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Background:Systemic sclerosis (SSc) is a progressive autoimmune disease affecting the skin as well as internal organs, including the heart. A few studies have identified a subclinical heart involvement in patients with no pulmonary hypertension. Changes in myocardial deformation are consistent with the idea of SSc-related cardiomyopathy as a primary condition affecting the heart globally through microvascular dysfunction and subsequent myocardial fibrosis.Objectives:The aim of the present study is to describe the progression of myocardial deformation in patients with SSc and no overt cardiac disease.Methods:Prospective longitudinal study enrolling consecutive SSc patients referred to the Clinica Medica, University Hospital ‘Ospedali Riuniti’, Ancona, Italy, from February 2016 to December 2018. All patients fulfilled the 2013 ACR/EULAR classification criteria for SSc. Patients with structural heart disease, heart failure, atrial fibrillation or pulmonary hypertension were excluded. Disease subset, antibodies pattern, cardiovascular risk factors and involvement of other organ systems were recorded for each patient. An echocardiographic exam was performed for all patients at baseline and during their follow-up evaluation. Standard and speckle-tracking derived variables for the systolic and diastolic function of the left ventricle (LV) and right ventricle (RV) were acquired. Speckle tracking analysis software (EchoPAC 13.0; GE Medical Systems, Milwaukee, USA) was used to assess the GLS of the left and right ventricle, excluding the ventricular septum from right ventricular GLS calculations.Results:Seventy-two patients (68 females, age 56.6±15.4 years) were enrolled. Common echocardiographic parameters of left and right systolic function were within normal range at baseline and did not change during follow-up. Mean GLS, however, worsened for both left (from -19.8±3.5% to -18.7±3.5%, p=.034) and right ventricle (from -20.9±6.1% to -18.7±5.4%, p=.013) during a median follow-up of 20 months (1st-3rd quartile 12-24 months). The increased impairment registered in SSc patients was homogenous across endocardial layers (LV from -22.5±-3.9 to -21.4±3.9, p=.041; RV from -24.2±6.2 to -20.6±5.9, p=.001), mesocardial layers (LV -19.7±3.6 to -18.7±3.5, p=.043; RV from -21.3±5.9 to -18.8±5.7, p=.012) and epicardial layers (LV from -17.1±3.0 to -16.4±3.1, p=.112, RV -18.8±6.3 to -16.0±8.4, p=.035), as well as myocardial segments. No difference in progression rate was observed stratifying patients according to disease subset or other clinical parameters.Conclusion:GLS impairment progressed over a 20-month follow-up period in a cohort of SSc patients without clinically overt cardiac involvement. Further studies are needed to assess the significance of subclinical heart involvement and its progression in patients with SSc.Disclosure of Interests:None declared

Background Systemic Sclerosis (SSc) is an autoimmune disease characterized by progressive deposition of extracellular matrix components in the skin and visceral organs (1). Recently, it has been shown that microbial translocation plays an important role in immune system activation (2), and that dietary changes may affect gut microbiota, altering immune system activation and conditioning the development of several autoimmune diseases (3). Objectives The aims of the study were to investigate: a) which serum biomarkers could be used to evaluate and monitor GI disease in SSc patients and b) if nutritional intervention may reduce GI involvement, immune system activation and, finally, improve clinical symptoms and quality of life of SSc patients. Methods Thirty-eight SSc patients affected by GI involvement were enrolled in the study. At baseline. the following serum biomarkers were evaluated: intestinal-type fatty acid-binding protein (I-FABP), lipopolysaccharide (LPS), and soluble CD14 (sCD14) serum levels, markers of enterocyte damage, microbial translocation and immune system activation, respectively. Moreover, in each examination clinical symptoms and patient's reported outcomes (SF-36) were collected. After six months from the assumption of a mediterranean diet with low introduction of meat and diary products (4), clinical symptoms and SF-36 were evaluated in all patients and sCD14, LPS and I-FABP in 14 SSc patients. Twenty-five normal subjects constituted the control group. Results At baseline, sCD14, LPS, and I-FABP resulted significantly higher in sera of SSc patients than healthy controls ([Fig. 1][1]A), and there was a strong correlation between sCD14/ I-FABP and LPS/I-FABP serum levels ([Fig. 1][1]B). Higher LPS plasma levels (β=10.2, 95% CI (2.6, 17.9), p=0.01, R2 =0.17), but not sCD14 and I-FABP, were associated with the presence of Small Intestine Bacterial Overgrowth (SIBO). There were no statistical differences between patients with and/or without elevated bowel transit time, as assessed by lactulose breath test. After 6 months of diet, a significant decrease of sCD14, LPS and I-FABP was observed and patients reported a consistent improvement of GI symptoms as well as of the quality of life ([Fig. 1][1]A-D). ![Figure][2] Conclusions This work suggests that GI damage, and the consequent microbial translocation, triggers immune system activation and sustain clinical symptoms in SSc patients. Moreover, specific nutritional intervention significantly improves the clinical symptoms and the GI damage (I-FABP), thus reducing microbial translocation (LPS) and immune system activation (sCD14). Gut microbioma and microbial translocation may play an important role in the activation of the immune system and, thus, in the pathogenesis of SSc disease. 1. Gabrielli A et al. NEJM 2009, 360(19). 2. Chevalier MF et al. PLoS Pathog 2013; 9(6). 3. Vieira SM et al. Lupus. 2014, 23(6). 4. Bifulco M Eur J Clin Nutr. 2015 69(9):1078. Disclosure of Interest None declared [1]: #F1 [2]: pending:yes

