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Results for “Scleroderma, Systemic”

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PubMed1994

Familial scleroderma--evidence for environmental versus genetic trigger.

Families with more than one case of scleroderma are unusual. Four families each with two members (in one case monozygotic twins) with scleroderma (systemic sclerosis, SSc) were identified. Clinical, immunogenetic and autoantibody studies were carried out. Multicase SSc families cited in the literature were reviewed. Each family pair shared cutaneous subset of disease severity, and SSc-associated autoantibody. HLA typing showed two pairs shared an HLA-DR allele associated with scleroderma (DR3 or DR5), while one also had alleles reported in association with their SSc-specific autoantibody. Review of dates and ages of onset suggested that the timing of onset of scleroderma is more likely to have an environmental trigger than to be encoded genetically.

Adult↗

PubMed2002

Treatment of scleroderma skin ulcers using becaplermin gel and hydrocolloid membrane.

Skin ulcers can be very painful and detrimental in patients with systemic sclerosis, or systemic scleroderma. A brief review of scleroderma skin ulcers is presented, as well as a case study that demonstrates the effectiveness of becaplermin gel supplemented by oral immunosuppressive agents in the treatment of ulcers resulting from systemic sclerosis. The time to healing (approximately 3 months) was comparable to that associated with the oral agents and surgical interventions specifically designed to help heal scleroderma ulcers. Except for incisional biopsy, no surgical procedures were performed.

Bandages↗

PubMed1984

Interstitial lung disease in scleroderma. Analysis by bronchoalveolar lavage.

Interstitial pulmonary fibrosis is a common feature of scleroderma (systemic sclerosis) which may result in impairment of pulmonary function and may be a major determinant of morbidity and mortality. Clinicopathologic observations suggest that interstitial and alveolar inflammation may appear prior to fibrosis. Using the bronchoalveolar lavage (BAL) technique, we have characterized the nature of the inflammatory process in the lower respiratory tracts of 19 non-smoking scleroderma patients. Eleven of 19 patients (58%) had increased percentages of neutrophils and/or eosinophils in BAL fluid. Five of 10 patients (50%) had elevations of IgG in BAL fluid. The presence of neutrophils was associated with a decreased lung diffusing capacity for carbon monoxide (P less than 0.05) and with more advanced radiographic features of interstitial fibrosis in patients with disease of more than 1 year's duration. This study suggests that scleroderma lung involvement may be characterized by an inflammatory alveolitis and that the presence of such inflammation may relate to the severity of the pulmonary disease.

Adult↗

PubMed1996

[Is mixed connective tissue disease a distinct rheumatic disease].

Mixed connective tissue disease (MCTD) as a distinct clinical entity is still controversial. To address the issue, the authors observed the evolution of 50 patients diagnosed as MCTD at our clinic, evaluated the reliability of three different diagnostic criteria proposed by Sharp, Alarcon-Segovia and Kasukawa respectively and performed HLA-A, -B and -DR antigen typing in 38 of the patients. The results showed that: (1) 13 (26.9%) of the 50 MCTD patients subsequently developed other connective tissue disease (OCTD) including 7 systemic lupus erythematosus (SLE), and 6 progressive systemic scleroderma (PSS). (2) among 23 of the MCTD patients fulfilling Sharp's criteria, 1 (4.3%) developed PSS, but among 23 of the patients fulfilling Kasukawa's, not Sharp's, 7 (30.4%) developed OCTD and among 27 of the patients fulfilling Alarcon-Segovia's, not Sharp's, 12 (44.4%) developed OCTD. (3) in the frequencies of DR, and DR5, there were significant differences between patients fulfilling Sharp's (60.9%, 56.5%) and the normal controls (24.3%, P < 0.005, RR = 4.7 and 21.4%, P < 0.005, RR = 4.6%), but no significant differences between the patients not fulfilling Sharp's and normal controls (P > 0.05). We concluded that: (1) MCTD is a distinct rheumatic disease. (2) Sharp's criteria is the most reliable for diagnosis of MCTD.

Adolescent↗

PubMed1990

[Acquired paraneoplastic hypertrichosis lanuginosa associated with scleroderma].

