Gastrointestinal Scleroderma Imaging

Gastrointestinal scleroderma is the third most common manifestation of scleroderma, or systemic sclerosis (SSc), after skin changes and Raynaud phenomenon. ^{[1, 2]} GI symptoms are the first manifestation of SSc in nearly 10% of cases. ^[3]  Scleroderma is a clinically heterogeneous connective tissue disorder that affects the skin; the wall of the blood vessels; and the internal organs, such as the gastrointestinal tract, lungs, heart, and kidneys. This disease is characterized by alterations of the microvasculature, disturbances of the immune system, and massive deposition of collagen and other matrix substances in the connective tissue. ^{[4, 2, 5, 6, 7, 8, 9, 10, 11, 12]}  

Histopathology of the gastrointestinal tract shows mild inflammatory infiltrates of the lamina propria and, in certain segments, atrophy and fragmentation of the smooth muscles, followed by collagen deposition and changes of the blood vessels. Histologic studies show mainly CD4 T cells, around blood vessels and at sites of active connective tissue formation in scleroderma, emphasizing the role of T lymphocytes in its pathogenesis. Most T-cells are positive for HLA-DR. The ratio of helper CD4+ T lymphocytes relative to suppressor/cytotoxic T lymphocytes is increased in patients with SSc. ^[4]  

Telangiectasias (arteriovenous malformations) can be seen in scleroderma throughout the gastrointestinal tract, including the stomach, small bowel, and colon. Massive gastrointestinal bleeding rarely results from these malformations in scleroderma. ^[4]  

In the gastrointestinal tract, scleroderma can cause progressive atrophy and collagenous fibrous replacement of the muscularis, which may affect any part or all of the gastrointestinal tract but is more prominent in the esophagus. The lower two thirds of the esophagus often develops a rubber hosepipe-like consistency. The mucosa undergoes atrophy, which may be thinned and ulcerated and is often associated with excessive deposition of collagen in the lamina propria and submucosa. Less severe changes generally occur in the walls of the stomach, small bowel, and large bowel. The villi and microvilli atrophy, which is the anatomic basis of malabsorption that is sometimes associated with SSc. The gut vessel walls contain perivascular mononuclear cell infiltrates and hyaline collagenous thickening. ^[4]  

Many patients with scleroderma do not have significant symptoms despite demonstrable abnormalities of gastrointestinal function. Thinning of the lips and reduced oral apparatus are frequent findings. Temporomandibular joint involvement may also limit mouth opening in some patients. Atrophy of the mucous membrane and tongue papilla with impaired taste perception has also been reported. ^[4]  

The gastrointestinal tract is frequently involved in scleroderma (40-45% of cases). The esophagus is involved in more than 85% of cases, with resultant dysphagia and phagodynia due to hypomotility, reflux, peptic esophagitis, Barrett metaplasia, and fibrotic strictures. The stomach is less frequently involved. Abnormalities include decreased motor activity and delayed gastric emptying and gastric dilatation (watermelon stomach). The small bowel is involved in approximately 45% of patients and may affect motility of the small bowel and large bowel, leading to pseudo-obstruction or malabsorption due to bacterial overgrowth. In addition, diverticular ulcerations, stenosis, chronic constipation, megacolon, and rectal prolapse have been described. ^[4]  

Liver involvement is rare and, less often, may be secondary as a sequela of pulmonary heart disease. However, an association with primary biliary cirrhosis has been described. Minor exocrine pancreatic insufficiency may occur and is often of no significance, but it may contribute to malabsorption.

Esophageal involvement may be silent or present with dysphagia and chest pain from reflux and defective esophageal muscular function. Chest pain can be a sign of myocardial/pericardial disease; therefore, investigating the heart becomes an integral part of the clinical management of gastrointestinal scleroderma.

