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Aspirin is the most commonly used medication worldwide. Beside its well-known anti-inflammatory effects, a role has emerged in the prevention of cardiovascular events. However, a significant benefit has been demonstrated in secondary cardiovascular prevention only, while there is limited evidence supporting a role in primary prevention. This discrepancy might depend on the that so far, the high-risk populations that will achieve the greatest benefits yet experiencing minimal harmful side effects have not been identified. Patients with autoimmune systemic rheumatic diseases have an increased risk of cardiovascular complications compared with the general population, which makes aspirin of potential value in these subjects. Moving from general aspects of aspirin pharmacology and specific issues in general population, the aim of this study is to review the evidence about the role of low-dose aspirin in primary cardiovascular prevention in autoimmune systemic rheumatic diseases.

Objectives The level of detail included when describing nailfold videocapillaroscopy (NVC) methods varies among research studies, making interpretation and comparison of results challenging. The overarching objective of the present study was to seek consensus on the reporting standards in NVC methodology for clinical research in rheumatic diseases and to propose a pragmatic reporting checklist. Methods Based on the items derived from a systematic review focused on this topic, a three-step web-based Delphi consensus on minimum reporting standards in NVC was performed among members of the European League against Rheumatism (EULAR) Study Group on Microcirculation in Rheumatic Diseases and the Scleroderma Clinical Trials Consortium. Results A total of 319 articles were selected by the systematic review, and 46 items were proposed in the Delphi process. This Delphi exercise was completed by 80 participants from 31 countries, including Australia and countries within Asia, Europe, North America and South America. Agreement was reached on items covering three main areas: patient preparation before NVC (15 items), device description (5 items) and examination details (13 items). Conclusion Based on the available evidence, the description of NVC methods was highly heterogeneous in the identified studies and differed markedly on several items. A reporting checklist of 33 items, based on practical suggestions made (using a Delphi process) by international participants, has been developed to provide guidance to improve and standardize the NVC methodology to be applied in future clinical research studies.

Gastrointestinal (GI) involvement is almost universal in patients with systemic sclerosis (SSc) and is associated with significant disease-related morbidity and mortality.1 The entire GI tract can be involved and other disease features (eg, low mood, terminal organ failure and functional hand impairment) can result in significant nutritional impairment. Severe GI involvement has been reported to occur in ~10% of patients with SSc and often occurs early in the course of the disease.2 However, identification of patients at high risk of clinically significant weight loss is extremely challenging, including from the high prevalence of GI symptoms in patients with SSc. Therefore, there is a need to understand high-risk patients including potentially modifiable risk factors, with a view to early intervention strategies. Against this background, the aim of this study was to examine potential clinical risk factors of significant weight loss in patients with SSc. We performed an analysis of patients with SSc enrolled in the multinational, longitudinal European League Against Rheumatism (EULAR) Scleroderma Trials and Research (EUSTAR) database. In our study, we defined significant weight loss as 4.5 kg and/or least 5% of their body weight at 5 months onwards.3 Patients with a recorded second visit after 3 months and before 12 months were included in the analysis. We adopted a pragmatic approach (relevant to clinical practice) in …

Objective Recent evidence suggests that some urinary biomarkers, namely Vascular Cell Adhesion Molecule-1 (VCAM-1), Intercellular Adhesion Molecule-1 (ICAM-1), Monocyte Chemoattractant Protein 1 (MCP-1), Neutrophil Gelatinase Associated Lipocalcin and Lipocalin-type Prostaglandin D-Synthetase (L-PGDS), might discriminate SLE patients with ongoing renal activity from those with stable disease. The objective of this study was to assess the role of these markers in predicting renal flares in comparison with conventional biomarkers and to derive a biomarker panel which may improve diagnostic accuracy. Methods Eligible participants were SLE patients prospectively followed at our clinic. Urinary biomarker levels were measured in urinary sample by ELISA assay and were compared by the unpaired Student’s t test or the Mann–Whitney U test as appropriate. Receiver operating characteristic analysis was used to calculate the area under the curve. Cox regression was used to identify independent factors associated with disease flares. Results Urine was collected from 61 patients. During 8 months’ follow-up, eight patients experienced a renal flare. Urinary L-PGDS, ICAM-1 and VCAM-1 levels were significantly increased in the patients who subsequently experienced a renal flare with respect to the remaining 53. At Cox regression analysis, L-PGDS, ICAM-1, VCAM-1, hypocomplementemia and anti-dsDNA antibodies were factors associated with renal flares. Based on receiver operating characteristic analysis, a combination of novel and conventional biomarkers demonstrated an excellent ability for accurately identifying a flare. Conclusion This study might suggest the usefulness of a novel biomarker panel in predicting a renal flare in SLE.

We aimed to evaluate in two large SSc French cohorts the prevalence and associated factors with the autoantibodies linked to erosive arthritis.448 SSc patients were recruited from May 2015 to January 2019. Standardized clinical and laboratory variables were collected in accordance with the EUSTAR database. ELISAs for IgM rheumatoid factor (RF), IgG anti-citrullinated proteins (ACPA) and IgG anti-carbamylated proteins antibodies (anti-CarP) were all determined in a central laboratory. The prevalence and clinical associations of the different antibodies were investigated.RF positivity was observed in 113 patients (25%) compared to 39 (9%) for ACPA and 63 (14%) for anti-CarP antibodies. Through multivariate regression analysis, both RF and ACPA positivity resulted to be associated with RA overlap disease (OR 5.7, 95% CI 2.3-13.8 and OR 44.1, 95% CI 15.4-126.3, respectively). Additionally, ACPA was found to be significantly related to synovitis/ tenosynovitis (OR 1.7, 95% CI 1.0-2.6). RF positivity was associated to a "vascular subset" (i.e. any major vascular complication) (OR 2.1, 95% CI 1.3-3.4). Moreover, anti-CarP antibodies were associated with a fibrotic subset and with digital ulcers (OR 2.0, 95% CI 1.1-3.6 and OR 1.9, 95% CI 1.1-3.4).We corroborated that ACPA could be useful in identifying patients with a more prominent joint disease and RA overlap disease. Of the most interest we found that anti-CarP antibodies could be a relevant biomarker related to fibrotic skin and lung disease.

Undifferentiated connective tissue disease at risk for systemic sclerosis (UCTD-risk-SSc), otherwise referred to as very early-early SSc, is a condition characterized by Raynaud's phenomenon with serum SSc marker autoantibodies and/or typical capillaroscopic findings and unsatisfying classification criteria for the disease. The aim of the present study was to assess the prevalence of right (RV) or left ventricular (LV) systolic and/or diastolic dysfunction by standard echocardiography and tissue Doppler imaging (TDI). Thirty patients with UCTD-risk-SSc (28 female, mean age 47 ± 13 years, range 21-70) and 30 age- and sex-matched controls underwent cardiac assessment by standard echocardiography and TDI. UCTD-risk-SSc patients and controls did not show any difference at standard echocardiography. Despite results falling within the respective normal ranges, TDI pointed out a mild impairment of LV and RV diastolic (E m 15 ± 4 vs. 19 ± 5, p = 0.0004; E/E m 6.1 ± 1.7 vs. 4.8 ± 1.2, p = 0.001; E t 14 ± 3 vs. 16 ± 2, p = 0.02; E t/A t 0.9 ± 0.4 vs. 1.3 ± 0.3, p = 0.002; E/E t 3.5 ± 1.2 vs. 4.2 ± 0.9, p = 0.02) and systolic function (S m 13 ± 3 vs. 15 ± 2 cm/s, p