Acquired hypertrichosis lanuginosa is universally recognized as an individual disease and seldom reported as a genuine paraneoplastic manifestation. We report the case of a 30-year old woman with acquired hypertrichosis lanuginosa. Due to the finding of a cervical lymph node metastasis, she was investigated for an internal neoplasm, but the original tumour could not be found by the usual methods. A bronchogenic carcinoma was discovered at autopsy. Beside hypertrichosis, this patient had other disorders not described in the literature as associated with that disease, viz.: progressive systemic scleroderma, fissured and hyperpigmented tongue, thrombocytopenia, galactorrhoea, axillary and pubic alopecia and overcurvature of toe nails. A review of similar cases in the literature provided clinical arguments in favour of the hormonal origin of this paraneoplastic hypertrichosis.

Adult↗

PubMed2006

Antineutrophil cytoplasmic antibody-positive crescentic glomerulonephritis in scleroderma--a different kind of renal crisis.

Renal disease remains a major source of morbidity and mortality in patients with scleroderma (systemic sclerosis, SSc). We describe the clinical course of 3 patients with diffuse cutaneous SSc presenting with renal disease subsequently found to have antibodies to myeloperoxidase (anti-MPO) and crescentic glomerulonephritis. The presence of antineutrophil cytoplasmic antibodies (ANCA) and anti-MPO defines a subset of patients with SSc who are susceptible to crescentic glomerulonephritis. These patients may present in a manner identical to scleroderma renal crisis, yet treatment requirements differ significantly. We suggest that the presence of ANCA be routinely evaluated when faced with renal failure in the setting of SSc.

Adult↗

PubMed1997

[A case of MPO-ANCA positive progressive systemic sclerosis with status epileptics].

A 37-year-old female, who had been suffering from progressive systemic sclerosis (PSS) with long-term renal failure, was diagnosed as MPO-ANCA positive PSS in active stage. She had systemic scleroderma, normotensive renal failure and pulmonary fibrosis. Respiratory management and steroid therapy under the control of CVVH were done for her treatment. She developed hemolytic anemia and thrombocytopenia during the treatment. She was diagnosed as microangiopathic hemolytic anemia, and was treated with plasma exchange treatment. About eight weeks after her admission, she developed status epileptics. Cerebral computed tomography and lumbar puncture did not reveal any abnormal sign. The case reported herein is a MPO-ANCA positive PSS with normotensive renal failure. Generally, PSS rarely reveals neurological sign. This case suggests possibility of association between MPO-ANCA and systemic vasculitis in PSS.

Adult↗

PubMed1979

Articular manifestations of mixed connective tissue disease.

All but one of 28 patients with mixed connective tissue disease (MCTD) who were studied prospectively had arthralgia, and 15 of them had noticed joint swelling. Arthralgia was the first symptom in 14 patients and one of the first two symptoms in 24. Arthralgia was pauciaticular in 4 and polyarticular in 23. Presence of morning stiffness in 15 patients, symmetrical joint swelling in 16, joint deformity in 6, marginal erosions in roentgenograms of the hands of 12, rheumatoid factor in 25, and subcutaneous nodules in 5 caused 24 of the 28 patients with MCTD to fulfill criteria for definite or classic rheumatoid arthritis. All patients, however, also had prominent signs or symptoms of scleroderma, systemic lupus eruthematosus, or polymyositis.

Adolescent↗

PubMed1996

Expression of interleukin-4 in scleroderma skin specimens and scleroderma fibroblast cultures. Potential role in fibrosis.

BACKGROUND: Scleroderma (systemic sclerosis) is a fibrotic disease characterized by an uncontrolled tissular accumulation of collagen. Several cytokines have been implicated in the fibroblast activation leading to fibrosis. For instance, we have previously demonstrated that interleukin-4 (IL-4) is a potent activator of collagen synthesis in fibroblast cultures. In this study, using immunocytochemical methods and in situ hybridization, we investigated the expression of IL-4 in normal and scleroderma skin and fibroblast cultures. OBSERVATIONS: Immunocytochemical studies with anti-IL-4 antibody were performed on biopsy specimens from 9 patients with normal skin and 11 patients with scleroderma. The label was intense or strong in 8 of the 11 scleroderma skin specimens, whereas it was negative or faint in 8 of the 9 normal skin specimens (P < .01). In situ hybridization demonstrated a significant increase of the number of IL-4 messenger RNA grains in scleroderma skin compared with normal skin (3.1 +/- 1.5 [mean +/- SD] vs 0.8 +/- 0.7; P < .001). A strongly positive labeling with the anti-IL-4 antibody was found in the 4 scleroderma fibroblast cultures, whereas it was negative in the 5 fibroblast control cultures (P < .05). CONCLUSIONS: Our results demonstrate that IL-4 is strongly expressed in the dermis of a large majority of patients with scleroderma and might be synthesized by scleroderma fibroblasts. We suggest that IL-4 is one of the cytokines implicated in the early steps of the fibrotic process.

