Juxtaglomerular hyperplasia and hyperreninemia in progressive systemic sclerosis complicated acute renal failure

The etiology of renal failure in progressive systemic sclerosis remains unexplained. In this patient with progressive systemic sclerosis rapidly progressive azotemia developed resulting in death. Kidney tissue obtained by percutaneous renal biopsy and later at autopsy revealed striking hyperplasia of the juxtaglomerular apparatus. The plasma renin activity measured by bioassay was extremely high. The clinical and morphologic findings in this patient suggest a possible pathophysiologic role for the renin-angiotensin system in the acute renal decompensation that occasionally occurs in progressive systemic sclerosis.     

Engraftment syndrome: a common cause for rash and fever following autologous hematopoietic stem cell transplantation for multiple sclerosis

Autologous hematopoietic stem cell transplantation (HSCT) is currently being evaluated as a therapy for patients with progressive multiple sclerosis (MS) at risk of debilitating neurological impairment. While preliminary results from a few studies have been reported, little is known about toxicities or outcome of HSCT for MS. We report a relatively frequent triad of non-infectious fever, rash and fatigue or lassitude that may also be associated with pruritis, pulmonary symptoms, and eosinophilia and frequently occurs around engraftment. This syndrome occurred in 26% of our series of patients (5/19) undergoing HSCT for multiple sclerosis. The engraftment syndrome is usually self-limited but may require intervention with systemic corticosteroids.     

Autologous and allogeneic mixed lymphocyte reactions in progressive systemic sclerosis

The autologous and allogeneic mixed lymphocyte reactions (MLR), observed when peripheral blood mononuclear cells from 20 patients with progressive systemic sclerosis were used, were compared with those of age-, sex-, and race-matched normal controls. Such cells were separated by gradient centrifugation of sheep red blood cell (E) rosettes into stimulator (E- or non-T cell) and responder (E + or T cell) populations. The autologous MLR of both the progressive systemic sclerosis and normal peripheral blood mononuclear cells varied widely but there was no statistical difference between the means of each group. In the allogeneic MLR, proliferation between progressive systemic sclerosis non-T cells and normal T cells was significantly less than that of normal non-T cells and progressive systemic sclerosis T cells (P = 0.001). A decreased autologous MLR, while noted with other autoimmune diseases, was lacking in progressive systemic sclerosis. This suggests a different defect. The differences in the allogeneic MLR also suggest that either progressive systemic sclerosis non-T cells were poor stimulators or T cells associated with this disease were better responders when compared with similarly prepared cell populations from normal individuals. The MLR differences could have also resulted from compositional subset alterations or the sharing of a common antigen. HLA-DR5 was found in 9 of the 17 white patients with progressive systemic sclerosis. Although these individuals were evenly distributed as low, medium, and high responders, this finding showed that some progressive systemic sclerosis non-T cells shared a common antigen.     

Gastrointestinal systemic sclerosis in serologic mixed connective tissue disease

Mixed connective tissue disease is a clinical entity defined by overlapping features of progressive systemic sclerosis, systemic lupus erythematosus, polymyositis, rheumatoid arthritis, and distinct serologic findings. Esophageal dilatation and dysmotility have been the only gastrointestinal manifestations reported. Three patients with serologic findings of mixed connective tissue disease and extensive gastrointestinal involvement compatible with the changes found in progressive systemic sclerosis are presented. Gastrointestinal manifestations of progressive systemic sclerosis are reviewed and were found to be indistinguishable from the findings in these patients.     

