Limited Scleroderma Research Articles

Is Anti-Topoisomerase I a Serum Marker of Pulmonary Involvement in Systemic Sclerosis?

To determine the value of the level of anti-topoisomerase I (anti-topo I) to evaluate lung involvement defined by abnormal high-resolution computed tomography (HRCT) score and pulmonary function tests (PFTs) in systemic sclerosis (SS). Forty-eight patients with SS, 20 with lung involvement and 28 with no lung involvement. PFT measurement, HRCT scoring of lung involvement, and anti-topo I assay by enzyme-linked immunosorbent assay. Normal anti-topo I level was defined as < 30. There was a significant association between cutaneous extent and anti-topo I level (6.5% of patients with limited cutaneous scleroderma had abnormal anti-topo I levels vs 70.6% of patients with diffuse cutaneous scleroderma, p = 0.0001). In patients with diffuse cutaneous scleroderma, pulmonary involvement was associated with a higher percentage of abnormal anti-topo I level: 91.7% vs 20% (p = 0.010). In patients with diffuse cutaneous scleroderma, a significant association was found between the class of anti-topoII level and total lung capacity (median, 69 in patients with abnormal anti-topo I level vs 87 in patients with normal anti-topo I level, p = 0.010), between the class of anti-topo I level and HRCT score (median, 12 in patients with abnormal anti-topo I level vs 5 in patients with normal anti-topo I level, p = 0.05). Anti-topo I can be considered as a marker of lung involvement in patients with diffuse cutaneous scleroderma.

Antimitochondrial Antibodies and Their Significance in Diffuse and Limited Scleroderma

The increased prevalence of primary biliary cirrhosis (PBC) in Sjogren's syndrome and scleroderma has been described. We determined the frequency of antimitochondrial antibodies (AMA) in limited scleroderma, compared with diffuse scleroderma, and have considered their clinical significance because they are known to be related to PBC. Outpatients with scleroderma were prospectively tested for the presence of AMA and to determine whether they had evidence of liver disease both clinically and by laboratory parameters. Sixty-one patients with scleroderma were tested for AMA. Thirty of these had diffuse scleroderma. Four patients, all of whom had limited disease (4 of 31 or 13%), had positive AMA. Two had known primary biliary cirrhosis. The other two participants with positive antibodies had no evidence of liver disease when examined clinically, but no liver biopsies were performed. They have been followed for >2 years, without clinical evidence of PBC. Our findings agree with the literature that shows that 8% to 15% of patients with limited scleroderma have AMA. AMA did not occur in diffuse scleroderma in our population. Screening for the occurrence of PBC in scleroderma with antimitochondrial antibodies in patients without signs or symptoms of liver disease is unnecessary because at this time, we would not give ursodeoxycholic acid to scleroderma patients with positive AMA and normal alkaline phosphatases who had no symptoms of PBC.

Bilateral Avascular Necrosis of the Lunate in a Patient with Severe Raynaudʼs Phenomenon and Scleroderma

We report a case of bilateral avascular necrosis of the lunate, Kienböck's disease, occurring in a patient with limited scleroderma and severe Raynaud's phenomenon who had never received corticosteroids. The patient also had bilateral congenital shortening of the ulnar, which can predispose to Kienböck's disease. The avascular necrosis of the lunate occurred during exacerbations of the Raynaud's phenomenon, which suggests that it was precipitated by the vascular changes associated with Raynaud's phenomenon in scleroderma. Avascular necrosis of the carpus should be considered in the differential diagnosis of patients with chronic wrist pain and scleroderma.

Association of clonally expanded T cells with the syndrome of primary biliary cirrhosis and limited scleroderma.

Clinical features of the CREST (calcinosis cutis, Raynaud's syndrome, esophageal dysmotility, sclerodactyly, and telangiectasias) syndrome are sometimes exhibited in patients with primary biliary cirrhosis (PBC), but the postulated autoimmune mechanisms behind these conditions are poorly understood. Clonally expanded T cells may play an important role in disease pathogenesis. In this study, overrepresentation of one T-cell receptor beta chain variable region, TCRBV3, was documented in patients with PBC and/or CREST. Overrepresentation of the TCRBV3 gene mRNA was demonstrated by semiquantitative reverse-transcriptase polymerase chain reaction (RT-PCR). T cells expressing TCRBV3 were analyzed by flow cytometry, were primarily CD8(+), and contained activated cells as assessed by expression of CD69. Clonally expanded T cells within this population were documented by both complementarity determining region 3 (CDR3) length polymorphism analysis and sequencing of T-cell receptor CDR3 cDNA. TCRBV3(+) clonal expansions were stable when followed for up to 5 years. The results of this study demonstrate that the T-cell repertoire of patients with PBC and CREST is characterized by expanded clonal populations of CD8(+) TCRBV3(+) T cells. These clonal expansions provide evidence that stimulation of clonal populations of CD8(+) T cells is associated with the clinical syndrome of PBC with CREST.

