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Urinary glycosaminoglycan (GAG) excretion was studied in 30 patients with established systemic sclerosis and compared with 30 normal controls. There was no significant difference in excretion values in the patient group as a whole, but in the group defined as 'incomplete CREST' urinary GAG values were lower than the group with 'diffuse disease' and controls.
Systemic sclerosis (SSc; scleroderma) results in the excessive deposition of extracellular matrix components in affected organs. This is partly due to enhanced synthesis; however, the role of degradative processes in this disease is still poorly understood. Sera of 32 patients with SSc (22 with the diffuse, 10 with the limited form) and of six patients with morphoea were assessed using radioimmunoassays for the cross-linked carboxy terminal telopeptide of type I collagen (ICTP) and for the amino terminal propeptide of type I procollagen (PINP) reflecting type I collagen degradation and synthesis, respectively. In 27 of the 32 patients with SSc, the concentration of ICTP was above the upper limit of the normal value (4.6 micrograms/L) and the mean level was clearly elevated at 7.92 micrograms/L. The ICTP concentration correlated with the skin score measuring the extent of the lesions, whereas no such correlation was found for PINP. The ICTP antigen in serum, studied by immunoblotting, had a molecular weight of about twice that of the trypsin-generated fragment isolated from human bone collagen. The mean concentration of serum PINP was 43.9 micrograms/L and no patient exceeded the upper limit of the normal range (80 micrograms/L). We report here for the first time that the concentration of the type I collagen degradation product ICTP in serum shows a close correlation with the extent of skin fibrosis in patients with SSc. We conclude that the increased deposition of type I collagen in this disease is accompanied by an increased turnover of this molecule, indicating a more complex derangement of synthetic and degradative processes than previously acknowledged.
In view of the documented perivascular mononuclear cell infiltration in the involved organs in scleroderma (SSc) and the reported accumulation of gammadelta-T cells in SSc skin and lung, we evaluated gammadelta-T cell interaction with endothelial cells (EC) in vitro. gammadelta- and alphabeta-T cells were isolated from BPMN of SSc patients with early diffuse disease and of matched control subjects by an immunomagnetic method after stimulation with mycobacterium lysate and interleukin-2 for 2 weeks. Lymphocyte adhesion, proliferation, and cytotoxicity to EC were investigated. SSc gammadelta-T cells adhered to cultured EC and proliferated at higher rates than control cells. Furthermore, significant EC cytotoxicity by SSc gammadelta was seen. The cytotoxicity was blocked by addition of anti-gammadelta-TCR antibody and by anti-granzyme A antibody but not by anti-MHC class I and II antibodies. Expression of granzyme A mRNA was seen in five/five SSc gammadelta-T cells and in one/five control cells. alphabeta-T cells from both SSc and control subjects were significantly less interactive with EC than gammadelta-T cells. The data demonstrate EC recognition by SSc gammadelta-T cells and propose gammadelta-T cells as a possible effector cell type in the immune pathogenesis of SSc.
At onset of systemic sclerosis (SSc), T cells have been found to oligoclonally expand in the skin, presumably in response to auto-antigens, but the T cell repertoire has not been evaluated at a later stage. To determine whether a perpetuating immune response contributes to the pathogenesis of stable SSc, the T cell repertoire was analysed in patients with diffuse (d) or limited (l) SSc, and compared to patients with primary Raynaud's phenomenon (RP) or healthy volunteers (Ctrl). The T cell repertoire (total, CD4 or CD8 sorted blood T cells) was analysed by qualitative and quantitative immunoscope (14 BV families analysed) in 11 untreated dSSc and 11 untreated lSSc, 10 RP and 11 Ctrl. To better detect in vivo activated cells, repertoire analysis was also performed on sorted CD4 T cells after in vitro culture with IL-2. In parallel, 6 skin biopsies from SSc patients were analysed. After 7-8 years of disease evolution, SSc patients did not show detectable clonal T cell expansions in the skin, even after tentative expansion from the biopsy with IL-2. Total T cell, sorted CD4 and CD8 T cell repertoires from the blood of patients with SSc did not show significant perturbation as compared to patients with RP and Ctrl. After IL-2 culture for 7 days, blood CD4 T cells from the patients did not preferentially expand as compared to RP and Ctrl. These findings suggest that antigen-driven immune responses may play a lesser role in established SSc than at disease onset.
