Vasculitis in patients with systemic sclerosis and severe digital ischaemia requiring amputation.

OBJECTIVES--To document the incidence of histological vasculitis in amputation specimens from patients with severe digital ischaemia secondary to systemic sclerosis (SSc), and to look for an association between anticardiolipin (aCL) antibodies and severe digital ischaemia in SSc. METHODS--This was a retrospective review of patients with SSc who underwent amputation for digital ischaemia over a three year period. RESULTS--Five of nine patients had histological vasculitis, four of whom had aCL antibodies, although these were not present in high titre. CONCLUSION--Vasculitis does occur in SSc, at least in that subgroup with severe peripheral ischaemia. These findings could have implications for treatment of this subgroup of patients with SSc.     

Association between systemic sclerosis and breast cancer: eight new cases and review of the literature

Several studies have demonstrated an increased frequency of cancer in patients with systemic sclerosis (SSc), specially lung and breast cancers. The pathogenesis of the association between SSc and cancer is not fully established. The aim of this study was to describe new cases of the association between SSc and breast cancer and to perform a review of the literature. We retrospectively studied the medical files of eight patients followed in our institution for SSc and breast cancer. We analyzed them with data available in the literature for a total of 46 patients. Cutaneous extension of SSc was clearly mentioned in 17 cases: the SSc was limited in 10 cases and diffuse in 7 cases The median age at the diagnosis of cancer was 54 years (range: 40–71). The median duration between SSc onset and breast cancer diagnosis was 11.5 months (range: 0–288). The duration between SSc onset and breast cancer diagnosis was 12 months in 27 of 44 patients (61.4%), and in 11 (25%) of them the diagnosis of both diseases was made simultaneously. It was clearly mentioned for 35 patients whether the diagnosis of breast cancer was made before or after the onset of SSc. The diagnosis of breast cancer was made before SSc onset in 17 of 35 patients (48.6%) and after SSc onset in 18 of 35 patients (51.4%). For 33 patients, the follow-up was available: 18 (54.5%) died, 11 (33.3%) of them within the 1st year after the diagnosis of the cancer. For none of the patients did the anticancer treatment improve the SSc. The close temporal relationship between SSc onset and breast cancer diagnosis is highly suggestive of a pathophysiological link. SSc is probably not a paraneoplastic disease since the anticancer treatment has no influence on the evolution of SSc. However, it can be suggested that SSc could be a disease facilitating breast cancer and/or metastases development.The first two authors have contributed equally to this work     

Serum levels of monocyte chemotactic protein-3/CCL7 are raised in patients with systemic sclerosis: association with extent of skin sclerosis and severity of pulmonary fibrosis

OBJECTIVE: To determine serum levels of monocyte chemotactic protein-3 (MCP-3) and its clinical associations in patients with systemic sclerosis (SSc). METHODS: Serum MCP-3 levels from 69 patients with SSc were examined by ELISA. RESULTS: Serum MCP-3 levels were raised in patients with SSc (n = 69) compared with healthy controls (n = 28). Patients with diffuse cutaneous SSc (n = 36) had higher levels of serum MCP-3 than those with limited cutaneous SSc (n = 33). Patients with raised MCP-3 levels had pulmonary fibrosis and decreased vital capacity (VC) more often than those with normal MCP-3 levels. MCP-3 levels correlated positively with the extent of skin fibrosis, and inversely with %VC and carbon monoxide transfer factor (Tlco) in patients with SSc. CONCLUSION: MCP-3 levels were increased in patients with SSc, and correlated with the extent of skin sclerosis and the severity of pulmonary fibrosis. These results suggest that MCP-3 may have a role in the development of fibrosis in SSc.     

