Levels of F2-isoprostanes in systemic sclerosis: correlation with clinical features.
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OBJECTIVE: Oxidative stress may be one of the important complex pathogenetic mechanisms that lead to damage in scleroderma; free radicals may provoke endothelial injury, fibroblast proliferation and fragmentation of autoantigens favouring induction of autoantibodies. The present study investigates the oxidant status in scleroderma patients by measuring the urinary concentration of 8-isoprostaglandin-F2alpha, an F2-isoprostane, and a product of free radical-mediated peroxidation of arachidonic acid. METHODS: Forty-three scleroderma patients (42 women and 1 man, mean age 54.1 yr, mean disease duration 9.0 yr) underwent clinical evaluation and instrumental investigations in order to assess skin, vascular, lung and heart involvement. Von Willebrand factor was evaluated as marker of vascular dysfunction in 36 out of the 43 cases. The urinary level of 8-isoprostaglandin-F2alpha was measured in all scleroderma patients and in the 43 age- and sex-matched healthy controls. RESULTS: Urinary levels of 8-isoprostaglandin-F2alpha were higher in scleroderma patients than in the healthy control group (341.7 vs 147.6 pg/mg creatinine; P < 0.001). Values of 8-isoprostaglandin-F2alpha were strongly correlated with the nailfold videocapillaroscopy pattern and lung involvement (P = 0.002 and 0.003, respectively), showing increasing levels with the progression of pulmonary severity. Correlation between 8-isoprostaglandin-F2alpha level and von Willebrand factor narrowly failed to reach statistical significance (P = 0.05). There was no correlation between 8-isoprostaglandin-F2alpha concentration and disease activity, vascular, skin and heart involvement, disease pattern or autoantibody profile. CONCLUSIONS: Our study further supports the role of oxidant stress in the pathogenesis of scleroderma, showing a strong correlation between a marker of free radical damage with both the severity of lung involvement and the videocapillaroscopic patterns. (+info)
Inflammatory myopathies in childhood: correlation between nailfold capillaroscopy findings and clinical and laboratory data.
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OBJECTIVE: Nailfold capillaroscopy is an important tool for the diagnosis and follow-up of patients with rheumatic diseases, in particular dermatomyositis and scleroderma. A relationship has been observed in adults between improved capillaroscopic findings and reduced disease activity. Our aim was to correlate disease activity (clinical and laboratory data) and nailfold capillaroscopy findings in 18 patients with inflammatory myopathies. METHODS: This prospective study included 13 juvenile dermatomyositis patients (Bohan and Peter criteria) (mean age of 8.8 years) and five patients with overlap syndrome (mean age of 15.7 years). We evaluated disease activity (skin abnormalities and muscle weakness, muscle enzymes and acute phase reactants) and its correlation with nailfold capillaroscopy findings (dilatation of isolated loops, dropout of surrounding vessels and giant capillary loops). We used a microscope with special light and magnification of 10 to 16X. RESULTS: Eighteen patients underwent a total of 26 capillaroscopic examinations, seven of them on two or more occasions (13 were performed during the active disease phase and 13 during remission). Twelve of the 13 examinations performed during the active phase exhibited scleroderma pattern and 8 of the 13 examinations performed during remission were normal. Therefore, in 20 of the 26 examinations clinical and laboratory data and nailfold capillaroscopy findings correlated (p = 0.01). CONCLUSIONS: Nailfold capillaroscopy is a non-invasive examination that offers satisfactory correlation with disease activity and could be a useful tool for the diagnosis and follow-up of inflammatory myopathies. (+info)
Circulating levels of Nepsilon-(carboxymethyl)lysine are increased in systemic sclerosis.