A study of the frequency of pericardial and pleural effusions in scleroderma.

To determine the frequency of pericardial and pleural effusions in scleroderma. Using a case-control format, patients with scleroderma and no known cardiac disease were recruited. Echocardiograms and chest radiographs were performed. Age- and gender-matched controls had echocardiograms performed which were read by a cardiologist, blinded to the diagnosis. The medical records of 60 other scleroderma patients were also reviewed. Thirty-seven scleroderma subjects were recruited, of whom 18 had diffuse disease. Only eight subjects with diffuse disease and five with limited scleroderma had normal echocardiograms compared to 20 of 37 controls (P < 0.1). Two had pericardial effusions, both with diffuse scleroderma, and none of the controls had effusions present. Pulmonary hypertension occurred in three with diffuse disease and no controls. A chart review of a further 60 patients with scleroderma was performed. Pleural effusions were identified in 7% (4/58) of the cohort of scleroderma patients and were more frequent in diffuse disease (10%). A total of 17% (4/23) of diffuse and 4% (1/23) of limited scleroderma patients had evidence of pericardial effusions. Pericardial effusions do occur in scleroderma without evidence of clinical cardiac dysfunction and are more common in diffuse scleroderma. Pleural effusions in scleroderma occur less frequently, in 70%.

Different patterns of endothelial cell activation in renal and pulmonary vascular disease in scleroderma.

Abnormal endothelial cell function is implicated in the development of scleroderma, and in major life-threatening complications of the disease. The nature of the stimulus leading to abnormal endothelial cell function in scleroderma, scleroderma renal crisis, and scleroderma-associated pulmonary hypertension was investigated by measurement of soluble adhesion molecules, shed by activated endothelial cells, in sera from patients with these conditions. In scleroderma renal crisis, mean levels of soluble E-selectin (p < 0.05 limited scleroderma, p < 0.0001 diffuse scleroderma), sVCAM-1 (soluble vascular cell adhesion molecule-1) (p < 0.05 limited scleroderma, p < 0.05 diffuse scleroderma), and sICAM-1 (soluble intercellular adhesion molecule-1) (p < 0.0001 limited scleroderma, p < 0.0001 diffuse scleroderma) were raised, supporting a model of endothelial cell activation in this complication. Evidence for endothelial cell activation in scleroderma-associated pulmonary hypertension was inconsistent, with normal sE-selectin and normal sVCAM-1 in sera from patients with limited scleroderma and pulmonary hypertension. The endothelial cell phenotype in scleroderma-associated pulmonary hypertension may resemble that of unstimulated cells. The pulmonary vascular and renal vascular lesions associated with scleroderma may arise by distinct pathogenic mechanisms.

Prazosin for Raynaud's phenomenon in progressive systemic sclerosis.

To determine the effects and toxicity of prazosin versus placebo proposed for the treatment of Raynaud's phenomenon (RP) in scleroderma. We searched the Cochrane Controlled Trials Register, and Medline up to December 1996 using the Cochrane Collaboration search strategy developed by Dickersin et al.(1994). Key words included: Raynaud's or vasospasm, scleroderma or progressive systemic sclerosis or connective tissue disease or autoimmune disease. Current Contents were searched up to and including April 7, 1997. All bibliographies of articles retrieved were searched and key experts in the area were contacted for additional and unpublished data. The initial search strategy included all languages. Randomized controlled trials comparing prazosin versus placebo were eligible if they reported clinical outcomes from the start of therapy. Trials with a greater than 35% dropout were excluded. Trials were included if patients with diffuse or limited scleroderma were the subjects. If patients with other connective tissue diseases or primary Raynaud's were included, the trial was used if the data on the scleroderma patients could be extracted from the paper. All data were abstracted by two independent and trained reviewers (DF, AT), and verified by a third reviewer (JP). Each trial was assessed independently by the same two reviewers for its quality using a validated quality assessment tool (Jadad 1996). Peto's odds ratios were calculated for all dichotomous outcomes and a weighted mean difference was carried out on all continuous outcomes. Fixed effects and random effects model were used if the data was homogeneous or heterogeneous, respectively. Two trials with a total of 40 patients were included. Prazosin has been found in two randomized controlled cross-over trials to be more effective than placebo in the treatment of Raynaud's secondary to scleroderma. However, the positive response is modest and side effects are not rare in those taking prazosin. Prazosin is modestly effective in the treatment of Raynaud's phenomenon secondary to scleroderma.

