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Results for “Scleroderma, Systemic”

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PubMed2006

Induction of apoptosis and fibrillin 1 expression in human dermal endothelial cells by scleroderma sera containing anti-endothelial cell antibodies.

OBJECTIVE: Sera from patients with scleroderma (systemic sclerosis [SSc]) contain anti-endothelial cell antibodies (AECAs) capable of inducing endothelial cell apoptosis. We sought to determine whether SSc sera containing anticentromere antibodies (ACAs) or anti-topoisomerase I antibodies (or, anti-Scl-70 antibodies) contain subsets of AECAs that trigger distinct pathways of apoptosis and gene expression in normal adult human dermal endothelial cells (HDECs). METHODS: Adult HDECs were grown to subconfluence and treated with control or SSc patient sera. Apoptosis was investigated by differential interference contrast (DIC) microscopy, microarrays of proapoptotic gene expression, caspase 3 protease activity, and flow cytometry for phosphatidyl serine translocation. RESULTS: Flow cytometry and DIC microscopy demonstrated that HDECs exposed to SSc sera containing either SSc autoantibody underwent apoptosis at much higher levels than those treated with control sera. While unique gene expression profiles were induced in HDECs by stimulation with SSc sera containing the respective autoantibody, similar patterns of increased gene expression of transcripts for the proapoptotic protease caspase 3 as well as the SSc autoantigen fibrillin 1 were demonstrated. Caspase 3 gene expression correlated with increased protease activity, and targeted inhibition of this protease partly blocked SSc serum-induced apoptosis. Immunohistochemistry studies of serum-stimulated HDECs demonstrated the aberrant expression of fibrillin 1 protein only in apoptotic endothelial cells treated with SSc sera containing AECAs. CONCLUSION: There are distinct AECA subsets in the sera of patients with limited SSc (with ACAs) and diffuse SSc (with anti-Scl-70) that induce unique patterns of HDEC gene expression in the setting of apoptosis associated with increased caspase 3 activity and the reexpression of endothelial cell fibrillin 1.

Adult↗

PubMed1983

Nailfold capillary abnormalities in childhood rheumatic diseases.

The nailfold capillary patterns of 84 patients with a variety of childhood rheumatic diseases and 34 normal control subjects were observed. Distinctive morphologic abnormalities with capillary dilation and dropout of surrounding structures were noted in two groups: patients with childhood dermatomyositis and with scleroderma (P less than 0.001). Among those with scleroderma, capillary abnormalities were found in all nine patients with systemic disease and in none of 10 patients with cutaneous disease only (Fisher's exact P less than 0.001). Of 25 patients with dermatomyositis for whom muscle biopsies were available for analysis, abnormal nailfold capillary pattern was found with highest prevalence in patients with two or more specific vascular lesions noted on biopsy (Fisher's exact P = 0.041). Nailfold capillary abnormalities are present in distinct populations of childhood rheumatic diseases, reflect the underlying vasculopathy of childhood dermatomyositis, and may be of diagnostic value in distinguishing localized from systemic scleroderma.

Adolescent↗

PubMed1988

Localization of collagen mRNA in normal and scleroderma skin by in-situ hybridization.

Scleroderma is a fibrotic disease occurring in a localized or systemic form. Disturbed regulation of connective tissue metabolism plays an important role in its pathogenesis. However, until now, most of the data available were obtained from studies of fibroblasts in culture and there is considerable doubt that fibroblasts in a monolayer reflect the in-vivo situation. Using in-situ hybridization with specific antisense RNAs on frozen sections of skin, cells were detected displaying enhanced messenger RNA levels for type I and type III collagen in patients with localized and systemic scleroderma. Activated fibroblastic cells were often located near blood vessels in the deep dermis of patients with early stages of the disease and were mostly surrounded by mononuclear cells. These findings are in agreement with the concept that the interaction of fibroblasts with 'immunocompetent cells' is crucial in the initial activation of connective tissue metabolism in fibrosis.

Adult↗

PubMed1995

Scleroderma and occupational exposure.