Michele Iudici, Rosaria Irace, Antonella Riccardi, Giovanna Cuomo, Serena Vettori, Gabriele Valentini Rheumatology Section, Department of Clinical and Experimental Medicine, Second University of Naples, Naples, Italy Introduction/objectives: To prospectively assess the quality of life (QoL) of patients affected by undifferentiated connective tissue diseases (UCTDs) and to identify factors associated with changes over time.Patients and methods: A total of 46 consecutive UCTD patients completed the Short-Form 36 (SF-36) questionnaire at presentation and then yearly. At each 6-month visit, all patients underwent a detailed history taking and a laboratory and physical assessment, in order to follow the evolution of the disease over time and to assess the the co-existence of fibromyalgia.Results: At presentation, scores lower than the average of the general population were detected in 34 (74%) and 41 (89%) patients in the physical and mental domains, respectively. No difference between patients with and without Raynaud’s phenomenon was detected. Fibromyalgia was the only independent variable associated with an impaired physical component summary score (p=0.0009). No patient feature was found to be associated with the basal mental component summary score. During 24months of follow-up, a significant improvement (ie, a change ≥5 from baseline) in physical component summary and mental component summary scores was observed in 14 (33.3%) and 20 (43.4%) patients, respectively. Patients who significantly improved in the physical domain more frequently had a history of glucocorticoids intake (p&nbsp

Background Systemic Lupus Erythematosus (SLE) is a multisystem autoimmune disease commonly characterized by periods of flares and quiescence. Conventional markers of disease activity (serum complement and anti-dsDNA antibodies) have a limited predictive value of disease flares. Recent evidence suggests that urine biomarkers are able to discriminate between SLE patients with ongoing renal activity and those without nephritis (1-2). Objectives To investigate if urinary Neutrophil Gelatinase Associated Lipocalcin (NGAL) and Lipocalin-type Prostaglandin D-Synthetase (L-PGDS) are early biomarkers that could be used as flare predictors in SLE. Methods Patients prospectively followed at our clinic from March 2017 to September 2018, who fulfilled classification criteria for SLE (3), were considered for the study. Flares were identified by SELENA-SLEDAI Flare Index (SFI) after 3 months of urine collection (4). NGAL and L-PGDS levels were measured in the second void urinary sample by ELISA. Data were compared by the unpaired student’s t test or the Mann–Whitney U test as appropriate. Logistic regression analysis was used to assess the independent baseline predictors of flares. Receiver operating characteristic (ROC) analysis was used to calculate the area under the curve (AUC) with associated 95% confidence interval (CI) to find the best cut-off values. Results Urine specimen was collected from 66 patients, including 64 females and 2 males with a median age at diagnosis of 27 years (IQR 21,5-38). During 3 months-follow-up, 18 (27%) out of the 66 patients experienced a single disease flare. Urinary levels of L-PGDS (Fig. 1) and NGAL (Fig. 2) significantly increased 12 weeks before a disease flare (p=0.0001 and p=0.002, respectively). Urinary NGAL levels correlated with anti-DNA antibody titre (r=0.254, p=0.042) and not with serum complement prior to the disease flare (P>0.05). Moreover, urinary L-PGDS slightly correlated with anti-DNA antibody titre (p=0.08), and was not associated with serum complement levels. Based on ROC analysis, urinary NGAL (AUC: 0.752) and L-PGDS (AUC: 0.811), outperformed conventional biomarkers (Table1). ROC analysis revealed that NGAL levels above 10.95ng/ml had a sensitivity of 84% and a specificity of 63% for flare prediction, while urine L-PGDS cut-off value in the ROC curve, 1500 ng/ml, predicted a flare with 78% sensitivity and 86% specificity. At multivariate analysis, NGAL and L-PGDS were independent predictors of flare with OR=10.34 (95% CI 1.46 – 73.05) and 24.85 (95% CI 4.32-142.68), respectively. Increase in anti-dsDNA antibodies levels also predicted flares with an OR of 6.70 (p=0.040), while hypocomplementemia was not a significant risk factor. Conclusion Urine NGAL and L-PGDS perform better than conventional markers in predicting a lupus flare in its incipient phase, in particular preceding the corresponding change in serum complement. Urinary NGAL and L-PGDS levels seem to be potential tools for monitoring patients with SLE. Further studies are needed to determine their clinical utility in everyday practice. References [1] Rubinstein T, et al. Rheumatol Oxf Engl. 2010;49:960–71. [2] Gupta R, et al. Clin Exp Rheumatol. 2015;33:694-8. [3] Tan EM, et al. Arthritis Rheum. 1982;25:1271–7. [4] Petri M, et al. NEJM2005;353: 2550-58. Disclosure of Interests Serena Fasano: None declared, Luciana Pierro: None declared, Alessia Borgia: None declared, Melania Alessia Coscia: None declared, Ranieri Formica: None declared, Antonella Riccardi: None declared, Francesco Ciccia Grant/research support from: CELGENE, PFIZER, Consultant for: UCB, NOVARTIS, CELGENE, PFIZER, LILLY, Paid instructor for: UCB, NOVARTIS, CELGENE, PFIZER, LILLY, JANSSEN, Speakers bureau: UCB, NOVARTIS, CELGENE, PFIZER, LILLY, JANSSEN, MSD, ROCHE, AMGEN

