GASTROENTEROLOGY 1990;98:1232-1238
Gastrointestinal Manifestations of Mixed Connective Tissue Disease JOHN B. MARSHALL, JOSEPH M. KRETSCHMAR, DONALD C. GERHARDT, DANIEL H. WINSHIP, DONNA WINN, EDWARD 1. TREADWELL, and GORDON C. SHARP Divisions of Gastroenterology and Immunology and Rheumatology, Department of Medicine, University of Missouri-Columbia School of Medicine; and Harry S Truman V.A. Hospital, Columbia, Missouri
We examined the gastrointestinal tract abnormalities in 61 patients with mixed connective tissue disease. The first 34 were part of a prospective longitudinal study that included manometric and radiographic evaluation of the esophagus. Heartburn (48%) and dysphagia (38%) were by far the most common gastrointestinal symptoms. Seventeen percent of patients undergoing manometry had distal esophageal aperistalsis, and 43% low-amplitude peristalsis «30 mmHg). Studies in 10 patients before and after treatment suggested that esophageal dysfunction in mixed connective tissue disease may be responsive to corticosteroids. Upper esophageal sphincter hypotension was also common. One patient had marked upper esophageal sphincter hypotension and recurrent aspiration, which resolved with corticosteroid therapy. Findings on radiographic studies of the stomach and small bowel in 54 patients and barium enemas in 16 patients were reviewed. Our series included one case each of malabsorption, colonic and small bowel perforations dueto vasculitis, chronic active hepatitis, and acute pancreatitis. In conclusion, any area of the gastrointestinal tract may be affected by mixed connective tissue disease, although the esophagus is the most common location. The gastrointestinal aspects of mixed connective tissue disease overlap with those of progressive systemic sclerosis, polymyositis, and systemic lupus erythematosus.
G
astrointestinal tract involvement has been reported with most of the connective tissue diseases (1,2). This has been best described for progressive systemic sclerosis (PSS, scleroderma), which can involve any area of the bowel (1-4). Mixed connective tissue disease (MCTD) is a syndrome characterized by
overlapping features of PSS, systemic lupus erythematosus (SLE), and polymyositis (PM), and unusually high titers of antibodies directed against the ribonucleoprotein (RNP) fraction of extractable nuclear antigen (ENA) (5-8). The esophageal motor abnormalities in MCTD have not been well characterized. In the original report of MCTD (5), some patients observed for relatively brief periods underwent cineesophagrams and esophageal motility studies. A more recent report described esophageal manometry in 17 MCTD patients (9). No information has been published concerning the response of esophageal dysfunction to corticosteroid therapy. Even less is known about extraesophageal gastrointestinal (GI) tract abnormalities. This report describes the GI tract abnormalities in our large series of 61 patients with MCTD, including many followed up longitudinally. Studies in some patients before and after treatment suggest that esophageal dysfunction in MCTD may be responsive to corticosteroids.
Methods Between 1970 and 1988, 61 patients with typical clinical and serological features of MCTD (5-7) were evaluated at the University of Missouri-Columbia and Harry S Truman V.A. Hospital. Thirty-four of these patients were evaluated as part of a prospective, longitudinal study carried out between 1970 and 1982. Pulmonary findings in these patients have been reported (10). This group of patients underwent careful study of esophageal motility, including radiographic and manometric examinations. Abbreviations used in this paper: ENA, extractable nuclear antigen; MCTD, mixed connective tissue disease; PM, polymyositis; PSS, progressive systemic sclerosis; RNP, ribonucleoprotein; SLE, systemic lupus erythematosus; UES, upper esophageal sphincter. @ 1990 by the American Gastroenterological Association 0016-5085/90/$3.00
May 1990
Radiographic examination of esophageal motility was assessed fluoroscopically and with cinerecording. including barium contrast in the prone oblique position. Esophageal manometry was performed in the MCTD patients and 20 normal controls as detailed below. Ten of the MCTD patients had manometric studies before and after initiation of corticosteroid therapy administered because of severe multisystem disease. All motility tracings were interpreted blindly by the same investigator. who was highly experienced in esophageal manometry. The manometric studies were done with a high-fidelity. low-compliance system. Before 1975. a 3-lumen polyvinyl catheter was used. with recording orifices 5 cm apart and oriented 120 0 from each other. From 1975 on. an ovalshaped. 4-lumen catheter assembly was used. with orifices 5 cm apart and at 90 0 angles (11). The internal diameter of each catheter lumen was 0.8 mm. and the 4-tube assembly had an external diameter of 3.2 x 4.5 mm. Each catheter was infused with distilled water by a pneumohydraulic capillary infusion system (Arndorfer Medical Specialties). Each manometric catheter was connected to a transducer (HewlettPackard) and in turn to a direct writing-recorder (HewlettPackard model 7758B). All subjects fasted for at least 6 h before the study. Lower esophageal sphincter (LES) pressure was determined using a station pull-through technique and measured as the mean of the individual end-expiratory pressures above gastric baseline pressure. The assembly was then positioned in the body of the esophagus with the distal catheter orifice 3 cm above the LES. Peristaltic activity was assessed with 10 swallows of 5 ml of water at intervals of at least 20-30 s. The amplitude of peristalsis in the distal esophagus was measured by