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In a patient with progressive systemic sclerosis (PSS), osteolysis of the posterior portion of the rib cage developed in an insidious fashion, without symptoms or preceding trauma. Six previous examples of rib resorption in PSS are reviewed. The destructive mechanism is unknown but may be related to endarteritis and ischemia.
Seventy-one patients with systemic sclerosis (SS) were typed for twenty-seven HLA alleles of the A and B loci, and the findings were related to both the extent of visceral disease and tests of cellular immune competence in a subgroup of fifty-two of these patients. Nineteen pa;ients with widespread visceral involvement and more rapidly progressive disease had an increased frequency of HLA-B8 (relative risk = 4.14; P less than 0.05) when compared to thirty-three less severely affected patients and 3000 controls. Patients with severe and progressive disease also had defective cell-mediated immunity with reductions in both the numbers of circulating thymus-dependent (T) lymphocytes and in the lymphocyte transformation response to phytohaemagglutinin. These findings suggest that a genetic factor, such as an abnormal immune response gene, may be involved in the progression of the disease.
This study investigated proteomic alterations in the pulmonary circulation of patients with pulmonary arterial hypertension associated with systemic sclerosis (PAH-SSc) by analyzing the transpulmonary protein gradient and comparing the proteomic profiles with systemic sclerosis (SSc) without PAH. Twenty women were included (10 PAH-SSc, 64.6 ± 10.8 years; 10 SSc, 62.8 ± 11.5 years). The transpulmonary gradient was defined as the difference in biomarker concentrations between wedge-position and pulmonary artery blood samples. Peptides were analysed using liquid chromatography-mass spectrometry, and differentially abundant proteins were identified with Proteome Discoverer. Protein-protein interaction networks were generated with STRING and visualized in Cytoscape. A total of 270 proteins were detected, with no significant transpulmonary gradient alterations. However, patients with PAH-SSc showed distinct proteomic profiles compared to SSc. Multivariate analysis identified 48 differentially abundant proteins in pulmonary artery plasma, with 15 overrepresented and 33 downregulated in PAH-SSc. Among these, the downregulation of transforming growth factor-beta-induced protein ig-h3 (TGFβI/ig-h3) points to a potential involvement of the TGF-β-related extracellular matrix remodelling pathway in PAH-SSc. However, further validation in larger and independent cohorts is required before its relevance as a biomarker or therapeutic target can be established. In conclusion, while no transpulmonary proteomic gradient was observed, the proteomic profiles of PAH-SSc and SSc were different. The profile in PAH-SSc was characterized by differences in immune response, lipid metabolism, and hemostatic proteins. SIGNIFICANCE: This study offers the first proteomic characterization of the transpulmonary gradient in PAH-SSc and SSc. Although no differences in the gradient were found, the pulmonary artery plasma proteome of PAH-SSc patients showed a distinct pattern compared to SSc. Several proteins associated with immune function, haemostasis, and cellular processes were altered, which may indicate specific pathophysiological features of PAH-SSc or suggest how lung dysfunction develops in SSc. Targeting dysregulated proteins like TGFβI/ig-h3 or addressing immune-coagulation imbalances may support future research studies. Overall, these findings refine the molecular profile of PAH-SSc and provide a basis for future large-scale studies aimed at clarifying disease mechanisms and identifying clinically relevant molecular signatures.
This report calls attention to the complete resorption of the mandibular condyle in progressive systemic sclerosis (scleroderma), a previously unreported finding. This was associated with osteolysis of the ipsilateral coronoid process, both mandibular angles, and autoamputation of the fingertips. The Panorex provides a simple, effective method for studying the mandible in systemic sclerosis. Similar mandibular osteolysis with vinyl chloride exposure is noted.
A case of systemic sclerosis with subcutaneous nodules is described. The nodules consisted of fibrinoid degeneration with surrounding fibrosis, but lacked the typical histiocytic palisade of the rheumatoid nodule. The patient had neither coexistent rheumatoid arthritis nor circulating rheumatoid factor.
Eleven out of 24 patients with systemic sclerosis had radiological features of inflammatory polyarthritis. Juxta-articular osteoporosis was present in 9 patients, erosions in 5 and loss of joint space in 6 patients. Only one patient had a positive rheumatoid factor. Titres of rheumatoid factor, anti-nuclear factor, and plasma viscosity were comparable in patients with and without radiological abnormalities. Measurements of grip strength and finger-palm flexion also were similar in the two groups. However, in individual cases joint or tendon sheath disease was associated with loss of function.