Sjögren's syndrome in progressive systemic sclerosis (scleroderma)

Sicca features of Sjögren's syndrome were investigated in 25 consecutive patients with progressive systemic sclerosis by means of clinical examination, Schirmer's tests, rose bengal staining tests, secretory parotid sialographies, scintillation scanning of salivary glands with ^99-mTc pertechnetate, radionuclide salivary excretion studies and lip biopsies for study of minor salivary glands.All 25 patients had at least one abnormal test and all but 3 patients had more than two abnormal tests.Pathologic findings in minor salivary glands included both lymphocytic infiltration and duct cell proliferation characteristic of Sjögren's syndrome, as well as collagen infiltration and disruption attributable to scleroderma. However, the finding of lacrimal and major salivary gland involvement indicates that Sjögren's syndrome does occur in the majority of patients with progressive systemic sclerosis. Because Sjögren's syndrome coexists almost exclusively with autoimmune disorders, our findings support the contention that progressive systemic sclerosis is related to autoimmunity.     

Enterocyte function in progressive systemic sclerosis as estimated by the deconjugation of pteroyltriglutamate to folic acid.

As a measure of enterocyte function, the deconjugation of pteroyl-L-glutamyl-gamma-L-glutamyl-gamma-L-glutamic acid to folic acid and subsequent active absorption was measured in 19 patients with progressive systemic sclerosis and compared with 14 controls. The absorption step of folic acid was identical in the two groups, while deconjugation of pteroyl-L-glutamyl-gamma-L-glutamyl-gamma-L-glutamic acid was significantly decreased in the patients with progressive systemic sclerosis. This observation suggests a primary epithelial defect of the small intestine in patients with progressive systemic sclerosis.     

Asymptomatic Osteolysis of Ribs and Clavicles in Progressive Systemic Sclerosis

Abstract: The association of severe osteolysis of clavicles and ribs in a patient with progressive systemic sclerosis is reported. The disappearance of the clavicles and upper ribs was not associated with any symptoms. The possible causes of this uncommon association are discussed.     

Prevalence and clinical correlates of pulmonary arterial hypertension in progressive systemic sclerosis

Forty-nine patients with progressive systemic sclerosis who had undergone extensive studies including pulmonary artery catheterization as part of an ongoing prospective study of the natural course of progressive systemic sclerosis were evaluated. The overall prevalence of pulmonary arterial hypertension in this population of patients with progressive systemic sclerosis was 33 percent, and among 10 subjects with the CREST syndrome the prevalence of pulmonary hypertension was 50 percent. The relation between pulmonary arterial hypertension documented at catheterization and abnormal results of noninvasive studies suggesting pulmonary hypertension, including physical examination, chest x-ray, electrocardiography, echocardiography, single-breath diffusing capacity, and vital capacity, was studied. Diffusing capacity was significantly lower in those patients with definite pulmonary hypertension (mean pulmonary artery pressure of 22 mg Hg or more) compared with those with a normal mean pulmonary artery pressure, and a diffusing capacity below 43 percent of predicted showed the greatest sensitivity (67 percent) of any single diagnostic test in detecting definite pulmonary hypertension. Chest x-ray suggesting pulmonary hypertension was the least sensitive of the tests evaluated, but showed the greatest specificity (100 percent) in identifying patients with pulmonary hypertension. A classification matrix based on discriminant function analysis utilizing the combination of diffusing capacity below 43 percent of predicted and chest x-ray and electrocardiographic findings correctly identified 75 percent of patients with definite pulmonary hypertension and 97 percent of patients with a normal pulmonary artery pressure, but failed to identify correctly patients with mild pulmonary hypertension (mean pulmonary artery pressure of 20 mm Hg). These findings indicate that specific noninvasive studies are helpful in assessing the likelihood of normal or definitely elevated pulmonary artery pressures in patients with progressive systemic sclerosis, but patients with mild pulmonary hypertension are not likely to be identified by these noninvasive studies.     

Cogan's syndrome: a systemic vasculitis.

Nonsyphilitic interstitial keratitis with vestibuloauditory dysfunction (Cogan's syndrome) is a rare clinical entity. We have reviewed 53 cases (including one of our own) of this disease. In 72 per cent of the affected patients there was an underlying systemic process, often a vasculitis. Ten per cent had fatal or near fatal aortic valvular disease, which has been shown to be amenable to surgical intervention. Other systemic manifestations have included congestive heart failure, gastrointestinal hemorrhage, adenopathy, splenomegaly, hypertension, musculoskeletal involvement and eosinophilia. The clinical course is extremely variable, ranging from months to over 15 years with a minimal five year survival of 28 per cent. Medical therapy with corticosteroids has been beneficial but has only limited effect on symptoms of vestibuloauditory dysfunction. Cogan's syndrome appears to be a manifestation of a systemic disorder which is often apparent only after long-term follow-up.     

