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Background The aim of this study was to evaluate and compare the internal and external responsiveness of a computed-aided method (CaM) with a conventional visual reader-based score (CoVR) to measure interstitial lung disease (ILD) in patients with systemic sclerosis (SSc) on high resolution computed tomography (HRCT). Methods Forty-five patients were evaluated in this retrospective cohort. HRCTs were collected at baseline and after 1 year. HRCT abnormalities were evaluated according to a CoVR (Warrick's method) and a quantitative CaM. Internal 1-year responsiveness was tested with a standardized mean response (SRM). Analyses of the receiver operating characteristic curves (ROCs) evaluated the sensitivity and specificity of the two methods to discriminate between clinically relevant progression and no relevant progression, using expert judgment as the gold standard (external responsiveness). Results In one year, lung involvement was stable/improved in 17 of the 45 patients (37.8%) and worsened in 28 patients (62.2%). HRCT scores changed moderately over the follow-up period. Using SFM, CaM was significantly more responsive in detecting changes due to treatment than the CoVR method. Likewise, in the analysis of the ROC curve, CaM scores showed the highest performance (AUC ROC CaM vs. CoVR, 0.951 vs. 0.807; p = 0.0065). Conclusion Quantitative analysis of CaM was more responsive than the CoVR method to accurately evaluate and monitor SSc-ILD progression or response to therapy.

The concern about the offspring’s health is one of the reasons for a reduced family size of women with rheumatic diseases (RD). Increased risk of autoimmune diseases (AD) and neurodevelopmental disorders (ND) has been reported in children born to patients with RD. Within a nationwide survey about reproductive issues of women with RD, we aimed at exploring the long-term outcome of their children. By surveying 398 patients who received their diagnosis of RD during childbearing age (before the age of 45), information about the offspring were obtained from 230 women who declared to have had children. A total of 148 (64.3%) patients were affected by connective tissue diseases (CTD) and 82 (35.7%) by chronic arthritis. Data on 299 children (156 males, 52.1%; mean age at the time of interview 17.1 ± 9.7 years) were collected. Twelve children (4.0%), who were born to patients with CTD in 75% of the cases, were affected by AD (8 cases of celiac disease). Eleven children had a certified diagnosis of ND (3.6%; 6 cases of learning disabilities); 9 of them were born to mothers with CTD (5 after maternal diagnosis). No association was found between ND and prenatal exposure to either maternal autoantibodies or anti-rheumatic drugs. Absolute numbers of offspring affected by AD and ND were low in a multicentre cohort of Italian women with RD. This information can be helpful for the counselling about reproductive issues, as the health outcomes of the offspring might not be an issue which discourage women with RD from having children.

Systemic sclerosis (SSc) is an autoimmune disease of unknown aetiology characterized by vascular lesions, immunological alterations and diffuse fibrosis of the skin and internal organs. Since recent evidence suggests that there is a link between metabolomics and immune mediated disease, serum metabolic profile of SSc patients and healthy controls was investigated by 1H-NMR and GC-MS techniques. The results indicated a lower level of aspartate, alanine, choline, glutamate, and glutarate in SSc patients compared with healthy controls. Moreover, comparing patients affected by limited SSc (lcSSc) and diffuse SSc (dcSSc), 6 discriminant metabolites were identified. The multivariate analysis performed using all the metabolites significantly different revealed glycolysis, gluconeogenesis, energetic pathways, glutamate metabolism, degradation of ketone bodies and pyruvate metabolism as the most important networks. Aspartate, alanine and citrate yielded a high area under receiver-operating characteristic (ROC) curves (AUC of 0.81; CI 0.726–0.93) for discriminating SSc patients from controls, whereas ROC curve generated with acetate, fructose, glutamate, glutamine, glycerol and glutarate (AUC of 0.84; CI 0.7–0.98) discriminated between lcSSc and dcSSc. These results indicated that serum NMR-based metabolomics profiling method is sensitive and specific enough to distinguish SSc from healthy controls and provided a feasible diagnostic tool for the diagnosis and classification of the disease.