Nine normotensive progressive systemic sclerosis patients with normal renal function underwent renal biopsy. Four specimens had prominent vascular abnormalities, two mild vascular abnormalities, and three were normal. Vascular deposits of C3 were present in all specimens. Plasma renin activity was elevated in three of four patients with prominent vascular abnormalities, one of two patients with mild vascular lesions, and none of two patients with normal biopsies. Plasma renin activity elevation in response to cold pressor testing in the four patients with prominent vascular lesions was 5.6 ng/ml.h compared to 0.55 ng/ml.h in those with mild or no lesions and 0.26 ng/ml.h in six control subjects. These data indicate that renal vascular lesions may be present in normotensive patients. Elevation or a substantial rise in plasma renin activity (1.8 ng/ml.h or greater) in response to cold pressor testing suggests preclinical renal involvement.
A patient with long-standing progressive systemic sclerosis developed calcification of the suprapatellar pouch. Chalky white synovial fluid from the knee joint contained many crystals that were characterized as apatite by X-ray diffraction. In this case massive amounts of cystals were presumably shed into the fluid from the heavily calcified synovium.
The case of a patient with progressive systemic sclerosis (PSS) who developed electro- and vectorcardiographic patterns of myocardial necrosis without clinical picture of myocardial infarction is reported. The coronarography showed no obstruction of coronary arteries and cineventriculography a hypodynamic enlarged left ventricle. The analysis of electrocardiograms from 43 other patients affected with PSS revealed myocardial necrosis in 5 of them. The clinical syndrome of myocardial infarction was absent in all these cases. Moreover, the hemodynamic investigation in 13 cases allowed to record a dip-plateau figure on the right ventricle pressure curve in 3 of them. In PSS, the electrocardiographic aspects of "necrosis" as well as hemodynamic restrictive findings or ventricular enlargement at ventriculography could indicate myocardial disease.
Six long term survivors of bone marrow transplants developed a syndrome similar to progressive systemic sclerosis (PSS). Cutaneous involvement (6/6), pulmonary disease (6/6), musculoskeletal involvement (4/6), keratoconjunctivitis/positive Schirmer's test (4/6), Raynaud's phenomenon (2/6), and renal and cardiac disease (1/6) were similar to findings in PSS patients. T and B lymphocyte counts and functions were also similar. This PSS-like syndrome, including visceral involvement, after bone marrow transplantation lends support to an immunologic hypothesis of the pathogenesis of progressive systemic sclerosis.
Cell-mediated immunity to skin extracts was studied by the macrophage migration inhibition test, lymphocyte transformation, and direct cytotoxicity to skin fibroblasts, in normal individuals and patients with progressive systemic sclerosis. The latter included 18 individuals with diffuse scleroderma and 12 with the CREST syndrome, a variant form of systemic sclerosis in which there is more limited involvement of the skin. Controls consisted of 13 patients with other connective tissue diseases and 16 normal individuals. Phosphate-buffered saline and 3 M KCl extracts of both normal and sclerodermatous skin were used as antigens. No evidence of lymphocyte reactivity was found by the lymphocyte transformation and direct cytotoxicity test procedures. However, the lymphocytes of patients with diffuse scleroderma did respond to extracts of both normal and sclerodermatous skin in the migration inhibition assay. 10 of 16 patients (62.5%) had migration indices below 2 SD of the normal range, 1 of 10 CREST patients and 1 of 13 patients with other connective tissue diseases showed similar reactivity. Antisera specific for immunoglobulin-bearing lymphocytes (B lymphocytes) and T lymphocytes were used to characterize the lymphocytes found in skin biopsies of patients with diffuse scleroderma. T lymphocytes made up the majority of lymphocytes in the skin infiltrates. These findings suggest that lymphocytes sensitized to skin extracts are present in patients with diffuse scleroderma. The cell-mediated immune reaction to skin antigens may be a factor in the pathogenesis of diffuse scleroderma.