Background: Calcium channel blockers (CCB) and angiotensin converting enzyme inhibitors (ACEinh) are known to improve in the short term, cardiac perfusion and function in patients with SSc (Parks JL et al. Rheum Dis Clin North Am 2014). No study has been carried out so far to investigate the long-term effectiveness of these drugs. Objectives: To address this topic and other aspects of the management of SSc, the DeSScipher (To decipher the optimal treatment of SSc) project was submitted to and financed by the European Community (FP7- HEALTH n°305495). Methods: From Dec.1, 2012 to Nov. 30, 2015, 512 SSc patients who, as inclusion criterion, had no significant gut or lung or kidney involvement, were treated for 0.5-4 years (median 2.31) with either (n= 359: group 1) vasodilator treatment (i.e. CCB, or ACE-inh or Angiotensin II receptor blockers [AgIIrb] or a combination of them i.e. CCB plus either ACEinh or AgIIrb) or (n= 153:group 2) no vasodilator therapy. The 296 patients of the 2 groups, who had been assessed at baseline and along the follow-up for conduction blocks (CB), ventricular arrhythmias (VA), pacemaker implantation (PMI), left ventricular ejection fraction (LVEF) Results: During 1164 patient-years follow-up,6/508 were implanted a PM,10/506 developed a LVEF Conclusion: Long term vasodilator therapy is likely to have a preventative role on the occurrence of myocardial manifestations of SSc. Disclosure of Interests: Antonella Riccardi: None declared, Dorte Husher: None declared, SERENA FASANO: None declared, Valentina Messiniti: None declared, Yannick Allanore Grant/research support from: Inventiva, F Hoffman La-Roche, Sanofi, BMS, Pfizer, Consultant for: Actelion, Bayer, BMS, Boehringer, Roche, Sanofi, Jerome Avouac Grant/research support from: research grant from Pfizer, Laszlo Czirjak: None declared, Veronika Lorand: None declared, Francesco Del Galdo: None declared, Giuseppina Abignano: None declared, Christopher Denton Grant/research support from: GlaxoSmithKline, Inventiva, CSF Behring, Consultant for: Roche-Genentech, Actelion, GlaxoSmithKline, Sanofi Aventis, Inventiva, CSL Behring, Boehringer Ingelheim, Bayer, Svetlana Nihtyanova: None declared, Oliver Distler Grant/research support from: Prof. Distler received research funding from Actelion, Bayer, Boehringer Ingelheim and Mitsubishi Tanabe to investigate potential treatments of scleroderma and its complications, Consultant for: Prof. Distler has/had consultancy relationship within the last 3 years with Actelion, AnaMar, Bayer, Boehringer Ingelheim, ChemomAb, espeRare foundation, Genentech/Roche, GSK, Inventiva, Italfarmaco, iQvia, Lilly, medac, MedImmune, Mitsubishi Tanabe Pharma, Pharmacyclics, Novartis, Pfizer, Sanofi, Serodapharm and UCB in the area of potential treatments of scleroderma and its complications. In addition, he had/has consultancy relationship within the last 3 years with A. Menarini, Amgen, Abbvie, GSK, Mepha, MSD, Pfizer and UCB in the field of arthritides and related disorders, Britta Maurer Grant/research support from: Grant/research support from AbbVie, Protagen, Novartis; congress support from MSD, Pfizer, Roche, and Actelion, Marco Matucci-Cerinic Grant/research support from: Actelion, MSD, Pfizer, BMS, Chemomab, Sanipedia, Speakers bureau: Actelion, BMS; MSD, Janssen, Serena Guiducci: None declared, Gabriela Riemekasten Consultant for: Chugai, F. Hoffmann-La Roche, Speakers bureau: Chugai, F. Hoffmann-La Roche, Elise Siegert Shareholder of: Astra Zeneca, Grant/research support from: Actelion, Consultant for: AEC Partners, Speakers bureau: Actelion, Norsk, Ulrich Walker Grant/research support from: Unrestricted grant from AbbVie for the creation of the COmPASS II app, Veronika Jaeger Grant/research support from: Has received an unrestricted grant from AbbVie to support the creation of the COmPASS II app, Marc Frerix: None declared, Ingo Helmut Tarner: None declared, Ulf Muller-Ladner Grant/research support from: Projekt supported by an unrestricted educational grant from Celgene GmbH., Gabriele Valentini Grant/research support from: MSD, Phizer, Consultant for: MSD, Phizer, biogen, Speakers bureau: MSD, amgen, biogen, lilly, sanofi, phizer

Background Disease activity as measured by the European Scleroderma Study Group Activity Index (EScSG-AI) (1) has been recently found to predict the development of damage over time in an early systemic sclerosis (SSc) cohort (2). The European Scleroderma Trials and Research Group Task Force for the Development of Revised Activity Criteria for SSc recently succeeded in identifying a preliminarily revised activity index (EUSTAR-AI) that had a greater construct validity than the EScSG-AI i.e. performing better in identifying patients with active disease (3). Objectives To assess in patients with SSc the predictive value of the EUSTAR-AI for disease severity accrual. Methods SSc patients from the EUSTAR database with a disease duration from the onset of the first non-Raynaud sign/symptom≤5 years were first extracted. Patients were considered for the study if they presented the following features: a)availability of items included in the EUSTAR-AI, in the EScSG-AI and in the Medsger severity scale at baseline and yearly for 2 consecutive years; b)availability of vital status at the last observation; c) availability of other disease features known to predict disease progression (male sex, clinical and serological subset). To capture the disease activity variations over time, we calculated the EUSTAR-AI and EScSG-AI adjusted mean (area under the curve over time divided by time interval). Disease progression was based on the Medsger severity scale and included accrual of a Δ≥1 summed severity score and of a Δ≥1 severity in each organ systems at the 2 year follow-up visit compared with the initial visit. To explore specific determinants of disease progression, logistic regression analysis was carried out. Results A total of 549 patients satisfied the entry criteria. At univariate logistic regression analysis (among sex, age, clinical and serological subset, EScSG-AI and EUSTAR-AI adjusted mean and baseline severity score), EScSG-AI adjusted mean (OR 1.41 95%CI 1.20-1.67), antiScl70 antibody positivity (OR 1.72 95%CI 1.20-2.47), diffuse subset (OR:1.46 95%CI 1.01-2.10) and EUSTAR-AI adjusted mean (OR 1.41 95%CI 1.23-1.61) predicted disease severity accrual. Multivariate analysis revealed that the EUSTAR-AI adjusted mean was the best predictor of disease progression (Table1). Moreover, at multivariate analysis the EUSTAR-AI adjusted mean also predicted severity accrual of lung (OR 1.32), heart (OR 1.40), skin (OR 1.48) and peripheral vascular disease (OR 1.45). Conclusion The adjusted mean EUSTAR-AI has a distinct predictive value for disease progression and development of severe organ involvement in SSc and works better than EScSG-AI. References [1] Valentini G, et al. Ann Rheum Dis 2001;60:592-8. [2] Nevskaya T, et al. Rheumatology (Oxford). 2017;56:1111-1122. [3] Valentini G, et al. Ann Rheum Dis. 2017;76:270-276. Disclosure of Interests Serena Fasano: None declared, Veronica Giacco: None declared, Antonella Riccardi: None declared, Valentina Messiniti: None declared, ALESSANDRA VACCA: None declared, Oliver Distler Grant/research support from: Prof. Distler received research funding from Actelion, Bayer, Boehringer Ingelheim and Mitsubishi Tanabe to investigate potential treatments of scleroderma and its complications, Consultant for: Prof. Distler has/had consultancy relationship within the last 3 years with Actelion, AnaMar, Bayer, Boehringer Ingelheim, ChemomAb, espeRare foundation, Genentech/Roche, GSK, Inventiva, Italfarmaco, iQvia, Lilly, medac, MedImmune, Mitsubishi Tanabe Pharma, Pharmacyclics, Novartis, Pfizer, Sanofi, Serodapharm and UCB in the area of potential treatments of scleroderma and its complications. In addition, he had/has consultancy relationship within the last 3 years with A. Menarini, Amgen, Abbvie, GSK, Mepha, MSD, Pfizer and UCB in the field of arthritides and related disorders, Otylia Kowalka Bielecka Consultant for: “OK-B received consulting fees or other remuneration from Bayer, Boehringer Ingelheim, Inventiva, Medac, Novartis and Roche”, Yannick Allanore Grant/research support from: Inventiva, F Hoffman La-Roche, Sanofi, BMS, Pfizer, Consultant for: Actelion, Bayer, BMS, Boehringer, Roche, Sanofi, Gabriele Valentini Grant/research support from: MSD, Phizer, Consultant for: MSD, Phizer, biogen, Speakers bureau: MSD, amgen, biogen, lilly, sanofi, phizer

BackgroundThe European Scleroderma Trials and Research Group (EUSTAR) recently developed a preliminarily revised activity index (AI) that performed better than the European Scleroderma Study Group Activity Index (EScSG-AI) in systemic sclerosis (SSc).ObjectiveTo assess the predictive value for short-term disease severity accrual of the EUSTAR-AI, as compared with those of the EScSG-AI and of known adverse prognostic factors.MethodsPatients with SSc from the EUSTAR database with a disease duration from the onset of the first non-Raynaud sign/symptom ≤5 years and a baseline visit between 2003 and 2014 were first extracted. To capture the disease activity variations over time, EUSTAR-AI and EScSG-AI adjusted means were calculated. The primary outcome was disease progression defined as a Δ≥1 in the Medsger’s severity score and in distinct items at the 2-year follow-up visit. Logistic regression analysis was carried out to identify predictive factors.Results549 patients were enrolled. At multivariate analysis, the EUSTAR-AI adjusted mean was the only predictor of any severity accrual and of that of lung and heart, skin and peripheral vascular disease over 2 years.ConclusionThe adjusted mean EUSTAR-AI has the best predictive value for disease progression and development of severe organ involvement over time in SSc.