The aim of our study was to assess the role of videofluorography (VFG) in the evaluation of swallowing and oesophageal peristalsis in patients with systemic sclerosis (SSc).From June 2014 to September 2017, 55 consecutive SSc patients, defined according to the 2013 ACR/EULAR classification criteria, underwent VFG study using a remote-controlled digital device. In order to evaluate possible abnormalities, 18 dynamic parameters were chosen, dividing the act of swallowing into three phases: oral, pharyngeal and oesophageal phases. The following dynamic radiological findings were considered: veil motility in phonation, leakage, drooling, salivation and presence of residues in the oral cavity, pharyngeal residues, penetration, aspiration, altered motility of the upper oesophageal sphincter, efficacy of primary peristaltic contractions, oesophageal clearance capacity, reflux, oesophagitis and motility of the lower oesophageal sphincter.The VFG study was well tolerated in all patients. Dysfunctions of oesophageal motility were common and included abnormal motility of UES (12.7%) and LES (76.4%), inadequate primary peristalsis (52.7%), abnormal secondary peristalsis (29.1%) and non-peristaltic contractions (40%). A defective oesophageal clearance was observed in 69.4% of patients. Moreover, most patients presented signs of oesophageal reflux (63.6%), oesophagitis (81.8%) and hiatal hernia (80%). Pharyngeal abnormalities were less common and involved up to 50% of patients. Oesophageal dysfunction and defective clearance were associated with dcSSc and pulmonary involvement.The VFG study is a useful technique for the morphological and functional evaluation of swallowing in SSc patients.

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

Objective The reproductive choices of women affected by rheumatic diseases (RD) can be influenced by several factors, including the quality of physician-patient communication. We conducted a survey on reproductive issues aiming at exploring the unmet needs of women with RD during childbearing age. Methods We administered 65 multiple-choice and 12 open-answer questions about pregnancy counselling, contraception, use of drugs during pregnancy and other women reproductive issues to 477 consecutive women with RD aged 18–55 years followed-up in 24 rheumatology centres in Italy. Analysis was restricted to 398 patients who received their diagnosis of RD before the age of 45. According to the RD diagnosis, patients were subdivided into 2 groups: connective tissue diseases (n = 249) and chronic arthritis (n = 149). Results At the time of interview, women in both groups had a mean age of 40 years. Nearly one third of patients in each group declared not to have received any counselling about either pregnancy desire nor contraception. A smaller family size than desired was reported by nearly 37% of patients, because of concerns related to maternal disease in one fourth of the cases. A “Disease Knowledge Index” (DKI) was created to investigate the degree of patients’ information about the implications of their RD on reproductive issues. Having received counselling was associated with higher DKI values and with a positive impact on family planning. Conclusion Italian women of childbearing age affected by RD reported several unmet needs in their knowledge about reproductive issues. Strategies are needed to implement and facilitate physician-patient communication.

Association of celiac disease (CD) with systemic autoimmune diseases (ADs) remains controversial. Awareness of CD in these patients is important to prevent complications, including lymphoproliferative disorders. We evaluated previously diagnosed CD prevalence in systemic lupus erythematosus (SLE), primary Sj&ouml, gren&rsquo, s syndrome (pSS) and systemic sclerosis (SSc) patients in comparison to 14,298 matched controls. All patients were screened for subclinical CD. Data from 1458 unselected consecutive SLE (580), pSS (354) and SSc (524) patients were collected. Previously biopsy-proven CD diagnosis and both CD- and AD-specific features were registered. All patients without previous CD were tested for IgA transglutaminase (TG). Anti-endomysium were tested in positive/borderline IgA TG. Duodenal biopsy was performed in IgA TG/endomysium+ to confirm CD. CD prevalence in AD was compared to that observed in 14,298 unselected sex- and age-matched adults who acted as controls. CD was more prevalent in pSS vs controls (6.78% vs 0.64%, p &lt, 0.0001). A trend towards higher prevalence was observed in SLE (1.38%, p = 0.058) and SSc (1.34%, p = 0.096). Higher CD prevalence was observed in diffuse cutaneous SSc (4.5%, p &le, 0.002 vs controls). Subclinical CD was found in two SLE patients and one pSS patient. CD diagnosis usually preceded that of AD. Primary SS and SSc&ndash, CD patients were younger at AD diagnosis in comparison to non-celiac patients. Autoimmune thyroiditis was associated with pSS and CD. CD prevalence is clearly increased in pSS and diffuse SSc in comparison to the general population. The association of CD with diffuse but not limited SSc may suggest different immunopathogenic mechanisms characterizing the two subsets. CD screening may be considered in pSS and diffuse SSc in young patients, particularly at the time of diagnosis.

