Esophageal disease in progressive systemic sclerosis

Opinion statement Progressive systemic sclerosis (PSS) or scleroderma is characterized by fibrosis of the skin and visceral organs. Gastrointestinal disease occurs in up to 90% of patients, with the esophagus being the most commonly affected organ. Heartburn, dysphagia, and regurgitation occur in most patients. Esophageal manometry aids in diagnosing PSS. Endoscopy rules out complications, such as Barrett’s esophagus, Candida esophagitis, and cancer. Lifestyle modifications should be implemented, including avoidance of alcohol, nicotine, and NSAIDs. Proton pump inhibitor therapy should be instituted, although it is unclear whether the dose should be adjusted according to symptoms or to 24-hour pH monitoring. Prokinetic agents are useful in the early stages of PSS when gastrointestinal musculature is still intact. Metoclopramide improves reflux, lower esophageal sphincter pressure, and gastric emptying but has an inconsistent effect on esophageal peristalsis. A decision on when to perform antireflux surgery, if at all, is controversial. Esophageal disease in PSS is a common and difficult-to-treat problem.     

Esophageal motor disturbances in progressive systemic sclerosis

Ten patients with progressive systemic sclerosis (PSS) and esophageal symptoms (group 1) and 10 control subjects were studied. Esophageal electromanometry using the intermittent pull-through technique and catheter perfusion with distilled water were performed in all patients and individuals. The variables studied were pressure amplitude in the lower esophageal sphincter (LES) (mmHg) and deglutition wave amplitude (mmHg at 5, 10 and 15 cm above LES). In PSS patients, the average LES pressure was 18.5 +/- 4.6 mmHg, and in control subjects it was 27 +/- 6.5 mmHg (p < 0.01). Deglutition wave amplitude at 5, 10 and 15 cm above LES was 13.2 +/- 7.5 mmHg, 12 +/- 3.7 mmHg and 15 +/- 3.3 mmHg, respectively, in PSS patients. In control subjects, it was 67.6 +/- 12.5 mmHg, 58.6 +/- 20.9 mmHg and 52.4 +/- 21.4 mmHg (p < 0.001). In PSS patients, the pressure amplitude in LES and in the body of the esophagus was lower than in control subjects. In PSS patients, esophageal manometry showed the absence of normal peristalsis.     

Esophageal function in progressive systemic sclerosis.

A prospective study was performed in 13 consecutive patients with systemic progressive sclerosis (PSS). For the diagnosis of impaired esophageal peristalsis cineradiography and manometry are equally useful. Esophageal suction biopsy allows the diagnosis of esophagitis but not of scleroderma. Mild to severe esophageal involvement was observed in 12 patients. In only one patient the esophagus was virtually normal. Dysfunction of the esophageal body may occur early in the course of the disease while incompetence of the lower esophageal sphincter is observed on an average after 7 to 8 years. Both impairment of peristalsis and pressure of the lower esophageal sphincter may lead to delayed esophageal clearance. Relaxation of LES is normal even in the absence of primary peristalsis. Extensive esophageal damage including severe gastroesophageal reflux may be present in the absence of esophageal symptoms.     

Esophageal dysfunction and radionuclide transit in progressive systemic sclerosis

Sixty patients with progressive systemic sclerosis (PSS) were studied by radionuclide esophageal transit (RT) and esophageal cineradiography. Fifty-two patients (87%) had abnormal RT with prolonged transit time and 28 (47%) had stagnation of radionuclide. RT was positively correlated to duration of disease (p less than 0.01). A positive correlation between transit time and the presence of dysphagia was observed. Reduced esophageal motility evaluated by cineradiography was observed in 44 patients (73%). In patients with moderate-severe esophageal dysfunction there was a positive association between prolonged RT and hypomotility at the radiological examination (p = 0.001). RT is a safe and non-invasive method which is more sensitive than cineradiography and might be used as a screening test to evaluate esophageal involvement in patients with PSS.     

Esophageal motility in progressive systemic sclerosis (PSS)

The evaluation of structural and functional abnormalities of the esophagus by manometry (using perfused tubes) and cine-radiography were compared in 25 subjects with progressive systemic sclerosis (PSS). Motility by both procedures was definitely abnormal in 19 subjects and normal in 3. The remaining 3 subjects had abnormal motility on manometry, coupled with cine-esophagrams interpreted as normal. Many structural abnormalities not demonstrated by manometry were identified by cine-radiography. Therefore, the initial diagnostic examination of motility in PSS should be the cine-esophagram.     

