[Show abstract][Hide abstract] ABSTRACT: Dermatomyositis (DM) is a major clinical subset of autoimmune myositis (AIM). The characteristic DM rash (Gottron papules, heliotrope rash) and perifascicular atrophy at skeletal muscle biopsy are regarded as specific features for this diagnosis. However, new concepts are challenging the current definition of DM. A modified Bohan and Peter classification of AIM was proposed in which the core concept was the inclusion of the diagnostic significance of overlap connective tissue disease features. In this clinical classification, a DM rash in association with myositis in the absence of overlap features indicates a diagnosis of pure DM. However, overlap features in association with myositis allow a diagnosis of overlap myositis (OM), irrespective of the presence or absence of the DM rash. Perifascicular atrophy may be present in both pure DM and OM. Recently, the presence of perifascicular atrophy in myositis without a DM rash was proposed as diagnostic of a novel entity, adermatopathic DM. We conducted the present study to evaluate these new concepts to further differentiate pure DM from OM.Using the modified Bohan and Peter classification, we performed a follow-up study of a longitudinal cohort of 100 consecutive adult French Canadian patients with AIM, including 44 patients with a DM phenotype, defined as a DM rash, and/or DM-type calcinosis, and/or the presence of perifascicular atrophy on muscle biopsy. A detailed evaluation was performed for overlap features, the extent and natural history of the DM rash, adermatopathic DM, DM-specific and overlap autoantibodies by protein A immunoprecipitation on coded serum samples, and associations with cancer and survival.Two distinct subsets were identified in patients with a DM phenotype: pure DM (n = 24) and OM with DM features, or OMDM (n = 20). In pure DM, the DM rash was a dominant finding. It was the first disease manifestation, was always present at the time of myositis diagnosis, and was associated with a high cutaneous score and chronicity. Concurrent heliotrope rash and Gottron papules (positive predictive value [PPV] 91%), as well as the V-sign and/or shawl sign (PPV 100%), were diagnostic of pure DM. Anti-Mi-2, anti-MJ, and anti-p155 autoantibodies were present in 50% of pure DM patients and were restricted to this subset (PPV 100%). Cancer was present in 21% of pure DM patients. The 15-year survival was excellent (92%).In contrast, in patients with OMDM, the first manifestation was proximal muscle weakness or other skeletal muscle-related complaints. The DM rash appeared at diagnosis or at follow-up, was associated with a low cutaneous extent score and was transient. Adermatopathic DM, which was absent in pure DM, was highly predictive (PPV 100%) of OMDM. Overlap autoantibodies (including anti-Jo-1, anti-PL-7, anti-PM-Scl, anti-U1RNP, and/or anti-U5-RNP) were found in 70% of OMDM patients. OMDM was not associated with cancer, but the 15-year survival was significantly decreased (65%).Perifascicular atrophy occurred as commonly in OMDM (n = 6/20, 30%) as in pure DM (n = 4/24, 17%) patients. These 6 OMDM patients had adermatopathic DM at myositis diagnosis, and only 1 of them developed a DM rash at follow-up, emphasizing the lack of specificity of perifascicular atrophy for pure DM.In conclusion, using the modified Bohan and Peter classification of AIM allowed identification of OMDM, a new clinical subset of OM. Furthermore, identification of OMDM allowed recognition of pure DM as a new entity that was distinct from OMDM or from OM without DM features. However, the absolute specificity of a DM rash and perifascicular muscle atrophy for the diagnosis of pure DM was lost. The distinctive clinical manifestations and autoantibody profiles presented are proposed as diagnostic criteria to differentiate pure DM from OMDM.
[Show abstract][Hide abstract] ABSTRACT: Autoimmune myositis encompasses various myositis-overlap syndromes, each being identified by the presence of serum marker autoantibodies. We describe a novel myositis-overlap syndrome in 4 patients characterized by the presence of a unique immunologic marker, autoantibodies to nuclear pore complexes. The clinical phenotype was characterized by prominent myositis in association with erosive, anti-CCP, and rheumatoid factor-positive arthritis, trigeminal neuralgia, mild interstitial lung disease, Raynaud phenomenon, and weight loss. The myositis was typically chronic, relapsing, and refractory to corticosteroids alone, but remitted with the addition of a second immunomodulating drug. There was no clinical or laboratory evidence for liver disease. The prognosis was good with 100% long-term survival (mean follow-up 19.5 yr).