OBJECTIVES: A case-referent study was conducted in the province of Trento, Italy, to investigate the possible association between occupational exposure and scleroderma (systemic and localized variants). METHODS: Twenty-one cases of scleroderma were ascertained from the computerized admission files of all of the local hospitals from 1976 to 1991. For each case, two age- and gender-matched referents were selected that were discharged from the hospital on the same day as the case. The subjects were interviewed with a structured questionnaire which included items for personal, work, and medical history. Exposure to organic solvents, other selected chemicals, silica dust, and hand-arm vibration was carefully investigated. RESULTS: A significant association was found between exposure to organic solvents (aromatic hydrocarbons) and scleroderma [odds ratio (OR) 9.28, 95% confidence interval (95% CI) 1.08-243.8]. For the men, the OR for exposure to silica was 5.20 (95% CI 0.48-74.1), whereas for the women it was 2.11 (95% CI 0.20-22.0) for exposure to other selected chemicals. CONCLUSIONS: The results of this case-referent study are consistent with those of previous case reports on the important role of occupation in the etiology of scleroderma. In particular, our findings confirm that exposure to organic solvents and silica is associated with this rare connective tissue disease.

Case-Control Studies↗

PubMedDate not supplied

Localized and systemic forms of scleroderma in adults and children .

Systemic sclerosis (SSc) presents a great deal of variability in the extent and severity of skin and internal organ involvement. The diagnostic and prognostic significance of autoantibodies in SSc is undisputed and the patient's autoantibody profile represents a fundamental tool for clinicians. Scleroderma is a rare condition in children. Unlike adults, localized scleroderma is more frequent than the systemic sclerosis, nevertheless it represents a disabling condition. In both conditions, no validated outcome measures and proven effective treatment is available to date.Raynaud's phenomenon (RP) is one the most common and significant clinical symptoms of SSc and therefore in patients with RP a capillaroscopic analysis should be carried out as soon as possible. The actual and select advantage of the early nailfold videocapillaroscopic (NVC) analysis is to distinguish between the primary RP and the secondary RP and to allow the early detection of SSc.

Adult↗

PubMed1997

Lymphocyte phenotyping in systemic sclerosis: a flow cytometry analysis of lymphocytes in bronchoalveolar lavage fluid.

OBJECTIVE: Patients with scleroderma (systemic sclerosis [SSc]) frequently develop interstitial lung disease. The purpose of this work was to evaluate the cell profile in the bronchoalveolar lavage fluid (BALF) in patients suffering from a diffuse form of systemic sclerosis as compared with healthy controls. STUDY DESIGN: Bronchoalveolar lavage was carried out in the right middle lobe of 25 untreated, nonsmoking patients with SSc and 12 healthy, nonsmoking volunteers. For the analysis of lymphocyte subsets, the following monoclonal antibodies were used: anti-CD3, anti-CD4, anti-CD8, anti-CD14, anti-CD16, anti-CD19, anti-CD25, anti-CD45, anti-CD56. Also, anti-HLA-DR and flow cytometry were used. RESULTS: We found an increase in the total number of cells with an increase in the percentage of lymphocytes and neutrophils in BALF from patients when compared with controls (P < .05). The proportion of lymphocytes, cytotoxic/suppressor CD8+ and activated lymphocytes T CD25+ were higher in patients' BALF (P < .05). The CD4+/CD8+ ratio in BALF from subjects was significantly lower than in controls. These findings were characteristic of patients with early-stage disease. CONCLUSION: Analysis of the BALF lymphocyte phenotype may be useful in the early detection of lung involvement in patients with SSc.

Adult↗

PubMed2003

Mortality and prognostic factors in Spanish patients with systemic sclerosis.