Impact of pain in health related quality of life of patients with systemic sclerosis

OBJECTIVES: Systemic sclerosis (SSc) has an heterogenous clinical pattern, with variable organ involvement and degrees of severity. Like in other rheumatic diseases, the self-questionnaires have been used to evaluate SSc globally. The aim of the study is as to evaluate the quality of life (QoL) in patients with either diffuse or limited SSc, and to examine the impact of pain on the QoL scores. METHODS: Patients with SSc, either diffuse or limited SSc, were included in a cross-sectional study. The QoL was evaluated with the short-form 36 (SF-36) and the functional repercussion with the SSc-modified Health Assessment Questionnaire (S-HAQ). RESULTS: A total of 89 patients (67 with diffuse and 22 with limited SSc) were included. The SF-36 score values were lower in SSc patients than those reported in the general population. The physical component scores (PCS) of the SF-36 was significantly worse in diffuse compared with limited SSc (P < 0.05). The PCS was significantly negatively related to the number of clinical manifestations (ANOVA, P < 0.0001). The mental component score (MCS) was not influenced by the type of SSc or the number of clinical manifestations presented by the patient. The QoL of SSc patients was highly correlated with pain (R = 0.69) and disability (R = 0.70). Interestingly, the QoL of SSc patients was only slightly correlated with cutaneous (R = 0.42) and pulmonary involvement (R = 0.57). CONCLUSION: The QoL of patients with SSc is strongly influenced by the type of SSc, the burden of clinical manifestations, the functional disability and by the pain, whatever its cause. The treatment of pain should be considered as priority to improve the QoL of SSc patients.     

Prevalence of anti-CCP antibodies in systemic sclerosis

Joint involvement in systemic sclerosis (SSc) commonly occurs as arthralgias, while a true arthritis is less frequent. The most common arthritis developing in SSc is rheumatoid arthritis (RA) and its diagnosis may be misled by concomitant joint contracture or tendon sheath involvement due to SSc. Anti-citrullinated cyclic peptide (CCP) antibodies are an emerging tool to diagnose RA and have shown to be more specific than rheumatoid factor. We assessed the prevalence of anti-CCP antibodies in SSc patients and evaluated their sensitivity and specificity for associated RA. Searching for RF and anti-CCP antibodies and joint examination were carried out in sixty consecutive SSc patients. Hands and feet standard x-rays were performed in patients complaining with arthralgia and/or arthritis. Six out of sixty (10%) SSc patients had RA according to 1987 ARA revised criteria. Anti-CCP were detected in 5 patients (sensitivity 83%) and RF was present in all RA patients (sensitivity 100%). However, anti-CCP antibodies had a much higher specificity (94%) than RF (41%) for RA. Our study suggests that anti-CCP antibodies are a useful test to identify patients with SSc having also RA. This is crucial in the management of SSc because may allow an adequate therapy of RA and prevent further joint damage in patients who already have a poor quality of life.     

Sjogren's syndrome is associated with and not secondary to systemic sclerosis

OBJECTIVES: When Sj?gren's syndrome (SS) is secondary to rheumatoid arthritis, the sicca syndrome is less serious and anti-SSA/SSB antibodies are found less frequently than in primary SS (pSS). When SS is associated with systemic lupus erythematosus, clinical and serological patterns are similar to those of pSS. We aimed to determine whether SS, accompanying systemic sclerosis (SSc), could be considered secondary to or associated with SSc and whether the coexistence of both modifies the severity and the outcome of each disease. Patients and METHODS: A retrospective multicentric study was conducted to compare (i) characteristics and complications of SS between 27 patients with SS and SSc (SS-SSc) and 202 patients with pSS, and (ii) the characteristics of SSc and complications between the SS-SSc group and 94 patients with SSc alone. RESULTS: SS features were similar in both SS-SSc and pSS patients, except for peripheral neuropathy and arthritis, which was more common in SS-SSc than in the pSS patients (P = 0.02 and 0.05, respectively). SSc appears to be less severe in patients with SS-SSc than SSc alone with a lower frequency of lung fibrosis (P = 0.05). Compared with patients with pSS or SSc alone, SS-SSc patients were more likely to have another autoimmune disorder and other autoantibodies (SS-SSc vs pSS, P = 0.02 and P = 0.03, respectively). CONCLUSION: SS seems to be associated with and not secondary to SSc. SS associated with SSc has the same features as pSS, but SSc seems to be less serious. Moreover, the association of SS and SSc is frequently accompanied by a spreading of autoimmunity.     