By indirect immunofluorescence on HEp-2 cells, sera from all 4 patients displayed a high titer of antinuclear autoantibodies (ANA) with a distinct punctate peripheral (rim) fluorescent pattern of the nuclear envelope characteristic of nuclear pore complexes. Reactivity with nuclear pore complexes was confirmed by immunoelectron microscopy. In a cohort of 100 French Canadian patients with autoimmune myositis, the nuclear pore complex fluorescent ANA pattern was restricted to these 4 patients (4%). It was not observed in sera from 393 adult patients with systemic sclerosis (n = 112), mixed connective tissue disease (n = 35), systemic lupus (n = 94), rheumatoid arthritis (n = 45), or other rheumatic diseases (n = 107), nor was it observed in 62 normal adults.
Autoantibodies to nuclear pore complexes were predominantly of IgG isotype. No other IgG autoantibody markers for defined connective tissue diseases or overlap syndromes were present, indicating a selective and highly focused immune response. In 3 patients, anti-nuclear pore complex autoantibody titers varied in parallel with myositis activity, suggesting a pathogenic link to pathophysiology. The nuclear pore complex proteins, that is, nucleoporins (nup), recognized by these sera were heterogeneous and included Nup358/RanBP2 (n = 2 patients), Nup90 (n = 1), Nup62 (n = 1), and gp210 (n = 1). Taken together the data suggest that nup autoantigens themselves drive the anti-nup autoimmune response. Immunogenetically, the 4 patients shared the DQA1∗0501 allele associated with an increased risk for autoimmune myositis.
In conclusion, we report an apparent novel subset of autoimmune myositis in our population of French Canadian patients with connective tissue diseases. This syndrome is recognized by the presence of a unique immunologic marker, autoantibodies to nuclear pore complexes that react with nups, consistent with an “anti-nup syndrome.”
[Show abstract][Hide abstract] ABSTRACT: Background Primary biliary cirrhosis (PBC) is frequently associated with connective tissue diseases, namely systemic sclerosis (SSc). Predictive factors for survival of patients with both PBC and SSc are controversial. In 2005, we started a prospective study of 100 PBC patients to determine the prevalence of SSc, to study the clinical, biological and microvascular aspects of patients that had both diseases, and to identify predictive factors for progression of hepatic disease. Results of first visit for 23 patients with PBC and SSc (PBC-SSc) and 23 patients with PBC only were presented during the 2008 EULAR congress.
Objectives to report the clinical, biological and microvascular features of PBC patients at first follow-up visit.
Methods The medical history, physical examination, biological investigations and quantitative nailfold capillary microscopy (NMC) were repeated at follow-up visit.
Results 90 patients were available for a second visit after a mean follow-up of 3.05 years. Among them 19 had PBC only and SSc was present in 22 (23%) patients (19 limited cutaneous SSc and 3 early SSc). Signs of portal hypertension or hepatic failure were present in 4 (9.7%) patients. In PBC-SSc patients, a typical NCM SSc pattern was observed in 17 (77%) patients and was identical at follow-up visit. No patient with CBP only developed abnormal NCM at follow-up study. The Mayo score was similar in patients with vs without SSc and no signifcant difference was observed for level of Alkaline Phosphatase in patients with versus without SSc.
Conclusions Presence of SSc did not worsen the evolution of PBC patients at first follow-up visit. In patients with SSc, the cutaneous and NCM patterns are stable. Long term follow-up is still ongoing to survey the occurrence of SSc associated complications, namely pulmonary hypertension and fibrosis.