Adult↗

PubMed1977

The systemic involvement in scleroderma.

A survey was made of the systemic involvement in 38 patients with scleroderma: 33 with the acrosclerotic form (Type 1, 18, Type 2, 15) and five with the diffuse form. The study comprised inquiry about symptoms, physical examination, and the laboratory tests, such as radiological examination of chest and hands, barium swallow and meal X-ray examination, electrocardiography, pulmonary function tests, haematology tests, examination for autoantibodies, and a battery of biochemical tests. Evidence of some systemic involvement (that is, in addition to skin) was almost universal. Similar disturbances occurred both in the acrosclerotic and in diffuse forms. The most common clinical involvement was that of the joints and gastrointestinal tract. The most common confirmatory signs were a positive "neck test" (tethering of the skin of the root of the neck and upper part of the chest on extending the head) and telangiectasia. The most common abnormalities in test results were those found in X-ray films of the hands (about 80%), and in pulmonary function, and barium swallow and meal X-ray studies (each about 70%). The most frequent abnormalities in the biochemical scan were increased levels of immunoglobulin M (IgM), and decreased creatine clearance.

Adult↗

PubMed1988

Carpal tunnel syndrome as the initial manifestation of scleroderma.

Two cases of scleroderma (systemic sclerosis) in which carpal tunnel syndrome was the initial manifestation are described. The development of persistent bilateral swelling of the hand after division of the transverse carpal ligament was a clue to the underlying disorder.

Aged↗

PubMed2004

Transcriptional profiling of the scleroderma fibroblast reveals a potential role for connective tissue growth factor (CTGF) in pathological fibrosis.

The cause of fibrotic disease is unknown. We have undertaken transcriptional profiling of dermal fibroblasts cultured from patients with the fibrotic disease scleroderma (systemic sclerosis, SSc) to identify genes overexpressed in fibrosis and have explored their contribution to the fibrotic phenotype. Connective tissue growth factor (CTGF, CCN2), a member of the CCN family of proteins, is overexpressed in SSc fibroblasts. In adult skin, CTGF is not normally expressed in dermal fibroblasts. However, CTGF is induced during the wound healing response and is constitutively overexpressed by fibroblasts present in fibrotic lesions. The overexpression of CTGF present in fibrotic lesions contributes to the phenotype of scleroderma in that CTGF promotes matrix deposition, and fibroblast adhesion and proliferation. In animal models, whereas either TGF beta or CTGF alone produce only a transient fibrotic response, CTGF and TGF beta act together to promote sustained fibrosis. Thus the constitutive overexpression of CTGF by fibroblasts present in fibrotic lesions would be expected to directly contribute to chronic, persistent fibrosis.

Animals↗

PubMed2004

Raynaud phenomenon and the vascular disease in scleroderma.

PURPOSE OF REVIEW: Raynaud phenomenon is the earliest and most common clinical manifestations of scleroderma (systemic sclerosis). Therefore, Raynaud phenomenon offers the best window into the investigation of the early steps in the pathogenesis of systemic sclerosis. This review focuses on the differential diagnosis of Raynaud phenomenon, the transition of Raynaud phenomenon to systemic sclerosis, mechanisms and consequences of vascular injury and dysfunction in systemic sclerosis, and therapeutic options. RECENT FINDINGS: Careful clinical evaluation using a simple definition of Raynaud phenomenon is the most reliable and reproducible method in the diagnosis. Although the assessment of vascular function by noninvasive methods is still not sensitive enough for the evaluation and follow-up of individual patients, it helps in the differential diagnosis and in population studies. Progressive deficiency in vasodilatory capacity of the vessels is proposed as a mechanism of Raynaud phenomenon, particularly in systemic sclerosis. In addition, decreased fibrinolysis and enhanced coagulation pathways undoubtedly contribute to vascular dysfunction. The mechanism of endothelial injury is still elusive, yet endothelial apoptosis mediated by antiendothelial antibodies is the most attractive hypothesis now. Therapies directed at the vascular disease continue to focus on the alleviation of vascular spasm. However, immunosuppressive therapy may influence the levels of vascular injury markers and thus may have an effect on the vascular disease itself. SUMMARY: Continued progress in the investigation of the vascular aspects of scleroderma is described in this review. Immune involvement in the early stages of the disease and mechanism of vascular repair in advance cases are some of the highlights of last year's progress.