Systemic sclerosis is characterized by excessive deposition of collagen and other matrix proteins in the skin and internal organs. One hypothesis supports fibroblast stimulation for production of excess amounts of collagen by factors present in the blood or released by cells composing inflammatory tissue infiltrates. Increased numbers of mast cells are present in the involved skin of patients with systemic sclerosis, and histamine has been thought to be a possible mediator of fibrosis in this and other fibrotic conditions. We therefore measured plasma histamine levels in 32 patients with systemic sclerosis and found elevated levels in 18 patients (56%). Elevated plasma histamine levels were more common in patients with diffuse disease (74%), in contrast to limited disease (31%). The degree of clinical activity and the duration of disease could not be correlated with histamine levels.
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BACKGROUND: A high prevalence of depressive symptoms has been described in systemic sclerosis (SSc), but no clear association with organ involvement or objective indices of disease severity has been depicted. To date, no effort has been made to determine the prevalence of depressive symptoms in Italian patients with SSc or to clarify their cause. METHODS: One-hundred-eleven SSc patients were asked to fill in the Beck Depression Inventory (BDI) questionnaire, the scleroderma Health Assessment Questionnaire (sHAQ) and two additional questions assessing the patient's familiar support and the social consequences of the patient's change in physical appearnace. RESULTS: Thirty-seven subjects (33.4%) presented mild to severe depressive symptoms (BDI >/=17). On univariate analysis the diffuse cutaneous form of the disease (p=0.019), higher pulmonary systolic pressures on echocardiogram (p=0.016), lower FVC percentage of predicted values (p=0.022), higher sHAQ values (p<0.001) or higher VAS values for pain (p=0.007), lung involvement (p=0.02), Raynaud's phenomenon severity (p=0.002), ulcers severity (p=0.006) or disease severity (p<0.001), were associated with the presence of pathologic depressive symptoms. On multivariate analysis only the VAS for disease severity relevant to BDI scores (p=0.016). Social behaviour changes due to SSc-related physical involvement were reported in 14 patients (38%) with depressive symptoms (p=0,006) and were more likely to be observed in younger patients (p=0.001) with a more severe Raynauds's phenomenon (p=0.013). CONCLUSIONS: Mild to severe depressive symptoms are common in SSc patients especially in those with a worse perception of disease severity, these patients should be carefully monitored and a psychological assistance counselled whenever necessary.
In order to determine the actual spectrum of abnormal esophageal motility, manometric patterns in 1013 consecutive tracings were established using a classification method that employs esophageal body and lower esophageal sphincter (LES) characteristics. Peristaltic performance and contraction wave parameters were measured in the esophageal body; basal pressure and relaxation were included for the LES. Nine hundred thirty (92%) of the tracings could be completely classified, and 33 different patterns were observed (915 occurring at a rate greater than 1%). Abnormalities were most common in contraction wave parameters (661 tracings, 65%), and least common in LES relaxation (105 tracings, 10%). Patterns most typical of achalasia and diffuse esophageal spasm were found in 6.4% and 5.0% of tracings, respectively. Statistical analysis of the patterns demonstrated that significant bidirectional predictive associations between categories were restricted to features representing pathology-based motor disorders (ie, achalasia and "scleroderma-esophagus"). This systematic classification method is capable of recognizing and cataloging common findings of motor dysfunction in the esophageal body and LES as well as uncommon patterns representing traditional motility disorders. Our findings provide reference data for clinical esophageal manometry.
OBJECTIVE: To develop an overview focusing on the utility of anti-Scl-70 autoantibody determinations in the rheumatic diseases. METHODS: Articles from electronic literature searches were retrieved, critiqued and data were extracted and pooled on anti-Scl-70 (topoisomerase I) in relation to history, optimal tests used for its detection, sensitivity, specificity, positive and negative likelihood ratios, indications, interpretation and pitfalls. RESULTS: Anti-Scl 70 antibodies are very useful in distinguishing systemic sclerosis (SSc) patients from healthy controls, from patients with other connective tissue diseases, and from unaffected family members. Among patients with SSc, anti-Scl-70 positivity is useful in predicting those at higher risk for diffuse cutaneous involvement and interstitial fibrosis/restrictive lung disease, though the latter has not been universally observed. Of the four different techniques notably immunodiffusion, immunoblotting, immunoprecipitation and enzyme-linked immunosorbent assay (ELISA) used to assay anti-Scl-70, immunodiffusion has been the most extensively validated. ELISAs are somewhat less specific than other techniques, especially in distinguishing SSc patients from those with other rheumatic diseases, though newer generation ELISAs have been developed to overcome the problem of low specificity inherent with the traditional techniques. As of yet, the need for serial testing of anti-Scl-70 has not been established. CONCLUSIONS: Evidence-based guidelines suggest that anti-Scl-70 antibodies are very useful in the diagnosis and clinical management of SSc patients and also to establish prognosis in these patients, particularly those with diffuse skin involvement.