Activation of the complement system in systemic sclerosis. Relationship to clinical severity

Using newly developed techniques, we investigated the complement pathways and the extent of their activation in patients with systemic sclerosis (SSc) of both the diffuse cutaneous and limited cutaneous types. Plasma levels of the fragments C3d, C4d, and Ba were measured in patients with SSc and in matched control subjects. All fragments and ratios were higher in SSc patients than in controls (P less than 0.05), demonstrating that complement activation occurs in SSc. Levels of C3d, C3d:C3, Ba, and Ba:factor B were higher in patients with diffuse cutaneous SSc patients than in controls (P less than 0.01). C3d, C3d:C3, C4d, and C4d:C4 levels were also higher in patients with limited cutaneous SSc than in controls (P less than 0.05). These results show that complement activation occurs in SSc patients and that it reflects clinical severity. Complement activation may therefore have a pathogenetic role in SSc, and its measurement may prove useful in monitoring the disease.     

Understanding diagnostic pathways in systemic sclerosis and systemic sclerosis-associated interstitial lung disease: A retrospective cohort study

Systemic sclerosis-associated interstitial lung disease (SSc-ILD) is usually detected in a patient known to have SSc but may be diagnosed prior to SSc. We probed an insurance database to investigate documentation of ILD prior to SSc. Using Optum’s Clinformatics^® Data Mart Database, we identified patients with an SSc index date between January 1, 2010, and September 30, 2015, based on International Classification of Diseases (ICD)-9-Clinical Modification (CM) codes, ≥2 medical claims associated with SSc on different dates within 1 year, and ≥3 years of continuous enrollment prior to SSc index date (ICD-9-CM cohort). We identified an ICD-10-CM cohort comprising patients with an SSc index date between October 1, 2017, and June 30, 2019, based on ICD-10-CM codes, ≥2 medical claims associated with SSc on different dates within 1 year, and ≥2 years of continuous enrollment prior to SSc index date. ILD was defined as ≥2 medical claims associated with ILD on different dates. The ICD-9-CM and ICD-10-CM cohorts comprised 1779 and 1032 patients, respectively. In these cohorts, respectively, 7.6% and 9.3% of patients had their second medical claim associated with ILD prior to their SSc index date, and 4.3% and 5.6% of patients had their second medical claim associated with ILD >1 year prior to the SSc index date. In this analysis, 4% to 6% of patients with SSc had claims for ILD >1 year prior to a claim for SSc. These data show that SSc can affect the lung early and demonstrate the importance of screening patients with SSc for ILD and patients with ILD for SSc.     

Angiogenesis and vasculogenesis in systemic sclerosis

In addition to inflammatory infiltrates and an accumulation of extracellular matrix proteins, vascular changes are a hallmark in the pathogenesis of systemic sclerosis (SSc). Consistent with the ongoing endothelial cell apoptosis, several markers of EC damage are up-regulated in the serum of SSc patients. Surprizingly, vascular endothelial growth factor (VEGF), a very potent angiogenic molecule, is overexpressed in SSc patients despite the insufficient angiogenesis. VEGF can protect patients from fingertip ulcers, but a prolonged overexpression of VEGF might have paradoxical effects leading to the formation of irregular vessels similar to that observed in SSc. Besides defective angiogenesis, recent studies suggest that vasculogenesis is also impaired in SSc patients with reduced numbers and functional defects of endothelial progenitor cells.     

Sklerodermie-assoziierte Autoantikörper – klinische und diagnostische Relevanz

In systemic sclerosis (SSc) and its variants, autoantibodies are the best known immunological aberration. In more than 95% of the patients, antinuclear antibodies or other autoantibodies can be detected. In about 90% of SSc patients with antinuclear antibodies, scleroderma associated autoantibodies highly specific for systemic sclerosis are found. These autoantibodies usually exclude each other in individual patients, and they are detectable early, persisting during the course of the disease. SSc patients characterized by scleroderma associated autoantibodies belong to disease subsets which are relatively homogeneous in clinical, genetic and prognostic terms. Besides these diagnostically relevant autoantibodies, numerous additional ones have also been described. These are neither SSc specific nor mutually exclusive, and their antigens have only been partially characterized. Some, however, are thought to be relevant to the as yet unanswered question of whether autoantibodies are directly involved in SSc pathogenesis.     