Background Systemic sclerosis (SSc) is a chronic autoimmune disease of unknown etiology, characterised by microvascular abnormalities, immune abnormalities and progressive cutaneous and internal organs fibrosis. Subclinical heart disease in SSc patients is common but difficult to detect through conventional imaging. Objectives We sought to evaluate speckle-tracking derived global longitudinal strain (GLS) as an early marker of subclinical systolic dysfunction in patients with SSc. Methods We enrolled 52 patients with SSc and 52 age and gender matched controls. Patients with structural heart disease, heart failure, atrial fibrillation or pulmonary hypertension were excluded. An echocardiographic exam was performed for all patients, and standard and specke-tracking derived variables for the systolic and diastolic function of the left ventricle (LV) and right ventricle (RV) were acquired. SSc variant, antibodies pattern, cardiovascular risk factors and involvement of other organ systems were recorded. Results Common parameters of left and right systolic function did not differ between SSc patients and controls and were on average well above the cut-off for normality (all p=NS). LV and RV GLS were significantly impaired in patients with SSc when compared to healthy controls (−19.2% vs. −21.1%; p=0.009 and −18.2% vs. −22.3%; p=0.012 respectively). In patients with SSc, GLS impairment was greater in basal segments when compared to midventricular and apical ones and homogeneous between the endo-, meso-, or epicardial layers of the RV, while LV showed an eccentric pattern with the epicardial layers mostly impaired. Using −20% as a cut-off for GLS, SSc patients had a 2.5-fold increased risk of subclinical LV systolic impairment (OR 2.5; 95% CI 1.1–5.5; p=0.027) and a 3.3-fold increased risk of subclinical RV systolic impairment when compared to age and gender matched controls (OR 3.3; 95% CI 1.4–7.7; p=0.004). Conclusions While traditional parameters are ineffective in detecting subclinical systolic impairment, a reduced GLS is common in patients with SSc and is significant for both LV and RV. While GLS impairment recognises a basal-apical gradient, transmural heart involvement seems different between RV and LV, suggesting a different mechanism of disease between the two ventricles. Disclosure of Interest None declared

To describe a single centre experience using combination therapy with rituximab (RTX) and mycophenolate mofetil (MMF) in a prospective series of systemic sclerosis (SSc) patients with pulmonary and cutaneous involvement, rapidly progressive or resistant to conventional therapy.RTX was administered 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 continuously. Cutaneous fibrosis was evaluated assessing modified Rodnan Skin Score (mRSS) and pulmonary involvement was evaluated performing pulmonary function tests, diffusing lung capacity for carbon monoxide and chest high-resolution computed tomography (HRCT). The radiological extension of the interstitial lung disease (ILD) at HRCT, was assessed with the conventional visual reader-based score (CoVR) and with a computerised-aided method (CaM) using a DICOM soft- ware.Eighteen SSc patients underwent combination therapy (F/M: 10/8, median age 51 years, median duration of disease 27 months). Data from fifteen patients were available at 12-month follow-up. The mRSS showed a significant improvement; a significant increase in forced vital capacity and forced expiratory volume in the first second were also observed. In addition, a signi cant reduction of the extension of ILD was detected when evaluated with CaM. No serious adverse events were observed during the follow-up period.Despite preliminary results and limited to a small number of patients, our data suggest that therapy with RTX and MMF is well tolerated, safe, and potentially effective for cutaneous and pulmonary involvement in SSc.