This study was designed to assess the relationship between breast implants and certain rheumatologic diseases (rheumatoid arthritis and diffuse connective tissue diseases). The study base was a rheumatological practice in Atlanta, Georgia that started in 1982 and began computerizing its records in 1985. The computerized records through May 1992 included 4229 women patients, 150 with breast implants and 721 with a diagnosis of rheumatoid arthritis (RA) and/or one of the connective tissue diseases (CTDs). Of the 721 patients who had been diagnosed as having rheumatoid arthritis (RA) and/or one of the connective tissue diseases (CTDs), 392 had rheumatoid arthritis, 344 had connective tissue disease, 15 had both rheumatoid arthritis and a connective tissue disease, and 33 had more than one connective tissue disease. Of the patients with connective tissue disease, 179 had systemic lupus erythematosus, 64 had scleroderma, 49 had Sjögren's syndrome, 36 had dermatomyositis or polymyositis, and 49 had mixed connective tissue disease. Data were analyzed by univariate and multivariate techniques including logistic regression. Significant variables included age at first visit, income strata, and period of first visit. Analyses were performed for each clinical diagnosis, for all connective tissue diseases together (CTDs), and for those with rheumatoid arthritis and/or connective tissue disease (RA/CTD). Analyses were performed on the total data base and on the records of new patients (1986-1992). The adjusted odds ratio for breast implants among women who entered the practice in 1986-1992 and were diagnosed as having rheumatoid arthritis and/or one of the connective tissue diseases (RA/CTDs) was 0.45 (0.22-0.90), for those with rheumatoid arthritis was 0.61 (0.28-1.49), for those with any of these specific diffuse connective tissue diseases was 0.34 (0.11-1.06) compared to those without the disease. For systemic lupus erythematosus, the odds ratio of 0.24 (0.03-1.75) was based on a single case who had the disease 5 yr before the implant. For Sjögren's syndrome, the odds ratio was 1.67 (0.39-7.13) based on two cases, one of whom had the disease 5 yr before the implant. The calculated odds ratios for scleroderma, dermatomyositis/polymyositis, and mixed connective tissue disease were zero since no cases were diagnosed among the patients with breast implants. This study found no evidence that women with breast implants are at an increased risk for having rheumatoid arthritis or other diffuse connective tissue disease.
AIM: To define clinical features of systemic sclerosis (SS) in age and sex aspects. MATERIAL AND METHODS: The study covered 100 patients aged 15 to 83 years with SS (24 males and 76 females) lasting for 1-15 years (mean 6.2 +/- 4.1 years). Groups of females and males, with disease onset age under 50 years (32 years) and over 50 years were compared. RESULTS: Males had a prevalent diffuse clinical form of SS with advanced skin syndrome, primarily indurative alterations, marked disturbances of microcirculation, abnormal heart rhythm and conduction, interstitial pulmonary fibrosis with development of pulmonary hypertension. The patients with late SS onset are characterized by development of visceral pathology within the first 3 years of the disease. CONCLUSION: In making SS diagnosis and in the disease treatment it is necessary to consider the patients' sex and age, peculiarities of the debut, clinical picture, course and prognosis.