Clinical manifestations of systemic sclerosis.

Systemic sclerosis is a multisystem disease characterized by inflammation and fibrosis of many organs. There are two major subsets, limited cutaneous (the old CREST syndrome) and diffuse cutaneous scleroderma. The major difference is the pace of disease. Limited scleroderma patients often have a long history of Raynaud's phenomenon before other symptoms. They have skin thickening limited to hands and frequently have problems with digital ulcers and esophageal dysmotility. Although generally a milder form than diffuse scleroderma, they can have life-threatening complications from small intestine hypomotility and pulmonary hypertension. Diffuse scleroderma patients have a much more acute onset, with many constitutional symptoms, arthritis, carpal tunnel syndrome, and marked swelling of hands and legs. They get widespread skin thickening, progressing from their fingers to their trunk. Internal organ problems, including gastrointestinal and pulmonary fibrosis, are common, but severe life-threatening involvement of the heart and kidneys occurs. Understanding the type of disease that occurs in these two subsets will enable the physician to anticipate problems, aggressively treat those that can be treated, and give the patient a better understanding of their disease.

Clinical images: Progressive calcifications and draining lesions following staphylococcal infection in a patient with limited scleroderma

Clinical images: Progressive calcifications and draining lesions following staphylococcal infection in a patient with limited scleroderma

Clinical images: Progressive calcifications and draining lesions following staphylococcal infection in a patient with limited scleroderma

Clinical images: Progressive calcifications and draining lesions following staphylococcal infection in a patient with limited scleroderma

The palpable tendon friction rub

AbstractObjective. To evaluate the clinical and prognostic significance of palpable tendon friction rubs in patients with systemic sclerosis (SSc).Methods. SSc patients evaluated prospectively at the University of Pittsburgh were examined serially for the presence of tendon friction rubs on physical examination. Demographic, clinical, and laboratory features of disease were obtained by patient examination, annual patient questionnaire, and medical record review. Patients were classified as having limited or diffuse scleroderma according to standard definitions. The prognostic significance of the presence of tendon friction rubs was determined using this comprehensive database.Results. The SSc patients (n = 1,305) were first evaluated during 1972 through 1991 and were followed up for a mean of 6.3 years. Tendon friction rubs were detected most frequently in patients who had or who developed diffuse cutaneous involvement. There were strong correlations between the presence of tendon friction rubs and symptoms and signs typical of diffuse scleroderma, including more severe skin thickening, more frequent heart and kidney involvement, and decreased survival. In multiple regression analyses, the presence of 1 or more tendon friction rubs was one of the best predictors of both evolution to diffuse scleroderma and reduced survival.Conclusion. The palpable tendon friction rub is an easily detected, inexpensively obtained physical examination finding which is highly associated with diffuse cutaneous scleroderma and decreased survival. This observation should lead to the early diagnosis of diffuse scleroderma and should identify patients at high risk for serious visceral involvement who are thus candidates for potential disease‐modifying therapy.

The palpable tendon friction rub: an important physical examination finding in patients with systemic sclerosis.

To evaluate the clinical and prognostic significance of palpable tendon friction rubs in patients with systemic sclerosis (SSc). SSc patients evaluated prospectively at the University of Pittsburgh were examined serially for the presence of tendon friction rubs on physical examination. Demographic, clinical, and laboratory features of disease were obtained by patient examination, annual patient questionnaire, and medical record review. Patients were classified as having limited or diffuse scleroderma according to standard definitions. The prognostic significance of the presence of tendon friction rubs was determined using this comprehensive database. The SSc patients (n = 1,305) were first evaluated during 1972 through 1991 and were followed up for a mean of 6.3 years. Tendon friction rubs were detected most frequently in patients who had or who developed diffuse cutaneous involvement. There were strong correlations between the presence of tendon friction rubs and symptoms and signs typical of diffuse scleroderma, including more severe skin thickening, more frequent heart and kidney involvement, and decreased survival. In multiple regression analyses, the presence of 1 or more tendon friction rubs was one of the best predictors of both evolution to diffuse scleroderma and reduced survival. The palpable tendon friction rub is an easily detected, inexpensively obtained physical examination finding which is highly associated with diffuse cutaneous scleroderma and decreased survival. This observation should lead to the early diagnosis of diffuse scleroderma and should identify patients at high risk for serious visceral involvement who are thus candidates for potential disease-modifying therapy.