Levels of circulating endothelial progenitor cells in systemic sclerosis

OBJECTIVE: Contradictory results have been reported regarding vasculogenesis in systemic sclerosis (SSc). Our aim was to investigate bone marrow-derived circulating endothelial precursors (EPCs) and activated circulating endothelial cells (CECs) in SSc patients. METHODS: Peripheral blood from consecutive patients with SSc hospitalised for systemic follow-up was analysed and compared with blood from patients with active refractory rheumatoid arthritis (RA) and osteoarthritis (OA). EPCs were quantified by cell sorting and flow cytometry and were identified as circulating CD34+CD133+ cells. Activated CECs were defined as CD105+CD62+CD105+CD102+CD105+CD106+ cells. RESULTS: Patients with SSc had higher putative EPC levels than OA patients, but lower levels than RA patients. In SSc patients, EPC levels increased with European disease activity score. Activated CEC levels were high in SSc patients and RA patients, but not correlated with EPC levels. CONCLUSION: These results together and previous data suggest that EPCs may be recruited during active vascular disease but that the sustained ischaemic conditions of SSc may eventually lead to EPCs depletion.     

Maximum blood flow and microvascular regulatory responses in systemic sclerosis

Objectives. To investigate microvascular function using laser Doppler imaging (LDI) following response to hyperaemia, neurovascular reflex and iontophoresis in systemic sclerosis (SSc) in comparison with primary Raynaud's phenomenon (PRP) and age-matched controls. A secondary aim was to evaluate if SSc patients with a higher Medsger vascular score have lower endothelial responses. Methods. Twenty patients with SSc, 10 PRP and 17 controls were studied. Patients with SSc were scored using the vascular component of the Medsger severity scale. A baseline LDI scan was performed on the dorsal aspect of both hands. Digital responses were quantified following maximum hyperaemic response (MHR), contralateral vasoconstrictor response (CLVc) and iontophoresis with acetylcholine (Ach)-endothelial dependent and sodium nitroprusside (SNP)-endothelial independent. Mean blood flow was quantified over a standard region of interest. Results. MHR was lower in SSc patients compared with controls (P < 0.001). A similar trend was seen when comparing SSc with PRP although this did not reach significance (P = 0.07). CLVc and Ach/MHR were lower in SSc vs PRP (P < 0.05) and controls (P < 0.001). No difference was observed in MHR, CLVc and Ach/MHR between PRP and controls. Overall, SNP/MHR was similar in all the three groups. SSc patients with a higher Medsger vascular score had lower endothelial-dependent (P < 0.01) and independent (P < 0.05) responses. Conclusion. SSc patients have abnormal microvascular regulatory responses compared with PRP and controls. This study also suggests that the degree of endothelial dysfunction may be related to the degree of peripheral vascular involvement.     

Disease subsets, antinuclear antibody profile, and clinical features in 127 French and 247 US adult patients with systemic sclerosis

OBJECTIVE: To investigate the specificities of antinuclear antibodies (ANA) associated with systemic sclerosis (SSc) disease classification and internal organ involvement among patients with SSc of different origins (European and American). METHODS: Serum samples from 374 adult patients diagnosed with SSc were studied: 127 French patients (Paris) were compared with 247 US patients (Pittsburgh). Patients were classified into diffuse cutaneous (dc) and limited cutaneous (lc) SSc subsets. Antibodies associated with SSc were determined by protein and/or RNA immunoprecipitation, indirect immunofluorescence, and immunodiffusion. RESULTS: SSc classification differed significantly in the 2 cohorts: lcSSc and overlap patients with lcSSc combined made up 76% of the French series versus 52% of the US group (p < 0.0001). The frequency of anti-RNA polymerase III antibody was significantly increased in US patients compared with French patients (p < 0.0001). The frequency of anti-topoisomerase I (topo I) antibody was significantly increased among French patients (p < 0.0048). Anti-topo I-positive French SSc patients were less likely to have dcSSc (38% vs 65%) and more likely to have milder disease than US anti-topo I-positive patients. The French dcSSc patients had lower proportions of joint/tendon manifestations and renal crisis (7% vs 17%), but more often had radiographic evidence of pulmonary fibrosis (57% vs 30%). French lcSSc patients had a lower frequency of pulmonary arterial hypertension than US lcSSc patients (9% vs 31%; p = 0.002). CONCLUSION: There are disease classification and SSc-related serum autoantibody differences between French and American patients with SSc. These differences help to explain variations in clinical features reported from different geographic regions.     