Raynaud's phenomenon (RP) is a clinical disorder characterized by recurrent, reversible episodes of digital vasospasm. RP can be classified as primary (pRP) or secondary, depending on whether it occurs as a benign condition (not disease-associated) or is associated with other diseases, mainly of the connective tissues. In both cases, it can be triggered by environmental factors, as indicated by the increased incidence of pRP episodes following exposure to cold, vibration injury or chemicals. The purpose of this prospective case-control study was to assess, in an Italian cohort of 132 pRP patients, the association of the phenomenon with demographic, lifestyle habits, environmental and work-related factors. Compared to healthy controls, pRP was found to be inversely associated with the use of contact lenses (OR = 0.4; p = 0.004) and of chlorous-based disinfectants (OR = 0.3; p

ObjectivesTo investigate the influence of vasodilator drugs on the occurrence of features depending on myocardial ischaemia/fibrosis (ventricular arrhythmias, Q waves, cardiac blocks, pacemaker implantation, left ventricular ejection fraction (LVEF) Methods601 patients with SSc were enrolled from 1 December 2012 to 30 November 2015 and had a second visit 0.5–4 years apart. 153 received no vasodilators; 448 received vasodilator therapy (ie, calcium channel blockers and/or ACE inhibitors or angiotensin II receptor blockers or combinations of them), 89 of them being also treated with either endothelin receptor antagonists or PDE5 inhibitors or prostanoids. Associations between the occurrence of myocardial disease manifestations and any demographic, disease and therapeutic aspect were investigated by Cox regression analysis. A Cox frailty survival model with centre of enrolment as random effect was performed.ResultsDuring 914 follow-up patient-years, 12 ventricular arrhythmias, 5 Q waves, 40 cardiac blocks, 6 pacemaker implantations and 19 reduced LVEF and/or congestive heart failure (CHF) occurred. In multivariate Cox regression analysis, vasodilator therapy was associated with a lower incidence of ventricular arrhythmias (p=0.03); low-dose acetylsalicylic acid (ASA) with a lower incidence of cardiac blocks and/or Q waves and/or pacemaker implantation (p=0.02); active disease with a higher incidence of LVEF ConclusionsThe present study might suggest a preventative effect on the occurrence of distinct myocardial manifestations by vasodilator therapy and low-dose ASA.

To identify the distribution of patients with systemic lupus erythematosus (SLE) in clusters according to the levels of health-related quality of life (HRQoL), entity of pain, fatigue and depression.We performed a hierarchical cluster analysis. The following measures were used as clustering variables, after canonical transformation: the SF36 physical and mental component summary (PCS and MCS), the Beck Depression Inventory II (entity of depression), the Facit-Fatigue, all assessed during the last visit. Consecutive SLE patients were enrolled from two Italian cohorts. Lupus remission was retrospectively assessed over a period of 5 years before the last visit and was defined as a continuative period of no clinical disease activity according to SLEDAI2K and the maximum dose of prednisone allowed of 5 mg/day.We enrolled 130 female SLE patients. We identified three clusters. The first cluster (43 patients) was characterised by the highest levels of MCS and PCS and the lowest entity of pain, fatigue and depression. Cluster 2 (35 patients) was defined by a reduction of MCS and increase of pain, fatigue and depression; conversely, PCS levels were similar to cluster 1. In cluster 3 (52 patients) we found a reduction of MCS and increase of depression and fatigue (similar to cluster 2) but also a decrease in PCS levels and Bodily Pain (meaning increase in pain). In cluster 3 we found a decreased prevalence of remission ≥5 years.Identification of clusters of patients according to HRQoL levels could be useful to improve SLE management, aiming at personalised medicine.

Prolonged remission (PR), defined as a 5-year consecutive period of no disease activity based on SLEDAI-2K, has been reported to be associated with a lower damage accrual over time in patients with systemic lupus erythematosus (SLE), as the consequence of a lower activity burden. Since disease activity is considered to play a role in the incidence of cardiovascular disease (CVD), we investigated the relationship, if any, between PR and the occurrence of a subsequent first CV event in patients with SLE. Out of 488 patients consecutively admitted to two tertiary Italian centers from November 1, 2000, to December 31, 2016, the 294 patients, who had been followed at least for 5 years, had not experienced any CV event at admission, and had been visited biannually during follow-up, were considered for the present study. The incidence of a first CV in patients who had achieved PR was compared with that registered in those who had not. Moreover, it was compared among PR patients subdivided into three groups: complete remission, clinical off-corticosteroids (offCR), and clinical on-corticosteroids remission (onCR). Kaplan–Meier curves and the log-rank test were used to analyze differences in event-free survival among groups. Cox regression was used to investigate disease and therapeutic features associated with the development of a first CV event. During 9 years median follow-up time, 24 (8.1%) CV events occurred. Out of the 294 patients, 126 (42.8%) had achieved PR. Kaplan–Meier analysis revealed a greater overall CV event-free rate in these patients as compared to both those with a shorter lasting remission and those who had never remitted (log-rank test χ2 = 14.43; p = 0.0001). In addition, CV outcome did not differ among PR patients, irrespectively the type of remission achieved (p > 0.05). At multivariate analysis, hydroxychloroquine therapy and PR resulted to be protective (HR 0.19; HR 0.18), while arterial hypertension and antiphospholipid positivity increased the risk of a first CV event (HR 2.61; HR 2.47). The PR, whichever the subtype, is associated with a better CV outcome and should be considered as a treat-to-target goal in the CV risk management of the lupus patient.

Objective To evaluate the impact of duration of remission on the health-related quality of life (HRQoL) of patients with systemic lupus erythematosus (SLE). Methods We conducted a 5-year retrospective study on two Italian cohorts. Remission was defined as a continuative period of no clinical disease activity, according to the Systemic Lupus Erythematosus Disease Activity Index 2 K, and a permitted maximum prednisone dose of 5 mg/day. HRQoL was measured using the 36-Item Short-Form Health Survey (SF36) during the last visit. Results We enrolled 136 female SLE patients. During observation, 15 (11%) patients had been in remission for ≥1 and Conclusion Lupus remission could improve the HRQoL of SLE patients, particularly when associated with appropriate management of depression and fatigue.

We read with great interest the article by Blaja, et al 1 on the challenge of very early systemic sclerosis (SSc). We have been addressing this topic for some years. Actually, VEDOSS (very early diagnosis of systemic sclerosis)2, subsequently renamed very early SSc3, was proposed before the development of the 2013 American College of … Address correspondence to Dr. A. Riccardi, Rheumatology Unit, Department of Precision Medicine, University of Campania Luigi Vanvitelli, Via Pansini 5, 80131 Naples, Italy. Email: antonellariccardi84{at}gmail.com.

