Systemic Sclerosis Sine Scleroderma: A Multicenter Study of 1417 Subjects

2014 ◽  
Vol 41 (11) ◽  
pp. 2179-2185 ◽  
Author(s):  
Sehriban Diab ◽  
Nathaniel Dostrovsky ◽  
Marie Hudson ◽  
Solène Tatibouet ◽  
Marvin J. Fritzler ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Interstitial Lung Disease ◽  
Rna Polymerase ◽  
Lung Disease ◽  
Multicenter Study ◽  
Research Group ◽  
Rna Polymerase Iii ◽  
Skin Involvement ◽  
Anticentromere Antibodies ◽  
Clinical Profiles

Objective.To describe the clinical and serological features of systemic sclerosis sine scleroderma (ssSSc) in a multicentered SSc cohort.Methods.Data from 1417 subjects in the Canadian Scleroderma Research Group registry were extracted to identify subjects with ssSSc, defined as SSc diagnosed by an expert rheumatologist, but without any sclerodactyly or skin involvement prior to baseline study visit or during followup. Clinical and serological features of ssSSc subjects were compared to limited (lcSSc) and diffuse cutaneous SSc (dcSSc) subjects.Results.At the first registry visit, only 57 subjects (4.0%) were identified as having ssSSc. Of these, 30 (2.1%) were reclassified as lcSSc within 1.9 years. Thus, only 27 ssSSc subjects (1.9%) remained, with mean followup of 2.4 years. Clinical profiles of ssSSc were generally similar or milder compared to lcSSc, and milder than dcSSc, including rates of interstitial lung disease (25.9% ssSSc, 25.4% lcSSc, 40.3% dcSSc). Patients with ssSSc had serological profiles similar to those with lcSSc, including high rates of anticentromere antibodies (50.0% ssSSc, 47.5% lcSSc, 12.1% dcSSc), and low rates of antitopoisomerase I (16.7% ssSSc, 7.0% lcSSc, 21.8% dcSSc) and anti-RNA polymerase III (0 ssSSc, 11.1% lcSSc, 34.9% dcSSc).Conclusion.The condition ssSSc is rare and resembles lcSSc. These observations suggest that ssSSc is most likely a forme fruste of lcSSc, and that the absence of skin involvement may in part be related to misclassification arising from early or subtle skin involvement. There is little evidence to consider ssSSc as a distinct clinical or serological subset of SSc.

scholarly journals AB0451 TO EVALUATE THE PREVALENCE OF INTERSTITIAL LUNG DISEASE (ILD) AND/OR PULMONARY ARTERIAL HYPERTENSION (PAH) IN PATIENTS AFFECTED BY SYSTEMIC SCLEROSIS (SSC) AND TO DETERMINE THE FACTORS ASSOCIATED WITH ILD

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1253.1-1253
Author(s):  
R. Ortega Castro ◽  
R. Mariscal-Ocaña ◽  
M. Rojas-Giménez ◽  
J. Calvo Gutierrez ◽  
A. Escudero Contreras ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Topoisomerase I ◽  
Systolic Pressure ◽  
University Hospital ◽  
Pulmonary Artery Systolic Pressure ◽  
Skin Involvement ◽  
Factors Associated ◽  
Anticentromere Antibodies