Increased arterial stiffness as the marker of vascular involvement in systemic sclerosis

OBJECTIVE: Endothelial dysfunction and vasculopathy of the small and large vessels are crucial pathogenic factors in systemic sclerosis (SSc). Accelerated atherosclerosis and impaired flow-mediated vasodilation have been described in SSc. We evaluated arterial stiffness in patients with SSc compared to healthy controls. METHODS: Augmentation index (AI) and pulse wave velocity (PWV) of the brachial artery were measured in 40 patients with SSc and 35 age and sex matched healthy controls using an arteriograph system. RESULTS: AI was significantly higher in SSc patients (9.02) compared to controls (-41.15) (p < 0.0001). PWV was similarly higher in patients with SSc (9.67 m/s) than in controls (8.00 m/s) (p = 0.0017). PWV was significantly higher in patients with localized SSc (10.04 +/- 2.01 m/s) compared to those with diffuse SSc (8.39 +/- 1.87 m/s) (p = 0.034). There was a significant, positive linear correlation between AI and PWV (r = 0.32, p = 0.045). We also observed significant correlations between AI and age (r = 0.31, p = 0.048), PWV and age (r = 0.36, p = 0.021), and PWV and disease duration (r = 0.40, p = 0.011) in SSc patients. CONCLUSION: Increased AI and PWV of the aorta in comparison to age and sex matched healthy controls indicate increased large-vessel stiffness in patients with SSc. PWV and AI are reproducible indicators of the presence and degree of arterial stiffening. Because arterial stiffness may correlate with disease duration and age in patients with SSc, it may be a useful diagnostic test in the assessment of arterial function. Increased vascular stiffness may be therapeutically targeted by statins and other vasoprotective agents during the management of SSc.     

Pulmonary-renal syndrome in systemic sclerosis: a report of three cases and review of the literature

We describe three cases of acute renal failure with diffuse alveolar hemorrhage, which is designated pulmonary-renal syndrome (PRS), in systemic sclerosis (SSc) and review the literature to better define this rare but severe complication of SSc. The clinical course of three SSc patients with acute renal failure and concomitant diffuse alveolar hemorrhage are reported, and the literature published between 1967 and 2005 is reviewed following a PubMed search. Including our cases, a total of 19 SSc patients with acute renal failure and concomitant diffuse alveolar hemorrhage have been reported. Pulmonary-renal syndrome developing in SSc patients can be categorized clinicopathologically into three entities: PRS with thrombotic microangiopathy, PRS with small vessel vasculitides accompanied with SSc, and d-penicillamine-induced Goodpasture-like syndrome. Patients with scleroderma PRS with thrombotic microangiopathy, to which group our all patients belong, often developed diffuse alveolar hemorrhage after receiving high-dose corticosteroid therapy. Pulmonary-renal syndrome is a fatal complication of SSc and results from different pathogenic processes. Prompt differential diagnosis between the subsets is critical, because therapeutic strategy may differ in the use of high-dose corticosteroid and plasma exchange between the subsets of PRS. Clinical courses of the patients with PRS with thrombotic microangiopathy suggest that high-dose corticosteroid therapy is a trigger of diffuse alveolar hemorrhage in patients with diffuse SSc with signs of thrombotic microangiopathy.     

