GASTROINTESTINAL MANIFESTATIONS OF SCLERODERMA

doi:10.1016/S0889-8553(05)70021-2

Gastroenterology Clinics of North America

Volume 27, Issue 3, 1 September 1998, Pages 563-594

https://doi.org/10.1016/S0889-8553(05)70021-2 Get rights and content

Scleroderma or progressive systemic sclerosis is a multisystem, multistage disorder of small arteries, microvessels, and connective tissue. The disease occurs in all races but affects women three to four times more than men. Initial symptoms typically occur in the 20s to 40s. There are approximately 10 new cases per 1 million adults per year. Systemic manifestations may include skin involvement; Raynaud's disease; polyarthritis; and lung, heart, kidney, and thyroid problems.¹³¹ The gastrointestinal tract may be involved, and this disease may affect the esophagus, stomach, or small or large bowel. The gastrointestinal symptoms related to scleroderma may precede the diagnosis of this condition by several years. Up to 90% of patients diagnosed with scleroderma have gastrointestinal manifestations.1, 8, 16, 22, 27, 90, 105 The gastrointestinal symptoms, although rarely life-limiting, can be the source of impaired quality of life for patients with this disease. The most common site of gastrointestinal involvement is the esophagus, which is involved in approximately 90% of patients.4, 59, 123 Other sites of involvement are not uncommon. Anorectal problems may be found in more than half of patients with scleroderma.⁴⁴ Intestinal involvement may be either small bowel (40% of patients) or large bowel (10% to 50% of patients).⁶⁵

This article explores the pathophysiology of the gastrointestinal manifestations of scleroderma and reviews the clinical presentation and complications. Treatment options and optimizing management of the patient with gastrointestinal symptoms secondary to scleroderma are also examined. Table 1 summarizes the gastrointestinal manifestations seen in patients with scleroderma.

Section snippets

PATHOPHYSIOLOGY

Overproduction of collagen, increased humoral immune activity, and abnormal cellular immune function all contribute to the development of scleroderma in all of the organ systems. The pathologic changes seen in scleroderma are similar throughout the gastrointestinal tract. The integrity of epithelial cell morphology and villus structures, where present, is maintained except in circumstances in which they are affected by secondary processes, such as gastroesophageal reflux or bacterial overgrowth.

SYMPTOMS AND MANIFESTATIONS BY ORGAN SYSTEM

Table 2 summarizes the gastrointestinal symptoms found in patients with scleroderma. Table 3 lists the diagnostic procedures and indications for these procedures for patients with gastrointestinal symptoms associated with scleroderma. The following is a detailed analysis of symptoms, with diagnostic and treatment strategies by organ system.

SUMMARY

Gastrointestinal involvement is commonly found in scleroderma. Gastrointestinal symptoms may be the presenting symptoms for the diagnosis and may precede the actual diagnosis by months to years. The esophagus is the most frequently affected, but functional problems of the anorectum, small bowel, colon, and stomach may occur. The pathophysiologic mechanism appears to be one of smooth muscle atrophy and, to a lesser degree, fibrosis. These changes result in gastrointestinal motility disturbances

References (137)

M. Abu-Shakra et al.
Gastrointestinal manifestations of systemic sclerosis
Semin Arthritis Rheum
(1994)
V. Annese et al.
Erythromycin accelerates gastric emptying by inducing antral contractions and improved gastroduodenal coordination
Gastroenterology
(1992)
P.M. Campbell et al.
Pathogenesis of systemic sclerosis: A vascular hypothesis
Semin Arthritis Rheum
(1975)
S. Cohen et al.
The gastrointestinal manifestations of scleroderma: Pathogenesis and management
Gastroenterology
(1980)
R. Compton
Scleroderma with diverticulosis and colonic obstruction
Am J Surg
(1969)
W.A. D'Angelo et al.
Pathologic observations in systemic sclerosis (scleroderma): A study of fifty-eight autopsy cases and fifty-eight matched controls
Am J Med
(1969)
J.E. Dill
Barrett's epithelium in scleroderma
Gastrointest Endosc
(1983)
DullJ.S. et al.
Successful treatment of gastroparesis with erythromycin in a patient with progressive systemic sclerosis
Am J Med
(1990)
M.P. Greydanus et al.
Abnormal postcibal antral and small bowel motility due to neuropathy or myopathy in systemic sclerosis
Gastroenterology
(1989)
B. Hallerback et al.
Omeprazole or ranitidine in long-term treatment of reflux esophagitis
Gastroenterology
(1994)

J. Hamel-Roy et al.

Comparative esophageal and anorectal motility in scleroderma

Gastroenterology

(1985)

M. Horowitz et al.

Effect of cisapride on gastric and esophageal emptying in progressive systemic sclerosis

Gastroenterology

(1987)

R.R. Horswell et al.