averaging the values obtained from the orifices 3 cm and 8 cm above the LES. The amplitude of peristalsis was also measured in the proximal esophagus. defined as the 7-cm segment located below the upper esophageal sphincter (UES). Upper esophageal sphincter pressure was measured using a station pull-through technique. at 0.5-cm increments. with recordings made in the anterior. posterior. right lateral, and left lateral positions. We also reviewed the extraesophageal GI tract abnormalities in our MCTD patients. Gastrointestinal symptoms in these patients were ascertained by reviewing the research data bases and charts of each patient. All patients underwent blood liver test determinations. which were examined. Many of the patients also underwent nonsystematic radiographic evaluation of extra esophageal areas of the gut which were reviewed as well. Serological studies in our patients included tests for fluorescent antinuclear antibody (5). antibodies to deoxyribonucleic acid (DNA) by hemagglutination (12) and Crithidia luciliae (13). and antibodies to nuclear RNP and Sm by hemagglutination and immunodiffusion (5.6). Student's t-test for unpaired observations was used to determine the statistical difference in esophageal pressures between the MCTD patients and the normal controls. The Wilcoxon signed rank test was used to determine the statistical difference in the esophageal manometric pressures before and after initiation of corticosteroid therapy in the MCTD patients so treated. Only p values 2 yr) steroid and thiazide use could not be completely excluded. Cardiopulmonary problems associated with her MCTD further complicated the hospital course and contributed to her death. Cardiopulmonary complications of MCTD and the use of steroids and cyclophosphamide also complicated the management of a 26-yr-old patient who developed multiple spontaneous perforations of the small bowel and colon associated pathologically with vasculitis and fibrinoid necrosis. Esophageal Manometry
Thirty-five patients had esophageal manometry tracings available for review. Table 3 lists the mean resting LES and esophageal body peristaltic pressures in the 35 MCTD patients and 20 normal controls. Lower esophageal sphincter pressure and amplitude of peristaltic pressures in the distal esophagus in the MCTD patients were significantly less than in the normal controls (p < 0.001). Six of the 35 patients Table 3. Resting Lower Esophagal Sphincter and Esophageal Body Peristaltic Pressures in Mixed Connective Tissue Disease Patients and Controls MCTD a (N = 35) LES Esophageal body Distal Proximal aMean
±
SEM (mmHg).
Controlsa (N = 20)
±
1
19
±
1
Gastrointestinal Manifestations of Mixed Connective Tissue Disease JOHN B. MARSHALL, JOSEPH M. KRETSCHMAR, DONALD C. GERHARDT, DANIEL H. WINSHIP, DONNA WINN, EDWARD 1. TREADWELL, and GORDON C. SHARP Divisions of Gastroenterology and Immunology and Rheumatology, Department of Medicine, University of Missouri-Columbia School of Medicine; and Harry S Truman V.A. Hospital, Columbia, Missouri
We examined the gastrointestinal tract abnormalities in 61 patients with mixed connective tissue disease. The first 34 were part of a prospective longitudinal study that included manometric and radiographic evaluation of the esophagus. Heartburn (48%) and dysphagia (38%) were by far the most common gastrointestinal symptoms. Seventeen percent of patients undergoing manometry had distal esophageal aperistalsis, and 43% low-amplitude peristalsis «30 mmHg). Studies in 10 patients before and after treatment suggested that esophageal dysfunction in mixed connective tissue disease may be responsive to corticosteroids. Upper esophageal sphincter hypotension was also common. One patient had marked upper esophageal sphincter hypotension and recurrent aspiration, which resolved with corticosteroid therapy. Findings on radiographic studies of the stomach and small bowel in 54 patients and barium enemas in 16 patients were reviewed. Our series included one case each of malabsorption, colonic and small bowel perforations dueto vasculitis, chronic active hepatitis, and acute pancreatitis. In conclusion, any area of the gastrointestinal tract may be affected by mixed connective tissue disease, although the esophagus is the most common location. The gastrointestinal aspects of mixed connective tissue disease overlap with those of progressive systemic sclerosis, polymyositis, and systemic lupus erythematosus.
G
astrointestinal tract involvement has been reported with most of the connective tissue diseases (1,2). This has been best described for progressive systemic sclerosis (PSS, scleroderma), which can involve any area of the bowel (1-4). Mixed connective tissue disease (MCTD) is a syndrome characterized by
overlapping features of PSS, systemic lupus erythematosus (SLE), and polymyositis (PM), and unusually high titers of antibodies directed against the ribonucleoprotein (RNP) fraction of extractable nuclear antigen (ENA) (5-8). The esophageal motor abnormalities in MCTD have not been well characterized. In the original report of MCTD (5), some patients observed for relatively brief periods underwent cineesophagrams and esophageal motility studies. A more recent report described esophageal manometry in 17 MCTD patients (9). No information has been published concerning the response of esophageal dysfunction to corticosteroid therapy. Even less is known about extraesophageal gastrointestinal (GI) tract abnormalities. This report describes the GI tract abnormalities in our large series of 61 patients with MCTD, including many followed up longitudinally. Studies in some patients before and after treatment suggest that esophageal dysfunction in MCTD may be responsive to corticosteroids.
