Problems and observations on progressive systemic scleroderma

At first the pathogenesis of sclerodermia is discussed. Disturbed immunological control mechanisms for the activity of fibroblasts with an increased humoral activity are mentioned as causes. Then relevant clinical changes in connection with own investigations are outlined and finally some therapeutic possibilities are mentioned. The pathobiochemical changes of the collagen metabolism of sclerodermia are analysed and own investigations about the laboratory parameters, hydroxyprolin and N-acetyl-neuraminic acid which summarizingly reflect the collagen metabolism in patients with sclerodermia follow. Finally diagnostic possibilities of a renal participation are shown with the help of a quantitative and qualitative protein analysis in the collective urine, in which case a particular point is to be made of the distinction of selectively and unselectively excreted proteins.     

Enthetic reactions of the hand in progressive scleroderma

Frequent bone changes in progressive systemic sclerosis are the marginal osteolysis, the arthritic erosions and also the reactions at the numerous entheses of the hand, where the resorptive reactions predominate the osteoproliferative ones. The most frequent resorptions occur at the proximal corners of the tufts. At the margin of the tufts there are also enthesitic reactions, but they do not mark the beginning of an acroosteolysis.     

Decreased blood fluidity in progressive systemic scleroderma

The aim was to define blood rheology in progressive systemic scleroderma (PSS). 55 patients were compared to controls. Blood and plasma viscosity, hematocrit, red cell aggregation, and deformability were measured. Except for hematocrit, all these variables are significantly altered, indicating a loss of blood fluidity in PSS. Drugs had no obvious effect on blood rheology, but the clinical picture did. The loss of blood fluidity in PSS is suggested to play a pathophysiological role in the initiation of Raynaud phenomena, from which all patients suffered.     

The heart in scleroderma

The heart is one of the major organs involved in scleroderma, the involvement of which can be manifested by myocardial disease, conduction system abnormalities, arrhythmias, or pericardial disease. Additionally, scleroderma renal crisis and pulmonary hypertension lead to significant cardiac dysfunction secondary to damage in the kidney and lung. This article summarizes the types and mechanism of abnormalities in the heart in scleroderma. The concept of cardiac dysfunction in scleroderma and other rheumatologic conditions has received new interest with the advent of newer noninvasive imaging techniques, as well as the interest in detecting subclinical disease. With this increased interest in cardiac manifestations in scleroderma comes the realization that long-term studies are needed to better assess the appropriate screening and treatment in this patient population.     

Immunomorphological and ultrastructural findings on the musculature in progressive scleroderma]

Muscle biopsies taken from 30 patients with generalized scleroderma were studied immuno-histologically as well as by light and electron microscopy. The immunological investigations have demonstrated that an increase of IgM and/or complement depositions in capillaries and in the walls of small arteries have been involved in most cases. Similar alterations were found in the subsarcolemmal zone. Vascular Ig-G precipitates were observed in the later stage of the disease only, whereas a positive reaction of fibrinogen have been proved in the most cases. By light and electron microscopy a variety of pathologic alterations have usually been found, but the most prominent changes involved were thickening of the capillary basement membrane and interstitial fibrosis. Scattered cellular infiltrates consisting of lymphocytes, histiocytes and plasmocytes were also seen either perivascularly or throughout the interstice. Around fibroblasts and capillaries, fine protocollagen fibrils and glycosaminoglycan filaments have been observed. They may partly represent fibrogenesis. Filamentous structures could be seen within the cytoplasm of numerous fibroblasts.     

Rapidly progressive scleroderma associated with carcinoma of the oesophagus.

A patient with scleroderma of recent onset was found to have a carcinoma of the oesophagus. The rapid progression of the scleroderma suggested the possibility that it represented a systemic manifestation of malignancy.     

Immune complexes in progressive systemic sclerosis (scleroderma)

Serum immune complexes were measured in 92 patients with progressive systemic sclerosis, and elevated levels were found as follows: Raji cell assay 72% (59% after pronase treatment of Raji cells), agarose gel electrophoresis 52%, and C1q binding 24%. Fortythree (47%) had abnormal results on two or more of these tests, but only 17 (18%) had normal results by all three assays. Computer-assisted analysis of immune complex results and extensive clinical and laboratory data compiled on these patients revealed that the patients with abnormal Raji cell assays more often had diffuse scleroderma, tendon friction rubs, and positive serum antinuclear antibody tests than did patients with negative results on Raji cell assays. Individuals with immune complexes detected by C1q binding had evidence of pulmonary involvement and positive serum rheumatoid factor more frequently than did patients whose C1q tests were negative.     

Skin thickness and collagen content in progressive systemic sclerosis and localized scleroderma

Skin biopsies of uniform location and surface area (7 mm diameter) were obtained from the extensor aspect of the forearm of 147 patients with progressive systemic sclerosis (PSS) (107 with diffuse scleroderma, 40 with the CREST syndrome variant) and 58 individuals with normal skin. After careful removal of all subcutaneous fatty tissue, the skin cores were weighed and their water and hydroxyproline content determined. Despite recent claims to the contrary, it was found that there is a marked and highly significant increase in the thickness of the skin during the indurative phase of PSS, and that this is associated with a proportionate increase in total dermal collagen content. A similar degree of thickening was found in the skin of patients with eosinophilic fasciitis and acromegaly. A close correlation was observed between clinical estimation of the degree of skin thickening and the weight of the skin biopsy cores. Change in the weight of skin cores was observed during the course of illness of the patients with PSS and may serve as a useful measurement of alteration in the degree of skin thickening.     

Heart involvement in progressive systemic sclerosis (generalized scleroderma)

17 patients with progressive systemic sclerosis were examined for cardiac involvement using standard ECG, chest X-ray, 24-h Holter ECG, and echocardiography. The control groups consisted of 7 patients with mixed connective tissue disease, 10 patients with systemic lupus erythematosus, and 10 patients with rheumatoid arthritis. The results disclosed a cardiac involvement of 70% using all 4 methods, which is more than is reported in the literature. The data also show that all 4 methods are necessary to diagnose the cardiac involvement. Conduction and rhythm disorders especially are more frequent than in other collagen vascular diseases. The use of calcium channel blockers is discussed as a new therapeutic possibility.