Effects of Calcitriol on Fibroblasts Derived from Skin of Scleroderma Patients
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Background: Scleroderma is a fibrotic disorder of unknown etiology that is characterized by excessive collagen synthesis and its deposition in the skin and various internal organs. Objective: To examine whether an overproduction of extracellular matrix molecules is a result of either increased fibroblast proliferation or increased collagen synthesis. As results of clinical trials with 1,25-dihydroxyvitamin D3 (calcitriol) have suggested beneficial effect in the treatment of scleroderma patients, the effects of calcitriol on fibroblasts derived from scleroderma and normal skin has been examined as well. Methods: Cultures of fibroblasts were established from biopsies from involved and uninvolved skin of scleroderma patients and from skin of healthy subjects, and compared with respect to proliferation, collagen synthesis and collagen lattice contraction. Results: No significant differences in cell proliferation and in the extent of fibroblast-induced collagen lattice contraction have been found between scleroderma and normal fibroblasts. Morphologically, fibroblasts derived from scleroderma patients exhibited a disorganized growth pattern in a monolayer culture in contrast to normal fibroblasts. Collagen synthesis tends to be higher in scleroderma fibroblasts as compared with controls. Calcitriol exerted an antiproliferative and antisynthetic effect on fibroblasts, which, however, did not discriminate healthy fibroblasts from fibroblasts derived from involved or uninvolved scleroderma plaques. Conclusions: Our findings suggest that collagen accumulation may not result from increased proliferation or altered dynamic properties of fibroblasts in a scleroderma lesion but from increased collagen biosynthesis. We additionally found that calcitriol does not selectively affect scleroderma fibroblasts.Keywords:
Scleroderma (fungus)
Dermal fibroblast
Scleroderma (fungus)
Connective Tissue Disorder
Systemic scleroderma
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78 cases of connective tissue diseases were observed among 33,250 pediatric dermatoses. Scleroderma is 5 times more frequent than lupus erythematosus and dermatomyositis in children and mainly affects females as well as in adults. The sclerotic changes may involve only a limited part of the skin connective tissue (localized scleroderma), all the skin connective tissue (generalized scleroderma) and the connective tissue of other organs besides the skin (systemic sclerosis). The most frequent clinical forms of scleroderma in children are treated and their pathogenesis is discussed also in the light of the relevant literature.
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Scleroderma (fungus)
Rheumatic disease
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Systemic lupus
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The utility of nailfold capillaroscopy in the evaluation of patients without Raynaud's phenomenon is unclear.This study aims to compare the utility of nailfold capillaroscopy for the early diagnosis of the scleroderma-spectrum of diseases in patients who present with Raynaud's phenomenon, undifferentiated non-Raynaud's phenomenon features and positive systemic sclerosis-associated antibodies without scleroderma-spectrum of disease features.Eligible patients were divided into three referral criteria groups: (I) Raynaud's phenomenon; (II) Undifferentiated non-Raynaud's phenomenon features and (III) Positive systemic sclerosis-associated autoantibodies without features to suggest scleroderma-spectrum of diseases. This includes systemic sclerosis, mixed connective tissue disease and dermatomyositis. The association between baseline scleroderma pattern on nailfold capillaroscopy (systemic sclerosis-nailfold capillaroscopy) and final diagnosis at follow-up was determined using logistic regression analysis. Test characteristics of nailfold capillaroscopy were compared and stratified by referral groups.Of 95 patients followed-up for a mean of 1.6 years, 28 (29.5%) patients developed scleroderma-spectrum of diseases, 36 (37.9%) patients had suspected/other connective tissue disease and 27 (28.4%) patients had no connective tissue disease. Baseline systemic sclerosis-nailfold capillaroscopy was significantly associated with the development of scleroderma-spectrum of diseases in patients from Group I (odds ratio, 7.1, p = 0.01) and Group II (odds ratio 7.3, p = 0.005). In Group II patients, nailfold capillaroscopy had a sensitivity, specificity, positive and negative predictive values of 71.4%, 76.5%, 55.6% and 86.7%, respectively. Specificity (81.8%) and PPV (69.2%) were the highest in Group I patients. Nailfold capillaroscopy had the highest negative predictive value in Group III (100%), followed by Group II (86.7%) and Group I (78.3%) patients.In addition to evaluating patients with Raynaud's phenomenon, nailfold capillaroscopy was useful in the evaluation and exclusion of scleroderma-spectrum of diseases in patients with undifferentiated non-Raynaud phenomenon features and those with systemic sclerosis-associated antibodies without features to suggest scleroderma-spectrum of diseases.