Scleroderma presenting as the malabsorption syndrome

Gastroenterology

(1961)

A.J.S. House et al.

The significance of an air oesophagogram visualised on conventional chest radiographs

Clin Radiol

(1977)

P. Jacob et al.

Proximal esophageal pH-metry in patients with “reflux laryngitis.”

Gastroenterology

(1991)

A. Kahan et al.

Gastrointestinal involvement in systemic sclerosis

Clin Dermatol

(1994)

D.A. Katzka et al.

Barrett's metaplasia and adenocarcinoma of the esophagus in scleroderma

Am J Med

(1987)

D.A. Katzka et al.

Azathioprine and hepatic venooclusive disease in renal transplant patients

Gastroenterology

(1986)

P. Kerlin et al.

Breath hydrogen testing in bacterial overgrowth of the small intestine

Gastroenterology

(1988)

H.A. Klein et al.

Comparative studies of esophageal function in systemic sclerosis

Gastroenterology

(1992)

G. Labo et al.

Interdigestive gastroduodenal motility and serum motilin levels in patients with idiopathic delay in gastric emptying

Gastroenterology

(1986)

G.J. Maddern et al.

Abnormalities of esophageal and gastric emptying in progressive systemic sclerosis

Gastroenterology

(1984)

A.M. Metcalf et al.

Simplified assessment of segmental colonic transit

Gastroenterology

(1987)

R.J. Petrokubi et al.

Cimetidine versus antacid in scleroderma in scleroderma with reflux esophagitis: A randomized double-blind controlled study

Gastroenterology

(1979)

W.D.W. Rees et al.

Interdigestive motor activity in patients with systemic sclerosis

Gastroenterology

(1982)

T.B. Reynolds et al.

Primary biliary cirrhosis with scleroderma, Raynaud's phenomenon and telangiectasia

Am J Med

(1971)

A. Akesson et al.

Gastrointestinal function in patients with progressive systemic sclerosis

Clin Rheumatol

(1985)

A. Akesson et al.

Gastrointestinal regulatory peptides in systemic sclerosis

Arthritis Rheum

(1993)

A. Akesson et al.

Organ manifestations in 100 patients with progressive systemic sclerosis: A comparison between the CREST syndrome and diffuse scleroderma

Br J Rheumatol

(1989)

P. Arhan et al.

Segmental colonic transit time

Dis Colon Rectum

(1981)

M. Atkinson et al.

Oesophageal changes in systemic sclerosis

Gut

(1966)

J.L. Ballard et al.

The gastrointestinal manifestations of generalized scleroderma

South Med J

(1969)

L.G. Bartholomew et al.

Chronic disease of the liver associated with systemic scleroderma

Am J Dig Dis

(1964)

G. Basilisco et al.

Anorectal dysfunction and delayed colonic transit in patients with progressive systemic sclerosis

Dig Dis Sci

(1993)

W.M. Battle et al.

Abnormal colonic motility in progressive systemic sclerosis

Ann Intern Med

(1981)

R. Bluestone et al.

Systemic sclerosis and small bowel involvement

Gut

(1969)

M. Bortolotti et al.

Gastric emptying and interdigestive antroduodenal motility in patients with esophageal scleroderma

Am J Gastroenterol

(1991)

A.J. Cameron et al.

Barrett's esophagus occurring as a complication of scleroderma

Mayo Clin Proc

(1978)

W.A. Cassada et al.

Involvement of the gastrointestinal tract by progressive systemic sclerosis

South Med J

(1968)

S. Cheng et al.

Home central venous hyperalimentation in fifteen patients with severe scleroderma bowel disease

Arthritis Rheum

(1989)

M.M. Chernin et al.