Systemic sclerosis (SSc) is a rare multisystem autoimmune disorder characterized by immune activation, vasculopathy, and abnormal collagen deposition in the skin and various internal organs. The gastrointestinal tract is involved in the limited cutaneous (lcSSc) and diffuse cutaneous (dcSSC) forms of the disease and is present in approximately 90% of patients with SSc. ^[4]

The severity of GI disease is a marker of worse prognosis and mortality in patients with SSc. Severe GI disease is associated with pseudo-obstruction and malabsorption and may result in dependence on enteral or total parenteral nutrition. ^[13] These complications are associated with recurrent hospitalizations, and malabsorption is an independent predictor of mortality. ^[14] Acute GI complications such as mechanical or pseudo-obstruction can be life-threatening in the context of other organ based involvement, especially cardiorespiratory disease. ^[4]

The esophagus is the most common site of GI involvement in SSc patients, with a high prevalence of gastroesophageal reflux disease (GERD), Barrett esophagus, and dysphagia. ^[15] Overall, the incidence of esophageal symptoms in SSc has been estimated at between 40 and 80%, even though a percentage of patients are totally asymptomatic despite their documented esophageal disease. Patients with esophageal involvement may report symptoms due to GERD, such as heartburn and regurgitation, and/or symptoms due to esophageal dysmotility, such as dysphagia and chest pain. ^[16] Chest pain can be a sign of myocardial/pericardial disease; therefore, investigating the heart becomes an integral part of the clinical management of gastrointestinal scleroderma.

Preferred examination

Conventional radiography is the mainstay of imaging scleroderma (see the radiographic images below). It is used to image the musculoskeletal system, lungs, and abdomen. Plain abdominal images may reveal bowel dilatation, features of constipation, intestinal obstruction, and perforation. Contrast-enhanced studies are generally used to evaluate gastrointestinal involvement in SSc. ^{[17, 9, 12, 18]}

Plain abdominal radiograph shows a gas-filled, dilated stomach (black arrow) and duodenum (red arrow). Barium-meal study in the same patient shows a dilated duodenum. Note also several diverticulae in the small bowel.

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Plain erect abdominal radiograph shows nonobstructed dilated loops of bowel with fluid levels. Chest radiograph in the same patient shows basal lung fibrosis.

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Plain erect abdominal radiograph shows nonobstructed dilated loops of bowel with fluid levels. Chest radiograph in the same patient shows basal lung fibrosis.

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Barium series (see below) should be performed only after careful consideration of the risks and benefits. When barium studies are performed, the patient should be vigorously purged soon thereafter, and follow-up radiographs should be obtained to confirm adequate removal of the barium agent.​ ^[13]  

Small bowel barium study shows a dilated duodenum, short strictures, and stagnation of the barium agent. Chest radiograph of the same patient shows basal fibrosis.

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Use of endoluminal ultrasonography to define transmural pathology is increasing. Ultrasonography is also useful in gastric-emptying studies. ^[19] Because thoracic symptoms in patients with SSc may be related to esophageal dysmotility, pulmonary hypertension, pericarditis, and pulmonary heart disease, echocardiography is an important imaging modality to differentiate between cardiogenic and noncardiogenic symptoms. ^[20]

Cross-sectional imaging studies, such as CT, are used in assessing thoracic disease and occasionally in the evaluation of abdominal complications of scleroderma. MRI has little if any role to play, though it may be useful in the differential diagnosis of musculoskeletal complications. Angiography may sometimes be required in the diagnosis and treatment of gastrointestinal bleeding. Radionuclide studies have a useful role in assessing esophageal and gastric motility.

Celiac and mesenteric angiography is an accurate means of demonstrating not only the site but also the cause of gastrointestinal bleeding; it also provides the means for therapeutic measures, such as pharmacologic or embolic control of bleeding.

Conventionally, radiography is usually used to detect musculoskeletal involvement, calcinosis, pulmonary fibrosis, and pericardial effusion. Clinical pericarditis is present in only 10-15% of patients with scleroderma and is more common in patients with limited disease. Pericarditis may mimic symptoms of esophageal involvement, and lung fibrosis often accompanies gastrointestinal scleroderma. ^{[21, 22]}

Gastric atony and dilation may occur, but involvement of the stomach is uncommon compared with involvement of other portions of the gastrointestinal tract. In rare instances, telangiectasia is the source of serious bleeding from the distal esophagus, stomach, or other gastrointestinal tract sites, especially in persons with limited cutaneous disease. All of these features may be depicted on an upper GI barium series, though the sensitivity of barium study is low in telangiectasia.

