scholarly journals POS0891 IMPROVED SURVIVAL IN SYSTEMIC SCLEROSIS PATIENTS DURING LAST DECADE: CURRENT FINDINGS AND COMPARISON WITH DIFFERENT PREVIOUS ITALIAN COHORTS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 701.2-702
Author(s):  
F. Cacciapaglia ◽  
E. De Lorenzis ◽  
M. G. Lazzaroni ◽  
A. Corrado ◽  
M. Fornaro ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
General Population ◽  
Death Rate ◽  
Topoisomerase I ◽  
Renal Involvement ◽  
Phosphodiesterase Inhibitor ◽  
Biologic Agent ◽  
World Population ◽  
Digital Ulcers ◽  
Cutaneous Involvement

Background:Systemic Sclerosis (SSc) is a chronic rheumatic disease characterized by an autoimmune disorder with vasculopathy that leads to an excess in collagen and other extracellular matrix proteins deposition. This process results in progressive fibrotic and vascular damage of skin and visceral organs. According to observational studies conducted in last decades, mean survival of SSc patients had improved with significant changes in causes of death.Objectives:To assess the 10-years survival in a large Italian multicentre cohort of SSc patients in the last decade compared to previous periods published since the 1980s, and to identify features that can justify any change.Methods:We retrospectively analysed all medical records of our longitudinal SSc cohorts, fulfilling 1980 ARA and/or 2013 EULAR/ACR Classification Criteria, with a median (IQR) follow-up of 91.5 (51-120) months from 4 Scleroderma Units since January 2009. All clinical, laboratory and instrumental findings have been recorded and analysed. Survival rate was calculated with Kaplan-Meier curves and log-rank tests, and Cox proportional hazards models were used to identify any predictor. Then, observed SSc survival was compared to those previously published and to that expected in the general population, calculated using official data published on the website United Nation World Population Prospects (www.macrotrends.net/countries/ITA/italy/death-rate).Results:Of 912 SSc patients (91.6% female; mean (SD) age at first non-Raynaud symptom (RS) 51 (15.4) years; median (IQR) disease duration from non-RS 24 (0-84.7) months) diffuse cutaneous involvement was defined in 182 (20%) patients. Anti-centromere and anti-topoisomerase-I were detected in 390 (42.8%) and 302 (33.1%) patients, respectively, while 220 (24.1%) presented antibodies for other extractible nuclear antigens. Prevalent non-Raynaud manifestations were interstitial lung disease detected in 459 (50.3%), digital ulcers in 395 (43.3%) and oesophagopathy in 371 (40.7%) patients, respectively, while other gastrointestinal manifestations were reported in 234 (25.7%) patients. Chronic renal failure was observed in 61 (6.7%) patients and pulmonary arterial hypertension (PAH) was confirmed at right heart catheterization in 38 (4.2%) patients. Three hundred twenty-two (35.3%) patients received immunosuppressant, 215 (23.5%) assumed an endothelin receptor antagonist and/or a 5-phosphodiesterase inhibitor, and 72 (7.9%) were treated with a biologic agent. The global 10-years survival was 89.4%; female gender (HR 0.33, CI95% 0.17-0.67), diffuse cutaneous involvement (HR 2.14, CI95% 1.17-3.91), presence of pulmonary hypertension (HR 2.61, CI95%1.31-5.16) and older age at non-RS (HR 1.1, CI95% 1.06-1.12) affected survival. Furthermore, as compared to previous Italian studies, our cohort showed a significant improvement in rate (see Figure 1).Conclusion:Survival in SSc patients has improved in last 5 decades but still reduced compared to that expected in general population above all 5 years after diagnosis. Early diagnosis, with reduced renal involvement, along with better screening and innovative therapeutic strategies may explain these achievements.Figure 1.Ten-years survival in SSc patients since 2009 (left); comparison of survival across different Italian SSc cohorts (box: current analysis) (right).References:[1]Giordano M, et al. The Journal of Rheumatology. 1986; 13:911-916.[2]Ferri C, et al. Medicine. 2002; 81:139-53.[3]Vettori S, et al. Reumatismo. 2010; 62(3):202-209.[4]Ferri C, et al. Autoimmun Rev. 2014; 13(10):1026-34.Disclosure of Interests:None declared

scholarly journals Functionally Active Antibodies to the Angiotensin II Type 1-Receptor Measured by a Luminometric Bioassay Do Not Correlate With Clinical Manifestations in Systemic Sclerosis: A Comparison With Antibodies to Vascular Receptors and Topoisomerase I Detected by ELISA