Esophageal dysfunction in patients with progressive systemic sclerosis and mixed connective tissue diseases

Esophageal motility was studied in 37 patients with progressive systemic sclerosis (PSS), 12 patients with mixed connective tissue disease (MCTD) and 40 controls by the manometry method, using an open tube and continuous perfusion, and by radiological examination. Radiology was normal in 17 patients with PSS and five patients with MCTD, and abnormal in 15 patients with PSS and three with MCTD. The most frequent abnormality was slow transit time of barium. Manometry of the esophageal body was normal in 20 patients with PSS and six patients with MCTD, and abnormal in 17 patients with PSS and six with MCTD. Lack of contraction in the middle lower segments of the esophagus was the abnormality most frequently observed. Lower esophageal sphincter pressure was significantly lower among patients with PSS and MCTD than among the controls. Dysphagia was reported by ten patients with PSS and by six patients with MCTD. Radiology and manometry showed similar changes in PSS and MCTD, but dysphagia was more frequent among patients with MCTD.     

Long-term griseofulvin treatment for progressive systemic sclerosis

Thirty-three patients with progressive systemic sclerosis (PSS) (24 women and 9 men, 27 with diffuse scleroderma and 6 with CREST syndrome) were treated with griseofulvin alone (375-500 mg/day) for 12-84 months (mean 33). Clinical and functional assessment of the results included: a self-evaluation (general status, skin toughness, cold sensitivity, dysphagia), a physical examination (fingerprint areas, chest expansion, mouth widening, grip strength) routine laboratory tests, electrocardiogram, glomerular filtration rate (GFR), esophagus and chest X-rays. After griseofulvin, a significant improvement was noted in 28/33 patients (85%) regarding subjective condition and skin thickening and elasticity, particularly in the trunk and proximal limbs (p less than 0.05 for chest expansion), and of GFR (p less than 0.01). Lung and esophageal involvement, on the whole, remained unchanged during the treatment, which does not appear to modify the progression of PSS myocardiopathy. No patient stopped using griseofulvin because of side effects. The present results show that griseofulvin is a safe drug for PSS treatment and that it can influence the skin and renal involvement.     

Esophageal manometry and pH-probe monitoring in the evaluation of gastroesophageal reflux in patients with progressive systemic sclerosis

Fifty-five patients with progressive systemic sclerosis (PSS) were evaluated with esophageal manometry, 12-h pH-probe monitoring in esophagus, and registration of symptoms of gastroesophageal reflux (GER). Thirty-nine patients had symptoms suggestive of GER. The 12-h pH-monitoring showed pathologic GER in 30 patients. We found that 33% of the patients with symptoms did not have pathologic GER, and 25% of the patients without symptoms had pathologic GER. Characteristic changes of impaired motility in the esophagus were found in 46 patients. When combining esophageal manometry, reflux measurement, and symptoms of GER, we found a positive correlation in 60% of patients with reduced peristalsis in the lower two-thirds of the esophagus and GER. We therefore recommend sensitive esophageal pH-monitoring in all PSS patients to ensure treatment of patients with pathologic GER.     

Malignant thymoma associated with progressive systemic sclerosis

A 65-year-old man manifested certain features of scleroderma several years before discovery of malignant thymoma. Following tumor resection, the signs and symptoms of scleroderma did not improve, and the patient experienced the abrupt onset of renal failure with malignant hypertension 7 months after the operation. The scleroderma renal crisis caused terminal renal failure, which was treated by chronic hemodialysis. This is the second reported case of thymoma associated with progressive systemic sclerosis (PSS). The authors suggest that thymoma and various immunologic disorders have a common etiologic factor which has not yet been found. This case emphasizes that thymectomy frequently has little effect on the course of the immunologic disease. The implications of the association of thymoma and PSS are discussed.     

Gastrointestinal function in patients with progressive systemic sclerosis

Summary In 24 patients with progressive systemic sclerosis (PSS) the pentagastrin-stimulated gastric acid secretion was determined to investigate if acid hypersecretion is associated with reflux-oesophagitis — the most common complication to oesophageal involvement in PSS. Gastro-oesophageal reflux was observed in 12, reflux-oesophagitis in 9 and oesophageal mycosis in 8 patients. Gastric acid secretion was increased in 13 (54%) patients and tended to be higher in patients with oesophagitis. Patients with reflux and increased acid secretion seemed to be free from oesophageal mycosis. Bacterial overgrowth and malabsorption are known complications to intestinal scleroderma and these items were investigated using non-invasive methods. Four patients had increased bile acid deconjugation, 3 had increased (¹⁴C)xylose degradation indicating bacterial overgrowth and 7 patients had decreased fat absorption in the triolein breath test. Nutritional status with respect to selenium, folate, cobalamine and fat-soluble vitamins was essentially normal.     

Secondary amyloidosis in progressive systemic sclerosis

Progressive systemic sclerosis (PSS) is a connective tissue disease that may affect many organs, including the kidneys. It is quite rare to see secondary amyloidosis due to PSS. We present a patient with a 9-year history of PSS who developed nephrotic syndrome, and whose renal biopsy was compatible with secondary amyloidosis. He died from massive upper gastrointestinal bleeding caused by oesophageal telangiectasia. Received: 23 August 2000 / Accepted: 26 February 2001