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Results for “Scleroderma, Diffuse”

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PubMed1992

Pulmonary function in systemic lupus erythematosus is related to distinct clinical, serologic, and nailfold capillary patterns.

PURPOSE: The purpose of this study was to investigate whether systemic lupus erythematosus (SLE) patients with interstitial lung disease represent a particular subset of patients characterized by the presence of clinical, serologic, and nailfold capillary patterns overlapping scleroderma. PATIENTS AND METHODS: In 57 consecutive patients with SLE, a standardized detailed history was obtained and a physical examination performed, directed at signs and symptoms of connective tissue diseases, in particular scleroderma. Additionally, pulmonary function testing, chest radiography, radionuclide transit studies of the esophagus, nailfold capillary microscopy, and detailed serologic studies directed at the antigenic specificities of antinuclear antibodies were performed. Patients were divided into three groups based on the results of pulmonary function testing, i.e., normal lung function, restriction, or isolated impairment of diffusion. Clinical, serologic, and nailfold capillary microscopic findings were compared among these three groups. RESULTS: Twenty patients had normal lung function, 19 had restrictive lung function loss, and 9 had an isolated impairment of the diffusing capacity (T1,CO). Patients with obstructive lung disease (n = 9) were excluded from analysis. Sclerodermatous changes of the hands were associated with a restrictive lung function pattern. Interstitial changes on chest radiograph were associated with isolated impairment of T1,CO. Nailfold capillary abnormalities correlated with decreased T1,CO and Dm, the component of T1,CO representing the diffusing capacity of the alveolocapillary membrane. Antibodies to U1-RNA were associated with restrictive lung function and decreased T1,CO. CONCLUSION: We conclude that interstitial lung disease is present in a subset of SLE patients characterized by an increased prevalence of scleroderma traits and anti-(U1)RNA antibodies. Microvascular changes may contribute to the development of interstitial lung disease in SLE as well as in scleroderma.

Adult↗
PubMed1993

Labial capillary microscopy in systemic sclerosis.

OBJECTIVES: To investigate whether in vivo capillary microscopy of the lower lip mucosa can be used to assess microvascular disease in systemic sclerosis. METHODS: Thirteen patients with systemic sclerosis and 11 healthy control subjects were studied by conventional nailfold capillary microscopy and labial capillaroscopy. The following parameters were analysed: loop length; loop width (maximum distance between the arteriolar and venular limbs); loop density (number of capillaries/mm2); venular plexus visibility; megacapillaries; and the architectural arrangement of the capillary network. RESULTS: A typical 'scleroderma pattern' at the nailfold was observed in 12 of 13 (92%) patients with systemic sclerosis. Labial capillaroscopy showed a different morphological pattern of microangiopathy. A diffuse architectural derangement of the capillary network was the most striking abnormality in 12 (92%) patients. Labial capillaries in the patients with systemic sclerosis were shorter (mean (SD) loop length 133 (32.2) microns) than in healthy controls (211 (48.4) microns) and showed an increased loop width (41.7 (13.1) v 27.6 (5.5) microns in controls. The loop density was 10.5 (4.6) capillaries/mm2 in patients with systemic sclerosis and 9 (1.7) capillaries/mm2 in controls. Labial capillaroscopy in patients with systemic sclerosis did not provide definite evidence of enlarged capillaries or avascular areas, or both, even where such abnormalities were clearly evident at the nailfold. CONCLUSIONS: This study shows that labial capillary microscopy is a simple, non-invasive technique which allows a careful morphological assessment of the mucosal microcirculation. Labial capillaroscopy in patients with systemic sclerosis showed significant microvascular changes with respect to the controls. The results of labial and nailfold capillaroscopy are not superimposable, even if some common findings, such as architectural derangement, are present.

Adult↗
PubMed1990

Pulmonary diffusing capacity disturbances are related to nailfold capillary changes in patients with Raynaud's phenomenon with and without an underlying connective tissue disease.