Background:According to the recent recommendations for Systemic Lupus Erythematosus (SLE), a progressive tapering until withdrawal of glucocorticoids (GC) is considered one of the main goals of SLE management (1). However, which patient may be a candidate for safe GC withdrawal has not been determined yet and a proportion of patients are kept on long-term low-dose prednisone despite clinical remission.Objectives:to evaluate the rate of low-dose GC withdrawal in SLE patients in remission and to identify predictors of flares.Methods:Eligible patients were SLE patients according to the ACR criteria (2) who were in prolonged clinical remission defined by a cSLEDAI=0 for at least 2 years and on a stable SLE treatment (immunosuppressive drugs and/or hydroxychloroquine (HCQ) and daily 5 mg prednisone). A SACQ period was defined as at least 1-year period with persistent serologic activity without clinical manifestations. Flares were defined by SELENA-SLEDAI Flare Index (3). Damage was assessed by SLICC damage index (SDI). Data were compared by the unpaired student’s t test or chi-squared test as appropriate. Predictors of flares after GC withdrawal were analyzed by Cox regression.Results:Out of 246 SLE patients registered in the Naples Lupus Clinic database, 132 eligible patients were identified. Among them, we selected 57 (43%) patients in whom a GC withdrawal was attempted. 75 (57%) patients were in the prednisone maintenance group.There were no significant differences between the two treatment groups (table 1). The proportion of patients experiencing a flare was not significantly lower in the maintenance group than in the withdrawal group (15/75 vs 16/57; p=0.28). Moreover, the proportion of patients who had an increase in the SDI at the end of follow up was similar between the two groups (14/75 vs 8/57; p=0.48). However, among the withdrawal group, the rate of flares was significantly higher in SACQ patients (10/22 vs 6/35; p=0.02), while the majority of serologically inactive patients (82%) successfully stopped GCs without subsequent flares. At Cox regression analysis (Table 2), duration of HCQ therapy and >4 year remission at withdrawal were protective factors, while a SACQ disease and history of lupus nephritis (LN) increased the risk of disease flare.Table 1.Baseline characteristics of 132 patients at study entryCharacteristicsWithdrawal group (n=57)Maintenance group (n=75)p-valueFemale, no. (%)54 (94)70 (93)0.73Age, years26.7±10.128.5±11.70.37Disease duration, years8.5±2.99.1±12.90.73History of lupus nephritis, no. (%)13(22)22(29)SDI score0.40±0.70.57±0.80.26Immunosuppressive drugs, no. (%)31 (54)33(44)0.16HCQ, no. (%)52 (91)66 (88)0.06Low C3, no. (%)28 (49)41(54)0.52Increased dsDNA Ab, no. (%)11 (19)19 (25)0.41Table 2.Factors predicting lupus flares during follow-up at Cox regression analysisVariablesHR95% CIp valueSACQ2.991.08 – 8.250.03Age0.970.93 – 1.020.29Disease duration0.990.94 – 1.040.84History of LN3.381.22-9.330.01SDI score1.130.63 – 2.010.66Immunosuppressive drugs2.390.86 – 6.620.09HCQ, ever2.920.43 – 35.20.95Duration of HCQ0.840.72 – 0.980.035years remission0.120.04 – 0.390.0003Conclusion:GC withdrawal is an achievable target in SLE and may be attempted in patients in complete remission. In SACQ patients, maintenance of 5mg prednisone is superior to its withdrawal in order to prevent flares. Long-term HCQ therapy and prolonged remission can significantly reduce the risk of disease relapse after GC withdrawal.References:[1]Fanouriakis A, et al. Ann Rheum Dis. 2019;78(6):736–45.[2]Tan EM, et al. Arthritis Rheum. 1982;25(11):1271–7.[3]Petri M, et al. Lupus. 1999;8(8):685–91.Disclosure of Interests:Serena Fasano: None declared, Luciana Pierro: None declared, Melania Alessia Coscia: None declared, laura Bucci: None declared, silvia scriffignano: None declared, Antonella Riccardi: None declared, francesco ciccia Grant/research support from: pfizer, novartis, roche, Consultant of: pfizer, novartis, lilly, abbvie, Speakers bureau: pfizer, novartis, lilly, abbvie

Background Undifferentiated connective tissue disease at risk for systemic sclerosis (UCTD-risk-SSc) is a condition characterised by Raynaud’s phenomenon and either SSc marker autoantibodies or typical capillaroscopic findings or both, unsatisfying classification criteria for SSc 1 and reported to evolve into definite SSc in about 50% of 60 cases over a 12–102 months follow-up time. 2 We found marker autoantibody positivity to predict the evolution into SSc satisfying 2013 ACR criteria for the disease. 3 Objectives To investigate in patients followed-up for a longer time if distinct marker autoantibody specificities have a different predictive value. Methods Sixty-five patients consecutively admitted to a tertiary Rheumatology Unit from November 1 st 2000 to December 31 st 2016 and diagnosed as UCTD-risk-SSc were enrolled in the study. Patients were monitored for a median of 27 months (range 6–144) and were evaluated twice yearly to assess disease progression. Kaplan-Meier curves and the log-rank test were used to analyse differences in fulfilling the criteria for SSc between subsets. Risk prediction was assessed by univariate Cox regression analysis. Results During follow-up 40/53 marker autoantibody-positive patients (75.5%) versus 3/12 (25%) marker autoantibody negative ones satisfied SSc criteria (p=0.006). Out of them, 11/12 (91.7%) anti-topoisomerase (Scl70) positive versus 29/40 (72.5%) anti-centromere (ACA) positive patients evolved into definite SSc (p=0.04). In univariate analysis, anti-Scl70 positivity increased by 2-fold the risk of a definite SSc outcome (HR 2.1 95% CI 0.9–4.4) with respect to ACA positivity (HR 0.5 95% CI 0.2–1.0) (p=0.05). In addition 3/3 (100%) patients with avascular areas at baseline versus 40/62 (64.5%) with megacapillaries only or no capillaroscopic abnormalities satisfied SSc criteria over a 12–38 months follow-up time (p=0.06). Conclusions We confirm that autoantibody positivity patients presents a faster evolution. Moreover we first detected an increased HR of Scl-70 versus ACA positivity and a potential role of baseline detected avascular areas. References [1] Valentini G. Undifferentiated Connective Tissue Disease at risk for systemic sclerosis (SSc) (so far referred to as very early/early SSc or pre-SSc). Autoimmun Rev2015. [2] Valentini G, et al. Early Systemic Sclerosis: Analysis of the Disease Course in Patients With Marker Autoantibody and/or Capillaroscopic Positivity. Arthritis Care Res2014. [3] van den Hoogen F, et al. 2013classification criteria for systemic sclerosis: an American college of rheumatology/European league against rheumatism collaborative initiative. Ann Rheum Dis2013. Disclosure of Interest None declared