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OBJECTIVE: Advanced glycation endproducts (AGEs), including Nepsilon-(carboxymethyl)lysine-protein adducts (CML) are involved in micro/macrovascular changes and are co-localized with adhesion molecules in inflamed tissues. Serum levels of CML were investigated in systemic sclerosis (SSc) characterized by microvascular modifications and correlated with indices of micro/macrovascular damage. METHODS: In 66 SSc patients (limited SSc, n = 55; diffuse SSc, n = 11) and 20 controls, CML serum levels were measured by enzyme-linked immunosorbent assay. Nailfold capillaroscopy, intima-media thickness (IMT) and the ankle-brachial index (ABI) were also recorded, to characterize micro/macrovascular involvement. RESULTS: CML levels were significantly higher in SSc (79.2 +/- 39 mg/ml vs 49.6 +/- 26.1 mg/ml, mean +/- s.d.; P<0.01), without significant differences between SSc subsets. CML levels were significantly higher in all capillaroscopic patterns: the 'early' pattern showed higher levels than 'active' and 'late' patterns. IMT was significantly higher in SSc (P<0.01) than in controls, whilst ABI was no different from controls. CONCLUSIONS: These data indicate that although both CML formation and macrovascular involvement are increased in SSc, there is no correlation between these two parameters. However, the characteristic early nailfold capillaroscopy changes of SSc are associated with proportionally greater CML formation, suggesting that AGEs are involved in SSc microangiopathy. (+info)
Nailfold capillaroscopy is useful for the diagnosis and follow-up of autoimmune rheumatic diseases. A future tool for the analysis of microvascular heart involvement?
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Raynaud's phenomenon (RP) represents the most frequent clinical aspect of cardio/microvascular involvement and is a key feature of several autoimmune rheumatic diseases. Moreover, RP is associated in a statistically significant manner with many coronary diseases. In normal conditions or in primary RP (excluding during the cold-exposure test), the normal nailfold capillaroscopic pattern shows a regular disposition of the capillary loops along with the nailbed. On the contrary, in subjects suffering from secondary RP, one or more alterations of the capillaroscopic findings should alert the physician of the possibility of a connective tissue disease not yet detected. Nailfold capillaroscopy (NV) represents the best method to analyse microvascular abnormalities in autoimmune rheumatic diseases. Architectural disorganization, giant capillaries, haemorrhages, loss of capillaries, angiogenesis and avascular areas characterize >95% of patients with overt scleroderma (SSc). The term 'SSc pattern' includes, all together, these sequential capillaroscopic changes typical to the microvascular involvement in SSc. The capillaroscopic aspects observed in dermatomyositis and in the undifferentiated connective tissue disease are generally reported as 'SSc-like pattern'. Effectively, and early in the disease, the peripheral microangiopathy may be well recognized and studied by nailfold capillaroscopy, or better with nailfold video capillaroscopy (NVC). The early differential diagnosis between primary and secondary RP is the best advantage NVC may offer. In addition, interesting capillaroscopic changes have been observed in systemic lupus erythematosus, anti-phospholipid syndrome and Sjogren's syndrome. Further epidemiological and clinical studies are needed to better standardize the NCV patterns. In future, the evaluation of nailfold capillaroscopy in autoimmune rheumatic diseases might represent a tool for the prediction of microvascular heart involvement by considering the systemic microvascular derangement at the capillary nailfold. (+info)
Cutaneous vascular alterations in psoriatic patients treated with cyclosporine.
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Videocapillaroscopy can be used to assess cutaneous microcirculation modifications in vivo, and therefore allows assessment of variations in the microvascular architecture in psoriatic subjects during treatment. The aim of this study was to observe and quantify the modifications of the superficial capillary bed in psoriatic plaques during treatment with cyclosporin A. Twelve patients with psoriasis vulgaris were treated with an initial dose of 4 mg/kg/day cyclosporin A over a period of 3 months with periodic clinical and capillaroscopic assessments. Clinical resolution of the lesions and a reduction in microcirculatory alterations was observed in 70% of patients, although none returned to a normal capillaroscopic pattern. (+info)
Capillarosecopic patterns in rheumatic diseases.
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Nailfold capillaroscopy (NVC) is a simple, non-invasive, inexpensive and useful method for the analysis of microvascular abnormalities found in several rheumatic disorders. The well-known Raynaud's phenomenon is a clinical condition that should promptly lead to a microvascular analysis, in order to distinguish its primary form (functional, not disease associated) from the secondary Raynaud's phenomenon (disease associated). NVC has an exceptional predictive value in this early distinction, and this may be the best advantage this technique can offer. Microvascular damage is a typical feature of Systemic Sclerosis (SSc) and more than 95% of the patients present architectural disorganization, giant capillaries, haemorrhages, loss of capillaries, avascular areas and neovascularization, as main microvascular abnormalities. These sequential capillaroscopic changes characterize the "scleroderma pattern" and reflect the SSc microangiopathy. In dermatomyositis and undifferentiated connective tissue disease the capillaroscopic aspects are generally named as "scleroderma-like pattern". Capillaroscopy changes have also been found in other systemic rheumatic diseases such as Systemic Lupus Erythematosus, Antiphospholipid Syndrome and Sjogren's Syndrome, further epidemiological and clinical studies are needed to better characterize and standardize nailfold capillaroscopy patterns in these disorders. (+info)
Vascular endothelial growth factor in systemic lupus erythematosus: relationship to disease activity, systemic organ manifestation, and nailfold capillaroscopic abnormalities.