Prevalence of Pulmonary Hypertension in Limited and Diffuse Scleroderma

To characterize the prevalence of undiagnosed pulmonary hypertension in patients with limited and diffuse scleroderma. Prospective cross-sectional study. University-based outpatient clinic. Thirty-four consecutive patients with limited (n = 29) or diffuse (n = 5) scleroderma but without the clinical diagnosis of pulmonary hypertension. All patients had 12-lead ECGs and two-dimensional and Doppler echocardiograms. The pulmonary artery systolic pressure (PAs) was calculated as the sum of the Doppler transtricuspid pressure gradient and the right atrial pressure as estimated by the caval respiratory index. Thirty-three patients (97%) had adequate spectral signals of tricuspid regurgitation. The velocity of tricuspid regurgitation ranged from 1.6 to 4.5 m/s. The calculated PAs ranged from 15 to 95 (mean +/- SD = 30 +/- 14 mm Hg). Twelve patients (35% of the total cohort) had pulmonary hypertension defined as PAs of 30 mm Hg or greater. Undiagnosed elevation of PAs is common in patients with scleroderma. Noninvasive assessment of PAs can be performed accurately in most patients independent of clinical signs of pulmonary hypertension. If successful treatment strategies are identified, it may be possible to identify patients early in the development of pulmonary hypertension and intervene before significant end-organ damage occurs.

Pulmonary hypertension in systemic sclerosis: an analysis of 17 patients.

A retrospective chart review was carried out on 344 patients with systemic sclerosis (SSc) followed prospectively for the occurrence of pulmonary hypertension (PHT). Seventeen patients (4.9%) were found to have PHT. Eight patients had isolated PHT, while in nine PHT was associated with restrictive lung disease (RLD). The subset with RLD developed PHT earlier, but had longer survival than patients with isolated PHT. Patients with limited scleroderma tend to develop isolated PHT, while in those with diffuse disease PHT is associated with RLD. Irrespective of disease type, PHT in SSc has an extremely poor prognosis with a median survival of 12 months following diagnosis.

Muskelbeteiligung bei der progressiven systemischen Sklerose

In many cases of systemic sclerosis clinical, laboratory or EMG findings reveal skeletal muscle involvement of various degrees. Myopathology allows a structural differentiation of three subgroups. Variable disease courses of systemic sclerosis seem to be - albeit not obligatory - associated with three types of skeletal muscle involvement. In limited scleroderma focal nodular myositis is the most common finding. Structural abnormalities in diffuse scleroderma are dominated by a diffuse polymyositis with an endomysial infiltration by cytotoxic (CD8+) T cells. Perimysial infiltration by Band (CD4+) T-lymphocytes indicating the polymyositis of the perifascicular type occurs most commonly in systemic sclerosis overlap syndromes. Myocardial involvement is a principal determinant of survival in systemic sclerosis. The myocardium shows patchy fibrosis. Because of different therapeutic consequences clinically suspected involvement of the skeletal muscle requires muscle biopsy. Myocardial involvement undergoes cardiological treatment.

High resolution computed tomography for the evaluation of lung involvement in 101 patients with scleroderma.

The aim of the study was to investigate the pulmonary parenchymal abnormalities by high resolution computed tomography (HRCT) in patients with various forms of scleroderma. Three scans were performed sequentially in all cases: one at the level of aortic arch, one at the tracheal carina and one 1-2 cm above the diaphragm. Seventy cases with limited, 21 patients with diffuse cutaneous systemic sclerosis and 10 cases with circumscribed scleroderma were investigated. The 21 patients with diffuse scleroderma included three normal HRCT scan (14%), three with ground glass attenuation (14%), one with ground glass attenuation with fibrosis, three with fibrosis (14%), six with subpleural and five with diffuse honeycombing. The majority of cases with extensive honeycombing of the lungs had anti-Sc! 70 autoantibody which was the characteristic antibody of the diffuse scleroderma subset. The 70 cases with limited cutaneous systemic sclerosis were characterized by normal HRCT (43%), ground glass opacity with or without fibrosis (18.6%), whereas fibrosis was detected in 22.9%, subpleural or diffuse honeycombing in 15.7% of the patients. Six of the ten cases with circumscribed scleroderma also showed a fibrosis. Cases with diffuse scleroderma are characterized by the presence of advanced fibrosis, whereas the extent of fibrosis is far less pronounced in limited scleroderma. Mild fibrosis may also be present in circumscribed scleroderma forms.