PURPOSE: The aim of this study was to evaluate whether pulmonary microvascular damage is part of a more generalized involvement of the microvasculature in the spectrum of scleroderma (Scl)-like syndromes. PATIENTS AND METHODS: We studied four groups of patients, all with Raynaud's phenomenon (RP), distinguished by the extent and nature of their underlying connective tissue disease. Twenty-two patients had primary RP (pRP), another 22 patients had RP and an undifferentiated connective tissue disease (uCTD), 15 patients had Scl, and eight patients had the CREST syndrome (CREST). Pulmonary vascular damage in these groups was assessed by measuring the pulmonary diffusing capacity (T1,CO) and its components: the diffusing capacity of the alveolocapillary membrane (Dm) and the pulmonary capillary blood volume (Vc). Results were compared with morphologic abnormalities of the nailfold capillaries, as determined by nailfold capillary microscopy, and related to the presence of antinuclear antibodies. RESULTS: Vc was below normal in 38% and 43% of patients with pRP and uCTD, respectively (versus 52% in patients with Scl or CREST combined). In contrast, Dm was below normal in only 5% and 26% of patients with pRP and uCTD, respectively (versus 61% in patients with Scl or CREST combined). In patients with Scl and CREST, Dm was significantly decreased as compared with the former groups (p less than 0.01). Dm was also the pulmonary function parameter that correlated most strongly with both nailfold capillary abnormalities and the presence of antinuclear antibodies, whereas Vc did not. CONCLUSION: Early pulmonary involvement in Scl syndromes is functionally characterized by a lowered Dm, correlating with morphologic changes of the nailfold capillaries. Decreased Vc is probably a reflection of RP of the pulmonary vasculature.

Adult↗
PubMed2002

Increased transcriptional activities of transforming growth factor beta receptors in scleroderma fibroblasts.

OBJECTIVE: To investigate the molecular mechanism of the overexpression of transforming growth factor beta receptors (TGF(beta)Rs) in dermal fibroblasts from patients with systemic sclerosis (SSc). METHODS: Dermal fibroblasts from 7 patients with diffuse SSc of recent onset and from 7 healthy individuals were studied. The expression of TGF(beta)R type I (TGF(beta)RI), TGF(beta)RII, and type I collagen proteins in dermal fibroblasts was determined by immunoblotting. TGF(beta)RI, TGF(beta)RII, and alpha2(I) collagen messenger RNA (mRNA) were evaluated by Northern blot analysis. The transcriptional activities of the TGF(beta)RI and TGF(beta)RII genes were examined by luciferase assay. RESULTS: SSc fibroblasts expressed increased levels of TGF(beta)RI and TGF(beta)RII protein and mRNA, as well as increased levels of type I collagen protein and alpha2(I) collagen mRNA. Moreover, the half-lives of TGF(beta)RI and TGF(beta)RII mRNA in SSc fibroblasts did not change compared with those in control dermal fibroblasts. The promoter activities of the TGF(beta)RI and TGF(beta)RII genes were both significantly increased in SSc fibroblasts compared with those in control fibroblasts. Calphostin C, a specific inhibitor of protein kinase C (PKC), inhibited TGF(beta)RI promoter activity in SSc fibroblasts, and LY294002, an inhibitor of phosphoinositide 3-kinase (PI 3-kinase), inhibited TGF(beta)RII promoter activity in SSc fibroblasts. Moreover, calphostin C and LY294002 inhibited the up-regulation of TGF(beta)RI and TGF(beta)RII mRNA, respectively, in SSc fibroblasts. CONCLUSION: These results suggest that increased levels of TGF(beta)Rs in SSc fibroblasts play a role in excessive collagen production, and that up-regulation of TGF(beta)R expression might occur at the transcriptional levels. PKC and/or PI 3-kinase might contribute to the up-regulation of TGF(beta)R expression in SSc fibroblasts.

Activin Receptors, Type I↗
PubMed1995

Massive pericardial effusion in scleroderma: a review of five cases.