A retrospective study of systemic sclerosis (SSc) in Blacks attending a tertiary hospital on the Witwatersrand, South Africa, was undertaken. The female:male ratio of the 63 patients was 4.6:1 and the mean age of onset of SSc was 36.1 yr. Four of the 11 males were ex-goldminers and nine females resided close to goldmines. Forty-one patients had diffuse cutaneous SSc (dcSSc), 18 had limited cutaneous SSc (lcSSc) and four were unclassified. Overall, 56% had pulmonary fibrosis, 37% had myositis and 98% were antinuclear antibody (ANA) positive, with a notable absence of anti-centromere antibodies. Subset comparisons showed myositis and a reduced forced vital capacity to be significantly more common with dcSSc than lcSSc. The only significant sex differences were that arthralgia/arthritis was more common in women, while calcinosis occurred more frequently in men. Seven of the eight known deaths occurred in patients with dcSSc. These findings, particularly the age of disease onset, predominance of the dcSSc subset, inflammatory features of myositis and a raised erythrocyte sedimentation rate, and absence of anti-centromere antibodies, are similar to those reported previously in African-Americans.
Two hundred and thirty-seven patients with systemic sclerosis were followed prospectively in a scleroderma clinic. The overall 3, 6, and 9-year survival rates were 86, 76 and 61 per cent respectively. Renal, cardiac and pulmonary disease, and older age at enrollment were adverse prognostic factors associated with reduced survival. There were no significant differences in survival between males and females or in patients with restricted compared to those with diffuse skin thickening. Death from systemic sclerosis was most frequently due to pulmonary hypertension, with fewer than expected deaths from renal or cardiac causes. Twenty-eight per cent of deaths were due to causes unrelated to systemic sclerosis, most commonly cancer and ischaemic heart disease, and in older patients.
OBJECTIVES: To report two patients with watermelon stomach associated with systemic sclerosis (SSc) and review the literature on that subject. METHODS: We describe the clinical presentation, course and outcome of our two patients and reviewed the medical literature registered in the MedLine PubMed database from 1966 to 1999 by using the key words watermelon stomach, gastric antral vascular ectasia, systemic sclerosis, scleroderma. RESULTS: The two patients presented with microcytic hypochromic anemia. Esophagogastroscopy showed multiple linear vascular malformations in the antrum compatible with watermelon stomach. They responded to Nd-Yag laser therapy with resolution of the lesions and improvement of the anemia. Patient 1 had a history of diffuse SSc while patient 2 developed limited SSc 2 years after the diagnosis of watermelon stomach. A literature review disclosed 16 documented case reports of watermelon stomach associated with SSc, 14 of whom were women. In most cases, watermelon stomach occurred in patients with established SSc but in some it antedated it by several years. In many cases, other autoimmune syndromes such as hypothyroidism, primary biliary cirrhosis, and Sjögren's syndrome were present. The presenting symptom was iron deficiency anemia, which in 11 cases was severe enough to require blood transfusions. Nine patients were successfully treated with several transendoscopic treatments, four required surgical intervention, and in three treatment was not specified. CONCLUSION: Although watermelon stomach is a rare syndrome, it is recognized as a cause of persistent bleeding in patients with SSc. Awareness of this condition may increase its recognition and treatment.
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It has been analyzed seven patients, five females and two males, affected by progressive systemic sclerosis. Their ages range from 35 to 60 years. Three of them correspond to the CREST syndrome named variant. There were made: physical examination, electrocardiogram, echocardiogram and radionuclide techniques such as: Thallium perfusion (T201) and ventriculography (Tc99). The cardiac examination of all the patients showed: Left myocardiopathy in six patients, as well right myocardiopathy in two of them. Four patients were affected by chronic cor pulmonale, due to pulmonary hypertension. All the patients had developed diffuse thallium perfusion defects as well, having abnormal resting left ventricular function in three patients and function abnormality from right ventricle in two patients. It is necessary to point out the importance of making such study systematically, even in the case cardiac symptoms absence.
Interstitial pulmonary fibrosis is a common manifestation of systemic sclerosis (SSc) and is a pathologic feature shared by a variety of other diseases. In these other disease processes, the glycoprotein fibronectin (FN) has been shown to be released by the alveolar macrophage, and is thus implicated in the development of fibrosis. We therefore studied the release of FN by alveolar macrophages obtained by bronchoalveolar lavage of 17 patients with SSc and 14 controls. We found that SSc alveolar macrophages released significantly more FN than did those of controls. Furthermore, the level of FN correlated positively with the level of inflammation determined by cellular analysis of lavage fluid and negatively with carbon monoxide diffusing capacity. FN may therefore play a role in the development of lung fibrosis in SSc and may be a marker of alveolitis.