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Abstract The prevalence of scleroderma‐type capillary abnormalities, as observed by in vivo microscopy, was determined in 173 patients from three rheumatic disease centers. The patients had a variety of connective tissue diseases: scleroderma (systemic sclerosis) 50; systemic lupus erythematosus 60; mixed connective tissue disease 26; Raynaud's disease 11; other rheumatic disorders 26. Enlarged and deformed capillary loops surrounded by relatively avascular areas, most prominently in the nailfolds, were found in 82% of patients with scleroderma and in 54% with mixed connective tissue disease. The rarity of these abnormalities in systemic lupus erythematosus (2%) despite the presence of Raynaud's phenomenon suggests that they are not an expression of the Raynaud's phenomenon frequently associated with scleroderma and mixed connective tissue disease. The single patient with Raynaud's disease and sclerodermatype capillary changes subsequently developed scleroderma.
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Systemic scleroderma
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Juvenile scleroderma is a rare connective tissue disease that involves the skin and subcutaneous tissue. Among all presentations of juvenile scleroderma, localized scleroderma (JLSc) is the most frequent, followed by systemic disease (JSSc) and eosinophilic fasciitis (EF). In posttransplantation chronic graft-versus-host disease (GvHD), scleroderma-like skin involvement can occur. Systemic forms of juvenile scleroderma and GvHD can affect the internal organs, such as the lungs, the gastrointestinal tract, the heart, and kidneys and cause disability and severe, sometimes lethal, complications. Here, the authors give an overview of different presentations of juvenile scleroderma. They report their experience with the different forms and presentations of scleroderma, diagnostic workups, treatment, and outcome of all forms of childhood scleroderma in the context of the existing literature.
Eosinophilic fasciitis
Scleroderma (fungus)
Systemic scleroderma
Localized Scleroderma
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Immunofluorescence (IF) investigations of the skin were performed in thirty patients with progressive systemic sclerosis (scleroderma) and eight patients with mixed connective tissue disease (MCTD). The results show that speckled epidermal nuclear immunoglobulin deposition occurs not only in MCTD but also in true scleroderma. Granular IgM deposition at the dermo-epidermal junction of light-exposed skin was detected in both groups of patients, but six of eight MCTD patients also showed a granular IgM band in non-exposed skin. Antinuclear antibodies (ANA) were demonstrated in the sera of 96% and 100% of patients with scleroderma and MCTD respectively. The pattern of nuclear IF staining in scleroderma included dense fine speckles, large coarse speckles, threads, nucleolar and centromere staining. In MCTD, by contrast, the ANA staining pattern consisted of threads. The significance of ANA titres and immunological specificities for the in vivo reaction of serum ANA with epidermal nuclear antigens is discussed.
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Immunofluorescence
Progressive systemic sclerosis
Systemic scleroderma
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Scleroderma, a systemic connective tissue disease, is relatively rare. Case reports of women with silicone breast implants who have developed scleroderma began appearing in the US medical literature in the 1980s. By mid-1993, of the 72 case reports of women with breast implants and connective tissue disease, 38 were reported to have scleroderma. As a result of the publication of these case reports, a number of epidemiologic studies were conducted to find out if silicone breast implants are associated with the development of scleroderma. Five case-control studies of scleroderma were done, plus four prospective studies of connective tissue diseases (including scleroderma) and breast implants. In eight other epidemiologic studies, no cases of scleroderma were identified among women with breast implants. This article includes a qualitative review of the epidemiologic studies and a quantitative summary (meta-analysis) of the case-control studies. Neither the case-control studies nor the other epidemiologic data support the hypothesis that scleroderma is associated with or causally related to breast implants.
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Systemic scleroderma
Patient-reported outcome
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Normal adult human dermal fibroblasts were cultured in the presence of sera from 142 subjects. Results of a fibroblast proliferation assay revealed that 16 of 42 patients with scleroderma, 1 of 25 with rheumatoid arthritis, 3 of 10 with systemic lupus erythematosus, 2 of 3 with mixed connective tissue disease and 0 of 42 normal controls had values outside the normal range. The activity of fibroblast growth promoting factor (FGPF) in the scleroderma group correlated with the skin involvement but not with involvement of any other organ system. The levels of FGPF were higher in the first 2 years of disease duration than at any other time. Our data suggest that fibroblast activation may be a key process in the pathogenesis of scleroderma.
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Pathogenesis
Systemic scleroderma
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