Background:Systemic sclerosis (SSc) is a chronic autoimmune disease that carries significant mortality. Despite diagnostic and therapeutic advances in recent years, there is still a significant percentage of patients who do not present a complete clinical response, with the associated increase in morbidity and mortality. Specifically, pulmonary disease is frequent and entails a poor prognosis, with interstitial lung disease (ILD) and pulmonary hypertension (PAH) being the two most important complications, the first and second cause of mortality, respectively.Objectives:To evaluate the prevalence of ILD and/or PAH in patients affected by SSc and to determine the factors associated with ILD.Methods:Cross-sectional observational study of 102 patients diagnosed with SSc (Limited, Diffuse, SSc without scleroderma or Pre-scleroderma), treated between 1975 and 2020 at the Reina Sofia University Hospital in Cordoba. A descriptive study of the cohort was carried out and factors independently associated with ILD were evaluated using a multiple logistic regression model.Results:102 patients were included, 87.3% of these were female with an average age of 50.8 (14) years. There were 20 deaths (19.8%), from which 55% died because of SSc and the main reason was ILD and/or PAH. Respiratory complications (as ILD or as PAH) were present in 59 patients (57.8%), of whom 52 were diagnosed with ILD (90.4% with a pattern of non-specific interstitial pneumonia) and 25 PAH, whose mean pulmonary artery systolic pressure was 47.16 (18.54) mmHg. Anti-topoisomerase I antibodies were positive in 34.6% of patients who developed ILD, while anticentromere antibodies were more frequent in SSc without interstitial lung disease (80%). Independent factors associated with ILD were type of SSc, proximal skin involvement, anticentromere antibodies, current treatment with corticoids and the death.Conclusion:Just over half of the patients with SSc have lung disease (as ILD or as PAH). The main risk factors associated with ILD are proximal skin involvement and treatment with glucocorticoids, probably in the context of more severe forms that require more treatment. Anticentromere antibodies are more prevalent in patients with Limited SSc and their expression decreases the risk of developing ILD in these patients.References:[1]Orlandi M, Barsotti S, Lepri G, et al. Clin Exp Rheumatol 2018 Jul-Aug; 36 Suppl 113: 3-23[2]Hao Y, Hudson M, Baron M, et al. Arthritis Rheumatol. 2017;69(5):1067-1077.[3]Furue M, Mitoma C, Mitoma H, et al. Immunol Res. 2017 Aug; 65: 790-7.[4]Nihtyanova SI, Schreiber BE, Ong VH, et al. Arthritis Rheumatol. 2014 Jun; 66: 1625-35.Disclosure of Interests:None declared.

scholarly journals Malignancies in Italian Patients with Systemic Sclerosis Positive for Anti-RNA Polymerase III Antibodies

2011 ◽  
Vol 38 (7) ◽  
pp. 1329-1334 ◽  
Author(s):  
PAOLO AIRO’ ◽  
ANGELA CERIBELLI ◽  
ILARIA CAVAZZANA ◽  
MARA TARABORELLI ◽  
STEFANIA ZINGARELLI ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Rna Polymerase ◽  
Temporal Relationship ◽  
Rna Polymerase Iii ◽  
Patients With Cancer ◽  
Polymerase Iii ◽  
Number Of Patients ◽  
I 11 ◽  
Anticentromere Antibodies ◽  
Close Temporal Relationship

Objective.To evaluate the frequency of malignancies in Italian patients with systemic sclerosis (SSc) and anti-RNA polymerase III (RNAP III), antitopoisomerase I (topo I), or anticentromere antibodies (ACA); and to characterize the temporal relationship between the 2 diseases, in order to confirm data suggesting a close temporal relationship between the onset of SSc and malignancy in American patients with anti-RNAP III antibodies.Methods.From a cohort of 466 consecutive SSc patients, 360 Italians with isolated positivity for anti-RNAP III (n = 16), anti-topo I (n = 101), or ACA (n = 243) were identified. Malignancy cases were divided according to their relationship with SSc onset into 3 categories: preceding, synchronous with, or metachronous to the onset of SSc (diagnosed more than 6 months before; 6 months before to 12 months after; and more than 12 months after onset of SSc, respectively).Results.Malignancies were more frequent in the anti-RNAP III group (7/16 patients), than in the anti-topo I (11/101) and ACA groups (21/243) (p < 0.001). This difference was accounted for by the number of patients with cancer synchronous to the onset of SSc (3/16 in the anti-RNAP III group vs 0/101 in the anti-topo I and 1/243 in the ACA group; p < 0.001), whereas neither the number of malignancies preceding nor those metachronous to the onset of SSc was significantly different between the groups.Conclusion.In a cohort of Italian patients with SSc we observed a significant association between malignancies synchronous to SSc onset and positivity for anti-RNAP III antibodies, similar to that described in American patients with SSc.