Background Cardiovascular disease (CVD) has emerged as one of the most important causes of mortality in systemic lupus erythematosus (SLE)1. In previous studies, disease activity, as assessed by SLEDAI (at the first visit or as mean annual value registered during follow-up), did not result to have any predictive role on the subsequent occurrence of CVD2–3. Objectives To investigate the relationship between prolonged remission and the occurrence of a subsequent first CV event in patients with SLE. Methods Out of 452 patients consecutively admitted to two tertiary Italian centres from November 1st 2000 to December 31st 2016, the 409 patients, who, at admission, had not experienced any CV event, had not received any anticoagulation therapy and had been visited at least biannually during follow-up, were considered for the present study. Prolonged remission was defined as a 5 year consecutive period of no disease activity based on SLEDAI-2K3.. Patients with prolonged remission were furtherly subdivided according to Zen et al4 into 3 groups: complete remission, clinical off-corticosteroids remission (offCR), clinical on-corticosteroids remission (onCR). Kaplan-Meier curves and the log-rank test were used to analyse differences in event-free survival between groups. Cox regression analysis was used to investigate disease and therapeutic features associated with the development of a first CV event. Results During 72 months median follow-up time, 29 (7.0%) CV events occurred (two events in patients who had undergone prolonged remission). Out of the 409 patients, 28 patients (6.8%) achieved a prolonged complete remission, 13 (3.1%) prolonged clinical offCR and 64 (15.5%) prolonged clinical onCR. Kaplan-Meier analysis revealed a greater overall CV event-free rate in patients achieving a prolonged remission compared to those in remission but for less than 5 years and patients not in remission (logrank test χ2=19.82; p=0.0001; figure 1). However, at Kaplan-Meier analysis, CV outcome was similar among patients in prolonged remission, irrespective of the type of remission achieved (p>0.05). At multivariate analysis, treatment with hydroxychloroquine for more than 5 years and prolonged remission were protective (HR 0.38; 95% CI 0.16–0.90; HR 0.08, 95% CI 0.01–0.53) while antiphospholipid syndrome increased the risk of a first CV event (HR 3.80; 95% CI 1.68–8.61). No differences were found between patients treated or not with aspirin. Nevertheless, among patients from Rome cohort, aspirin was only prescribed to patients with high traditional CV risk score. Conclusions A prolonged remission, whichever the subtype, is associated with a better CV outcome and should be considered as a treat-to-target goal in the CV risk management of the lupus patient. References [1] Cervera R, et al. Medicine (Baltimore)2003. [2] Iudici M, et al. Rheumatology (Oxford)2016. [3] Fasano S, et al. Lupus2017. [4] Zen M, et al. Ann Rheum Dis2017. Disclosure of Interest None declared

Background Cardiovascular (CV) disease is the leading cause of premature death among Systemic Lupus Erythematosus (SLE) patients1. Several studies have analysed the incidence of CV events in SLE patients. However, the majority of them have been conducted in American and North European countries 2–7. At the best of our knowledge, no studies in Italy have considered cumulative incidence and incidence rate of CV events in Italy. Objectives The present study is devoted to estimate the incidence of a first ever CV event in Italian lupus patients from five rheumatologic tertiary units from North, Centre and South Italy and to search for features associated with and potentially causative of the detected differences. Methods Clinical charts of SLE patients consecutively admitted to five Italian rheumatologic centres from November 1 st 2000 and December 31 st 2016 were retrospectively studied. Patients selected were free of CV events at baseline. CV cumulative incidence was evaluated as the proportion of patients who experienced a new CV event over the follow up period. CV incidence rate was expressed as the number of events in the cohort divided by the total number of years at risk. Our incidence was compared with that detected in the Italian general population and those reported in SLE cohorts from other countries. Results The median duration of follow-up was 6 years (IQR=3–11). During the observational period, 39(cumulative incidence=7.6%) of the 511 patients had a first CV event with an incidence rate of 10.4/1000 person-years i.e. 12 times higher than in the general population. The CV cumulative incidence detected in our Italian cohort was similar to that reported in the Spanish cohort, but lower than those from North European and American cohorts. The Italian cohort differed from other SLE cohorts in some traditional risk factors (smoke, hypertension, dyslipidemia) and treatment with aspirin and hydroxychloroquine.(table1) Conclusions Our study confirmed the increased CV risk in SLE compared with the general population. However, the incidence of CV events in our SLE series was lower than that detected in North European and American lupus cohorts. These disparities could be ascribed to the differences in the prevalences of traditional CV risk factors among the distinct cohorts. Nevertheless, our CV cumulative incidence was very similar to that detected in the Spanish cohort, despite their higher frequency of traditional risk factors. For this evidence, the geographic (Mediterranean) origin deserve to be considered. On the other hand, the slight difference detected between our series and Baltimore cohort2(where patients were examined every 3 months) underlines the need of a strict follow-up of the SLE patient. References [1] Cervera R, et al. Medicine (Baltimore)2003. [2] Magder LS, Petri M. Am J Epidemiol2012. [3] Bertoli AM, et al. Lupus2009. [4] Bartels CM, et al. J Rheumatol2014. [5] Gustafsson J, et al. Arthritis Res Ther2009. [6] Hermansen M-L, et al. Rheumatol Oxf Engl2017. [7] Fernandez-Nebro A, et al. Medicine (Baltimore)2015. Disclosure of Interest None declared

Background Patients with Systemic Lupus Erythematosus (SLE) present an increased incidence of Cardio-Vascular Events (CVE) compared to general population, and the difference with healthy subjects is particularly evident in young SLE women. Objectives The aim of this study is to assess the predictive ability of established 10 years CV risk models in SLE Methods A retrospective analysis of two Italian SLE prospective cohorts was performed. SLE patients without previous CVE, with age ≥25 years, a minimum continuative follow-up of 10 years and sufficient data to calculate the 10 years risk scores were enrolled. The 10 years CVE risk scores were calculated at the first observation and all CVE were prospectively recorded in the following 10 years. We calculated the following scores: the QRisk3, the Framingham CV disease 10 years score, the HeartScore (Europe Low Risk) and the SLE CV Risk Score proposed by Petri et al. Discriminatory ability for CV risk prediction was estimated by the area under the receiver operating characteristic curve. Hosmer-Lemeshov (HL) tests was used to evaluate calibration comparing the observed versus expected number of events Results Analysis was performed on 131 SLE patients (mean baseline age of 37±11 years). We observed 10 CVE during the 10 years follow-up from baseline (3 acute coronary syndrome, 4 stroke, 1 transitory ischaemic attack and 2 peripheral artery disease). The AUC values were 0.75 (95% CI 0.55–0.94) for QRisk3, 0.66 (0.45–0.88) for Framingham score, 0.62 (0.41–0.82) for the HeartScore and 0.7 (95% CI 0.55–0.85) for the SLE CV risk score. The p values of HL test were 0.8 for Qrisk3 and SLE CV score and 0.4 for Framingham score and HeartScore, suggesting a good model fit for all the CV risk scores. Considering scores with better discriminative ability and calibration, 20% of CVE were observed with Qrisk3 score lower then 3.6% and with SLE CV risk score between 6% and 8%. Discriminative ability and calibration were not improved by multiplying by 2 the Framingham score and the HeartScore. Conclusions The available CV risk scores demonstrate a moderate predictive ability of 10 years CVE in SLE. We observed a better model fit for QRisk3 and SLE CV risk score. Nevertheless, a considerable proportion of patients, with very low predicted CV risk, developed CVE during follow-up. References [1] Petri MLS. Systemic lupus erythematosus Cardiovascular Risk Equation. [Abstract]. Arthritis Rheum2012;64. [2] Urowitz MB, Ibanez D, Su J, et al. Modified Framingham Risk factor score for systemic lupus erythematosus. J Rheumatol2016;43:875–9. Disclosure of Interest None declared