Idiopathic Calcific Panereatitis, CRST Syndrome and Progressive Systemic Sclerosis

A 43-year old man with CRST syndrome (calcinosis, Raynaud's phenomenon, sclerodactyly and telangiectasia) and progressive systemic sclerosis presented with a four-year history of relapsing abdominal pain, the result of chronic pancreatitis, not associated with alcoholism, biliary disease, or any of the known causes of pancreatitis. He had a good response to retrograde pancreatic duct drainage but exhibited management problems and complications that may be peculiar to the systemic sclerosis patient with pancreatitis. A cause and effect relationship between progressive systemic sclerosis and pancreatic disease is not proven but we believe there is evidence to suggest such a relationship.     

Progressive Systemsklerose (diffuse Sklerodermie) und Goodpasture'sches Syndrom bei einer 47jährigen Frau

In a 47-year-old woman, suffering for 3 years of progressive systemic sclerosis (diffuse sclerodermia), Goodpasture's syndrome with a typical membranous proliferative glomerulonephritis and an acute hemosiderosis of the lungs was found in the late stage of the disease. Death was caused by uremia and cardio-respiratory insufficiency. In addition post-mortem examination revealed chronic intersititial nephrosis with pyramidal necrosis as well as eosinophilic infiltrates in the lung tissue and in the bronchial lumina. With the present knowledge, it is impossible to determine whether progressive systemic sclerosis and Goodpasture's syndrome are two independent nosological entities, or whether Goodpasture's syndrome is a part of the picture of the late stage of progressive systemic sclerosis.     

Solid-phase radionuclide esophageal transit in progressive systemic sclerosis

BACKGROUND/AIMS: In most patients with progressive systemic sclerosis the esophagus is affected. Reflux symptoms are most frequent whilst dysphagia also occurs. The radionuclide esophageal transit study is a sensitive screening test for esophageal dysfunction. In this study, we evaluated the esophageal motility of patients with progressive systemic sclerosis using a solid-phase radionuclide esophageal study. METHODOLOGY: Thirty-two patients with progressive systemic sclerosis and 30 normal volunteers were studied with solid-phase radionuclide esophageal study. Each subject was placed in a supine position above a gamma camera linked to a computer and was given a 4-mL bolus of solid gelatin containing 1 mCi of Tc-99m phytate. Data were acquired in the list mode. RESULTS: Twenty-nine of the 32 patients (91%) had abnormal findings from the study. CONCLUSIONS: The radionuclide esophageal transit study can be regarded as a useful tool for evaluating the esophageal function in patients with progressive systemic sclerosis and in the follow-up of treatment.     

Factors predicting development of renal involvement in progressive systemic sclerosis