Humans↗

PubMed1985

[Protein, RNA and DNA synthesis in skin fibroblast cultures from healthy donors and patients with rheumatic diseases].

Synthesis of protein, RNA and DNA was studied in skin fibroblast cultures of healthy donors and patients with systemic scleroderma (SSD) and in those with rheumatoid arthritis (RA) with the use of 14C-protein hydrolyzate, 14C-uridine and 14C-thymidine, respectively. A study was also made of the stimulation of 14C-proline incorporation in protein fibroblasts upon addition to serum-free media of 5% bovine embryonic serum. The stability of RNA in fibroblasts was tested. It was shown that the rate of protein synthesis was 11 times higher in fibroblasts of RA patients and 6 times higher in those of SSD patients as compared to the rate of protein synthesis in fibroblasts of normal subjects. The rate of DNA synthesis in skin fibroblasts of RA patients was 15 times higher and in those of SSD patients 4 times higher than normal. In both RA and SSD patients, the synthesis of short-labeled RNA was 2-3 times higher than normal. The addition of embryonic serum increased 2-3 times the incorporation of 14C-proline in protein skin fibroblasts of SSD patients. It was found that all RNA in skin fibroblasts was represented by long-living molecules and that 30-40% of short-labeled RNA in skin fibroblasts of healthy donors and SSD patients underwent degradation within 1-2 hours. The data obtained indicate that fibroblasts of the two pathologies under study are characterized by considerable differences in the synthesis of DNA and the activity of the protein-synthesizing system.

Arthritis, Rheumatoid↗

PubMed1986

[Comparative cutaneous measurement of oxygen pressure (pcuO2) in healthy individuals and in patients with progressive scleroderma].

A modified method combining the two methods of measuring either tissue oxygen tension (pO2) or transcutaneous pO2, which have already been proven in other clinical fields, is presented for application in particular skin diseases. This so-called "cutaneous pO2 measurement" (pcuO2) is based on measurements from commercially available transcutaneous pO2 devices, but produces moderate hyperemia through the lower electrode temperature (e.g., 40.5 degrees C) instead of maximal hyperemia (by 44 degrees-45 degrees C temperature). Values obtained this way depend more upon local skin properties, including peripheral capillary flow, than on the arterial pO2. Thus the data are termed cutaneous pO2 (pcuO2). With this method, over 140 measurements were carried out on 14 healthy subjects and 14 patients with progressive systemic scleroderma (PSS); the measurements were made at various skin sites (interdigital fold II/III, back of mid-hand) and under different conditions (3-min upper arm arterial occlusion, 5-min arm muscle activity, cold stimulus to fingers). The pcuO2 values obtained from the PSS patients were significantly below (0-15 mm Hg) those from the healthy subjects (15-42 mm Hg). Fall and recovery times for pcuO2 (during and after arterial occlusion) were prolonged about twice as long in the patients. The pcuO2 reactions to muscle activity and cold stimulus were also significantly delayed in the patients as compared to the subjects. The modified method of cutaneous oxygen tension measurement presented can be employed for more precise assessment of the degree and severity of vascular disorder in PSS, and it is complementary to other clinical methods.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed2005

Fibroblast expression of the coactivator p300 governs the intensity of profibrotic response to transforming growth factor beta.

