RESUMO
OBJECTIVE: Calcinosis is a debilitating complication of systemic sclerosis (SSc) with no effective treatments. We sought to identify clinical correlations and to characterize complications and disability associated with calcinosis in a multi-center, international cohort of SSc patients. METHODS: We established a cohort of 568 consecutive SSc patients who fulfill 2013 revised ACR/EULAR criteria at 10 centers within North America, Australia, and Mexico. Calcinosis was defined as subcutaneous calcium deposition by imaging and/or physical examination, or a clear history of extruded calcium. All patients completed the Scleroderma Health Assessment Questionnaire Disability Index and Cochin Hand Functional Scale. RESULTS: 215 (38%) patients had calcinosis. In multivariable analysis, disease duration (OR=1.24, p = 0.029), digital ischemia (OR=1.8, p = 0.002) and Acro-osteolysis (OR=2.97, p = 0.008) were significantly associated with calcinosis. In the subset of patients with bone densitometry (n = 68), patients with calcinosis had significantly lower median T-scores than patients without (-2.2 vs. -1.7, p = 0.004). The most common location of calcinosis lesions was the hands (70%), particularly the thumbs (19%) with decreasing frequency moving to the fifth fingers (8%). The most common complications were tenderness (29% of patients) and spontaneous extrusion of calcinosis through the skin (20%), while infection was rare (2%). Disability and hand function were worse in patients with calcinosis, particularly if locations in addition to the fingers/thumbs were involved. CONCLUSIONS: We confirmed a strong association between calcinosis and digital ischemia. Calcinosis in SSc patients most commonly affects the hands and is associated with a high burden of disability and hand dysfunction.
Assuntos
Acro-Osteólise , Calcinose , Escleroderma Sistêmico , Calcinose/diagnóstico por imagem , Calcinose/etiologia , Mãos , Humanos , Isquemia , Escleroderma Sistêmico/complicaçõesRESUMO
Characterization of the extent to which particular combinations of autoimmune diseases occur in excess of that expected by chance may offer new insights into possible common pathophysiological mechanisms. The goal of this study was to investigate the spectrum of polyautoimmunity (i.e. autoimmune diseases co-occurring within patients) and familial autoimmunity (i.e. diverse autoimmune diseases co-occurring within families) in patients with systemic sclerosis (SSc). A cross-sectional study of two convenience samples of patients with SSc, one in Canada and the other in Colombia, was performed. History of other autoimmune diseases in the SSc patients as well as a family history of autoimmunity was obtained. Of 719 patients, 273 (38%) had at least one other autoimmune disease. A total of 366 autoimmune diseases were reported, of which the most frequent were autoimmune thyroid disease (AITD, 38%), rheumatoid arthritis (RA, 21%), Sjögren's syndrome (18%), and primary biliary cirrhosis (4%). There were 260 (36%) patients with first-degree relatives with at least one autoimmune disease, of which the most frequent were RA (18%) and AITD (9%). Having at least one first-degree relative with autoimmune disease was a significant predictor of polyautoimmunity in SSc patients. No significant differences in polyautoimmunity or familial autoimmunity were noted between diffuse and limited subsets of disease. Our results indicate that polyautoimmunity is frequent in patients with SSc and autoimmune diseases cluster within families of these patients. Clinically different autoimmune phenotypes might share common susceptibility variants, which acting in epistatic pleiotropy may represent risk factors for autoimmunity.