2021 ◽  
Vol 12 ◽  
Author(s):  
Lukas Bankamp ◽  
Beate Preuß ◽  
Ann-Christin Pecher ◽  
Nicola Beucke ◽  
Jörg Henes ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Angiotensin Ii ◽  
Liver Diseases ◽  
Topoisomerase I ◽  
Clinical Manifestations ◽  
Digital Ulcers ◽  
Healthy Controls ◽  
Healthy Individuals ◽  
Organ Manifestations

Objectives1) To detect functionally active antibodies(abs) to the angiotensin II type-1-receptor (AT1R) by a novel luminometric assay. 2) To assess their prevalence in systemic sclerosis (SSc), other collagen disorders, as well as in further chronic inflammatory disorders including autoimmune, toxic and chronic viral diseases. 3) To compare these abs with anti-AT1R antibodies by ELISA as well as with antibodies to endothelin-type-A receptors (ETA1) and to topoisomerase I (topo-I) with respect to their specificity and clinical relevance.MethodsSera from 98 SSc-patients, 110 patients with other chronic inflammatory rheumatic disorders, 97 patients with autoimmune liver diseases, 57 patients with toxic or chronic viral liver diseases and 36 healthy controls were analyzed. A luminometric bioassay was established with Huh-7-cells constitutively expressing the AT1R. Patients’ sera were also tested by commercially available ELISA for anti-AT1R, -ETA1- and by an in-house ELISA for anti–topo-I-abs.ResultsFifty-two percent of the SSc-patients had functionally active anti-AT1R-abs with stimulatory (34%) or inhibitory capacity (18%). They were present also in up to 59% of patients with other rheumatic diseases but only 22% of healthy individuals (sensitivity 52%, specificity 53%). The functionally active antibodies detected by the luminometric assay did not correlate with anti-AT1R-, -ETA1- or -topo-I-abs measured by ELISA, but there was a strong correlation between anti-topo-I-, AT1R-, and -ETA1-ab reactivity measured by ELISA. Sensitivities of 55%, 28% and 47% and specificities of 66%, 87%, and 99% were calculated for these anti-AT1R-, -ETA1-, and anti-topo-I-abs, respectively. Functionally active abs did not correlate with disease severity or any organ manifestation. In contrast, abs to topo-I, AT1R, and ETA1 were associated with digital ulcers, pulmonary- and esophageal manifestation.ConclusionsFunctionally active anti-AT1R-abs can be detected in SSc-patients but do not correlate with disease activity. They are not specific for this disease and occur also in other autoimmune disorders and even viral or toxic diseases. Also, the vascular antibodies detected by ELISA are not SSc-specific but correlated with disease manifestations. In contrast, anti-topo-I-abs were confirmed to be a highly specific biomarker for both, diagnosis and organ manifestations of SSc.

scholarly journals AB0589 THE IMPORTANCE OF A SYSTEMIC SCLEROSIS CLINIC IN A TERTIARY REFERRAL CENTER – A PORTUGUESE EXPERIENCE

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1591.1-1591
Author(s):  
P. Martins ◽  
E. Dourado ◽  
J. E. Fonseca ◽  
I. Cordeiro ◽  
C. Resende
Keyword(s):  
Pulmonary Hypertension ◽  
Systemic Sclerosis ◽  
Pulmonary Fibrosis ◽  
Topoisomerase I ◽  
Rna Polymerase Iii ◽  
Gastric Disease ◽  
Digital Ulcers ◽  
Medical Specialties ◽  
Patient Pathways ◽  
Kidney Involvement