OBJECTIVE: To determine survival and mortality in a cohort of Spanish patients with scleroderma (systemic sclerosis, SSc) and to analyse whether survival is influenced by demographic, clinical or immunological variables or the extent of skin involvement. METHODS: The study included 79 patients diagnosed with SSc and taking part in a study to determine the extent of sclerosis, visceral involvement and immunological alterations. We studied the number of observed and expected deaths (the expected number being based on age- and sex-specific rates in the background population) and derived standardized mortality ratios with their 95% confidence intervals (CI). Cumulative survival after onset of the first symptom was estimated according to the Kaplan-Meier method. The Cox method was used to identify the prognostic factors. RESULTS: The mortality rate was 0.0249 deaths per person-year. Survival at 15 yr was 0.62 (95% CI 0.410-0.778). The standardized mortality ratio was 429.4% (95% CI 222-750). On crude analysis, lung involvement [forced vital capacity (FVC) <70%, pulmonary hypertension], SSc renal crisis, an active capillaroscopic pattern, pericardial effusion and age over 60 yr at diagnosis were associated with shorter survival. On multivariate analysis, only age at diagnosis over 60 yr, FVC <70% and SSc renal crisis were independent prognostic factors. CONCLUSIONS: The mortality rate associated with SSc showed a four-fold increase compared with the background population. Lung involvement and sclerodermal renal crisis were found to be independently associated with reduced survival.

Adolescent↗

PubMed1986

Megacolon in a collagen vascular overlap syndrome.

Mixed connective tissue disease is a syndrome having clinical features of scleroderma, systemic lupus erythematosus, and polymyositis with a unique combination of clinical and laboratory findings. Not all patients with clinical features of more than one connective tissue disease fit the mixed connective disorders category; therefore, the term "overlap syndrome" is applied to patients with features of two or more connective tissue diseases. Gastrointestinal involvement in progressive systemic sclerosis is common, with the esophagus being the usual site, followed by the small bowel, colon, and stomach. Colonic involvement is reported to occur in 10 to 50 percent of cases and is typically manifested radiographically as wide-mouthed diverticular saculations. Symptoms secondary to colonic involvement are rare but occasionally serious, such as impaction of barium or feces. A case is described in which systemic lupus erythematosus coexisted with previously undiagnosed scleroderma involving predominantly the gastrointestinal tract and resulting in megacolon.

Esophagus↗

PubMed2003

Are isolated antinucleolar antibodies a marker of scleroderma?

This study was designed to determine the prevalence and positive predictive value of isolated antinucleolar antibody (ANA) in scleroderma patients. We identified 73 rheumatology clinic patients with isolated ANAs. ANA titers greater than 1:160 were considered positive. The overall prevalence of isolated ANAs was 2.9%. The prevalence of isolated ANAs in scleroderma, systemic lupus erythematosus (SLE), and rheumatoid arthritis were 20.3%, 2.68%, and 3.3%, respectively. Scleroderma and SLE were present in 12 patients (16.4%) each. Other rheumatologic disorders identified in these patients were RA (12.3%), undifferentiated connective tissue disease (8.2%), mixed connective tissue disease (4.1%), vasculitis (6.8%), fibromyalgia (8.2%), osteoarthritis (5.4%), crystal-related arthropathy (6.8%), seronegative arthritis (2.7%), sarcoidosis (4.1%), and others (8.2%). There were no statistically significant differences in the median ANA titers in scleroderma versus systemic lupus (P = 0.16) or undifferentiated connective tissue disease (P = 0.18). The median titers were higher in scleroderma in comparison with rheumatoid arthritis (P = 0.01), osteoarthritis (P = 0.007), fibromyalgia (P = 0.001), and crystal-related arthropathy (P = 0.009). Isolated ANAs have poor sensitivity (20.3%) and the positive predictive value for this test is only 16.4% for scleroderma.

Journal Article↗

PubMed1989

Racial differences in antinuclear antibody patterns and clinical manifestations of scleroderma.

The profile of antinuclear antibodies (ANA) in 49 Thais with scleroderma (systemic sclerosis) was compared with that in 68 white Australians with scleroderma. Forty-eight (98%) of the Thais and all (100%) of the white Australians were positive for ANA, with the majority (100% and 97%, respectively) showing a diffuse speckled pattern of nuclear fluorescence. The distribution of the patterns was different in the 2 races; 35 (71%) of the Thais and 17 (25%) of the Australians showed staining of the nucleolus, and 1 (2%) of the Thais and 35 (51%) of the Australians showed staining of the centromeres. The frequency of precipitating antibodies to extractable nuclear antigens was also strikingly different: 86% in Thais and 26% in Australians (P less than 0.001). Precipitating antibodies to Scl-70 (topoisomerase I), the predominant extractable nuclear antigen in patients with scleroderma, were detected in 37 (76%) of the Thais and 18 (26%) of the Australians, and these were shown by Western blotting to react with the Scl-70 (topoisomerase I)-associated polypeptides. Differences in the frequencies of the ANA specificities in the 2 races were consistent with differences in the clinical manifestations of scleroderma; all of the Thai patients, in contrast to 15% of the Australian patients, had diffuse scleroderma with widespread skin involvement. This suggest that environmental or genetic factors may influence the expression of scleroderma.