Non-invasive diagnostic and functional evaluation of cardiac involvement in patients with systemic sclerosis

Elevated serum brain natriuretic peptide (BNP) released from myocytes of ventricles upon stretch have been found in patients with isolated right ventricular (RV) pressure overload. However, limited data suggest that serum BNP may be elevated in systemic sclerosis (SSc) patients, especially with RV dysfunction. We assessed serum N-terminal proBNP (NT-proBNP) in SSc and evaluated whether it reflects the severity of RV overload. We prospectively studied 51 consecutive patients (47F, mean age 53.3 +/- 15.2 years) with SSc (mean disease duration 9 +/- 12.4 years). The control group formed 31 healthy subjects (27F, mean age 52.6 +/- 12.1 years). NT-proBNP level, 6-minute walking test (6MWT), and transthoracic echocardiography (TTE) for the assessment of RV overload were performed. Serum NT-proBNP exceeded the reference value of 125 pg/mL in 31 (61%) SSc patients. The mean serum log NT-proBNP concentration in SSc was higher than in controls (2.138 +/- 0.527 vs. 1.634 +/- 0.420 pg/mL, p < 0.001). 13 (25%) SSc patients have tricuspid regurgitation peak gradient (TRPG) exceeding 31 mmHg reflecting pulmonary arterial hypertension (PAH). The SSc presented other echocardiographic signs of RV overload. Mean 6MWT distance was shorter in SSc than in controls (528 +/- 100 vs. 617 +/- 80 m, p < 0.001). NT-proBNP level correlated positively with TRPG, RV diameter, RV Tei index and negatively with 6MWT distance. ROC analysis identified >115 pg/ml as the best NT-proBNP threshold predicting PAH for SSc patients (sensitivity 92%, specificity 44%). Results of our study suggest that NT-proBNP measurement is a useful screening method for PAH in SSc patients. Since elevated plasma NT-proBNP level reflects the degree of right ventricular overload and limitation of exercise capacity, abnormal NT-proBNP levels should imply further evaluation including echocardiography.     

Incidence of lymphoma in systemic sclerosis: a retrospective analysis of 218 Hungarian patients with systemic sclerosis

Recent results suggest that B cells may have multiple pathogenic roles in systemic sclerosis (SSc) and there may be increased incidence of B cell lymphomas in SSc. Here, we assessed the prevalence of lymphomas in a large SSc cohort. We analyzed data of 218 Hungarian patients undergoing follow-ups in our institutions between 1995 and 2007. During this follow-up period, there were three SSc patients, who eventually developed B cell lymphoma. The first case is a woman with diffuse cutaneous form of SSc (dcSSc) including pulmonary, cardiac, gastrointestinal, and renal manifestations and anti-topoisomerase I antibody positivity. B cell chronic lymphocytic leukemia (B-CLL) with Zap70 expression (Rai I stage) developed 2 years after the onset of SSc. The second case is a woman with dcSSc presenting with pulmonary, cardiac, and gastroesophageal manifestations. Twenty-one months after disease onset, a chronic small lymphocytic B cell non-Hodgkin's lymphoma was diagnosed from retroperitoneal lymph nodes. Our third case is a woman with dcSSc and no internal organ manifestations. She also developed Zap70-positive B-CLL, stage Rai I 9 months after the onset of SSc. Thus, there were three cases of B cell lymphoma among our 218 SSc patients (1.38%). The association of scleroderma and non-Hodgkin's lymphoma may be a rather uncommon feature; however, the incidence of lymphoma among Hungarian SSc patients may be 1.9-2.5 times higher than that in the general population. In our three patients, B cell lymphoma developed within 2 years after the onset of SSc. Altered B cell function implicated in the pathogenesis of SSc may lead to the development of lymphoid malignancies.     