Background:Systemic sclerosis (SSc) is a rare systemic rheumatic disease (SRD) characterized by small vessel inflammation and fibrosis of skin and internal organs. Pulmonary and cardiac involvement contribute to both morbidity and mortality associated with the disease. A multidisciplinary approach with strict monitoring is therefore key to attain clinical success.Objectives:To describe the organization and patient pathways of our SSc outpatient clinic.Methods:Observational study using data extracted from Reuma.pt/SSc (a subset of the Rheumatic Diseases Portuguese Register). Data extracted included demographic variables and clinical and immunological manifestations. The disease was classified according to the 2013 ACR/EULAR criteria. Our SSc clinic is managed by two dedicated Rheumatologists and up to two Rheumatology residents on a weekly basis, but it is a dynamic multidisciplinary clinic where various medical specialties collaborate closely. There are two associated subspecialty clinics (pulmonary hypertension and pulmonary fibrosis) where the Rheumatologists engage with pneumologists and cardiologists, allowing greater collaboration in the management of these patients. Patients’ data is systematically registered in Reuma.pt/SSc as a part of the routine activity of this clinic, contributing to real-world data on SSc.Results:A total of 220 patients were registered between July 2011 and June 2019. 196 (89.1%) were female, with a mean age of 58.9±14 years and a mean disease duration of 14.6±9 years. Ninety-seven patients (44.1%) had limited cutaneous SSc, 52 (23.6%) had diffuse cutaneous SSc, 35 (15.9%) had overlap SSc, 24 (10.9%) had preclinical SSc and 12 (5.4%) had SSc sine scleroderma. Raynaud phenomenon was present in 92% of the SSc patients and 40% had a history of digital ulcers. Gastrointestinal manifestations included esophageal dismotility in 39.5% of patients, gastric disease in 24.4% and intestinal involvement in 15.5%. Pulmonary involvement was found in 47.6% of SSc patients, heart disease in 43.6% and kidney involvement in only two patients. Antinuclear antibodies were positive in 92.2% of the patients, anti-centromere in 44.1%, anti-topoisomerase I antibodies in 39.1%, anti-U1RNP in 4.5% and only three patients had anti-PM-Scl and one had anti-RNA polymerase III. 31 patients were lost to follow-up and 32 died. 18 patients are currently being followed up in the pulmonary hypertension clinic and seven in the pulmonary fibrosis clinic.Conclusion:The implementation of a standardized approach with regular multidisciplinary work has proven very helpful in evaluating patients with SSc. The continuous registry of patients in Reuma.pt/SSc has been essential for patient care, research and healthcare planning.Disclosure of Interests:None declared

scholarly journals Reassessing the Role of the Active TGF-β1 as a Biomarker in Systemic Sclerosis: Association of Serum Levels with Clinical Manifestations

2016 ◽  
Vol 2016 ◽  
pp. 1-6 ◽  
Author(s):  
Andréa Tavares Dantas ◽  
Sayonara Maria Calado Gonçalves ◽  
Anderson Rodrigues de Almeida ◽  
Rafaela Silva Guimarães Gonçalves ◽  
Maria Clara Pinheiro Duarte Sampaio ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Clinical Manifestations ◽  
Serum Levels ◽  
Vascular Involvement ◽  
Digital Ulcers ◽  
Serum Samples ◽  
Peripheral Blood Mononuclear ◽  
Pbmc Culture ◽  
Significant Difference ◽  
Skin Biopsies

Objective. To determine active TGF-β1 (aTGF-β1) levels in serum, skin, and peripheral blood mononuclear cell (PBMC) culture supernatants and to understand their associations with clinical parameters in systemic sclerosis (SSc) patients.Methods. We evaluated serum samples from 56 SSc patients and 24 healthy controls (HC). In 20 SSc patients, we quantified spontaneous or anti-CD3/CD28 stimulated production of aTGF-β1 by PBMC. The aTGF-β1 levels were measured by ELISA. Skin biopsies were obtained from 13 SSc patients and six HC, and TGFB1 expression was analyzed by RT-PCR.Results. TGF-β1 serum levels were significantly higher in SSc patients than in HC (p< 0.0001). Patients with increased TGF-β1 serum levels were more likely to have diffuse subset (p= 0.02), digital ulcers (p= 0.02), lung fibrosis (p< 0.0001), positive antitopoisomerase I (p= 0.03), and higher modified Rodnan score (p= 0.046). Most of our culture supernatant samples had undetectable levels of TGF-β1. No significant difference in TGFB1 expression was observed in the SSc skin compared with HC skin.Conclusion. Raised active TGF-β1 serum levels and their association with clinical manifestations in scleroderma patients suggest that this cytokine could be a marker of fibrotic and vascular involvement in SSc.