scholarly journals Antifibroblast antibodies from systemic sclerosis patients bind to α-enolase and are associated with interstitial lung disease

2009 ◽  
Vol 69 (2) ◽  
pp. 428-433 ◽  
Author(s):  
B Terrier ◽  
M C Tamby ◽  
L Camoin ◽  
P Guilpain ◽  
A Bérezné ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Human Fibroblasts ◽  
Target Antigen ◽  
Diffusion Capacity ◽  
Serum Igg ◽  
Normal Human ◽  
Anticentromere Antibodies ◽  
Pulmonary Arterial

Objective:To identify target antigens of antifibroblast antibodies (AFA) in systemic sclerosis (SSc) patients.Patients and Methods:In the first part, sera from 24 SSc patients (12 with pulmonary arterial hypertension (PAH) and 12 without) and 36 idiopathic PAH patients, tested in pooled sera for groups of three, were compared with a sera pool from 14 healthy controls (HC). Serum IgG reactivity was analysed by the use of a two-dimensional electrophoresis and immunoblotting technique with normal human fibroblasts antigens. In the second part, serum IgG reactivity for two groups: 158 SSc, 67 idiopathic PAH and 100 HC; and 35 SSc and 50 HC was tested against α-enolase from Saccharomyces cerevisiae and recombinant human (rHu) α-enolase, respectively, on ELISA.Results:In the first part, α-enolase was identified as a main target antigen of AFA from SSc patients. In the second part, 37/158 (23%) SSc patients, 6/67 (9%) idiopathic PAH patients and 4/100 (4%) HC (p<0.001) had anti-S cerevisiae α-enolase antibodies; 12/35 (34%) SSc patients and 3/50 (6%) HC had anti-rHu α-enolase antibodies (p = 0.001). In SSc, the presence of anti-S cerevisiae α-enolase antibodies was associated with interstitial lung disease (ILD), decreased total lung capacity (73.2% vs 89.7%; p<0.001) and diffusion capacity for carbon monoxide (47.4% vs 62.3%; p<0.001), and antitopoisomerase 1 antibodies (46% vs 21%; p = 0.005) but not anticentromere antibodies (11% vs 34%; p = 0.006). Results were similar with rHu α-enolase testing.Conclusion:In SSc, AFA recognise α-enolase and are associated with ILD and antitopoisomerase antibodies.

scholarly journals Are There Clinical Differences in Limited Systemic Sclerosis according to Extension of Skin Involvement?

2014 ◽  
Vol 2014 ◽  
pp. 1-5
Author(s):  
Marina Scolnik ◽  
Luis J. Catoggio ◽  
Eliana Lancioni ◽  
Mirtha R. Sabelli ◽  
Carla M. Saucedo ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Interstitial Lung Disease ◽  
Skin Involvement ◽  
Male Ratio ◽  
Limited Systemic Sclerosis ◽  
Anticentromere Antibodies ◽  
Type 3

Objectives. To examine the characteristics of our patients with limited systemic sclerosis (lSSc) for differences between Barnett Type 1 (sclerodactyly only) and Type 2 or intermediate (acrosclerosis-distal but may reach up to elbows and/or knees plus face) subsets.Methods. Records of patients between January 1, 2000, and December 31, 2011, with SSc or those with anti-Scl-70, anticentromere, or antinucleolar antibodies were reviewed. Only cases fulfilling ACR 1980 criteria were included and classified as diffuse or limited according to LeRoy’s criteria. Limited SSc was separated into sclerodactyly and acrosclerosis (Barnett’s Types 1 and 2).Results. 234 SSc patients (216 females) fulfilled criteria. Female/male ratio was 12 : 1; 24% had dSSc and 76% lSSC (64% Type 1 and 12% Type 2). Total follow-up was 688 patient-years. Within lSSC, the Type 2 group had significantly shorter duration of Raynaud’s and more anti-Scl-70 and less anticentromere antibodies. In particular, interstitial lung disease (ILD) was significantly more prevalent in Type 2 group and similar to Type 3.Conclusions. These results appear to confirm that extension of skin involvement within limited SSc may identify two different subsets with clinical and serologic characteristics.