Background Systemic Sclerosis (SSc) is a chronic systemic disease characterized by immune abnormalities, microangiopathy and progressive fibrosis of skin and internal organs. Only few therapeutic options have shown a proved disease-modifying effect for skin thickening and SSc-associated interstitial lung disease. Rituximab (RTX) and Mycophenolate Mofetil (MMF) have separately proven some evidence of efficacy and safety in clinical trials or case series Objectives Assess efficacy and safety of a combination therapy, with RTX and MMF in a cohort of SSc patients with pulmonary and cutaneous involvement rapidly progressive or resistant to conventional therapy. Methods Eligible patients were treated with RTX in two different regimens (1000 mg fortnightly x 2 or 375 mg/m2/week for 4 consecutive weeks) at baseline and after 6 months, associated with MMF 2000 mg/day. They received anti-infective prophylaxis with Valacyclovir 1000 mg and Cotrimoxazole 160/800 mg alternate days. Patients with previous malignancy or HBV, HCV or TB infection or connective overlap were excluded. Patients underwent clinical and laboratory evaluation every 3 months. Skin involvement was assessed by using the modified Rodnan Skin Score (mRSS) performed by the same physician at baseline and after 3, 6 and 12 months. Chest high-resolution computed tomography (HRCT) and pulmonary function tests (PFTs) and single-breath diffusing capacity were performed at baseline, after 6 and 12 months. The assessment of the extension of pulmonary fibrosis (PF) was analysed with the semiquantitative Warrick score and with the OsiriX quantitative computerized analysis. Data were analysed by Friedman test (GraphPadPrism V5). Results 18 SSc patients were enrolled (M/F: 8/10, median age 51y, median disease 1 y, diffuse SSc 9, limited SSc 9). Three patients withdrew from the study: one was lost to follow-up, one had a minor infusion reaction which led to RTX discontinuation and one died for different causes. The analysis includes all 15 of 18 patients who completed 12 months of follow-up. The mRSS showed a statistically significant improvement (p**=0,0036), more remarkable in patients with diffuse cutaneous SSc. Concerning PFTs there was a statistically significant increase of FVC (p**=0,0093), FEV1 (p**=0,0061), with stable values of DLCO (p=0,3375). The HRCT scan showed an improvement statistically significant evaluated with analysis by OsiriX (p*=0,0331), while the Warrick score showed a not significant trend toward improvement. No serious adverse events were observed during the follow-up. In two patients the MMF dose was reduced for mild neutropenia. Conclusions Despite preliminary and limited to a small number of patients, our results suggest that combination therapy with RTX and MMF is well tolerated, safe, and potentially effective for cutaneous and pulmonary involvement in SSc patients. Disclosure of Interest None declared

Background Systemic Sclerosis (SSc) is a rare systemic disease characterized by immune abnormalities, widespread vascular injury and progressive fibrosis of skin and internal organs. Currently, only few therapeutic options have shown a proved disease-modifying effect for skin thickening and SSc-associated interstitial lung disease. Objectives To assess efficacy and safety of a combination therapy, with rituximab (RTX) and mycophenolate ofetil (MMF), in rapidly progressive or resistant to conventional therapy SSc patients with pulmonary and cutaneous involvement. Methods Patients received RTX infusion (1000 mg at day 0 and after two weeks) at baseline and after 6 months, associated with MMF 2000 mg/day from day + 15. They received anti-infective prophylaxis whit valacyclovir 1000 mg and cotrimoxazole 160/800 mg alternate days. Patients with previous malignancy or HBV, HCV or TB infection were excluded. Patients underwent clinical and laboratory evaluation every 3 months. Skin involvement was assessed by using the modified Rodnan Skin Score (mRSS). The chest high-resolution computed tomography (HRCT) and the pulmonary function tests and single-breath diffusing capacity were performed at baseline and after 6 and 12 months. Lung fibrosis at the HRCT scans was analyzed with a semi-quantitative scoring method (Fraticelli P et al. Arthritis Res Ther. 2014 Jul 8;16(4):R144). Forced vital capacity (FVC), total lung capacity (TLC) and diffusing capacity of the lung for carbon monoxide (DLCO) were considered for pulmonary function assessment. Data were analyzed by Wilcoxon matched paired signed rank test. Results Eighteen SSc patients were enrolled (M/F: 8/10, median duration of disease 52 y, median age 2y, diffuse SSc 9, limited SSc 9). Two patients withdrew from the clinical study, one was lost to follow-up and the other one had a minor infusion reaction which led to RTX discontinuation. The preliminary analysis includes 12 of 18 patients who completed the 6 month follow-up. The mRSS showed a trend to improvement (p=0.1347), which, however, was not statistically significant. The improvement in patients with the diffuse cutaneous SSc was more remarkable. There was a significantly increase of FVC (p=0.0494) and TLC (p=0.0412); DLCO (p=0.7891) improved but not significantly. The HRCT pattern improved in two patients reduction of the number of lung segments with ground-glass appearance, while patients with prevalent reticular pattern or advanced honeycombing remained stable. No serious adverse events were observed during the follow-up. In one patient the MMF dose was reduced for mild neutropenia and one patient required cotrimoxazole discontinuation for mild macrocytic anemia. Conclusions Despite preliminary and limited to a small number of patients, our results suggest that combination therapy with RTX and MMF is well tolerated, safe, and potentially effective for cutaneous and pulmonary involvement in SSc patients. Disclosure of Interest None declared