Disclosure of Interest None Declared
No preview · Article · Jan 2014 · Annals of the Rheumatic Diseases
[Show abstract][Hide abstract] ABSTRACT: Systemic sclerosis (SSc) is a rare disease requiring multicentre collaboration to reveal comprehensive details of disease-related causes for morbidity and mortality.
The European League Against Rheumatism (EULAR) Scleroderma Trials and Research (EUSTAR) group initiated a database to prospectively gather key data of patients with SSc using a minimal essential dataset that was reorganised in 2008 introducing new items. Baseline visit data of patients who were registered between 2004 and 2011 were analysed using descriptive statistics.
In June 2011, 7655 patients (2838 with diffuse cutaneous (dc) and 4481 with limited cutaneous (lc) SSc who fulfilled the American College of Rheumatology diagnostic criteria had been registered in 174 centres, mainly European. The most prominent hallmarks of disease were Raynaud's phenomenon (96.3%), antinuclear antibodies (93.4%) and a typical capillaroscopic pattern (90.9%). Scleroderma was more common on fingers and hands than on any other part of the skin. Proton pump inhibitors (65.2%), calcium channel blockers (52.7%), and corticosteroids (45.3%) were most often prescribed. Among the immunosuppressant agents, cyclophosphamide was used more often in dcSSc than in lcSSc.
The EUSTAR database provides an abundance of information on the true clinical face of SSc that will be helpful in improving the classification of SSc and its subsets and for developing more specific therapeutic recommendations.
Full-text · Article · May 2012 · Annals of the rheumatic diseases
[Show abstract][Hide abstract] ABSTRACT: Few studies have evaluated the long-term economic consequences of deep vein thrombosis (DVT). None of them have incorporated prospectively collected clinical data to ensure accurate identification of incident cases of DVT and DVT-related health outcomes of interest, such as post-thrombotic syndrome (PTS).
To prospectively quantify medical and non-medical resource use and costs related to DVT during 2 years following diagnosis, and to identify clinical determinants of costs.
Three hundred and fifty-five consecutive patients with acute DVT were recruited at seven Canadian hospital centers. Resource use and cost information were retrieved from three sources: weekly patient-completed cost diaries, nurse-completed case report forms, and the Quebec provincial administrative healthcare database (RAMQ).
The rate of DVT-related hospitalization was 3.5 per 100 patient-years (95% confidence interval [CI] 2.2-4.9). Patients reported a mean (standard deviation) of 15.0 (14.5) physician visits and 0.7 (1.2) other healthcare professional visits. The average cost of DVT was $5180 (95% CI $4344-6017) in Canadian dollars, with 51.6% of costs being attributable to non-medical resource use. Multivariate analysis identified four independent predictors of costs: concomitant pulmonary embolism (relative increase in cost [RIC] 3.16; 95% CI 2.18-4.58), unprovoked DVT (RIC 1.65; 95% CI 1.28-2.13), development of PTS during follow-up (RIC 1.35; 95% CI 1.05-1.74), and management of DVT in the inpatient setting (RIC 1.79; 95% CI 1.33-2.40).
The economic burden of DVT is substantial. The use of measures to prevent the occurrence of PTS and favoring outpatient care of DVT has the potential to diminish costs.
Full-text · Article · Sep 2011 · Journal of Thrombosis and Haemostasis
[Show abstract][Hide abstract] ABSTRACT: Few studies have evaluated the long-term economic consequences of deep venous thrombosis (DVT). None of them incorporated prospectively collected clinical data to ensure accurate identification of incident cases of DVT and DVT-related health outcomes of interest such as post-thrombotic syndrome (PTS). Objectives: To prospectively quantify medical and non-medical resource use and costs related to DVT during two years following diagnosis, and to identify clinical determinants of costs. Methods: 355 consecutive patients with acute DVT were recruited at 7 Canadian hospital centers. Resource use and cost information were retrieved from 3 sources: weekly patient-completed cost diaries, nurse-completed case report forms and the Quebec provincial administrative healthcare database ("RAMQ"). Results: The rate of DVT-related hospitalization was 3.5 per 100 patient-years (95% CI 2.2, 4.9). Patients reported a mean (SD) of 15.0 (14.5) physician visits and 0.7 (1.2) other healthcare professionals visits. The average cost of DVT was $5180 (95% CI $4344, $6017) in Canadian dollars with 51.6% of costs attributable to non-medical resource use. Multivariate analysis identified 4 independent predictors of costs: concomitant pulmonary embolism (relative increase in cost [RIC]: 3.16; 95% CI 2.18, 4.58), unprovoked DVT (RIC: 1.65; 95% CI 1.28, 2.13), development of PTS during follow-up (RIC: 1.35; 95% CI 1.05, 1.74), and management of DVT in the inpatient setting (RIC: 1.79; 95% CI 1.33, 2.40). Conclusions: Economic burden of DVT is substantial. Use of measures to prevent occurrence of PTS and favoring outpatient care of DVT has the potential to diminish costs.