Anti-Th/To Are Common Antinucleolar Autoantibodies in Italian Patients with Scleroderma

2010 ◽  
Vol 37 (10) ◽  
pp. 2071-2075 ◽  
Author(s):  
ANGELA CERIBELLI ◽  
ILARIA CAVAZZANA ◽  
FRANCO FRANCESCHINI ◽  
PAOLO AIRÒ ◽  
ANGELA TINCANI ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Interstitial Lung Disease ◽  
Pulmonary Function ◽  
Rna Polymerase ◽  
Rna Polymerase Iii ◽  
Clinical Manifestations ◽  
Cell Extract ◽  
Clinical Laboratories ◽  
Autoantibody Profile ◽  
Autoantibody Profiles

Objective.Patients with scleroderma (systemic sclerosis; SSc) can be classified into subsets based on autoantibody profile and clinical features. Specificities such as anti-Th/To and anti-fibrillarin (U3RNP) are detectable mainly by immunoprecipitation (IP), which is not widely used in clinical laboratories. We examined the autoantibody profiles and clinical manifestations in a cohort of Italian patients with SSc, focusing on anti-Th/To and anticentromere (ACA) antibodies, associated with limited cutaneous SSc (lcSSc).Methods.Sera from 216 consecutive patients with SSc were tested for ACA (by indirect immunofluorescence), antitopoisomerase I (topo I; by counterimmunoelectrophoresis), and anti-RNA polymerase III (RNAPIII; by ELISA). Forty-one sera negative for these specificities were tested by IP analysis of proteins (35S-methionine labeled K562 cell extract) and RNA (silver staining).Results.Among 216 SSc patients analyzed, anti-topo I, ACA, and anti-RNAPIII were detected in 38% (81/216), 31% (67/216) and 7% (15/216), respectively. Among 41 sera negative for ACA, anti-topo I, and anti-RNAPIII and which were tested by IP, 14 were nucleolar stain-positive. Eight out of 14 (57%) showed anti-Th/To reactivity, but no anti-U3RNP was found. In comparison with ACA-positive patients, anti-Th/To-positive patients were younger (p = 0.0046) and more commonly were male (p = 0.0006). All 8 anti-Th/To-positive and all but one ACA-positive patients had lcSSc. Interstitial lung disease (ILD) and pericarditis were more frequent in anti-Th/To-positive patients.Conclusion.Anti-Th/To are common in antinucleolar antibody-positive Italian patients with SSc. Anti-Th/To and ACA patients had lcSSc, with excellent prognosis. The anti-Th/To group had frequent pericarditis and ILD, although impairment of pulmonary function appeared mild.

RNA polymerase III autoantibodies may indicate renal and more severe skin involvement in systemic sclerosis

2015 ◽  
Vol 55 (8) ◽  
pp. 882-885 ◽  
Author(s):  
Sarah Terras ◽  
Hans Hartenstein ◽  
Stefan Höxtermann ◽  
Thilo Gambichler ◽  
Alexander Kreuter
Keyword(s):  
Systemic Sclerosis ◽  
Rna Polymerase ◽  
Rna Polymerase Iii ◽  
Skin Involvement ◽  
Polymerase Iii

Interstitial lung disease is associated with an increased risk of lung cancer in systemic sclerosis: Longitudinal data from the Canadian Scleroderma Research Group

2018 ◽  
Vol 3 (3) ◽  
pp. 221-227 ◽  
Author(s):  
Lama Sakr ◽  
Marie Hudson ◽  
Mianbo Wang ◽  
Elie Younanian ◽  
Murray Baron ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Systemic Sclerosis ◽  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Research Group ◽  
Drug Exposure ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Smoking History ◽  
Increased Risk