scholarly journals AB0566 NAILFOLD EXTENT OF REDUCED CAPILLARY DENSITY IS ASSOCIATED WITH DIGITAL ULCERS AND WITH AN INCREASED RISK OF DIGITAL ULCERS IN SYSTEMIC SCLEROSIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1580.2-1580
Author(s):  
R. De Angelis ◽  
F. Salaffi
Keyword(s):  
Systemic Sclerosis ◽  
Laboratory Data ◽  
Quantitative Measure ◽  
Capillary Density ◽  
Optical Probe ◽  
Typical Feature ◽  
Slight Reduction ◽  
Digital Ulcers ◽  
Increased Risk ◽  
Significant Difference

Background:A growing evidence supports the role of microvasculopathy as a primary pathogenic event in systemic sclerosis (SSc). The most commonly used imaging technique to identify microangiopathy in SSc is high magnification videocapillaroscopy (NVC), and reduced capillary density and/or capillary loss, which is a typical feature of “scleroderma microangiopathy”, easily identified by NVC, has been associated with digital ulcers (DUs). Different approaches have been proposed to measure capillary density or capillary loss. Some of these were qualitative methods, others semi-quantitative, others only concerned a limited nailfold area, without ever evaluating the overall density, which is more suitable for quantitative estimate.Objectives:To assess the association between the extent of different values of nailfold capillary density and the presence of DUs and to identify the risk of developing DUs, based on quantitative parameters.Methods:The study involved 54 SSc selected patients (47 women and 7 men, mean age 59.5 years, 50 with limited and 4 with diffuse). The study population came from an ongoing database, that includes clinical and laboratory data of patients with definite SSc. A videocapillaroscope (VideoCap® 3.0, DS Medica, Milan, Italy) with a 200x optical probe was used. During examination, eight fingers (fingers 2–5 of each hand), 4 fields per finger, according to the standard literature were assessed. For each patient, a total of 32 images were collected, then classified as having either “normal”, “non-specific” or the “scleroderma pattern” (SP). Capillary density was defined as the number of capillaries/mm in the distal row, regardless of its shape and morphology. Avascular areas were defined by the absence of loops within a width/area extending over more than 500 microns. For each patient, the SP images were further graded with no/slight reduction of the capillary density (7-9 loops/mm) (NOR), with a well-defined reduction of capillary density (6-4 loops/mm) (RED) and with loss of capillaries (<4) plus avascular areas (AA). Then, the overall percentages were calculated (the number with SP, the number with NOR, with RED and with AA, respect to 32), thus obtaining the quantitative measures. All data were analysed using the MedCalc® version 18.6; 64-bit (MedCalc Software, Mariakerke, Belgium).Results:A total of 1728 images were analyzed. Patients with DUs were 16/54 (29.6%). All patients had a SP, but only five patients showed a SP along the entire nailfold. A comparison between patients with or without DUs showed a significant difference both for the overall extent of AA (p=0.032), and particularly for the overall extent of RED (p<0.001). No significant difference was found regarding the overall extent of the SP (p=0.085). Factor significantly associated with DUs in multivariate analysis was the overall extent of RED (p=0.0286). The ROC curve was very effective at discriminating the capillary feature able to distinguish patients with DUs from patients without DUs. The discriminatory power of the overall extent of RED was very good, with an AUC of 0.948 (95 % CI 0.852 ± 0.990). Then, we calculated the cut-off values of the overall extent of RED for presence/absence of DUs with the highest combination of sensitivity and specificity. The resulting cut-off value (Yourden index of 0.825) was >68.7 (sensitivity 92.31 %; specificity 90.24 %) with a LR+ of 9.46.Conclusion:Our data strongly support that the capillary density between 4 and 6 loops/mm is the best capillaroscopic quantitative measure associated with DUs and able to discriminate the probability of having DUs. If all SSc-specific antibodies and/or other laboratory/clinical parameters are not yet available, the overall capillary density can allow physicians to assess SSc patients easily, regarding DUs and risk for developing DUs.Disclosure of Interests:None declared

scholarly journals AB0621 TOLERABILITY AND SAFETY OF ACETYLSALICYLIC ACID IN PATIENTS WITH SYSTEMIC SCLEROSIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1606.2-1606
Author(s):  
L. Verardi ◽  
E. De Lorenzis ◽  
G. Natalello ◽  
L. Gigante ◽  
U. La Porta ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Adverse Events ◽  
Low Dose ◽  
Disease Duration ◽  
Rank Test ◽  
Digital Ulcers ◽  
Log Rank Test ◽  
Gastrointestinal Intolerance ◽  
Male Sex ◽  
Observation Period