Medical records of five patients with scleroderma (SSc), each of whom had pericardial effusion with an estimated volume of more than 200 ml, were reviewed to study the clinical and immunological significance of massive pericardial effusion in SSc. Diffuse SSc (4/5), with a wide area of pigmentation (4/5), flexion contracture (4/5), oesophageal hypomotility (5/5), pulmonary fibrosis (4/5) and autoantibodies to topoisomerase I (3/5) were the common features in this group. High protein, lactate dehydrogenase and low white blood cell count were the characteristics of pericardial fluid. None of the patients had signs of acute pericarditis. Four of the five cases died within 9 months of the diagnosis of pericarditis; two with renal failure, one with cardiac tamponade and another with sudden death. The pericarditis in diffuse SSc, especially in cases with anti-topoisomerase I, may be characterized by a chronic form of pericarditis with poor prognosis, often complicated by renal failure.

Adult↗
PubMed2003

Emergencies in rheumatology.

Rheumatological conditions can sometimes present as emergencies. These can occur due to the disease process or may be iatrogenic. Some of the important articular emergencies are septic arthritis, acute polyarthritis and atlanto-axial dislocation. Classical polyarteritis nodosa may present with massive gastro-intestinal bleeding, intestinal perforation or acute pancreatitis. Adult respiratory distress syndrome, bilateral pneumonitis and diffuse alveolar haemorrhage due to systemic lupus erythematosus or systemic necrotising vasculitis and ventilatory failure due to polymyositis are some of the respiratory emergencies. Scleroderma is well known to cause renal crisis which can be fatal if not diagnosed and managed promptly. Microscopic polyangiitis and Wegener's granulomatosis may cause rapidly progressive renal failure. Cerebrovascular accident, cortical vein thrombosis, seizures and acute psychosis are important neurological complications of rheumatic disease. Cardiac emergencies include tamponade, acute myocarditis and acute myocardial infarction. Vision can be threatened in Behcet's disease, temporal arteritis and seronegative spondylarthritis. Catastrophic antiphospholipid syndrome is a devastating emergency. The management of above emergencies includes critical care, immunosuppression when indicated and withdrawal of the offending drug. Anticoagulants have to be used in the management of antiphospholipid syndrome. A good understanding of these conditions is of paramount importance for proper management.

Cardiovascular Diseases↗
PubMed1997

Recurrent acute scleroderma renal crisis complicated by thrombotic thrombocytopenic purpura.

Acute renal crisis as an early manifestation of scleroderma is underemphasized, and its recurrence after initial successful therapy is rare. We describe a 32-year-old woman who presented with scleroderma renal crisis. A second episode of apparent renal crisis, however, was complicated by thrombotic thrombocytopenic purpura, which led to pancreatitis, a large cerebral infarction, and fatal outcome despite intensive therapy. This case illustrates the complexity and severity of diffuse systemic sclerosis presenting with multiple, major organ complications.

Acute Disease↗
PubMed1994

[Pulmonary involvement in scleroderma assessed with high-resolution computerized tomography and functional tests].

This study was aimed at investigating and analyzing lung involvement in scleroderma patients with different imaging methods, toward a rational diagnostic approach. Twenty-four patients with systemic sclerosis were examined with pulmonary function tests (PFT), spirometry and diffusing capacity for carbon monoxide (DLCO), chest radiography and high-resolution Computed Tomography (HRCT). Abnormal findings were present in 42% of cases on X-ray films and in 71% of cases on HRCT images. PFT was abnormal in the spirometries of 42% of cases and in DLCO tests in 50% of cases. The most common findings at HRCT were the small reticular and the ground-glass patterns. HRCT emerged as the most effective method to evaluate lung involvement in systemic sclerosis. In our series, HRCT allowed possibly curable lung lesions to be differentiated from incurable ones. However, HRCT is suggested in the patients with impaired pulmonary function to allow treatment choice; on the contrary, in the patients with no functional impairment, HRCT adds little information to clinical findings, showing only limited focal lesions.

Adult↗
PubMed1999

Polyneuropathy as initial manifestation of systemic sclerosis (scleroderma).