Assuntos
Autoimunidade/genética , Predisposição Genética para Doença , Escleroderma Sistêmico/genética , Escleroderma Sistêmico/imunologia , Canadá/epidemiologia , Colômbia/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Escleroderma Sistêmico/epidemiologiaRESUMO
The objective was to investigate the frequency of anti-cyclic citrullinated peptides (CCP) antibodies in systemic sclerosis (SSc) and primary biliary cirrhosis (PBC), utilizing a new "third generation" anti-CCP ELISA (anti-CCP3) kit and a conventional anti-CCP2 assay. Patients with PBC, SSc, RA, and normal controls were included in the study. Serum samples were screened for autoantibodies by indirect immunofluorescence (IIF), antibodies to CCP by a second- and third-generation ELISA, antibodies to "scleroderma" antigens (CENP B, Scl-70, PM/Scl and fibrillarin-Scl-34) by a line immunoassay (LIA), and IgM RF by ELISA. The frequency of anti-CCP2 antibodies in SSc and PBC samples was 14.8% (11/74) and 6.2% (5/80), respectively, and the frequency of anti-CCP3 antibodies in SSc was 13.5% (10/74) and in PBC was 3.7% (3/80). By comparison, in the RA group the frequency of anti-CCP3 and anti-CCP2 antibodies was 79.1% (38/48) and 77% (37/48), respectively. Anti-CCP3 ELISA had a sensitivity, specificity, and positive and negative likelihood ratios (LR) of 79% (95% confidence interval [CI] = 64-89%), 93% (95% CI = 88-96%), 11.8 (95% CI = 6.8-20.3), and 0.22 (95% CI = 0.12-0.38), respectively. By comparison, the anti-CCP2 assay had a sensitivity, specificity, and positive and negative LRs of 77% (95% CI = 62-87), 90% (95% CI = 85-94), 8.3 (95% CI = 5.2-13.2), and 0.25 (95% CI = 0.15-0.42), respectively. In patients with SSc, there was an association of anti-CCP2 antibodies with the presence of arthritis, but there was no association of anti-CCP2 or anti-CCP3 with anti-CENP B, anti-Scl 70, or RF. This study confirmed the high specificity and sensitivity of both anti-CCP assays for the diagnosis of RA. The presence of anti-CCP antibodies in SSc was only correlated with the presence of arthritis.
Assuntos
Artrite Reumatoide/imunologia , Autoanticorpos/análise , Cirrose Hepática Biliar/imunologia , Peptídeos Cíclicos/imunologia , Escleroderma Sistêmico/imunologia , Artrite Reumatoide/diagnóstico , Autoanticorpos/imunologia , Ensaio de Imunoadsorção Enzimática , Feminino , Técnica Indireta de Fluorescência para Anticorpo , Humanos , Cirrose Hepática Biliar/diagnóstico , Masculino , Pessoa de Meia-Idade , Escleroderma Sistêmico/diagnósticoRESUMO
OBJECTIVE: To determine serological and clinical variables associated with anti-RNA polymerase III (RNAP-III) antibodies in patients with systemic sclerosis (SSc) using a new ELISA method. METHODS: Sera from 242 patients with SSc were collected from 14 Canadian clinics. Control sera were from 287 blood donors, and 42 patients with infectious disease, 30 with rheumatoid arthritis (RA), and 30 with systemic lupus erythematosus (SLE). Antibodies to RNAP-III were detected by an ELISA kit and antibodies to other cellular antigens were identified by indirect immunofluorescence (IIF) on HEp-2 cell substrate, line immunoassay, immunoprecipitation of recombinant protein, and addressable laser bead immunoassay (ALBIA). RESULTS: Anti-RNAP-III antibodies were detected in 47/242 (19.4%) SSc sera, 0% RA and SLE sera, 1/287 blood donor sera, and 2/42 infectious disease sera. Diffuse disease (59.5%) was more common than limited disease (36.1%) in the anti-RNAP-III-positive patients (p = 0.006) and there was an association between the presence of anti-RNAP-III and kidney and joint/tendon involvement, but there was no association with a nucleolar IIF pattern, lung involvement, or other clinical indicators. There was a negative association between the presence of anti-RNAP-III antibodies and anticentromere by IIF (p = 0.00004) and anti-Scl-70 by ALBIA (p = 0.0005) and line immunoassay (p = 0.003), suggesting a virtually exclusive presence of these antibodies in SSc. CONCLUSION: Anti-RNAP-III autoantibodies were found in nearly 20% of SSc patients but in less than 1% of controls, thus detection of this antibody is a useful marker to help diagnose SSc. As well, this antibody has prognostic utility, since it is associated with scleroderma renal crisis and the diffuse cutaneous form of SSc.