CREST Syndrome

A variant of systemic sclerosis (scleroderma), CREST syndrome affects a relatively small number of patients. CREST (also called limited cutaneous scleroderma) has a more favorable prognosis than the diffuse form of scleroderma. However, as with most of the connective tissue diseases, the daily issues faced by patients are frequently difficult to manage and require diligent support from the health care team. This article summarizes the clinical manifestations and potential management plan to help the patient cope with this little-understood syndrome. The nursing care model follows a problem-oriented approach for nursing management.

Gastrointestinal manifestations of systemic sclerosis

Gastrointestinal (Gl) manifestations of systemic sclerosis (SSc) were found in 82% of 262 patients followed up prospectively. Esophageal dysmotility, lower esophageal sphincter laxity, bacterial overgrowth, and wide mouth diverticuli were the most common findings. The disease is usually diffuse with multiple levels of involvement. Gastrointestinal involvement was not significantly correlated with gender, age at SSc diagnosis or disease type (limited or diffuse scleroderma). Upper Gl symptoms develop early in the course of SSc and may not correlate with objective findings. Various investigations, treatment regimens, and less frequent disease manifestations are reviewed and discussed.

Endothelin and collagen vascular disease: a review with special reference to Raynaud's phenomenon and systemic sclerosis.

Endothelin-1 (ET-1), endothelin-2, and endothelin-3, a family of 21-aminoacid peptides, are potent, long-acting vasoconstrictors of mammalian blood vessels. Elevated levels of ET-1 have been found in the circulation of patients with various diseases, all of which have some degree of vascular involvement that is associated with endothelial cell activation. These diseases include systemic sclerosis, primary and secondary Raynaud's phenomenon, pulmonary hypertension, Buerger's disease, and Takayasu's arteritis. The role of circulating ET-1 in the pathogenesis of the vascular and fibrotic lesions in these conditions remains to be elucidated. This review focuses on the recent findings of the clinical significance and pathogenetic role of endothelin in collagen vascular diseases, especially in Raynaud's phenomenon and systemic sclerosis. Although the etiology of systemic sclerosis is unknown, a vascular pathogenesis is supported by a variety of clinical and laboratory observations. The fact that plasma levels of ET-1 are elevated in patients with systemic sclerosis and this elevation is more remarkable in patients with diffuse scleroderma compared with limited scleroderma patients might further support the vascular pathogenesis of systemic sclerosis.

Treatment of systemic sclerosis.

Although there have been no major breakthroughs in scleroderma therapy, new treatments have been tested in patients with systemic sclerosis, including both interferon alfa and interferon gamma. These biologic agents can reduce collagen synthesis, which is a rational target for scleroderma therapy. Debate about the use of photopheresis continues, and it was suggested in a recent editorial that photopheresis is no better than D-penicillamine in the treatment of scleroderma and is more expensive. Cyclosporine appears to have frequent renal toxicity when used to treat scleroderma. Outcome measurements have been concentrated on in scleroderma trials. Several types of scleroderma classifications were compared, and the classification of diffuse and limited scleroderma was strongly related to disease severity. Skin score was systematically compared with mapping the surface area of involved skin, and the skin score was found to be more reliable. A possible prognostic indicator in scleroderma is high-resolution pulmonary computed tomography, which is sensitive in early detection of scleroderma-associated interstitial lung disease. Classification of Raynaud's phenomenon into primary and secondary forms has been proposed, and further testing of the criteria and long-term follow-up is necessary to validate this classification. Over the past year, treatment of vasospasm with prostacyclin analogues has been efficacious with iloprost but not with low-dose oral cicaprost. Tissue plasminogen activator is not beneficial in the treatment of Raynaud's phenomenon. A report of radical microarteriolysis for the treatment of refractory Raynaud's phenomenon seems promising, warranting further investigation.