Upon evaluation of 40 subjects with progressive systemic sclerosis (PSS), a significant association of HLA antigens A9 and Aw24 (a subgroup of A9) was found with diffuse scleroderma. HLA-Aw23 (a second subgroup of A9) was also increased in the patients, however, this was not statistically significant. Diffuse scleroderma appears to be one of the few diseases that shows an association with the HLA-A locus.
The amount of dermal collagen is increased in systemic sclerosis. However, unlike certain inflammatory conditions, the relative proportions of Type I and Type III collagens are closely similar to those found in normal adult dermis. Similarly, no change in the distribution of the collagen types could be detected by immunofluorescent staining, although a considerable thickening of the epidermis was clearly evident in all the sclerotic lesions examined.
Peripheral blood lymphocytes from twenty patients with progressive systemic sclerosis (PSS) were analysed for the numbers and proportions of B lymphocytes possessing surface immunoglobulin, cells with Fc receptors, T cella and T cells with receptors for IgM (T mu) or IgG (T gamma). In patients with PSS, B cells and lymphocytes with Fc receptors were comparable in both numbers and proportions to those of the control group. Circulating T lymphocytes were significantly fewer in the patient group. T mu cells were decreased and T gamma cells increased, resulting in lower T mu/T gamma ratios as compared to controls. This study demonstrates a profound imbalance between T mu and T gamma cells (containing a population of helper or suppressor cells, respectively). These results are discussed in relation to immunodeficiencies observed in patients with PSS.
Clearance rates of soluble radioaerosols of sodium pertechnetate (99mTcO4; mol wt 163) and diethylenetriaminepenta-acetate (99mTc-DTPA; mol wt 492) were determined in seven normal subjects and ten patients with systemic sclerosis affecting the lungs. Twenty millicuries (mCi) each of 99mTcO4 and 99mTc-DTPA in 5 ml saline were aerosolised and inhaled using a disposable "Blount" nebuliser on two different days. Two regions of interest over each posterior lung field were monitored with scintillation camera, and data were stored on magnetic tape using a Hewlett Packard Data Analyser. Decreasing levels of radioactivity were plotted semilogarithmically and half-time (T 1 1/2) removal rates were calculated. The T 1 1/2) values in normal subjects did not differ significantly from T 142 values of the patients with TcO4. However, the removal rates of the higher molecular weight solute were significantly faster from lower lung zones in patients with systemic sclerosis than in the normal subjects. The faster absorption of DTPA from lower lung zones of the patients could be due to regional abnormalities of alveolar epithelium at the lung bases, presumably as a result of greater retractive forces secondary to fibrosis.
The CREST syndrome refers to a disorder comprising the manifestations of calcinosis, Raynaud's phenomenon, esophageal dysfunction, sclerodactyly, and telangiectasia. Thirteen CREST patients (two with CRST) were compared with 26 patients with systemic sclerosis but without the full manifestations of the CRST syndrome. No significant difference was found between the groups in the age of onset of Raynaud's phenomenon, degree of multiphasic digital color changes, ulcerations of fingers, sclerodactyly, or in the frequency of abnormal esophageal peristalsis or dysphagia. Laboratory results were similar, including the frequency of an elevated ESR. However, the CREST patients had a significantly lower frequency of arthralgia (54%) and arthritis (15%) than did those with scleroderma (88% and 65%, respectively). All but one of the CREST patients were women, which was a greater proportion than found among scleroderma cases (69%), and all were white (P less than .05). Most patients with the CREST syndrome had rather severe acrosclerosis. At last evaluation, four patients were chronically ill and three had died. The CREST and CRST syndromes are closely related disorders that seem to be part of the spectrum of systemic sclerosis.
Five cases of unusual esophageal diverticula associated with progressive systemic sclerosis (scleroderma) or collagen vascular disease are presented. These wide-mouthed saccular diverticula were infrequently seen in a group of PSS patients with the typical motility disturbance of esophageal involvement and are reminiscent of the diverticula of the colon involved by PSS.
In a controlled study of barium swallow radiographs in systemic sclerosis, longitudinal oesophageal mucosal folds were absent in eight of 30 patients and in one of 30 control subjects (P less than 0.03). Patients without mucosal folds developed Raynaud's phenomenon at an earlier age than those who retained their mucosal folds (P less than 0.05). A loss of oesophageal mucosal folds did not necessarily signify more severe visceral or cutaneous disease.