We report the first case of a young female patient who developed a sensory-motor polyneuropathy, without any skin or internal involvement characteristic of SSc, but with a serological positivity of antitopoisomerase I antibodies. After 4 years she developed a rapid skin tightening with lung involvement, in a full blown picture of the diffuse subset of SSc. The case suggests that the peripheral nervous system deserves more attention, in particular in the earliest phase of SSc.

Adult↗
PubMed1994

Internal involvement in localized scleroderma.

We studied 76 consecutive patients with localized scleroderma (morphea with or without linear scleroderma) and analyzed the frequency, prognosis, and predictors of internal involvement in a subset of 53 patients systematically investigated for the presence of such involvement. Internal involvement was found by systematic examination in 16 patients. Only 2 of them, including 1 patient who developed systemic scleroderma, had symptomatic and severe visceral disease. The other 14 patients had asymptomatic and minor abnormalities consisting of abnormal lower sphincter pressure, and/or peristaltic failure in the esophagus and slightly impaired carbon monoxide diffusion in the lung. Frequent seroimmunologic abnormalities had no predictive value. Three parameters were found to be associated with internal involvement: male gender (p < 0.05), increasing number of plaque-like lesions (p = 0.02) and hypergamma-globulinemia at 1st examination (p < 0.005). Mild esophageal and pulmonary involvement are not rare in morphea but are usually silent. In our series, after a median follow-up of 48 months, such involvement did not impair the prognosis. The mildness of these visceral abnormalities suggests that they do not justify routine detection in asymptomatic patients. Morphea and systemic scleroderma behave as 2 different diseases.

Female↗
PubMed1977

Pulmonary function in scleroderma.

Pulmonary function tests were performed in 45 patients with scleroderma. Thirteen patients (29%) were found to have restrictive disease, 12 patients (27%) were found to have obstructive disease, and 19 patients (42%) had small airway disease (SAD). Smoking did not seem to be a factor underlying either obstructive or small airway disease in these patients. A low diffusing capacity was most common in patients with restrictive disease and rarely the only abnormality in pulmonary function. SAD was usually found in patients who had normal chest radiographs and no pulmonary symptoms and was often the only abnormality. SAD is therefore an early and sensitive indicator of pulmonary involvement in scleroderma.

Adult↗
PubMed2003

[Case of scleroderma with congestive heart failure in which myocardial injury was detected by scintigraphy].

A 38-year-old woman with systemic sclerosis was admitted to our hospital because of dyspnea and finger ulcer. Chest X-p showed cardiomegaly and pleural effusion. Echocardiogram revealed diffuse hypokinesis of the left ventricle (ejection fraction 32%). Thallium scintigraphy demonstrated patchy perfusion defects. She was diagnosed as having congestive heart failure due to myocardial fibrosis, and was treated successfully with diuretics, cardiotonics, and beta-blocker. Scintigraphy may be useful to detect an early cardiac involvement in patients with systemic sclerosis, and intense pharmacological treatment might be started even before the patient develops symptoms.

Adrenergic beta-Antagonists↗
PubMed2005

Interleukin-10 genotypes are associated with systemic sclerosis and influence disease-associated autoimmune responses.

Systemic sclerosis (SSc; scleroderma) is a connective tissue disease, characterized by fibrotic, immunological, and vascular abnormalities. Interleukin-10 (IL-10) is an anti-inflammatory cytokine that modulates collagen production and B-cell survival. To determine if certain IL-10 genotypes are risk factors for the development of SSc and influence disease-associated autoimmune responses, 248 Caucasian and 264 Japanese SSc patients and controls were genotyped for three loci: -3575, -2849, and -2763. Sera from patients were characterized for SSc-associated autoantibodies. In Caucasians, at -3575 and -2763, the frequency of AA homozygotes was higher in patients as compared with controls (P=0.0005; P=0.002). In Japanese subjects, the frequency of AC heterozygotes at -2763 was higher, and that of CC homozygotes lower, in patients with diffuse SSc as compared to controls (P=0.04). Particular IL-10 genotypes were associated with SSc-related autoantibodies. These results suggest that IL-10 genotypes contribute to the etiology of scleroderma.

