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 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.     

系统性硬化症患者高分辨率测压下食管动力特点

目的 应用高分辨率测压的方法对系统性硬化症患者食管运动功能及其与食管症状的关系进行研究.方法 选择临床确诊为系统性硬化症的患者18例,均接受36通道高分辨率食管测压检查,记录食管括约肌静息压力、10次5 ml水及10 ml水连续吞咽状态下食管体部蠕动情况.结果 18例受试者中失蠕动8例,弱蠕动9例(频发性无蠕动及大缺损性弱蠕动7例),下食管括约肌压力降低8例.连续吞咽中88.9％的患者未见蠕动波出现.10例存在食管症状者中,失蠕动患者6例,食管体部弱蠕动4例.无食管症状者中,2例失蠕动,5例食管体部弱蠕动.结论 食管功能异常在系统性硬化症患者中发生率较高,疾病早期无食管症状者即可出现食管动力异常.     

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.     

Conjugal progressive systemic sclerosis

INTRODUCTION: Familial occurrence of progressive systemic sclerosis is unusual. The occurrence of conjugal scleroderma is exceptional. EXEGESIS: We report here a case of systemic sclerosis in a wife and husband who both developed the onset of illness within a 10-year period. Solvent exposure was noted. CONCLUSION: The etiology of systemic sclerosis remains unknown. Environmental factors may play role in its pathogenesis.     

Pulmonary changes in progressive systemic sclerosis

The pulmonary changes of progressive systemic sclerosis in 8 cases were reported. The major clinical complaints were unproductive cough and exertional dyspnea. Pulmonary function tests showed restrictive ventilatory defects and impaired diffusing capacity in most of the cases examined. On chest X-rays, diffuse mottling and linear densities were seen in lungs, predominately in the basal regions. On pathological examinations, pulmonary interstitial fibrosis occurred in early stage of the disease. The results showed that pulmonary involvement may be an early event in progressive systemic sclerosis.     

Anorectal abnormalities in progressive systemic sclerosis

Seventeen patients with progressive systemic sclerosis (PSS) were evaluated with manometry for anorectal function, and an additional 36 age-matched normal subjects were collected as a control group. The study group had a significant decrement of maximum basal pressure (MBP), 42.6±27.0 mm Hg, in PSS as compared with the control group, 71.2±24.9 mm Hg (P=.0004). The difference in the functional length (FL) of the anal canal, PSS∶control=2.4±1.0 cm∶3.7±0.5 cm (P=.0001); the volume of first defecating sensation, PSS∶control=66.3 ±35.2 ml∶125.1±43.8 ml; the voluntary component, the difference between maximum squeeze pressure (MSP) and MBP, PSS∶control=116.6±73.6 mm Hg∶61.8±35.9 mm Hg (P=.0087), were also found to be statistically significant. Nevertheless, the MSP and maximal tolerable capacity (Vmax) showed no difference in these two groups (MSP, PSS∶control=159.3±88.1 mm Hg∶132.9±44.9 mm Hg,P=.259), (Vmax, PSS∶control=193.1±67.7 ml∶230.0±60.9 ml,P=.0526), Twelve (71 percent) of 17 patients did not have rectoanal inhibitory reflex, and paradoxical contraction during rectal balloon inflation was noted in ten patients. Nine patients had different degrees of anal incontinence and abnormal anometric profiles were found in six of eight asymptomatic patients. Therefore, only two patients (12 percent) had neither symptoms nor anometric evidence of anorectal involvement in PSS. Two patients with long-standing disease received posterior anal repair for stool incontinence, the postoperative results were satisfactory both subjectively and objectively. The average MBP increased from 0 to 20 mm Hg, average FL from 0 to 1.5 cm. Patients complained less frequently about stool incontinence or soiling, and their daily life is now more comfortable. The analysis indicates that anorectal function in PSS is affected much more frequently and earlier than thought. Anorectal manometry can be used as an adjuvant in diagnosing controversial cases. Once anal incontinence occurs, posterior anal repair can achieve good results after six months of follow-up.     

Trigeminal neuropathy in progressive systemic sclerosis

Trigeminal neuropathy was identified in 16 (4 percent) of 442 consecutive patients with progressive systemic sclerosis (PSS) who were first evaluated during the period between 1972 and 1980. These cases, together with 25 others that are adequately documented in the literature, were reviewed and compared with the 426 cases of PSS (96 percent) without trigeminal neuropathy, Trigeminal neuropathy occurred most frequently in young women with PSS in overlap with other disorders, particularly the mixed connective tissue disease syndrome with clinical evidence of myositis. Serum antibodies to ribonucleoprotein were identified in nine (45 percent) of 20 PSS patients with trigeminal neuropathy as compared to 25 (8 percent) of 329 PSS patients without trigeminal neuropathy. Leukopenia, hypothyroidism, and Sjogren's syndrome were also found to be associated with trigeminal neuropathy.     