Background Interstitial lung disease (ILD) and pulmonary hypertension are the leading cause of morbidity and mortality in systemic sclerosis (SSc). Although a ventilatory obstructive pattern, due to large airways impairment, has been rarely observed in SSc, a potential involvement of smaller airways (SA) has been suggested in previous reports. Recently, impulse oscillometry (IOS), a non-invasive forced oscillation technique, has been advocated as a valuable diagnostic tool for a sensitive assessment of SA. Objectives The main objectives of the present study was to investigate the prevalence of SA dysfunction by IOS in SSc patients compared to healthy controls, and to evaluate the correlation between SA dysfunction and selected radiological and clinical disease-related features. Methods Consecutive SSc patients were included in the present study according to eligibility criteria; controls were health volunteers. Both cases and controls underwent IOS measurements; cases also underwent pulmonary function tests and St. George9s respiratory questionnaire. Radiological features were assessed on the latest chest high resolution computed tomography (HRTC) scan available in the twelve months before study enrolment, evaluating for both SA signs of disease and ILD. A SA involvement at IOS was defined as R5-R20 ≥0.07 kPa/L/sec. Odds ratios and 95% confidence intervals for the IOS value was computed using multiple logistic regression models. Correlation between SA dysfunction and selected parameters were assessed using Pearson9s correlation coefficient. Results 92 cases (M/F 14/78, mean age 57.06) and 84 controls (M/F 15/69, mean age 54.28) were included in the present study. The R5-R20≥0.07 kpa/L/sec was found in 20.65% of cases and in 3.57% of controls. The OR was 7.027 (95% CI 1.99–24.72, p Conclusions A significant involvement of SA was found in a substantial proportion of SSc patients, compared to healthy controls. Moreover, this seemed to be associated with a more severe functional obstructive and restrictive impairment, and with higher PAPs values. Therefore, our findings suggests that SA may be a potential, less known, target of disease, and further studies are needed to assess prognostic and therapeutic implications of this pathologic feature. Disclosure of Interest None declared

Background Celiac disease (CD) is an inflammatory and immune-mediated gluten-dependent enteropathy occurring in genetically susceptible individuals. CD is recognized to affect between 0.6% and 1% of worldwide population, with wide regional differences. Disease clinical features are protean and highlight the systemic nature of the disease. In recent years, an increased prevalence of CD has been also reported in patients with connective tissue diseases (CTDs). This association may be due to a shared genetic predisposition, to immunological mechanisms and/or exposure to a common triggering event. However, this observation remains controversial since data are usually based on descriptive case reports. Different methods of antibody detection and enrolled population sample size may contribute to result discordance. Moreover, CD diagnosis is often delayed because disease clinical spectrum may be atypical mimicking rheumatologic conditions and autoimmune disease itself may display typical symptoms of CD. Undoubtedly, awareness of CD occurrence in CTDs is important to prevent potential long-term systemic complications related to an unrecognized CD in these patients. Objectives To evaluate the prevalence of overt and subclinical CD and features of the disease in a large cohort of patients with systemic lupus erythematosus (SLE), systemic sclerosis (SSc) and primary Sjogren9s syndrome (pSS) with a multicenter prospective study involving 9 Italian Rheumatology Units. Methods Data from consecutive 580 SLE, 354 pSS and 524 SSc patients were collected. Disease-specific features were registered in patients with known CD. Remaining patients were tested for IgA transglutaminase (Eu-tTG® human IgA new, Eurospital S.p.A., Trieste). Anti-endomysium (EMA) IgA and IgG were tested in IgA tTG positive and borderline patients. Esophagogastroduodenoscopy with duodenal biopsy was proposed in IgA tTG+/EMA+, IgA tTG-/EMA+ and IgA tTG±/EMA+ patients. Results CD prevalence was 1,7% in SLE, 7% in pSS and 1,3% in SSc patients. Higher frequency of elevated liver enzymes was detected in SLE-CD and of herpetiform dermatitis in SSc-CD patients in comparison to the other groups (p Conclusions The results of the present large multicenter study confirm higher prevalence of CD in CTD patients, especially in pSS. Screening of CD may be considered in younger patients with CTD and lower age at diagnosis. The strong association of CD with the diffuse type of SSc is of note and suggests that different, still unexplored, pathogenic mechanisms may characterize the two subsets of the disease. Disclosure of Interest None declared