Adolescent↗

PubMed1980

Detection of sclerosis-inducing glycosaminoglycan in the skin of an amine-induced experimental skin sclerosis.

The presence of sclerosis-inducing glycosaminoglycan in the skin was confirmed in an experimental skin sclerosis induced by a chemical compound. An experimental skin sclerosis was first produced in the mouse with bis(4-amino-3-methylcyclohexyl)methane. Out of glycosaminoglycans isolated from the slightly changed skin of this experimental skin sclerosis, the one having a heparan sulfate-like structure was able to again induce sclerotic skin changes in another mouse. The chemical composition of this sclerosis-inducing glycosaminoglycan was somewhat similar to that of the scleroderma-inducing glycosaminoglycan isolated previously from the urine of patients with systemic scleroderma.

Animals↗

PubMed1995

Systemic sclerosis sine scleroderma: an unusual presentation in scleroderma renal crisis.

Renal involvement in systemic sclerosis (SSc) has a negative influence on prognosis. Cases of SSc sine scleroderma have been reported in which organ failure occurred but was not accompanied by cutaneous damage, which in some instances did develop later. We describe a patient who, after 6 months of symmetric polyarthritis, developed rapid progressive renal failure without skin changes. A diagnosis of scleroderma renal crisis, confirmed histologically, was made. Anti-RNAP III antibodies were positive. The patient developed typical scleroderma skin changes after renal failure. Despite treatment, SSc advanced to fatal endstage renal disease.

Antibodies↗

PubMed2005

Heart involvement and systemic sclerosis.

Scleroderma heart involvement (SHI) is often manifest, and virtually always present when accurately searched and holds a significant prognostic value. Myocardial involvement by patchy fibrosis (secondary to both repeated ischaemia and immunoinflammatory damage) leads to ventricular diastolic dysfunction, whereas right ventricle overload and failure may complicate pulmonary hypertension. Left ventricular systolic dysfunction is present in a minority of patients, namely those presenting atherosclerotic coronary artery disease and/or arterial hypertension, sometimes triggered by sclerodermic renal involvement. Dysrhythmias and conduction disturbances are considered an hallmark of SHI, facilitated by autonomic dysfunction. SHI is frequently linked to parenchimal and/or vascular lung disease; they determine symptom occurrence, particularly dyspnoea, fatigue, palpitations and chest pain when pericardium is affected. Accurate cardiologic baseline screening and subsequent follow-up are mandatory in all patients, initially consisting in some noninvasive diagnostic procedures: visit, electrocardiogram (EKG), chest X-ray, Doppler-echocardiography. When needed, these examinations should be integrated by EKG Holter-monitoring, cardiopulmonary stress tests, cardiac magnetic resonance imaging, nuclear studies of myocardial function and perfusion, cardiac catheterization to better estimate pulmonary hypertension, and cardiac natriuretic hormone evaluation. Several vasodilator approaches (prostacycline or NO/endothelin) may counteract the microvascular dysfunction at peripheral and cardiopulmonary level, and fight the sequelae of pulmonary hypertension.

Fibrosis↗

PubMed2002

[A case of scleroderma with pancytopenia due to lack of trace elements].

