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Results for “Scleroderma, Diffuse”

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At least 703 records · Page 39Linked to original sources
PubMed2001

Lack of association of a functionally relevant single nucleotide polymorphism of matrix metalloproteinase-1 promoter with systemic sclerosis (scleroderma).

Matrix metalloproteinase 1 (MMP-1) is necessary for degradation of interstitial collagen types I, II, and III, which are the major constituents of the extracellular matrix (ECM). Increased expression of MMP-1 has been correlated with invasiveness of certain malignancies and cartilage degradation in rheumatoid arthritis. Increased transcriptional activity of MMP-1 has been reported with a single nucleotide polymorphism (SNP) of the MMP-1 promoter. Systemic sclerosis (SSc) is characterized by increased accumulation and turnover of collagen and other components of ECM. Previous studies have reported increased expression of MMP-1 transcripts in SSc fibroblasts. Therefore, we sought to determine if SSc patients with early disease (< or =5 years) from a multi-ethnic cohort were more or less likely than ethnically-matched normal controls to have an increased frequency of the high promoter activity MMP-1 genotype and whether MMP-1 promoter genotypes correlated with any of the major clinical manifestations of SSc. The results show that the frequency of the high activity promoter genotype in either the heterozygous or homozygous state did not differ significantly between SSc patients and ethnically-matched controls, or between SSc patients with either diffuse or limited scleroderma. Furthermore, MMP-1 promoter genotypes did not significantly correlate with any of the major clinical manifestations of SSc.

Humans↗
PubMed1993

Chest CT in patients with scleroderma: prevalence of asymptomatic esophageal dilatation and mediastinal lymphadenopathy.

OBJECTIVE: The high-resolution CT findings of chronic diffuse interstitial lung disease associated with scleroderma have been reported previously. This study determined the prevalence of esophageal dilatation and mediastinal adenopathy on high-resolution CT scans in patients with this disease. MATERIALS AND METHODS: We retrospectively reviewed the high-resolution CT scans of 25 patients with scleroderma who had diffuse interstitial lung disease. Esophageal dilatation was diagnosed if the esophagus below the aortic arch had a single, large, nonloculated collection of intraluminal air on four or more consecutive axial images and if the luminal diameter of such an air-filled esophagus exceeded 10 mm in the coronal plane. The presence of fluid or an air-fluid level was also considered abnormal. For mediastinal adenopathy, we used the American Thoracic Society lymph node mapping scheme and the size criteria described previously. RESULTS: Asymptomatic esophageal dilatation was detected in 20 patients (80%) and mediastinal adenopathy was present in 15 (60%). CONCLUSION: Our results suggest that CT is useful in the detection of mediastinal adenopathy and asymptomatic esophageal involvement in patients with scleroderma. These findings can be used to narrow the differential diagnosis in patients in whom CT shows diffuse interstitial lung disease. Furthermore, the early detection of esophageal involvement in these patients shows the need for treatment to forestall the complications of esophageal dysmotility and accompanying chronic gastroesophageal reflux.

Adult↗
PubMed1986

Radionuclide esophageal transit. A screening test for esophageal disorders.

Radionuclide esophageal transit (RET) is a noninvasive method of studying esophageal function. The purpose of this study was to evaluate RET as a screening test for motility disorders in symptomatic patients. Esophageal manometry and RET were performed in 16 volunteers and in 34 patients who were referred for motility evaluation. Each RET study consisted of two swallows of labeled water with the patient in the supine position under a gamma camera. Six patients had achalasia, two had scleroderma, two had diffuse esophageal spasms, and five had a nonspecific motor disorder. In each case the RET time was prolonged (greater than 15 s). Ten patients had reflux esophagitis; two of these had both abnormal manometry results and prolonged RET times. There were nine patients with upper gastrointestinal tract symptoms but normal manometry results and the RET test was positive in two patients. There were no false-negative RET results. The agreement between the RET and manometry results in this series was 96% (48/50). This preliminary experience suggests that RET is as sensitive as manometry for identifying motility disorders.

Adult↗
PubMed1998

A case study and national database report of progressive systemic sclerosis and associated conditions.