Methods Between 1970 and 1988, 61 patients with typical clinical and serological features of MCTD (5-7) were evaluated at the University of Missouri-Columbia and Harry S Truman V.A. Hospital. Thirty-four of these patients were evaluated as part of a prospective, longitudinal study carried out between 1970 and 1982. Pulmonary findings in these patients have been reported (10). This group of patients underwent careful study of esophageal motility, including radiographic and manometric examinations. Abbreviations used in this paper: ENA, extractable nuclear antigen; MCTD, mixed connective tissue disease; PM, polymyositis; PSS, progressive systemic sclerosis; RNP, ribonucleoprotein; SLE, systemic lupus erythematosus; UES, upper esophageal sphincter. @ 1990 by the American Gastroenterological Association 0016-5085/90/$3.00
May 1990
Radiographic examination of esophageal motility was assessed fluoroscopically and with cinerecording. including barium contrast in the prone oblique position. Esophageal manometry was performed in the MCTD patients and 20 normal controls as detailed below. Ten of the MCTD patients had manometric studies before and after initiation of corticosteroid therapy administered because of severe multisystem disease. All motility tracings were interpreted blindly by the same investigator. who was highly experienced in esophageal manometry. The manometric studies were done with a high-fidelity. low-compliance system. Before 1975. a 3-lumen polyvinyl catheter was used. with recording orifices 5 cm apart and oriented 120 0 from each other. From 1975 on. an ovalshaped. 4-lumen catheter assembly was used. with orifices 5 cm apart and at 90 0 angles (11). The internal diameter of each catheter lumen was 0.8 mm. and the 4-tube assembly had an external diameter of 3.2 x 4.5 mm. Each catheter was infused with distilled water by a pneumohydraulic capillary infusion system (Arndorfer Medical Specialties). Each manometric catheter was connected to a transducer (HewlettPackard) and in turn to a direct writing-recorder (HewlettPackard model 7758B). All subjects fasted for at least 6 h before the study. Lower esophageal sphincter (LES) pressure was determined using a station pull-through technique and measured as the mean of the individual end-expiratory pressures above gastric baseline pressure. The assembly was then positioned in the body of the esophagus with the distal catheter orifice 3 cm above the LES. Peristaltic activity was assessed with 10 swallows of 5 ml of water at intervals of at least 20-30 s. The amplitude of peristalsis in the distal esophagus was measured by averaging the values obtained from the orifices 3 cm and 8 cm above the LES. The amplitude of peristalsis was also measured in the proximal esophagus. defined as the 7-cm segment located below the upper esophageal sphincter (UES). Upper esophageal sphincter pressure was measured using a station pull-through technique. at 0.5-cm increments. with recordings made in the anterior. posterior. right lateral, and left lateral positions. We also reviewed the extraesophageal GI tract abnormalities in our MCTD patients. Gastrointestinal symptoms in these patients were ascertained by reviewing the research data bases and charts of each patient. All patients underwent blood liver test determinations. which were examined. Many of the patients also underwent nonsystematic radiographic evaluation of extra esophageal areas of the gut which were reviewed as well. Serological studies in our patients included tests for fluorescent antinuclear antibody (5). antibodies to deoxyribonucleic acid (DNA) by hemagglutination (12) and Crithidia luciliae (13). and antibodies to nuclear RNP and Sm by hemagglutination and immunodiffusion (5.6). Student's t-test for unpaired observations was used to determine the statistical difference in esophageal pressures between the MCTD patients and the normal controls. The Wilcoxon signed rank test was used to determine the statistical difference in the esophageal manometric pressures before and after initiation of corticosteroid therapy in the MCTD patients so treated. Only p values 2 yr) steroid and thiazide use could not be completely excluded. Cardiopulmonary problems associated with her MCTD further complicated the hospital course and contributed to her death. Cardiopulmonary complications of MCTD and the use of steroids and cyclophosphamide also complicated the management of a 26-yr-old patient who developed multiple spontaneous perforations of the small bowel and colon associated pathologically with vasculitis and fibrinoid necrosis. Esophageal Manometry
Thirty-five patients had esophageal manometry tracings available for review. Table 3 lists the mean resting LES and esophageal body peristaltic pressures in the 35 MCTD patients and 20 normal controls. Lower esophageal sphincter pressure and amplitude of peristaltic pressures in the distal esophagus in the MCTD patients were significantly less than in the normal controls (p < 0.001). Six of the 35 patients Table 3. Resting Lower Esophagal Sphincter and Esophageal Body Peristaltic Pressures in Mixed Connective Tissue Disease Patients and Controls MCTD a (N = 35) LES Esophageal body Distal Proximal aMean
±
SEM (mmHg).
Controlsa (N = 20)
±
1
19
±
1