[Show abstract][Hide abstract] ABSTRACT: The pathophysiology of post-thrombotic syndrome (PTS) is postulated to involve persistent venous obstruction and venous valvular reflux.
To study the association between D-dimer level, valvular reflux and the PTS in a well-defined cohort of deep vein thrombosis (DVT) patients.
Consecutive patients with acute symptomatic DVT were recruited at eight centers and were followed for 24months. D-dimer was measured at 4months. A standardized ultrasound assessment for popliteal valvular reflux was performed at 12months. Using the Villalta scale, patients were assessed for PTS during follow-up by evaluators who were unaware of D-dimer or reflux results. Results: Three hundred and eighty-seven patients were recruited; of these, 305 provided blood samples for D-dimer and 233 had a 12-month reflux assessment. PTS developed in 45.1% of subjects. Mean D-dimer was significantly higher in patients with vs. without PTS (712.0 vs. 444.0μgL(-1) ; P=0.02). In logistic regression analyses adjusted for warfarin use at the time of D-dimer determination and risk factors for PTS, D-dimer level significantly predicted PTS (P=0.03); when stratifying for warfarin use at the time of blood draw, adjusted odds ratio (OR) for developing PTS per unit difference in log D-dimer was 2.33 (95% CI 0.89, 6.10) in those not on warfarin vs. 1.25 (95% CI 0.87, 1.79) in those on warfarin. Ipsilateral reflux was more frequent in patients with moderate-to-severe PTS than in patients with mild PTS (65% vs. 40%, respectively; P=0.01) and was independently associated with moderate-to-severe PTS in logistic regression analyses (P=0.01).
D-dimer levels, measured 4months after DVT in patients not on warfarin, are associated with subsequent development of PTS. Venous valvular reflux is associated with moderate-to-severe PTS.
Full-text · Article · Oct 2010 · Journal of Thrombosis and Haemostasis
[Show abstract][Hide abstract] ABSTRACT: To identify in patients with Raynaud's phenomenon (RP) independent markers that predict progression to definite systemic sclerosis (SSc) and to determine in patients with progression to SSc the type and sequence of microvascular damage and its relationship to SSc-specific autoantibodies.
Consecutive patients referred for evaluation of RP who had no definite connective tissue disease were evaluated for microvascular damage by nailfold capillary microscopy (NCM) and for anticentromere (anti-CENP-B), anti-Th/To, anti-topoisomerase I, and anti-RNA polymerase III (anti-RNAP III) autoantibodies by specific assays. Patients were studied prospectively.
Of the 586 patients who were followed up for 3,197 person-years, 74 (12.6%) developed definite SSc. A characteristic sequence of microvascular damage was identified, starting with enlarged capillaries, followed by capillary loss, and then by capillary telangiectases. Definite SSc was diagnosed in close temporal relationship to capillary loss. Enlarged capillaries, capillary loss, and SSc-specific autoantibodies independently predicted definite SSc. Anti-CENP-B and anti-Th/To antibodies predicted enlarged capillaries; these autoantibodies and anti-RNAP III predicted capillary loss. Each autoantibody was associated with a distinct time course of microvascular damage. At followup, 79.5% of patients with 1 of these autoantibodies and abnormal findings on NCM at baseline had developed definite SSc. Patients with both baseline predictors were 60 times more likely to develop definite SSc. The data validated the proposed criteria for early SSc.