OBJECTIVE: Transforming growth factor beta (TGFbeta) induces profibrotic responses in normal fibroblasts, and plays a fundamental role in the pathogenesis of fibrosis in scleroderma (systemic sclerosis [SSc]). The intensity of cellular responses elicited by cytokines is modulated by transcriptional coactivators such as the histone acetylase p300. The objective of these studies was to delineate the physiologic role of p300 in Smad-dependent profibrotic responses elicited by TGFbeta. METHODS: Ectopic p300 was transiently expressed in normal dermal fibroblasts. Cellular p300 levels were suppressed using p300-specific ribozymes. The regulation of gene expression was examined by transient transfection assays, Northern blotting, and immunoblot analysis. The expression of p300 in normal and scleroderma fibroblasts was evaluated by confocal microscopy and immunoblotting, and p300 levels in skin from mice with experimental scleroderma were assessed by immunohistochemistry. RESULTS: In normal fibroblasts, TGFbeta induced an increase in the levels of p300. Forced expression of ectopic p300 in these cells dramatically enhanced the magnitude of TGFbeta responses, whereas selective depletion of p300 using ribozyme resulted in abrogation of TGFbeta-induced collagen synthesis and promoter activity. Furthermore, TGFbeta lost its ability to induce Smad-dependent transcription in p300-depleted fibroblasts. These responses could be fully rescued with ectopic p300. Abrogation of Smad-mediated TGFbeta signaling was not due to alterations in the levels or the ligand-dependent phosphorylation or intracellular trafficking of endogenous Smads. Immunohistochemical analysis demonstrated substantially increased p300 expression in lesional skin from mice with chronic graft-versus-host disease, an animal model of scleroderma. Furthermore, levels of p300 were 2-3-fold higher in cultured fibroblasts derived from SSc patients than in fibroblasts from matched normal controls. CONCLUSION: These results establish, for the first time, that the coactivator histone acetylase p300, itself a target of TGFbeta regulation, is an essential component of the cellular TGFbeta signal transduction pathways mediating stimulation of collagen synthesis in fibroblasts. Since the cellular abundance of p300 appears to govern the intensity of profibrotic responses elicited by TGFbeta, elevated p300 expression in lesional tissue may contribute to the progression of skin fibrosis in scleroderma.

Acetyltransferases↗

PubMed2001

Recognition and management of scleroderma in children.

Juvenile scleroderma is a rare disease of childhood. The 2 main forms are localised and systemic scleroderma, although the pathogenesis of both forms is still unclear. The main clinical characteristic is the presence of skin sclerosis. Localised scleroderma can be divided into 3 different subtypes: morphoea, linear scleroderma and 'coup de sabre' lesions. The incidence is 0.2 to 0.4 per 100,000. 25 to 40% of patients are rheumatoid factor positive and 23 to 67% antinuclear antibody positive. An increased number of eosinophils occur in 31% of patients. Systemic sclerosis is an even rarer disease; approximately 10% of patients evolve the disease before the age of 18 years. The clinical presentation and disease course differ from the adult disease. This is reflected in the much better outcome. With regard to therapeutic options, there is still no gold standard for either form of the disease.

Child, Preschool↗

PubMed1996

A critical assessment of the relationship between silicone breast implants and connective tissue diseases.

Concerns regarding the possible role of breast implants (particularly silicone breast implants) in the development of connective tissue diseases were raised by case reports of connective tissue diseases in women with breast implants. Case reports, however, are not appropriate for causation assessment. Within the past few years, epidemiologic studies have begun to appear. Based on a comprehensive literature search, 15 epidemiologic studies on breast implants and connective tissue diseases, which satisfied certain basic epidemiologic requirements, were included in the critical assessment. These studies utilized either the case-control or the cohort study design. Although each individual study was relatively small, and the statistical power to detect a modest risk increase in specific categories of connective tissue diseases was limited, the results of these studies, however, were strikingly consistent, particularly those reported in case-control studies. To increase statistical power and to take the consistency of results into consideration, meta-analyses were used to summarize results from individual studies quantitatively. Based on data from case-control studies, meta-analyses of rheumatoid arthritis, systemic sclerosis (scleroderma), and systemic lupus erythematosus were performed. These case-control studies represented a combined database of approximately 4000 cases of connective tissue diseases, and the power was sufficient to detect a relatively small increase in risk. Based on the meta-analyses, the relative risks (95% confidence intervals) were 0.85 (0.48-1.51) for rheumatoid arthritis, 0.82 (0. 50-1.35) for systemic sclerosis, and 0.33 (0.06-2.03) for systemic lupus erythematosus, indicating that there was no increased risk of connective tissue diseases associated with breast implants. The findings derived from the meta-analyses of case-control studies were supported by results from cohort or prospective studies. It was concluded that epidemiologic data did not provide any evidence for a causal relationship between silicone breast implants and connective tissue diseases.

Arthritis, Rheumatoid↗