Steady-state mRNA levels of collagens I, III, fibronectin, and collagenase in skin biopsies of systemic sclerosis patients.

Total RNA was extracted from skin biopsies of nine patients suffering from systemic sclerosis (SSc). Steady-state mRNA levels of collagen alpha 1(I) and alpha 1(III), collagenase, fibronectin, and beta-actin were studied using specific cDNA probes and compared to those of 12 sex- and age-matched healthy individuals. There was a more than three-fold elevation of collagen I mRNA levels in SSc skin compared to controls. No difference was found, however, for collagen III, collagenase, and fibronectin mRNA levels in SSc and control biopsies. The selective increase of collagen alpha 1(I) mRNA levels indicates a specific alteration of fibroblast metabolism in scleroderma. Analysis of mRNA levels in skin biopsies might not only offer a direct approach to the understanding of the pathophysiology of SSc, but also facilitate the monitoring of fibrotic activity in SSc patients during therapeutic trials.     

Exacerbation of progressive scleroderma following roentgen therapy

In a 38-year-old female patient suffering from progressive scleroderma and breast carcinoma the clinical features were exacerbated and became generalized after radiotherapy, and unfortunately regressed only transiently during aggressive polychemotherapy. Links between progressive scleroderma and carcinoma and the immune system are discussed. The risk of post-irradiation worsening of progressive scleroderma is pointed out.     

Intravenous dexamethasone‐cyclophosphamide pulse therapy in comparison with oral methylprednisolone‐azathioprine therapy in patients with pemphigus: Results of a multicenter prospectively randomized study

Background: Pemphigus is a potentially life‐threatening autoimmune blistering skin disease usually treated with high‐dose corticosteroids in combination with immunosuppressive drugs. In a multicenter, prospectively randomized study we compared efficacy and side effects of a dexamethasone‐cyclophosphamide (D/C) pulse therapy with a methylprednisolone‐azathioprine (M/A) therapy in 22 patients with newly diagnosed pemphigus vulgaris and pemphigus foliaceus. Patients and methods: The 11 patients of the M/A group were treated with daily doses of methylprednisolone (initially 2 mg/kg body weight) and azathioprine (2 – 2,5 mg/kg body weight) which were subsequently tapered. D/C pulse therapy in 11 patients consisted of intravenous administration of 100 mg dexamethasone/d on 3 consecutive days along with cyclophosphamide (500 mg) on day one. Pulses were initially repeated every 2 – 4 weeks and then at increasing intervals. In between the pulses, oral cyclophosphamide (50 mg) was given daily for 6 months. Results: Within 24 months after treatment initiation, 5/11 patients of the D/C group had a remission (complete remissions after discontinuation of therapy in 3 patients) and 6/11 patients had a progression. In the M/A group, there were remissions in 9/11 patients (complete remissions after discontinuation of therapy in 3 patients) and progression in 1/11 patients. There were more relapses in M/A therapy after remission than in D/C therapy. Side effects were more common in the M/A group. These differences were not significant (p > 0,05). Conclusion: Because of the high number of progressions in patients treated with D/C therapy, we can not confirm the encouraging results of earlier reports about pulse D/C therapy. Nevertheless D/C therapy seemed to be better tolerated and, in case of primary efficacy, was associated with fewer recurrences than M/A therapy.     

Silica-induced scleroderma

In a survey done in East Germany between 1981 and 1988, we found that 93 of 120 male scleroderma patients had long-term exposure to silica dust. We describe our findings in 12 patients with scleroderma and silicosis. The exposure time to silica dust was between 3 and 34 years; the interval between the beginning of exposure and the onset of scleroderma averaged 27.3 years (range 9 to 40 years). Antinuclear antibodies in titers between 80 and 10,240 with nucleolar and/or speckled patterns were found in 10 patients, antibodies against double-stranded DNA in three, Scl-70 (topoisomerase I) in three, and anticentromere antibodies in five. The following markers of collagen metabolism were increased in serum: beta-galactosidase in 12 patients, laminin peptide-P1 in 10 patients, N-terminal procollagen type III peptide in 10, and urinary sialic acid excretion in 7. We propose that crystalline particles of silica less than 5 microns may be phagocytosed by macrophages and release lymphokines and monokines, which activate fibroblasts and enhance their collagen and glycosaminoglycan synthesis. In addition, silica may act as an adjuvant to increase immune reactivity.     

Lysine acetylsalicylate decreases proliferation and extracellular matrix gene expression rate in keloid fibroblasts in vitro

BACKGROUND: In genetically predisposed individuals keloids are formed as benign collagenous tumors. OBJECTIVE: The purpose of this study was to investigate whether the proliferation and matrix gene expression of keloid fibroblasts is differently influenced by the anti-inflammatory active drug lysine acetylsalicylate (LAS) when compared to normal skin fibroblasts in vitro. METHODS: Normal skin and keloid fibroblasts derived from human donors were compared. RESULTS: Excessive scarring and the formation of keloids are (at least in part) due to an overproduction of collagen types I and III. The results show a significant dose-dependent anti-proliferative effect of lysine acetylsalicylate. At the level of gene expression we observed a pronounced inhibitory effect of LAS on procollagen I and III mRNA synthesis, whereas matrix metalloproteinase 1 and tissue inhibitor of metalloproteinases 1 were not altered. CONCLUSIONS: Further clinical studies are planned to evaluate these effects of a high-dose treatment of keloids with LAS.     

Zentrifugal wachsende erythrosquamöse Plaques nach Westafrika-Aufenthalt

Ohne Zusammenfassung     

Livedo racemosa mit Ulzerationen Zyklische Therapie mit Iloprost (Ilomedin®)-Infusionen

A 43 year old woman suffered from an intermittent painful livedo racemosa at the back since her childhood. Her clinical course was complicated by ulcerations. In careful clinical investigations no signs of an underlying disease could be found, in particular a Sneddon syndrome could be excluded. By means of both conservative and surgical treatments, initial healing of the ulcerations was achieved but relapses occurred. Cyclic infusions of iloprost achieved long-term clearing of the ulcerations and disappearance of the pain. To the best of our knowledge the effectiveness of this treatment has not been described for this disease in the literature.     

The monoclonal antibody AS02 recognizes a protein on human fibroblasts being highly homologous to Thy-1

Abstract Recently, we described a novel fibroblast-restricted monoclonal antibody (mAb AS02) that recognizes a membrane-bound antigen. Characterization and isolation of the corresponding antigen showed that mAb AS02 recognized a protein on human fibroblasts that is highly homologous or identical to human Thy-1 antigen (CD90). Partial amino acid sequencing of the corresponding mAb AS02 antigen and comparison with known proteins revealed a 100% homology of the sequenced peptides to the human Thy-1 antigen. Cross-immunodepletion studies with mAb AS02 and an anti-Thy-1 antibody confirmed these results. Utilizing two-dimensional (2D) gel electrophoresis of fibroblast cell extracts and purified antigen, mAb AS02 and the anti-Thy-1-antibody recognized identical protein spots. Furthermore, we demonstrated many identical biochemical properties of the corresponding AS02 antigen and Thy-1 antigen, such as the molecular weight of the core protein and deglycosylation products and the detection of a GPI anchor. In functional assays, the attachment of fibroblasts to collagen I and fibronectin was increased after incubation of fibroblasts with mAb AS02. Therefore, the Thy-1 antigen appears to be involved in the regulation of the adherence of human dermal fibroblasts. Received: 6 November 1997