A high percentage of patients with connective tissue disease have significant esophageal motility disorders. Investigations are more likely to be positive with the CREST syndrome (calcinosis, Raynaud phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasia) than with other connective tissue diseases, even if dysphagia is present. Barium meal study and manometry are more useful than esophagoduodenoscopy. The sensitivity of esophagography for all manometric esophageal disorders is 56%, and its specificity is 91%. However, when nonspecific esophageal motility is excluded, the sensitivity rises to 89%. ^[17]

Esophageal involvement may mimic achalasia and esophageal peptic ulceration. Small bowel dilation may mimic small bowel obstruction. Large bowel dilation may mimic Hirschsprung disease. Gas may be released into the peritoneum from pneumatosis intestinalis and may mimic a perforated abdominal viscus.

Conventional radiography or barium enema study of the colon

The following findings may be observed in colonic scleroderma (see the images below):

• Large bowel constipation is common and may be seen on conventional radiographs or a barium enema study.

• In rare cases, diarrhea is noted, but more frequently, constipation and lower abdominal distention or fecal impaction manifestations of colonic involvement are present.

• Patents with scleroderma have decreased distensibility of the colon that is not necessarily correlated with symptoms.

• Large-mouthed pseudodiverticula are seen on the antimesenteric border, mostly in the transverse and descending colon.

• In advanced disease, the haustra are effaced.

• The colon may be markedly dilated.

• Stercoral ulceration may complicate colonic scleroderma.

• Reduced anorectal motility, compliance, and sphincter pressure are reported; rectal incontinence and prolapse are uncommon but disabling problems; these complications may be imaged by using a barium defecogram.

  Large bowel barium study in a patient with scleroderma/systemic sclerosis (SSc) shows marked constipation and pneumatosis coli. Same findings are shown on CT scan.

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  Large bowel barium study in a patient with scleroderma/systemic sclerosis (SSc) shows diverticulae on antimesenteric border.

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  Large bowel barium study in a patient with known gastrointestinal scleroderma shows marked constipation. Knee radiograph in the same patient shows soft tissue calcinosis.

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Barium study of the esophagus

Contrast-enhanced studies (barium series) are generally used in the investigation of gastrointestinal involvement in scleroderma. The esophagus is studied by means of barium swallow study, which may show the following results:

• Hypotonia and diminished peristalsis in the lower two thirds of the esophagus

• Esophageal activity in the upper third is usually normal, as it contains striated muscle

• Loss of the mucosal longitudinal folds

• Mild to moderate esophageal dilatation

• Patulous appearance of the lower esophageal sphincter

• Impaired emptying of the esophagus with the patient in the recumbent position

• Gastroesophageal reflux (elicited in >70% of patients)

• Erosions and superficial ulcers in the lower esophagus may be associated with gastroesophageal reflux

• Fusiform stricture 4-5 cm above the gastroesophageal border secondary to reflux esophagitis

• Barrett esophagus, often associated with gastroesophageal reflux, may involve a long esophageal stricture in the mid and/or lower esophagus, a large and deep wide-mouthed esophageal ulcer, and a fine reticular mucosal pattern distal to the stricture

• Adenocarcinoma associated with Barrett esophagus ^[23]  

Barium study of the small bowel

In scleroderma, small bowel disease occurs in up to 45% cases and is usually a poor prognostic indicator. The disease process is rapidly progressive once the small bowel is involved. The mainstay of small bowel imaging remains barium examination, which may show the following (see the images below):

• A malabsorption pattern may occur with the fragmentation/flocculation of barium

• Excessive fluid may be observed in the small bowel, which is due to bowel dilation and bacterial overgrowth causing barium dilution and poor coating

• Transit time may be delayed, with barium retention in the duodenum for up to 24 hours

• Marked dilatation of small bowel may give rise to megaduodenum or megajejunum, which mimics small bowel obstruction

• An abrupt cutoff may be noted at the level of the superior mesenteric artery because of atrophy of the neural cells with hypoperistalsis

• Tightly packed mucosal folds may be present in the hidebound pattern, or accordion pattern

• The mucosal folds may be normal despite histologic evidence of disease

• The study may show asymmetric pseudodiverticulae/sacculations with squared tops with broad bases on the mesenteric side

• Occasionally, pneumatosis intestinalis occurs in patients with advanced bowel disease; in this situation, intestinal gas dissects into the bowel wall or into the peritoneal cavity, mimicking a perforated bowel

  Plain abdominal radiograph shows a gas-filled, dilated stomach (black arrow) and duodenum (red arrow). Barium-meal study in the same patient shows a dilated duodenum. Note also several diverticulae in the small bowel.