Objective: The literature supports an increased risk of malignancy in systemic sclerosis, including lung cancer. Our objective was to identify potential independent predictors of lung cancer risk in systemic sclerosis. Methods: We used a cohort of 1560 systemic sclerosis patients from the Canadian Scleroderma Research Group, enrolled from 2004 and followed for a maximum of 11 years. Time to lung cancer was calculated from the onset of the first non-Raynaud’s symptoms. Baseline demographic, clinical, and serological characteristics of patients with and without lung cancer were compared. Cox proportional hazards models were used to estimate the effects of demographic variables, exposure to smoking, disease duration, disease subset (diffuse vs limited), immunosuppressant drug exposure, and presence of interstitial lung disease on the risk of lung cancer. Results: Over the 5519 total person-years of follow-up, 18 SSc patients were diagnosed with lung cancer after cohort entry (3.2 cancers per 1000 person-years). In univariate comparisons, cancer cases were more likely to be male, to have a smoking history, and to have interstitial lung disease than non-cases. In multivariate analysis, interstitial lung disease was independently associated with the risk of lung cancer (hazard ratio: 2.95, 95% confidence interval: 1.10–7.87). Conclusion: In addition to known demographic (male sex) and lifestyle risk factors (smoking), interstitial lung disease is an independent risk factor for lung cancer in systemic sclerosis. These results have implications for lung cancer screening in systemic sclerosis.

Thoracic lymphadenopathy as possible predictor of the onset of interstitial lung disease in systemic sclerosis patients without lung involvement at baseline visit: A retrospective analysis

2020 ◽  
Vol 5 (3) ◽  
pp. 210-218
Author(s):  
Cinzia Rotondo ◽  
Livio Urso ◽  
Emanuela Praino ◽  
Fabio Cacciapaglia ◽  
Addolorata Corrado ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Systemic Sclerosis ◽  
High Resolution ◽  
Interstitial Lung Disease ◽  
Confidence Interval ◽  
Lung Disease ◽  
Disease Onset ◽  
High Resolution Computed Tomography ◽  
Anticentromere Antibodies

Objective: To evaluate clinical, laboratory, or radiographic predictors of the onset of interstitial lung disease in systemic sclerosis. Methods: Sixty-five out of 220 systemic sclerosis outpatients, without interstitial lung disease at baseline and with ⩾3 chest high resolution computed tomography scans during follow-up were recruited. Thoracic lymphadenopathy and interstitial lung disease were assessed by chest high resolution computed tomography. Hazard ratio (95% confidence interval) of interstitial lung disease occurrence was assessed by Cox regression models, adjusting patient’s demographics and disease characteristics. Sensitivity, specificity, and accuracy of the interstitial lung disease predictors were evaluated by receiver operating characteristic analysis. Results: The development of interstitial lung disease was observed in 44/65 (68%) patients. Thoracic lymphadenopathies was detected in 40/65 (61%) patients, of whom 36 (82%) developed interstitial lung disease, but only four patients with thoracic lymphadenopathies did not develop ILD at last visit of follow-up (19%) (p = 0.0001). Adjusted hazard ratio of systemic sclerosis-interstitial lung disease onset was 5.8 (95% confidence interval, 2.0–16.5) for thoracic lymphadenopathy, which preceded by 108 ± 98 weeks the systemic sclerosis-interstitial lung disease detection. Thoracic lymphadenopathy had 84% specificity, 81% sensitivity, and 0.82 accuracy to predict interstitial lung disease. In particular, anticentromere antibodies or limited cutaneous subset of systemic sclerosis patients with thoracic lymphadenopathy showed earlier interstitial lung disease onset than those without lymphadenopathy. In addition, patients who developed interstitial lung disease had higher frequency of anti-Scl-70 (57% vs 19%; p = 0.009) and diffuse cutaneous subset (29% vs 3%; p = 0.02) than those who did not. Conclusions: Thoracic lymphadenopathy was the strongest independent predictor of systemic sclerosis-interstitial lung disease, mostly in anticentromere antibodies and limited cutaneous subset of systemic sclerosis patients. Further prospective studies are needed to confirm our preliminary data and to understand whether thoracic lymphadenopathies may have a pathogenetic role in interstitial lung disease development.

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