We report the case of a 34-year-old white woman with a history of progressive systemic scleroderma (PSS) and diffuse alveolar hemorrhage (DAH) that may be either a rare complication of PSS or induced by D-penicillamine. The DAH progressed to hemoptysis and led to intubation for airway protection. The patient progressed to acute renal failure. Her chest x-ray revealed diffuse bilateral infiltrates. She developed pulmonary fibrosis with secondary pulmonary hypertension. She experienced a brief period of improvement of her respiratory status after steroid treatment. We also report a database of 21,442 decedents with PSS over a 15-year period from 1979 to 1994. Our report demonstrates that of over 21,000 decedents, only 0.2% had pulmonary hemorrhage or hemoptysis or both listed as a cause of death. The data also demonstrate that PSS was the underlying cause of death more frequently in younger people. Age-adjusted mortality rates were higher for blacks than for whites and for women than for men.

Acute Kidney Injury↗
PubMed2003

Keloidal scleroderma.

Progressive systemic sclerosis (PSS) can involve the skin diffusely or in a limited way. Rarely cutaneous involvement can assume a hypertrophic form, described in the literature as keloidal scleroderma. The authors describe a PSS patient who presented cutaneous manifestations compatible with the diagnosis of this clinical situation. The clinical features, pathogenic mechanism and therapeutic approach are discussed and a broad review of the literature is given.

Adult↗
PubMed2000

Avascular areas on nailfold capillary microscopy of patients with Wegener's granulomatosis.

Over the past 25 years, nailfold capillary microscopy (NCM) has gained diagnostic value in the field of rheumatology based on descriptive data from patients with distinct connective tissue diseases (CTD). We prospectively analysed NCM findings from 116 patients selected for NCM by one of the following indications: (1) suspected diffuse or limited scleroderma or dermatomyositis, (2) evaluation of Raynaud's phenomenon (RP) or (3) suspected small-vessel vasculitis. Nailfold haemorrhages, and enlarged and tortuous nailfold capillaries ('lupus pattern') were found to comparable degrees in patients with CTD and primary RP. Only giant loops, bushy capillaries and avascular areas indicated CTD; 92% of patients with Wegener's granulomatosis (WG) had avascular areas. From all nailfold capillary abnormalities, only bushy capillaries, giant loops and avascular areas support a suspected CTD. A lupus-like pattern is not diagnostic. Avascular areas are a typical abnormality in patients with WG, for which NCM findings have not been described previously.

Adult↗
PubMed2004

The rationale behind autologous autoimmune hematopoietic stem cell transplant conditioning regimens: concerns over the use of total-body irradiation in systemic sclerosis.

Hematopoietic stem cell transplantation (HSCT) is becoming an increasingly recognized indication for treatment of autoimmune diseases and severe immune-mediated disorders. However, multicenter registry data have demonstrated higher than anticipated early toxicity, approximately 10% for autoimmune diseases in general, and 20-27% for diffuse systemic sclerosis (scleroderma). If uncorrected, this high treatment-related mortality will hinder development of stem cell therapy for immune-mediated diseases. In order to develop safer regimens, we address some pitfalls and concepts involved in design and selection of conditioning regimens for autoimmune diseases in general, and because it is associated with the highest regimen-related toxicity, scleroderma in specific.

Autoimmune Diseases↗
PubMedDate not supplied

Dysphagia in aging.

Dysphagia is a common problem in older patients and is becoming a larger health care problem as the populations of the United States and other developed countries rapidly age. Changes in physiology with aging are seen in the upper esophageal sphincter and pharyngeal region in both symptomatic and asymptomatic older individuals. Age related changes in the esophageal body and lower esophageal sphincter are more difficult to identify, while esophageal sensation certainly is blunted with age. Stroke, Parkinson's disease, amyotrophic lateral sclerosis, Zenker's diverticula, and several other motility and structural disorders may cause oropharyngeal dysphagia in an older patient. Esophageal dysphagia can also be caused by both disorders of motility (achalasia, diffuse esophageal spasm, scleroderma and others) and structure (malignancy, strictures, rings, external compression, and others). Many of these disorders have an increased prevalence in older patients and should be sought with an appropriate diagnostic evaluation in older patients. The treatment of dysphagia in older patients is similar to that in younger patients, but more invasive therapies such as surgery may not be possible in some older patients making less aggressive medical and endoscopic therapy more attractive.

Aged↗
PubMedDate not supplied

POEMS syndrome: a case report.

A case of POEMS syndrome in a 43-year-old male with polyneuropathy, osteolytic lesion of the basin due to solitary IgA-lambda plasmacytoma, cutaneous scleroderma-like changes, diffuse lymphadenopathy and hepatosplenomegaly is described. Liver biopsy showed a regenerative process of the parenchyma without laboratory and histologic evidence of necrosis. A peculiar finding was the onset of a right hemiparesis in the absence of signs of vascular disease or other predisposing factors. The possible links between the peculiar elements of the POEMS syndrome are briefly analyzed and discussed.