Background Previous study from our group have pointed out a lower number of cardiovascular (CV) events in Italian patients with Systemic Lupus Erythematosus (SLE) than in North European and American ones. This study aims to assess the incidence of the first CV event in a large, multicenter, Italian cohort of patients with SLE and search for differences in disease and traditional risk factors among distinct cohorts. Methods Clinical charts of SLE patients consecutively admitted to five Italian rheumatologic centres from November 1 st 2000 and December 31 st 2015 were retrospectively studied. Patients selected were free of CV events at baseline. CV incidence rate was expressed as the number of events in the cohort divided by the total number of years at risk. CV cumulative incidence were evaluated as the proportion of patients who experienced a new CV event over the follow up period. Our incidence was compared with that detected in the Italian general population and those reported in SLE cohorts from other countries. Results The median duration of follow-up was 6 years (IQR=3–11). During the observational period, 37(cumulative incidence=7.2%) patients had a first episode of CV event with an incidence rate of 10.1/1000 person-years i.e 12 times higher than in the general population. The CV incidence rate and cumulative incidence detected in our Italian cohort was lower than those from North European and American cohorts. The Italian cohort differed from other SLE cohorts in some traditional risk factors (smoke, hypertension, dyslipidemia) and treatment with aspirin and hydroxychloroquine. Conclusion Our results confirmed that Italian lupus patients suffer a high incidence of CV disease compared with general population. However, this incidence was lower than that detected in North European and American lupus cohorts

Previous study from our group has pointed out a lower number of cardiovascular (CV) events in Italian patients with systemic lupus erythematosus (SLE) than in North European and American ones. This study aims to assess the incidence of the first CV event in a large, multicenter, Italian cohort of patients with SLE and search for differences in disease and traditional risk factors among distinct cohorts. Clinical charts of SLE patients consecutively admitted to 5 Italian rheumatologic centers from November 1st 2000 to December 31st 2015 and free of CV events at baseline were retrospectively studied. CV cumulative incidence (ie, the proportion of patients who experienced a new CV event over the follow-up period) and CV incidence rate (ie, the number of events in the cohort divided by the total number of years at risk) were evaluated. The detected incidences were compared with those reported in SLE cohorts from other countries. The median duration of follow-up was 6 years (IQR=3-11). During the observational period, 37 (cumulative incidence=7.2%) patients had a first episode of CV event with an incidence rate of 10.1/1000 person-years. The CV cumulative incidence and incidence rate detected in our Italian cohort were lower than those from most North European and American cohorts, characterized by a high impact of traditional risk factors. Nevertheless, the cumulative incidence was similar to that reported in a Spanish cohort with a high frequency of traditional risk factors (geographic impact), while the incidence rate was only slightly higher than that in the Baltimore cohort, which is characterized by a strict follow-up of patients (medical impact). Our results confirmed that Italian lupus patients have a low incidence of CV events. Moreover, the geographic origin, traditional risk factors, and medical approach appear to have an impact on CV disease in SLE. Abbreviations: ACR = American College of Rheumatology, aPL = antiphospholipid antibody, ASA = aspirin, CV = cardiovascular, HCQ = hydroxychloroquine, SCORE = Systematic COronary Risk Evaluation, SLE = systemic lupus erythematosus.

Background Systemic lupus erythematosus (SLE) is associated with an increased cardiovascular (CV) risk (1). By retrospectively investigating a one centre cohort, we have recently reported that low-dose aspirin (ASA) use is associated with a reduced CV risk in SLE (2) and long-term hydroxychloroquine (HCQ) exposure may have an additive effect (3). Objectives This study was conducted on 2 Italian SLE cohorts to confirm these results and assess the role, if any, of statins. Methods Clinical charts of SLE patients consecutively admitted to 2 University Rheumatology Units from November 2000 to December 2014 who, at admission, had not experienced any CV event, were investigated. ASA, HCQ and statins use and the occurrence of any CV event, were recorded at each visit. Kaplan-Meier analysis was performed to determine the HCQ exposure status associated with a higher CV-free survival. Cox regression analysis was carried out to identify factors independently associated with a first CV event. Results A total of 291 SLE patients were included in the study and followed for a median of 8 years. During follow-up, 16 CV events occurred. Kaplan Meier analysis revealed a greater CV event-free rate in the 120 ASA-treated patients taking HCQ at standard dose for more than 5 years than in the 98 patients treated with ASA alone or with HCQ for less than 5 years (Figure 1). At univariate analysis, patients with a first CV event compared with those without any thrombotic events were antiphospholipid antibody (aPL) positive (P=0.017 HR 2.91) and had significantly higher blood pressure (P=0.017 HR 3.58), hypercholesterolemia (P=0,015 HR 3.40) and higher disease damage at last visit (P=0,032 HR 1.56). Moreover, ASA treatment (P=0,012 HR 0.27) and HCQ use (P=0,012 HR 0.26) for more than 5 years were negative predictors, while statins use did not show any association (P=0.619). All other variables examined, including smoking, obesity, hypertriglyceridaemia, diabetes mellitus, disease activity, severe SLE, other medications (immunosuppressive agents, steroids) were not associated, either positively or negatively, with the occurrence of CV events. At multivariate analysis, taking ASA and HCQ for more than 5 years were protective against thrombosis (HR 0.24 and HR 0.27, respectively), while aPL positivity (HR 4.32) increased the risk of a first CV event. Conclusions Use of antimalarials for more than 5 years is associated with a reduced risk of a first thrombosis in SLE patients and the HCQ-ASA combination seems to synergistically reduce further the CV risk. Larger, prospective studies are needed to provide a better definition of the role of these drugs in CV primary prevention in SLE. References Cervera R, et al. Morbidity and mortality in systemic lupus erythematosus during a 10-year period: a comparison of early and late manifestations in a cohort of 1,000 patients.Medicine (Baltimore). 2003. Iudici M, et al. Low-dose aspirin as primary prophylaxis for cardiovascular events in systemic lupus erythematosus: a long-term retrospective cohort study. RheumatolOxfEngl 2016. Fasano S, et al. Long-Term Hydroxychloroquine Therapy and Low-Dose Aspirin May Have an Additive Effectiveness in the Primary Prevention of Cardiovascular Events in Patients with Systemic Lupus Erythematosus [abstract]. Arthritis Rheumatol 2016. Disclosure of Interest None declared

Background Undifferentiated connective tissue disease at risk for Systemic Sclerosis (UCTD-risk-SSc), previously referred to as very early SSc, is a condition characterized by Raynaud9s phenomenon (RP) with SSc marker autoantibodies and/or typical capillaroscopic findings and unsatisfying classification criteria for the disease (1). UCTD-risk- SSc patients have been reported to present, in about 40% of the cases, a preclinical vascular internal organ disease as detected by a diffusing lung capacity for CO Objectives Aim of the present study was to assess the prevalence of right (RV) or left ventricle (LV) systolic and/or diastolic dysfunction by standard echocardiography and tissue Doppler imaging (TDI). Methods Thirty patients with UCTD-risk-SSc (28 female, aged 47±13 years, range 21–70) and 30 age- and sex-matched controls underwent cardiac assessment by standard echocardiography and TDI. Results UCTD-risk-SSc patients and controls did not show any difference at standard echocardiographic evaluation. In particular, an inverted E/A ratio was pointed out in 10/30 patients and 7/30 controls (p=ns). TDI showed a mild impairment of LV and RV diastolic (Em15±4 vs 19±5, p Conclusions Our study shows that UCTD-risk-SSc patients present a previously unrecognized, mild biventricular systolic and diastolic dysfunction as compared to controls. The pathophysiologic meaning (i.e.intramyocardial artery disease and/or patchy fibrosis) as well the predictive value of developing overt SScin the short time await to be elucidated. Disclosure of Interest None declared