Digestive involvement in progressive systemic sclerosis

We studied 14 patients with PSS, 12 females and 2 males with a mean age of 43.6 and a medium of 8 years disease. All of the patients were selected for this study according to updated ARA criteria and were included in a prospective protocol to investigate digestive involvement. This protocol consists of a complete medical history, physical examination, radiologic and endoscopic studies, parasitological and microbial flora investigation. The symptoms more frequently seen were: pyrosis (78%), gastroesophageal regurgitation (50%), flatulence (50%), dysphagia (42%) and chronic diarrhea (21%). The radiologic findings commonly seen were: distal esophageal aperistalsis (78%), gastroesophageal reflux (57%), dilatation of intestinal loops (35%), changes of the mucosal folds (35%). A mild esophagitis was seen endoscopically in 64% of the patients, moderate and severe in 7% respectively. The study of the microbial flora showed contaminations with enterobacteria in 5 patients (35%). After statistical analysis we concluded that the digestive compromise by PSS is frequent, being the esophagus more commonly affected (80%), at the beginning in the form of reflux esophagitis and later in esophageal stenosis, the compromise of the small intestine (40%) is manifested by chronic diarrhea or dyspeptic flatulence, which correlates well the radiologic findings and the bacterial overgrowth in this organ. The colonic compromise generally is asymptomatic, and the common finding is dilatation os the colonic loops. Finally, the bacterial overgrowth in the small intestine is a secondary involvement to the intestinal compromise of Progressive Systemic Sclerosis.     

Fibrinogen turnover in progressive systemic sclerosis

Large amounts of fibrin are seen in the intima of the renal arterioles in progressive systemic sclerosis (scleroderma). The half-life or half disappearance time of plasma fibrinogen in 15 patients with scleroderma was studied using 125I fibrinogen to find whether there is an increased turnover of plasma fibrinogen paralleling this morphologic abnormality. Patients had a more rapid fibrinogen turnover than normal controls (60.7 versus 90.6 hours); the subgroup of patients with "progressive" scleroderma had a more rapid fibrinogen half-life than those with "stable" scleroderma (56.5 versus 73.2 hours). The mean fibrinogen half-life of 8 patients given intravenous heparin increased to within one standard deviation of normal, a finding that suggested that the fibrinogen molecule in these patients was capable of normal survival. There was a considerable variation of normal survival. There was a considerable variation of fibrinogen half-lives in individual scleroderma patients over time (not seen in the normal controls) which may be the result of intermittently increased fibrinogen consumption.     

The esophagus in progressive systemic sclerosis

Progressive systemic sclerosis commonly involves the esophagus. Both conventional recumbent barium esophagrams with fluoroscopy and esophageal manometry have been used to determine such involvement. In an attempt to ascertain which of these two modalities is more sensitive in detecting esophageal disease, 27 patients with biopsy-proven progressive systemic sclerosis were studied. Manometry provided the more accurate index of esophageal involvement. Indeed, as demonstrated in this study, normal barium studies do not exclude extensive esophageal disease.     

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     

Antinuclear antibodies in progressive systemic sclerosis

Sera from 84 patients with progressive systemic sclerosis (PSS) were tested for the presence of antinuclear antibodies by immunofluorescence on HEp2 cells and gel immunodiffusion. Fluorescent antinuclear antibodies were detected in 80 subjects with PSS (95%). Ninety-three percent of patients with CREST syndrome and 3% of those with diffuse scleroderma had a centromere staining. Precipitating antibodies were found in 57% of PSS sera and identified as anti-Scl 70 in 42 cases (50%). This specificity was found in 42 of 70 subjects with diffuse scleroderma (60%); another patient was positive for anti-nRNP antibodies, and 5 more sera from PSS patients showed precipitin lines of unknown specificity. No serum from 14 patients with CREST syndrome was positive for anti-Scl 70 antibodies. Significant relationships have been found between centromere staining and CREST syndrome (p less than 0.0005) and between the presence of anti-Scl 70 antibodies and the diffuse form of scleroderma (p less than 0.0005). The latter specificity is strongly associated with grainy speckled pattern on HEp2 fluorescence (p less than 0.0005). These data suggest that anti-Scl 70 antibodies and anti-centromere antibodies are useful markers for different subgroups of patients with PSS.