Background:Systemic Sclerosis (SSc) is characterized by an increased incidence of macro- and microvascular complications. Current evidences on efficacy, safety and tolerability of acetylsalicylic acid (ASA) in SSc patients are limited, and the indication to this treatment is based on the experience of each single centre or physician. Esophagus and stomach are the portions of the digestive tract that are more frequently affected by adverse events due to ASA exposure.Objectives:We evaluated the incidence of adverse events associated with low-dose ASA treatment in a cohort of patients affected by SSc.Methods:Demographic data and disease features of 302 patients affected by SSc treated with low-dose ASA were collected and patients were followed-up for a median period of 6.9 years (range: 0-20 years). The proportion of patients taking ASA for secondary prevention for cardiovascular disease was also noted. The incidence of discontinuation of the drug, gastrointestinal intolerance, bleeding and death in the observation period was recorded.Results:Patients had a median age of 54.0 years (19.6-89.4); 91.9% were female, 13.2% were smokers and 44.0% had a BMI≥30Kg/m2. The prevalence of ischemic heart disease, peripheral vascular disease and stroke was of 8.6%, 5.3% and 3.3%, respectively; 48.7% of the patient took ASA in primary cardiovascular prevention. Therapy started after a median disease duration of 4.8 years (range: 0.0- 30.1 years) since the first non-Raynaud symptom and 56.6% of patients had an early disease (less than three years of disease duration). During the observation period, 30 patients (14.3 per 1000 person-years) discontinued ASA after an average period of assumption of 4.6 years (range: 0.3-18.0 years). The main adverse events were heartburn, dyspepsia and hematochezia, recorded in 18 patients (8.6 per 1000 person-years). Eight of them (3.8 per 1000 person-years) had evidence of digestive tract bleeding. Five patients (2.4 per 1000 person-years) discontinued ASA due to recurrent epistaxis. Twenty-eight patients (13.4 per 1000 person-years) died in the follow-up period, 16 of these (7.6 per 1000 person-years) because of SSc-related causes. None of them had evidence of major bleeding. We used Kaplan-Meier analysis to evaluate the incidence of ASA discontinuation. The history of digital ulcers (Log rank test X24.7, p=0.037) and male sex (Log rank test X24.3, p=0.03) were associated with a higher cumulative ASA discontinuation rate due to gastrointestinal intolerance.Conclusion:In our cohort of SSc patients, ASA resulted safe and well tolerated in most cases, despite the risk of gastroesophageal abnormalities due to disease. Although this comforting results, taking in account the lack of controlled-randomized trials about efficacy and safety, the choice to start antiplatelet therapy with ASA should be mandatorily preceded by a careful evaluation of risks and benefits. Furthermore, an attentive monitoring for possible adverse effects is needed during ASA treatment. Patients with digital ulcers and male sex could present less drug tolerability.References:[1]Valentini G et al. Ann Rheum Dis 2019. Beckett VL et al. Arthritis Rheum 1984. Kavian N et al. Vascul Pharmacol 2015. Lavie CJ et al. Curr Probl Cardiol 2017.Disclosure of Interests:Lucrezia Verardi: None declared, Enrico De Lorenzis: None declared, Gerlando Natalello: None declared, Laura Gigante: None declared, Umberto La Porta: None declared, Elisa Gremese Consultant of: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck Sharp & Dohme, Novartis, Sanofi, UCB, Roche, Pfizer, Speakers bureau: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck Sharp & Dohme, Novartis, Sanofi, UCB, Roche, Pfizer, Silvia Laura Bosello Speakers bureau: Abbvie, Pfizer, Boehringer

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