Renal involvement or "scleroderma renal crisis" developed in 60 patients with progressive systemic sclerosis evaluated at the University of Pittsburgh during the period from 1972 to 1982. Forty-seven of these patients had progressive systemic sclerosis with diffuse scleroderma, representing 18 percent of persons with progressive systemic sclerosis and diffuse scleroderma evaluated during this time period. Ten additional patients did not have truncal scleroderma but were suspected of having incompletely developed diffuse scleroderma. Only three patients were classified as having progressive systemic sclerosis with the CREST syndrome. Renal crisis was observed early in the course of the illness, a mean of 3.2 years after onset. During May and June, this complication developed in fewer patients than expected. Thirty-six patients who had diffuse scleroderma and renal involvement after their initial Pittsburgh evaluation were compared with 212 who had diffuse scleroderma without renal involvement during follow-up. The patients with renal involvement had a shorter mean disease duration at the time of their first evaluation (2.4 versus 4.2 years, p less than 0.05) and less frequently had digital pitting scars (29 versus 54 percent), but no other significant clinical, laboratory, or serologic differences were noted. Data available for 31 patients with renal involvement during the six months preceding the onset of renal disease were analyzed. Blood pressure, serum creatinine, urine protein and red blood cells, and plasma renin levels were similar in these patients and the 212 patients without renal involvement. More patients with renal involvement had anemia or clinical evidence of cardiac involvement during this period compared with the patients without renal involvement. During the 12-month period prior to renal involvement, seven of 16 (44 percent) patients with such involvement had an impressive increase in skin thickening on physical examination compared with only 23 of 180 (14 percent) patients without renal involvement at any time during their course. Thus, the subset of patients with diffuse scleroderma who show rapid progression of their skin thickening early in the illness with development of anemia, pericardial effusion, or congestive heart failure have a high risk of "scleroderma renal crisis."     

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.     

Abnormal appearance of the internal anal sphincter at ultrasound: a specific feature of progressive systemic sclerosis?: The debate is not closed

Endosonography is now an effective tool for the assessment of anorectal pathologies. We present a case of rectal prolapse in a patient with progressive systemic sclerosis, with low resting anal pressure, no rectoanal inhibitory reflex in manometry, and a thin, heterogeneous, difficult to delineate, internal sphincter on endoanal ultrasound. We also provide a review of the literature on anorectal involvement in progressive systemic sclerosis.     

Atrioventricular nodal function in progressive systemic sclerosis: electrophysiological and morphological findings.

Electrophysiological data consistent with atrioventricular nodal dysfunction were obtained in 10 out of 19 patients with progressive systemic sclerosis (scleroderma). Conducting system studies were carried out in a further seven patients with progressive systemic sclerosis. In each the proximal portion of the atrioventricular node was consistently found to be smaller and more slender. It is postulated that there is a relation between proximal atrioventricular nodal structural alterations and impaired atrioventricular nodal function.     

Nifedipine and esophageal dysfunction in progressive systemic sclerosis. A controlled manometric study

We evaluated the effect of the calcium channel blocking agent, nifedipine, on esophageal dysfunction in 15 patients with progressive systemic sclerosis, using a double-blind, randomized, crossover, placebo-controlled manometric study. Nifedipine significantly decreased lower esophageal sphincter pressure in these patients; this reduced lower esophageal sphincter pressure may cause gastroesophageal reflux. Thus, nifedipine may have detrimental effects on progressive systemic sclerosis patients.     

Interstitial lung disease as the first manifestation of systemic sclerosis

We describe three patients with progressive fibrosing interstitial lung disease (ILD) as the first and only manifestation of systemic sclerosis. In one patient the presence of anti-Scl-70 autoantibodies suggested systemic sclerosis to be the underlying cause of the disease. In the two other subjects, however, anti-Scl-70 antibodies were negative. In these patients the lung disease preceded other manifestations of systemic sclerosis by several years. Diagnosis, prognosis and treatment of systemic sclerosisassociated ILD is discussed.     

PM-Scl-Antikörper positive systemische Sklerodermie assoziiert mit Einschlusskörper-Myositis

We describe a 72- year-old patient with a ten year history of anti-PM-Scl positive systemic sclerosis associated with inclusion-body myositis. While the association of dermatomyositis and polymyositis with anti-PM-Scl positive systemic sclerosis is frequently reported, inclusion-body myositis was, to the best of our knowledge, only previously described once in association with anti-PM-Scl-positive systemic sclerosis. The distinction between inclusion-body myositis and other forms of inflammatory myopathy, like the histopathologically well distinguishable polymyositis or dermatomyositis, is relevant because of the poor response of inclusion- body myositis to immunosuppressive treatment. Our case underlines that in patients with anti-PM-Scl-positive systemic sclerosis and treatment resistant progressive myopathy the diagnosis of inclusion body myositis should be considered.