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INTRODUCTION: The aim of the study was to evaluate whether vascular endothelial growth factor (VEGF) serum level is associated with systemic organ involvement, microvascular changes as determined by nailfold capillaroscopy, and disease activity of systemic lupus erythematosus (SLE). MATERIALS AND METHODS: Serum levels of VEGF were determined by an enzyme-linked immunosorbent assay in 47 SLE patients and in 30 healthy controls. Nailfold capillaroscopy was performed in all patients and healthy subjects. RESULTS: Morphological changes were observed by nailfold capillaroscopy in 45 of 47 (95.7%) SLE patients. Mild capillary changes were found in 16 (34%), moderate in 21 (44.7%), and severe in 8 (17%) SLE patients. All patients with systemic organ involvement showed severe or moderate changes in nailfold capillaroscopy. In comparison with the control group, a higher serum concentration of VEGF in SLE patients was demonstrated (p<0.05). Furthermore, significant differences in VEGF serum concentration between SLE patients with systemic involvement and controls were found (p<0.01). Comparison between patients with active and inactive SLE according to SLEDAI score showed a significantly higher concentration of VEGF in the sera of patients with active SLE (p<0.01). The SLE patients with severe and moderate changes in nailfold capillaroscopy showed significantly higher VEGF serum levels than SLE patients with mild changes (p<0.05) or healthy controls (p<0.01). Moreover, the VEGF serum level correlated significantly with ESR (r=0.580, p<0.0001) and CRP (r=0.512, p<0.005). CONCLUSIONS: Our data suggest that VEGF serum level may be a useful marker of disease activity and internal organ involvement in SLE patients. Abnormalities in nailfold capillaroscopy may reflect the extent of microvascular involvement and are associated with systemic manifestation in SLE. (+info)
Scleroderma patients nailfold videocapillaroscopic patterns are associated with disease subset and disease severity.
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OBJECTIVE: To evaluate in a large group of scleroderma patients, the association of nailfold videocapillaroscopic patterns with both demographic and clinical features. METHODS: One hundred and three Italian patients (91 women and 12 men, mean age 54.3 years, median disease duration 7 yrs, 68 with limited and 35 with diffuse subset of disease), consecutively enrolled for the study, underwent nailfold videocapillaroscopy; the microvascular alterations were classified into three different patterns, early, active and late. The nailfold videocapillaroscopic patterns were correlated with such numerous clinical features as sex, age, disease duration, disease subset, disease activity, haematochemical data, involvement of skin, heart, lung and peripheral vessels. RESULTS: Nailfold videocapillaroscopic patterns were significantly associated with disease subsets (P = 0.018). Severity of skin, lung, heart and peripheral vascular involvement progressively increased across nailfold videocapillaroscopic patterns, from early to late pattern (P < 0.001 for cutaneous and peripheral vascular involvement; P = 0.003 and 0.002 for lung and heart involvement, respectively) as well as homocysteine plasma levels (P = 0.02). Patients with late pattern showed an increased risk to have an active disease [OR (odds ratio) 3.50; 95% CI (confidence interval) 1.31-9.39], to present digital ulcers (OR 5.74; 95% CI 2.08-15.89) and moderate to severe skin (OR 5.28; 95% CI 1.93-14.19), heart (OR 5.75; 95% CI 2.04-16.21) and lung involvement (OR 4.41; 95% CI 1.63-11.92). CONCLUSIONS: Our study showed that scleroderma microangiopathy correlates with disease subset and severity of peripheral vascular, skin, heart and lung involvement; patients with late pattern showed an increased risk to have an active disease and to show a moderate/severe skin or visceral involvement compared to patients with early and active patterns. Therefore nailfold videocapillaroscopy, a simple, non-invasive and non-expensive investigation, is useful in staging scleroderma patients and also provides prognostic information. (+info)