Efficacy of radiologic studies in the detection of Barrett's esophagus

AJR Am J Roentgenol

(1986)

B. Chernow et al.

Pulmonary aspiration as a consequence of gastroesophageal reflux: A diagnostic approach

Dig Dis Sci

(1979)

A.K. Clarke et al.

Rheumatic disorders in primary biliary cirrhosis

Ann Rheum Dis

(1978)

S. Cohen et al.

The pathogenesis of esophageal dysfunction in scleroderma and Raynaud's disease

J Clin Invest

(1972)

E. Corazziari et al.

Effect of T51619 on distal oesophageal motor activity and gastric emptying

Ital J Gastroenterol

(1983)

K.S. Culp et al.

Autoimmune associations in primary biliary cirrhosis

Mayo Clin Proc

(1982)

G. D'Angelo et al.

Rectal prolapse in scleroderma: Case report and review of the colonic complications of scleroderma

Can J Surg

(1985)

P. Denes et al.

Esophageal motility and pulmonary function in progressive systemic sclerosis

Respiration

(1981)

K.J. DiGregorio et al.

Acute abdominal emergencies in patients with rheumatic disease

A.J. DiMarino et al.

Duodenal myoelectric activity in scleroderma: Abnormal responses to mechanical and hormonal stimuli

N Engl J Med

(1973)

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GASTROINTESTINAL MANIFESTATIONS OF SCLERODERMA

Section snippets

PATHOPHYSIOLOGY

SYMPTOMS AND MANIFESTATIONS BY ORGAN SYSTEM

SUMMARY

Semin Arthritis Rheum

Gastroenterology

Semin Arthritis Rheum

Gastroenterology

Am J Surg

Am J Med

Gastrointest Endosc

Am J Med

Gastroenterology

Gastroenterology

Gastroenterology

Gastroenterology

Gastroenterology

Clin Radiol

Gastroenterology

Clin Dermatol

Am J Med

Gastroenterology

Gastroenterology

Gastroenterology

Gastroenterology

Gastroenterology

Gastroenterology

Gastroenterology

Gastroenterology

Am J Med

Gastrointestinal function in patients with progressive systemic sclerosis

Clin Rheumatol

Gastrointestinal regulatory peptides in systemic sclerosis

Arthritis Rheum

Organ manifestations in 100 patients with progressive systemic sclerosis: A comparison between the CREST syndrome and diffuse scleroderma

Br J Rheumatol

Segmental colonic transit time

Dis Colon Rectum

Oesophageal changes in systemic sclerosis

Gut

The gastrointestinal manifestations of generalized scleroderma

South Med J

Chronic disease of the liver associated with systemic scleroderma

Am J Dig Dis

Anorectal dysfunction and delayed colonic transit in patients with progressive systemic sclerosis

Dig Dis Sci

Abnormal colonic motility in progressive systemic sclerosis

Ann Intern Med

Systemic sclerosis and small bowel involvement

Gut

Gastric emptying and interdigestive antroduodenal motility in patients with esophageal scleroderma

Am J Gastroenterol

Barrett's esophagus occurring as a complication of scleroderma

Mayo Clin Proc

Involvement of the gastrointestinal tract by progressive systemic sclerosis

South Med J

Home central venous hyperalimentation in fifteen patients with severe scleroderma bowel disease

Arthritis Rheum

Efficacy of radiologic studies in the detection of Barrett's esophagus

AJR Am J Roentgenol

Pulmonary aspiration as a consequence of gastroesophageal reflux: A diagnostic approach

Dig Dis Sci

Rheumatic disorders in primary biliary cirrhosis

Ann Rheum Dis

The pathogenesis of esophageal dysfunction in scleroderma and Raynaud's disease

J Clin Invest

Effect of T51619 on distal oesophageal motor activity and gastric emptying

Ital J Gastroenterol

Autoimmune associations in primary biliary cirrhosis

Mayo Clin Proc

Rectal prolapse in scleroderma: Case report and review of the colonic complications of scleroderma

Can J Surg

Esophageal motility and pulmonary function in progressive systemic sclerosis

Respiration

Acute abdominal emergencies in patients with rheumatic disease

Duodenal myoelectric activity in scleroderma: Abnormal responses to mechanical and hormonal stimuli

N Engl J Med