frequently involved as the esophagus; in addition, patients with abnormal esophageal manometry almost always had abnormal anorectal motility.[5]

Bosentan is not yet approved for treatment of finger ulcers in scleroderma. To date, one clinical trial, the Randomized Placebo-controlled Investigation of Digital ulcers in Scleroderma (RAPIDS-1),[6] was performed in scleroderma patients with or without digital ulcers at baseline. The study results showed that bosentan significantly reduced the number of new digital ulcers vs placebo. An additional study, Efficacy and Safety of Oral Bosentan on Healing/Prevention of Digital (Finger) Ulcers in Scleroderma Patients, is currently enrolled and hopefully will confirm the earlier study and lead to FDA approval.

Involvement of the gut occurs with equal frequency among patients with the diffuse (dcSSc) and limited (lcSSc) subtypes of SSc. It is rare in localized scleroderma syndromes. The presence of malabsorption and esophageal dysfunction among patients with SSc is associated with an unfavorable prognosis. Among 264 patients with dcSSc, for example, 5% died from GI complications.[7] It is therefore important to recognize such involvement.

Because manometric abnormalities are present in over 80% of cases of SSc, such measurements remain the most accurate method for evaluating esophageal function in this disorder. The procedure, however, is time-consuming and may have low patient acceptance. By comparison, scintigraphy is noninvasive, easy to perform, and has high patient acceptance. For these reasons, scintigraphy (if available) may be preferred for disease detection in asymptomatic disease.[8] Although esophagoscopy provides little information on smooth muscle function, it enables accurate diagnosis of mucosal abnormalities such as reflux esophagitis, candidiasis, Barrett's esophagus, and esophageal stricture.

Rarely, severe involvement of the stomach results in gastroparesis with intractable vomiting, which may cause weight loss and nutritional deficiencies. The symptoms are intermittent, with remissions lasting several months. Massive upper gastrointestinal bleeding secondary to mucosal telangiectasia can also occur. Gastric antral venous ectasia (GAVE) is an increasingly recognized complication of SSc. It is best diagnosed by gastroscopy. Clinical suspicion should be high, particularly in patients with unexplained iron-deficiency anemia.

Approximately 10% to 30% of patients with SSc have evidence of malabsorption. Intestinal stasis with overgrowth of bacteria is considered to be the major cause of this complication. One study, for example, performed jejunal aspirates in 20 unselected patients with SSc; bacterial overgrowth, defined as >10(6) organisms/mL, was present in one third.[9] The majority of patients with bacterial overgrowth had small bowel involvement and steatorrhea; by comparison, patients with normal bacterial counts had normal intestinal function.[10,11]

How bacteria impair nutrient digestion or cellular transport in patients with malabsorption is still poorly understood. One proposed mechanism is that bacteria deconjugate and dehydroxylate conjugated bile salts, thereby reducing fat emulsification and micelle formation. Additional possibilities include vasculopathy, lymphatic obstruction, wall fibrosis, impaired motility, and pancreatic dysfunction. However, apart from minimal inflammatory cell infiltrates, villous morphology appears normal. The gold standard for the detection of bacterial overgrowth is small bowel aspiration. It is not ideal, however, since it is invasive and may need to be repeated due to bacteria regrowth. By comparison, the glucose hydrogen breath test is a noninvasive examination, although false-negative results may occur when the predominant organisms produce carbon dioxide. One study compared a per-endoscopic method of small bowel aspiration using a sterile double-lumen tube with the glucose hydrogen breath test.[12] Of the 21 patients studied, only 1 had a false-negative glucose hydrogen breath test for bacterial overgrowth. There were no false positives.


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