In RP evolving to definite SSc, microvascular damage is dynamic and sequential, while SSc-specific autoantibodies are associated with the course and type of capillary abnormalities. Abnormal findings on NCM at baseline together with an SSc-specific autoantibody indicate a very high probability of developing definite SSc, whereas their absence rules out this outcome.
Full-text · Article · Dec 2008 · Arthritis & Rheumatology
[Show abstract][Hide abstract] ABSTRACT: The reason some patients with deep venous thrombosis (DVT) develop the postthrombotic syndrome is not well understood.
To determine the frequency, time course, and predictors of the postthrombotic syndrome after acute DVT.
Prospective, multicenter cohort study.
8 Canadian hospital centers.
387 outpatients and inpatients who received an objective diagnosis of acute symptomatic DVT were recruited from 2001 to 2004.
Standardized assessments for the postthrombotic syndrome using the Villalta scale at 1, 4, 8, 12, and 24 months after enrollment. Mean postthrombotic score and severity category at each interval was calculated. Predictors of postthrombotic score profiles over time since diagnosis of DVT were identified by using linear mixed modeling.
At all study intervals, about 30% of patients had mild (score, 5 to 9), 10% had moderate (score, 10 to 14), and 3% had severe (score >14 or ulcer) postthrombotic syndrome. Greater postthrombotic severity category at the 1-month visit strongly predicted higher mean postthrombotic scores throughout 24 months of follow-up (1.97, 5.03, and 7.00 increase in Villalta score for mild, moderate, and severe 1-month severity categories, respectively, vs. none; P < 0.001). Additional predictors of higher scores over time were venous thrombosis of the common femoral or iliac vein (2.23 increase in score vs. distal [calf] venous thrombosis; P < 0.001), higher body mass index (0.14 increase in score per kg/m(2); P < 0.001), previous ipsilateral venous thrombosis (1.78 increase in score; P = 0.001), older age (0.30 increase in score per 10-year age increase; P = 0.011), and female sex (0.79 increase in score; P = 0.020).
Decisions to prescribe compression stockings were left to treating physicians rather than by protocol. Because international normalized ratio data were unavailable, the relationship between anticoagulation quality and Villalta scores could not be assessed.
The postthrombotic syndrome occurs frequently after DVT. Patients with extensive DVT and those with more severe postthrombotic manifestations 1 month after DVT have poorer long-term outcomes.
Full-text · Article · Nov 2008 · Annals of internal medicine
[Show abstract][Hide abstract] ABSTRACT: We prospectively measured change in quality of life (QOL) during the 2 years after a diagnosis of deep vein thrombosis (DVT) and evaluated determinants of QOL, including development of the post-thrombotic syndrome (PTS).
Consecutive patients with acute DVT were recruited from 2001 to 2004 at eight hospitals in Canada. At study visits at baseline, and 1, 4, 8, 12 and 24 months, clinical data were collected, standardized PTS assessments were performed, and QOL questionnaires were self-completed. Generic QOL was measured using the Short-Form Health Survey-36 (SF-36) questionnaire. Venous disease-specific QOL was measured using the Venous Insufficiency Epidemiological and Economic Study (VEINES)-QOL/Sym questionnaire. The change in QOL scores over a 2-year follow-up was assessed. The influence of PTS and other characteristics on QOL at 2 years was evaluated using multivariable regression analyses.
Among the 387 patients recruited, the average age was 56 years, two-thirds were outpatients, and 60% had proximal DVT. The cumulative incidence of PTS was 47%. On average, QOL scores improved during follow-up. However, patients who developed PTS had lower scores at all visits and significantly less improvement in QOL over time (P-values for PTS*time interaction were 0.001, 0.012, 0.014 and 0.006 for PCS, MCS, VEINES-QOL and VEINES-Sym). Multivariable regression analyses showed that PTS (P < 0.0001), age (P = 0.0009), proximal DVT (P = 0.01) and inpatient status (P = 0.04) independently predicted 2-year SF-36 PCS scores. PTS alone independently predicted 2-year VEINES-QOL (P < 0.0001) and VEINES-Sym (P < 0.0001) scores.