Background Some abnormalities in nailfold videocapillaroscopy (NVC), such as the presence of micro-haemorrhages (MHEs), micro-thromboses (MTs), giant capillaries (GCs) and reduction in the number of capillaries (nCs), suggest a disease activity (DA) phase in systemic sclerosis (SSc). In a previous paper, we showed that the number of micro-haemorrhages and micro-thromboses (the so-called NEMO score) was the NVC feature more closely associated with DA. The present study was aimed at validating the NEMO score as a measure of DA in patients with SSc. Methods Two cohorts of 122 and 97 patients with SSc who were referred to two different rheumatology units, one in Milan and one in Naples, respectively, constituted the validation cohorts. The NEMO score, the total number of GCs and the mean nCs per digit were the parameters defined in each patient by eight-finger NVC. An expert operator analysed the NVCs in each of the participating units. The European Scleroderma Study Group (ESSG) index was used to define the DA level in each patient at the time of NVC examination. Results The NEMO score was the NVC parameter more strictly correlated with the ESSG score in both the Milan and Naples cohorts (p

Previous studies of the occurrence of interstitial lung disease (ILD) in undifferentiated connective tissue diseases (UCTD) were conducted in patients admitted to Respiratory Medicine Units. The aim of the present prospective study was to investigate lung involvement in UCTD patients admitted to a Rheumatology Unit. Eighty-one consecutive UCTD patients were enrolled in the study. Each patient underwent history and physical examination, routine laboratory investigations, antinuclear antibody (ANA) profiling, B-mode echocardiography, and lung function study according to previously reported methods. Lung high resolution computed tomography (HRCT) was performed in patients who provided informed consent. Six patients (7.4%) had a history of grade II dyspnea. Three of them had a DLCO ranging from 42 to 55% of the predicted value; and a HRCT-documented ILD with a non-specific interstitial pneumonia (NSIP) pattern. Symptoms in the other three patients were due to cardiac disease. None of the 75 asymptomatic patients, had relevant findings at physical examination, 26/75 had a DLCO

Objectives: Undifferentiated connective tissue disease at risk for Systemic Sclerosis (UCTD-risk-SSc) is a condition characterized by Raynaud9s phenomenon (RP) with SSc marker autoantibodies and/or typical capillaroscopic findings and unsatisfying classification criteria for the disease. UCTD-risk- SSc patients have been reported to show a preclinical vascular internal organ disease in about 40% of the patients. The present study is devoted to assess the prevalence of right (RV) or left ventricle (LV) systolic and/or diastolic dysfunction as assessed by tissue Doppler imaging (TDI). Methods: Fifty-three patients with UCTD-risk-SSc (46 female, aged 45±12 years, range 16-67) and 52 age- and sex-matched controls underwent cardiac assessment by standard echocardiography and TDI. Results: UCTD-risk-SSc patients and controls did not show any difference at standard echocardiographic evaluation. In particular, an inverted E/A ratio was pointed out in 14/53 patients and 12/52 controls (p=ns). TDI showed a mild impairment of LV and RV diastolic (E m 16±5 vs 19±5, p m 6.3±3.0 vs 4.9±1.4, p=0.005; E t 16±4 vs 18±3, p=0.03; E t /A t 1.1±0.4 vs 1.3±0.4, p m 11±3 vs 14±2 cm/sec, p t 14±3 vs 16±3 cm/sec, p=0.01) in UCTD- risk-SSc patients in comparison to controls. Estimated pulmonary artery systolic pressure (27±5 vs 25±4; p=0.07) and TAPSE (23±3 vs 23±4; p=0.20) were not significantly different between the 2 groups. Conclusions: Our study shows that UCTD-risk-SSc patients present a previously unrecognized, mild biventricular systolic and diastolic dysfunction as compared to controls.

The aim of the study was to evaluate CXCL4 levels in undifferentiated connective tissue disease at risk for SSc (UCTD-SSc-risk) and confirm its increase and investigate its prognostic value. Serum CXCL4 levels were measured in 45 patients and 24 controls. CXCL4 was significantly higher in UCTD-SSc-risk patients than in controls. It resulted higher in patients with a shorter disease duration and in those lacking capillaroscopic alterations. We confirm that CXCL4 levels are increased in UCTD-risk-SSc patients. Further studies are needed to investigate the role of CXCL4 assessment in UCTD-risk-SSc.

CXCL4 is an antiangiogenic and immunomodulatory chemokine. We aimed to investigate serum levels of CXCL4 in primary Sjögren’s syndrome (pSS), looking for associations with disease features. Thirty-nine consecutive pSS patients underwent clinical-serological assessment and nailfold videocapillaroscopy (NVC). Thirty-six patients and 30 controls affected by osteoarthritis were also investigated for serum levels of CXCL4 and soluble E-selectin (sE-selectin). CXCL4 was higher in pSS patients than in controls (1.79 [0.2–11.18] vs 1.023 ng/ml [0.02–14.45], pÂ

Background Patients with UCTD (1) have been reported to present lung involvement most frequently characterized by nonspecific interstitial pneumonia (NSIP) at High Resolution Computerized Assial Tomography (HR-CAT), FVC and DLCO values lower than predicted (2). Objectives To investigate UCTD patients for the presence of lung involvement and search for demographic, serological, capillaroscopic and organ involvement features associated with it. Methods Eighty-six patients consecutively admitted to the Rheumatology Unit of the Second University of Naples and satisfying criteria for the classification of UCTD (1) were enrolled into the study. Patients presenting with any major CTD marker autoantibody other than anti-Ro (SSA) and/or scleroderma capillaroscopic specific pattern were excluded. Each patient underwent a careful history, a complete physical examination, evaluation of serum Antinuclear (ANA) and anti Extraible Nuclear Antigens antibody (anti-ENA), videocapillaroscopy, echo-Doppler-cardiography with evaluation of Left ventricular E/A ratio. Those who consented also underwent HR-CAT and esophagotonometry. Interstitial lung disease (ILD) was defined by HR-CAT or, if unavailable, by FVC Results The table lists the features detected in the patients subdivided according to the presence of lung involvement. DLCO An isolated reduction of DLCO resulted the be the most frequent finding and might depend on pulmonary vascular disease. Anti-SSA positivity and Capillaroscopic alterations were detected more frequently in patients with lung involvement (either isolated reduction of DLCO or ILD). Conclusions We detected a prevalence of ILD in UCTD lower than previously reported (2) (80%). Nevertheless, we found an isolated reduction of DLCO in about 35% of the UCTD patients. Lung involvement resulted to be significantly associated with capillaroscopic alterations and anti-SSA positivity. References Mosca M, Tani C, Vagnani S, Carli L, Bombardieri S.The diagnosis and classification of undifferentiated connective tissue diseases. J Autoimmun. 2014;48–49:50–2 Kinder BW, Collard HR, Koth L, Daikh DI, Wolters PJ, Elicker B, Jones KD, King TE Jr. Am J Respir Crit Care Med. Oct 1;176(7):691–7 Disclosure of Interest None declared