Patients with scleroderma may have increased risk of osteoporosis. A comparison to rheumatoid arthritis and noninflammatory musculoskeletal conditions

OBJECTIVE: To investigate if subjects with scleroderma (systemic sclerosis, SSc) have increased risk for developing osteoporosis (OP). METHODS: A survey assessing demographics, diagnosis/investigations for OP, and risk factors for OP was mailed to 129 patients with SSc, 158 controls with noninflammatory musculoskeletal (MSK) disease, and 230 positive controls with rheumatoid arthritis (RA). All available charts were reviewed and results were included in analyses of demographics, OP status, past bone mineral density (BMD), and past steroid use. In addition, we recorded BMD results (T score) of SSc patients with their matched RA controls. Analyses adjusted for age were done for SSc versus MSK and SSc versus RA. RESULTS: The response rate was 61% for patients with SSc (n = 28 diffuse, 51 limited disease), RA 67%, and MSK 59%; however, through chart review, 159 SSc, 140 MSK, and 235 RA patients were included in the analyses. Mean age and proportion of women did not differ between groups. Disease duration was longer in RA versus SSc group (16.5 vs 11.5 yrs; p < 0.0001). The prevalence of OP in SSc was similar to RA controls (19.4% vs 16.7%; p = 0.38) but likely higher than MSK controls (12.2%; p = 0.054). Subjects with SSc reported a higher rate of disability (41.0% vs 15.6%; p = 0.0001) and less family history of OP (22.8% vs 46.7%; p = 0.0006) compared with the MSK control group. There were no differences between groups in reports of fracture (35% SSc, 43% MSK, 37% RA; p = 0.5) or OP related fractures (4% SSc, 11% MSK, 11% RA; p = 0.5). Subjects with SSc were less likely to have had a BMD done in the past compared to RA (40.9% vs 62.6%; p = 0.0001). Subjects with RA who reported OP had longer disease duration than RA without OP (18 +/- 1.7 yrs vs 12 +/- 0.8; p = 0.0009). Results from the chart review showed that the T scores of SSc (n = 56, mean age 62.9 +/- SD 10.1 yrs) at lumbar spine (SSc -1.01 vs RA -0.97), femoral neck (SSc -2.07 vs RA -1.46; p = 0.01, adjusting for age p = 0.26), and total hip region (SSc -1.52 vs RA -1.25) were comparable to or even lower than the RA group (n = 56, mean age 62.2 +/- SD 10.7 yrs). CONCLUSION:The prevalence of OP in patients with SSc was comparable to those with RA, but higher than in the MSK group. Age was found to be an important factor, as expected. Also, our results indicated that BMD (T score) in SSc was similar to or even lower than in patients with RA. Increasing the awareness to order BMD measurements in patients with SSc may be warranted based on our results, especially for older patients.     

Direct binding of anti-DNA topoisomerase I autoantibodies to the cell surface of fibroblasts in patients with systemic sclerosis

OBJECTIVE: Fibroblasts play a crucial role in the development of systemic sclerosis (SSc), and antifibroblast antibodies (AFAs) capable of inducing a proinflammatory phenotype in fibroblasts have been detected in the sera of SSc patients. This study examined the prevalence of AFAs in SSc and other diseases and the possible correlation between AFAs and known antinuclear antibody specificities in SSc patients. METHODS: Sera from 99 patients with SSc, 123 patients with other autoimmune and nonautoimmune diseases, and 30 age- and sex-matched healthy controls were examined. AFA prevalence was assessed by flow cytometry and further characterized by indirect immunofluorescence, enzyme-linked immunosorbent assay (ELISA), and immunoblotting. Anti-topoisomerase I (anti-topo I) from SSc sera were purified by affinity chromatography on topo I. RESULTS: AFAs were more common in SSc patients (26.3%) than in any other disease groups studied. The presence of AFA was significantly associated with pulmonary involvement and death. AFA-positive sera from SSc patients bound to all human and rodent fibroblasts tested, but not to human primary endothelial cells or smooth muscle cells. All SSc AFAs strongly reacted with topo I by ELISA and immunoblotting. The binding intensity of SSc AFAs correlated strongly with reactivity against topo I on immunoblots of fibroblast extracts and with the immunofluorescence pattern typical of anti-topo I on permeabilized cells. Total IgG and affinity-purified anti-topo I from AFA-positive SSc sera were found to react with the surface of unpermeabilized fibroblasts by flow cytometry as well as by immunofluorescence and confocal microscopy. CONCLUSION: This is the first report establishing that AFAs in SSc are strongly correlated with anti-topo I and, furthermore, that anti-topo I antibodies themselves display AFA activity by reacting with determinants at the fibroblast surface.