Development of PTS is the principal determinant of health-related QOL 2 years after DVT. Our study provides prognostic information on patient-reported outcomes after DVT and emphasizes the need for effective prevention and treatment of the PTS.
Full-text · Article · Jul 2008 · Journal of Thrombosis and Haemostasis
[Show abstract][Hide abstract] ABSTRACT: To assess the validity of VEINES-QOL/Sym, a patient-reported questionnaire to evaluate quality of life and symptoms in patients with deep venous thrombosis (DVT).
Psychometric study within the Venous Thrombosis Outcomes (VETO) Study, a prospective cohort study of long-term outcomes after DVT. A total of 359 English- and French-speaking patients with acute, objectively diagnosed DVT were recruited at seven hospitals in Quebec, Canada. The VEINES-QOL/Sym questionnaire, a 26-item patient-reported measure that generates separate summary scores for symptoms (VEINES-Sym) and quality of life (VEINES-QOL) was evaluated for acceptability, reliability, validity, and responsiveness in VETO Study subjects.
Standard psychometric tests confirmed the acceptability (missing data, item endorsement frequencies, floor and ceiling effects), reliability (internal consistency, item-total and inter-item correlations, test-retest), validity (content, construct, convergent, discriminant, known groups), and responsiveness to clinical change of the VEINES-QOL/Sym in patients with DVT.
The VEINES-QOL/Sym is a practical and scientifically sound patient-reported measure of outcomes that was developed using gold-standard methods. VEINES-QOL/Sym is valid and reliable for use as a measure of quality of life and symptoms in patients with acute DVT and provides a rigorous tool to allow more comprehensive evaluation of outcomes in clinical trials and epidemiological studies of patients with DVT.
Full-text · Article · Nov 2006 · Journal of Clinical Epidemiology
[Show abstract][Hide abstract] ABSTRACT: To our knowledge, the burden of deep venous thrombosis from the patient's perspective has not been quantified. We evaluated health-related quality of life (QOL) after deep vein thrombosis and compared results with general population norms.
This was a multicenter prospective cohort study of 359 consecutive eligible patients with deep vein thrombosis recruited at 7 Canadian hospital centers. Quality of life was assessed at baseline and at 1 and 4 months after diagnosis using generic (36-Item Short-Form Health Survey) and disease-specific (Venous Insufficiency Epidemiological and Economic Study [VEINES]-QOL and VEINES symptom [VEINES-Sym] questionnaires) measures. Changes in QOL scores during the 4-month period were calculated, and determinants of lack of improvement in QOL were evaluated.
During the 4 months, mean 36-Item Short-Form Health Survey physical and mental component summary scores improved by 5.1 and 4.6 points, respectively, and VEINES-QOL and VEINES-Sym scores improved by 3.1 and 2.2 points, respectively (P < .001 for time trend for all measures). However, about one third of patients had worsening of QOL during follow-up. Multivariate analyses showed that worsening of the postthrombotic syndrome score was an independent predictor of worsening of 36-Item Short-Form Health Survey physical component summary (P = .04), VEINES-QOL (P < .001), and VEINES-Sym (P < .001) scores. The 36-Item Short-Form Health Survey physical component summary scores were lower than population norms at all points assessed.
On average, QOL improves during the 4 months following deep vein thrombosis. However, in about one third of patients, QOL deteriorates, and at 4 months, average QOL remains poorer than population norms. Worsening of the postthrombotic syndrome score is associated with worsening of QOL.