A 66-year-old woman with systemic scleroderma developed pancytopenia (white blood cell 750/microliter, neutrophilic cell 201/microliter, red blood cell 166 x 10(4)/microliter, hemoglobin 5.3 g/dl, hematocrit 18.1%, platelet cell 8.2 x 10(4)/microliter) 7 months after the initiation of intravenous hyper-alimentation for chronic ileus. Serum copper and zinc levels were 3 and 46 micrograms/dl, respectively. Provision of trace elements led to increase blood cell counts as well as serum copper and zinc levels. She also developed watery diarrhea frequent times a day and hypoproteinemia during the lack of trace elements. Evidence of protein-losing gastroenteropathy was shown by gastrointestinal scintigraphy using 99mTc-human serum albumin half a year after provision of trace elements and it was not shown one and a half years after continuous provision of trace elements. As patients with scleroderma sometimes develop gastrointestinal problems and are needed intravenous nutrition of long duration, they should be paid attention to lack of trace elements that can be a cause of hematologic complications.

Aged↗

PubMed1982

Antinuclear antibodies as immunologic markers for a benign subset and different clinical characteristics of scleroderma.

Antinuclear antibody (ANA) test results were correlated with the clinical status of 56 patients with systemic scleroderma. Three groups were identified. (1) The speckled pattern represented a benign clinical subset. Acrosclerosis, Raynaud's phenomenon, calcinosis, and esophageal dysmotility characterized this group. None of these patients had pulmonary, renal, or cardiac disease. (2) Two patterns and ANA-negative test results were associated with a different incidence of certain clinical characteristics. The thready pattern was associated with pulmonary involvement. Diffuse skin involvement and Raynaud's phenomenon were found with the nucleolar pattern. Patients with ANA-negative test results had the most severe disease, including renal failure. (3) Two patterns were not associated with different clinical characteristics. These were the small speckle-like thready pattern and the homogeneous pattern. This study supports the theory that ANA patterns may be used as immunologic markers for different clinical characteristics of patients with scleroderma as they have already been used in lupus erythematosus.

Antibodies, Antinuclear↗

PubMed1984

[What can be expected of biological tests in scleroderma?].

Biological investigations are useful from three main view points in systemic scleroderma: diagnosis: the demonstration of antinuclear antibodies which are quite specific for these conditions: antinuclear anti-ECT (nRNP, Scl 70, KU, PM 1) and anticentromere antibodies; prognosis: the presence of some antibodies is associated with a more favourable outcome: anti-nRNP and Sharp's syndrome, anti-centromere and the CREST syndrome, anti-KU and syndromes overlapping with polymyositis; pathogenic: the study of abnormalities of T-lymphocyte function, immunogenetic (HLA grouping) studies, cytotoxic factors for vascular endothelium, mitogenic factors of fibroblasts and the "chromosome breaking" factor.

Antibodies, Antinuclear↗

PubMed1990

[Unusual manifestation of scleroderma of the trunk].

We present the case of an 81-year-old women with progressive systemic scleroderma. In addition to the typical manifestations of diffuse (truncal) scleroderma, including involvement of the esophagus, lungs and muscles, there were two unusual findings: large, non-sclerosing areas on the trunk simulating the disabling type of circumscribed scleroderma and high titers of anticentromere antibodies, while there were no anti-Scl-70 antibodies. The disease responded to treatment with griseofulvin.

Aged↗

PubMed1995

[Changes in the gastrointestinal system of children with inflammatory systemic connective tissue diseases].

Functional and morphological changes of the gastrointestinal system were assessed in patients suffering from juvenile chronic arthritis, juvenile systemic erythematosus and juvenile systemic scleroderma. The results of endoscopic investigation of the gastrointestinal tract showed inflammatory changes and cardiac and pylorus atony. Ultrasonography results suggested hepatic and pancreatic inflammatory changes, steatosis and/or amyloidosis. The above-mentioned changes were confirmed by morphological investigation (biopsy and/or autopsy). The results of the capacity tests performed in JCA (systemic form) patients revealed an impairment of liver detoxication function, and pancreas and bowel functional capacity as well. Additionally, intolerance against lactose, casein and alpha- and beta-lactoglobulin was found in most of the patients. Some symptoms of malnutrition were observed in all of them. Such factors as underlying disease severity, adverse drug effects, environmental factors (infections, nutrition) were taken into consideration as probable causes of the gastrointestinal system damage.

Adolescent↗