Autoimmunity↗
PubMed2002

Increased circulating concentrations of the counteradhesive proteins SPARC and thrombospondin-1 in systemic sclerosis (scleroderma). Relationship to platelet and endothelial cell activation.

OBJECTIVE: To determine whether circulating concentrations of the counteradhesive proteins SPARC (secreted protein acidic and rich in cysteine) and thrombospondin-1 (TSP-1) are elevated in scleroderma (systemic sclerosis, SSc). The relationship of these counteradhesive proteins to measures of platelet and endothelial cell activation was examined. METHODS: Plasma from 45 patients with SSc (26 limited form, 19 diffuse) and 22 age and sex matched controls was assayed for SPARC, TSP-1, beta-thromboglobulin (betaTG), and platelet factor 4 (PF4), 2 distinct platelet a-granule products, and soluble E-selectin, a marker of endothelial cell activation. RESULTS: The mean (+/- SE) SPARC concentration was greater in patients with limited SSc (124.0 +/- 9.6 ng/ml) compared to controls (66.8 +/- 8.0 ng/ml) (p = 0.0005), whereas in patients with diffuse SSc (74.1 +/- 7.9 ng/ml) it was not. Elevated SPARC concentrations in the limited SSc group could not be ascribed to either platelet or endothelial cell activation. TSP-1 concentrations were also increased in SSc patients (n = 29) compared to controls (n = 11) (2.98 +/- 0.12 vs 2.4 +/- 0.21 log transformed ng/ml; p < 0.02). Unlike SPARC, TSP-1 concentrations correlated with both betaTG (r = 0.57, p = 0.0014) and PF4 (r = 0.41, p = 0.026) levels, indicating that increased TSP-1 could, in part, be explained through elevated platelet a-granule release in SSc patients. Plasma levels of betaTG, PF4, and E-selectin were each similarly elevated (p < 0.003) in patients with both limited and diffuse SSc compared to controls. CONCLUSION: That circulating SPARC and TSP-1 are elevated in patients with SSc raises the possibility that counteradhesive proteins, which regulate vascular organization and remodeling, might contribute to the pathogenesis of SSc vasculopathy.

Adult↗
PubMed2005

Constitutively phosphorylated Smad3 interacts with Sp1 and p300 in scleroderma fibroblasts.

OBJECTIVE: To elucidate the role of transforming growth factor-beta (TGF-beta)/Smad signalling in the increased expression of the collagen gene in systemic sclerosis (SSc) fibroblasts. METHODS: Dermal fibroblasts from seven patients with diffuse SSc of recent onset and from seven healthy individuals were studied. The expression levels of Smad2, Smad3 and Smad4 proteins were determined by immunoblotting. Smad3 phosphorylation and the interaction of Smad3 with Sp1 or p300 were analysed using immunoprecipitation. The effects of overexpression of Smad proteins or Sp1 on the human alpha2(I) collagen gene transcription were investigated with chloramphenicol acetyltransferase (CAT) assays using the -772 COL1A2/CAT construct. RESULTS: Constitutive increased Smad3 phosphorylation was detected in SSc fibroblasts compared with normal fibroblasts. Increased interaction of Smad3 with Sp1 as well as p300 was also detected in SSc fibroblasts. The overexpression of Smad3 caused an increase of up to 5-fold in COL1A2 promoter activity in normal fibroblasts, while Smad3 caused a small increase in COL1A2 promoter activity in SSc fibroblasts. However, neither Smad2 nor Smad4 caused significant effects in COL1A2 promoter activity in normal fibroblasts or SSc fibroblasts. The overexpression of Sp1 caused further increase in COL1A2 promoter activity stimulated by TGF-beta in normal fibroblasts, but did not change COL1A2 promoter activity in the presence of TGF-beta in SSc fibroblasts. The combined overexpression of Smad3 and Sp1 significantly enhanced TGF-beta response in normal fibroblasts, but less markedly in SSc fibroblasts. CONCLUSIONS: These results suggested that SSc fibroblasts are less sensitive to exogenous TGF-beta stimulation because they are already activated by the autocrine TGF-beta loop.

Cells, Cultured↗