No preview · Article · May 2005 · Archives of Internal Medicine
[Show abstract][Hide abstract] ABSTRACT: Our first objective was to report the presenting features of systemic sclerosis (SSc) in a large cohort of French Canadian patients encompassing the full spectrum of the disease. Our second objective was to identify among these presenting features factors predictive for mortality and to compare these data with those of other series. Between 1984 and 1999, SSc was diagnosed at first presentation in 309 consecutive and unselected French Canadian patients at a single SSc center; the patients were enrolled in a prospective study and followed until September 2000. Patients were categorized into 4 subsets based on sclerodermatous skin extent: diffuse (trunk, n = 29), intermediate (proximal to metacarpophalangeal joints without trunk, n = 78), limited (sclerodactyly only, n = 152), or normal skin (n = 50) subsets. Data collection was according to a protocol encompassing 215 variables and including nailfold capillary microscopy. Standardized mortality ratios were computed using ageand gender-specific annual mortality rates in the Province of Quebec general population. Vital status was obtained from the Quebec Statistics Institute. The overall cohort female to male ratio was 6:1. Presenting features varied in frequency in each subset. Anticentromere antibodies were most common in the normal skin and limited SSc subsets (50% of patients), and less common in intermediate and diffuse subsets (34.6% and 3.4%, respectively) (p < 0.0001). The frequency of antibodies to DNA-topoisomerase I (anti-topo I) in diffuse SSc was 13.8%. By nailfold capillary microscopy, severe capillary loss was not restricted to any subset. However, the rate of onset of severe capillary loss strikingly varied among the subsets (p < 0.0001). Death occurred in 66 (21.3%) patients. SSc was the major cause of death (n = 35, 53%), followed by cancer and atherosclerosis. In the limited, intermediate, and diffuse subsets, 43.8%, 57.1%, and 100% of the deaths were SSc-related, respectively (p = 0.004). For deaths due to SSc, cumulative survival rates for these subsets were 97%, 94%, and 78% at 5 years, and 89%, 86%, and 62% at 10 years, respectively. Survival curves were significantly different (p = 0.0001). By stepwise Cox regression, independent predictors for mortality were skin involvement of the trunk, age, carbon monoxide diffusion capacity of the lungs (DLCO) ≤ 70% of predicted normal value, erythrocyte sedimentation rate ≥ 25 mm/h, and hemoglobin level ≤ 12.5 g/dL. The observed mortality increased from 2% in patients with none of these predictors to 75% in patients with all predictors. Standardized mortality ratios were 2.71, 2.76, and 6.17 in the limited, intermediate, and diffuse subsets, respectively. Further dividing of the intermediate group into skin involvement below versus above the elbow revealed no difference in the frequency of clinical manifestations, anticentromere antibodies, anti-topo I, and mortality. To our knowledge, the present study is the first report on a large French Canadian SSc cohort. The frequency of anti-topo I in diffuse SSc is the lowest reported thus far. The data provide compelling evidence in favor of a distinct intermediate SSc subset. Several factors predictive for mortality were identified at baseline. These factors are easy to determine and may provide a rationale for close medical surveillance and early therapeutic intervention in patients at high risk for mortality. Comparison with other series suggests that despite different ethnicities and geographic environments, North American and European patients with SSc share similar prognostic factors and overall prognosis. Despite improved survival, SSc continues to be associated with high excess mortality.
[Show abstract][Hide abstract] ABSTRACT: To evaluate an enzyme-linked immunosorbent assay (ELISA) for anticentromere autoantibodies (ACA).
Sera from 611 patients with scleroderma, CREST (calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, telangiectasias), Raynaud's disease, and connective tissue disease control patients were studied by ELISA using the fusion protein CENP-B, by immunofluorescence on dividing HEp-2 cells, and by immunoblotting on chromosomes and CENP-B.
Compared with immunofluorescence, the CENP-B ELISA sensitivity was 94% and the specificity was 93%. In 19.7% of the cases, there was a probability of a false-positive result and in 1.9%, a probability of a false-negative result, yielding positive and negative predictive values of 0.80 and 0.98, respectively.
The CENP-B ELISA is a sensitive and specific assay for ACA.
No preview · Article · Mar 1994 · Arthritis & Rheumatology