Bone Neoplasms↗
PubMed1989

Isolated pulmonary hypertension in the grandchild of a kindred with scleroderma (systemic sclerosis): "neonatal scleroderma"?

We report a small kindred in which the father and daughter with positive antinuclear antibodies (ANA) (proband) had diffuse cutaneous and visceral scleroderma (systemic sclerosis, SSc), antitopoisomerase autoantibodies and shared the HLA-A23 C- B- DR5 DRw52 DQw3 haplotype. The ANA- granddaughter (daughter of the proband) was noted to have severe isolated pulmonary hypertension within the first 6 months of life, and had the other maternal HLA-A1 Cw8 B14 DR1 DQw1 haplotype, which included a B1, B2 duplication of the C4B allele. All 3 members shared DRw52. The possibility that neonatal pulmonary hypertension represents an isolated autoimmune disease or a hitherto undescribed neonatal syndrome is proposed and the immunogenetic autoantibody implications are discussed.

Antibodies, Antinuclear↗
PubMed2006

Antibodies to fibroblasts in idiopathic and scleroderma-associated pulmonary hypertension.

The aim of the present study was to investigate the presence of anti-fibroblast antibodies in patients with idiopathic or scleroderma-associated pulmonary arterial hypertension (PAH) and healthy controls. PAH was documented by right-heart catheterisation (mean pulmonary artery pressure at rest >25 mmHg). Serum immunoglobulin (Ig)G and IgM reactivities of patients with idiopathic PAH (n = 35), scleroderma-associated PAH (n = 10), diffuse (n = 10) or limited cutaneous (n = 10) scleroderma without PAH and age- and sex-matched healthy individuals (n = 65) were analysed by cell-based ELISA and immunoblotting on normal human fibroblasts. As assessed by ELISA, 14 out of 35 (40%) patients with idiopathic PAH and three out of 10 (30%) patients with scleroderma-associated PAH expressed anti-fibroblast IgG antibodies. IgG from all individuals bound to one major 40-kDa protein band. IgG from patients with idiopathic PAH bound to two 25- and 60-kDa bands with a higher intensity than IgG from other individuals. In conclusion, immunoglobulin G anti-fibroblast antibodies are present in the serum of patients with pulmonary arterial hypertension. Immunoglobulin G from patients with idiopathic pulmonary arterial hypertension or scleroderma-associated pulmonary arterial hypertension express distinct reactivity profiles with fibroblasts antigens, suggesting distinct target antigens.

Adult↗
PubMedDate not supplied

Open label trial of tamoxifen in scleroderma.

BACKGROUND: Previous reports have suggested that treatment with the selective estrogen antagonist tamoxifen may be effective in diminishing primary and secondary Raynaud's vasospasm, including cases occurring in the setting of scleroderma. Tamoxifen treatment has also been associated with improvement of retroperitoneal fibrosis and desmoid tumors, conditions also associated with abnormal fibroblast proliferation. Tamoxifen increases production of the immunosuppressive cytokine TGF beta which modulates fibroblast activity. The potential effect of tamoxifen on vascular reactivity and fibrotic lesions raised questions about its utility as a therapeutic agent in scleroderma. OBJECTIVE: To determine the utility of tamoxifen therapy in scleroderma. METHODS: Open label preliminary, prospective, proof of concept study of tamoxifen. RESULTS: Fifteen patients (3 male, 12 female) with scleroderma were enrolled (10 diffuse disease, 5 CREST). Mean age was 55 (34-75) years. Mean duration of scleroderma was 9.3 (1-25) years. Two patients were excluded. For 13 patients, mean duration of treatment was 7 (1.5-32) months. Two of 13 patients treated with tamoxifen experienced transient improvement. They did not appear to have clinical features that identified them as a unique subset. Both patients subsequently relapsed, in one case 12 months, and in the other 24 months after treatment. CONCLUSION: Based on these results, we would not recommend tamoxifen for further large scale studies in scleroderma.

Aged↗
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↗
PubMed1979

Eosinophilic fasciitis: an early variant of scleroderma.