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  Left, Barium-meal study shows a dilated duodenum. Right, High-resolution CT (HRCT) scan of the thorax in the same patient shows lung fibrosis.

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  Small bowel barium study shows a dilated duodenum, short strictures, and stagnation of the barium agent. Chest radiograph of the same patient shows basal fibrosis.

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  Three-hour image from a small bowel study shows irregular loops in the small bowel and delayed transit. Radiograph of the hands in the same patient shows penciling of the terminal phalanges.

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Cineradiography

Using cineradiography, Campbell and Schultz found that abnormal peristalsis (absent or diminished) was 67% sensitive for scleroderma. Although a high sensitivity value (87%) for cineradiography can be obtained by considering any peristaltic abnormality as a sign of scleroderma, this is achieved at the price of an undesirably high number of false-positive results (specificity, 40%) 

Computed tomography is generally not used to evaluate gastrointestinal involvement, but it may be indicated in staging esophageal cancer, in assessing intestinal obstruction and bowel perforation, and in establishing the differential diagnosis of primary biliary cirrhosis associated with scleroderma.

Pneumatosis cystoides intestinalis (PCI) is a rare but life-threatening gastrointestinal complication in the course of scleroderma-related conditions. PCI is characterized by the appearance of intramural clusters of gas in the small and large bowel wall on plain radiographs and/or CT scans and is often accompanied by a pneumoperitoneum. One study concluded that recognition of PCI is necessary for appropriate therapeutic application. In patients with underlying scleroderma-related conditions and symptoms of abdominal emergency, recruitment of multidisciplinary teams, including a rheumatologist, gastroenterologist, imaging specialist, and surgeon familiar with intestinal complications of scleroderma-related conditions, is warranted. ^[24]

CT is the examination of choice in alveolitis and pulmonary fibrosis associated with scleroderma. CT is also a sensitive means of differentiating various causes of jaundice and/or abnormal liver function test results.

Ultrasonography is an extremely sensitive means of differentiating various causes of jaundice in the context of primary biliary cirrhosis associated with scleroderma and is a sensitive means of screening patients presenting with abdominal pain in association with scleroderma. It is increasingly being used for cross-sectional imaging of the bowel. Ultrasonography remains operator dependent, and images can be degraded by fat, patient habitus, gas, and bones. Therefore, a potential for false-positive or false-negative findings always exists. ^[19]

Motility disorders of the gallbladder seem to play a minor role in upper GI tract involvement in systemic sclerosis, whereas motility disorders of the stomach are frequent and can be easily recognized on noninvasive real-time ultrasonography. ^[25]

The development of ultrasound probes based on 6F to 10F catheters has made high-resolution endoluminal ultrasonography available for use in a variety of lumina. Endoluminal ultrasonography with frequencies of 9-20 MHz has been used for evaluation of a wide range of abnormalities, including esophageal varices, various submucosal lesions, and fibrosis in scleroderma. This technique may expand diagnostic capabilities of ultrasonography, providing important information for decision making relative to patient care and minimally invasive interventional procedures. ^[26]

Radionuclide esophageal transit testing is a safe and noninvasive method that is more sensitive than cineradiography. This method might be used as a screening test to evaluate esophageal involvement in patients with progressive scleroderma. ^[27]

Wojas-Pelc et al performed esophageal scintigraphy in 30 patients with scleroderma to define the relationship between subjective symptoms of the esophagus and results of esophageal scintigraphy. Independent of esophageal dysmotility symptoms, which were noted by patients, esophageal scintigraphy registered changes in 97% of the patients. The most common esophageal dysmotility was observed in the lower part of the esophagus. Statistically, dysmotility of the central portion of the esophagus was observed more often in patients with diagnosed scleroderma than in others. ^[28]

Technetium-labeled RBCs or technetium sulfur colloid scanning is often used as an initial screening tool in diagnosing the site of gastrointestinal bleeding. The sensitivity of labeled RBC for gastrointestinal hemorrhage is 93%, and the specificity is 95%. The sensitivity of sulfur colloid for the bleeding site is only 12%, but it has a specificity of 100%.

Scintigraphy can provide a sensitive quantitative index of esophageal dysmotility. In scleroderma, the esophageal clearance of a semisolid test meal is well correlated with the results of barium studies, manometry, and ultrasonography. The severity of associated gastroesophageal reflux can also be reliably assessed.