Eosinophilic fasciitis, originally reported as a syndrome distinct from scleroderma, appears now to be an early inflammatory variant of scleroderma. No less than one half of the cases reported as eosinophilic fasciitis have convincing features of scleroderma, including Raynaud's phenomenon, esophageal dysmotility, restrictive lung disease, diffuse hyperpigmentation, synovitis, flexion contractures, dermal sclerosis, colonic diverticula, scleroderma kidney, positive latex fixation test, and the presence of serum antinuclear antibodies (ANA). Clinical presentations of scleroderma range from isolated acrosclerosis to rapidly progressive systemic sclerosis. As clinical experience and long-term follow-up data on eosinophilic fasciitis accumulate, it appears that the syndrome may well represent another variant in the scleroderma spectrum. Reported here is a case which presented clinically and histologically as eosinophilic fasciitis, but which progressed over 3 years to diffuse, histologically confirmed scleroderma.

Eosinophils↗
PubMed1992

Pulmonary manifestations of scleroderma.

Scleroderma is a severe systemic collagen vascular disease of unknown cause characterized by marked vascular and connective tissue abnormalities. The lungs are commonly involved in scleroderma, ranking only behind the skin, the peripheral vasculature, and the esophagus in frequency of organ involvement. Respiratory symptoms are, in a very few cases, the presenting manifestation of the disease. Abnormalities of pulmonary function in affected patients include a restrictive ventilatory defect, air flow obstruction, and a depressed diffusing capacity for carbon monoxide, which may be an isolated early finding. Interstitial lung disease and honeycombed lung are the most common pulmonary parenchymal abnormalities seen on chest radiographs. Enlargement of the cardiac silhouette and pulmonary artery due to scleroderma-induced pulmonary vascular disease is also noted. High-resolution computed tomography (HRCT) apparently is a sensitive, potentially useful technique for detecting occult interstitial lung disease in patients with scleroderma. Bronchoalveolar lavage usually shows an increase in total cell count and in the percentage of granulocytes; occasionally, there is a predominantly mononuclear (lymphocytic) cell alveolitis. Premortem and postmortem studies reveal two predominant lung lesions: (1) interstitial lung disease and (2) pulmonary vascular disease. Pulmonary vascular disease may occur in the absence of interstitial lung disease, particularly in patients with limited, as opposed to diffuse, scleroderma. The overall mortality rate in scleroderma is 50% at 7 years, and pulmonary complications are the major cause of death. No prospective, well-controlled studies have established that treatment alters the natural course of pulmonary disease in patients with scleroderma. Both D-penicillamine and cyclophosphamide have shown promise for treating patients with interstitial lung disease, and nifedipine may be useful for treating patients with early pulmonary vascular disease.

Humans↗
PubMed1989

Treatment of systemic sclerosis.

Proper classification of patients into diffuse cutaneous and limited cutaneous subsets and the anticipation of complications are the keys to the management of individuals with systemic sclerosis (scleroderma). Patients with early diffuse disease and rapidly progressive skin thickening are at highest risk to develop serious internal organ involvement (intestine, lung, heart, kidney) and should be considered for disease modifying therapy. The targets of the disease and sites of possible intervention are vascular endothelium (vasoprotection agents), mononuclear cell subsets (immunosuppressive agents), and fibroblasts (colchicine, D-penicillamine). A number of new therapeutic agents with sound scientific rationale are undergoing therapy trials. Much can be done to improve the lifestyle of the scleroderma sufferer. The most dramatic recent development is the ability to reverse kidney involvement with prompt use of angiotensin converting enzyme inhibitors and modern methods of renal dialysis and transplantation. Scleroderma is not a hopeless disease.

Humans↗
PubMed1991

Treatment of systemic sclerosis.

Proper classification of patients into diffuse cutaneous and limited cutaneous subsets and the anticipation of complications are the keys to the management of subjects with systemic sclerosis (scleroderma). Patients with early diffuse disease and rapidly progressive skin thickening are at highest risk of developing serious disease of the internal organs (intestine, lung, heart, kidney) and should be considered for disease modifying treatment. The targets of the disease and sites of possible intervention are vascular endothelium (vasoprotective agents), mononuclear cell subsets (immunosuppressive agents), and fibroblasts (colchicine, D-penicillamine). A number of new agents with sound scientific rationale are currently undergoing therapeutic trials. Much can be done to improve the lifestyle of those with scleroderma. The most dramatic recent development is the ability to reverse kidney disease by the prompt use of angiotensin converting enzyme inhibitors and modern methods of renal dialysis and transplantation. Scleroderma is not a hopeless disease.

Colchicine↗