Background Systemic Sclerosis (SSc) is a chronic autoimmune disease characterized by proliferative vascular lesions and progressive fibrosis of skin and internal organs, including the gastrointestinal tract. Gastrointestinal involvement is a very frequent complication, reported in up to 90% of SSc patients in both limited (lSSc) and diffuse (dSSc) cutaneous forms, and it is one of the earliest events. Objectives To evaluate the correlation between radiological items analyzed by videofluoroscopy swallow study and clinical patterns of patients SSc. Methods 55 patients (M/F: 6/49; median age 56y; median disease 6y, lSSc /dSSc:36/19; anti-Scl70+:21/55, ACA+:18/55, only ANA+:16/55), with a diagnosis of SSc and a history of dysphagia underwent a dynamic and morphological study of the oral, pharyngeal and esophageal phases of swallowing with videofluoroscopy. The oral and pharyngeal esophageal phases were performed in the upright position, while the esophageal phase was performed in the prone-oblique position, after administration of contrast material either in bolus form or diluted. Data were analyzed by radiologist with experience in videofluoroscopy for the evaluation of 17 videofluoroscopy items, of which, 4 concerning the oral, 4 the pharyngeal and 9 the esophageal phase, respectively. Results were expressed in a binary system. Then the main relevant videofluoroscopy findings were correlated with the principal scleroderma pattern of disease: lSSc vs dSSc; disease duration (more than 2 years) and subset of autoantibodies. Results Radiological study of swallowing disorders showed for oral phase: inadequate velar elevation in 4%, leakage in 15%, drooling in none (0%) and stasis of bolus in mouth in 4% of the patients. As for pharyngeal phase: stasis of bolus on pharyngeal in 49%, penetration in the laryngeal aditus in 53%, post-swallowing aspiration in 22%, abnormal upper esophageal sphincter behavior in 13% of the cases. Concerning esophageal phase: inadequate primary peristalsis in 53%, abnormal secondary peristalsis in 29%, non-peristaltic contractions in 40%, defects of clearance in 69%, abnormal lower esophageal sphincter behavior in 76%, hiatal hernia in 80%, esophageal reflux in 56%, esophagitis in 82% of the patients, nobody presented esophageal luminal stenosis. When we analyzed the swallowing disorders in different conditions we found that these are prevalent in patients with more than 2 year of disease, although may be found also early. Conversely, we have not found a significant prevalence between the lSSc or the dSSc, or a particular correlation with different patterns of autoantibodies. Conclusions Our study demonstrated relevant abnormalities in swallowing functions in high number of patients with SSc. Pharyngeal and esophageal phases are the most affected, also early. Swallowing disorders increase with disease progression and involve similarly the limited or the diffuse SSc. An early and detailed diagnosis, supported by a semi-quantitative analysis with the use of videofluoroscopy scores, may be useful to guide the appropriate therapeutic approach, either rehabilitative or pharmacological, and finally, to improve the patient9s quality of life. Extensive studies are necessary to confirm and transfer our data into clinical practice. Disclosure of Interest None declared

One of the earliest events in the pathogenesis of systemic sclerosis (SSc) is microvasculature damage with intimal hyperplasia and accumulation of cells expressing PDGF receptor. Stimulatory autoantibodies targeting PDGF receptor have been detected in SSc patients and demonstrated to induce fibrosis in vivo and convert in vitro normal fibroblasts into SSc-like cells. Since there is no evidence of the role of anti PDGF receptor autoantibodies in the pathogenesis of SSc vascular lesions, we investigated the biologic effect of agonistic anti PDGF receptor autoantibodies from SSc patients on human pulmonary vascular smooth muscle cells and the signaling pathways involved. The synthetic (proliferation, migration and type I collagen gene 1chain expression and contractile (smooth muscle-myosin heavy chain and smooth muscle-calponin expression) profiles of human pulmonary artery smooth muscle cells were assessed in vitro after incubation with SSc anti PDGF receptors stimulatory autoantibodies. The role of reactive oxygen species, NOX isoforms and mechanistic target of rapamycin (mTOR) was investigated. Human pulmonary artery smooth muscle cells acquired a synthetic phenotype characterized by higher growth rate, migratory activity, gene expression of type I collagen gene 1chain, and less expression of markers characteristic of the contractile phenotype such as smooth muscle-myosin heavy chain and smoth muscle-calponin when stimulated with PDGF and autoantibodies against PDGF receptor, but not with normal IgG. This phenotypic profile is mediated by increased generation of reactive oxygen species, expression of NOX4 and mTORC1. Our data indicate that agonistic anti PDGF receptor autoantibodies may contribute to the pathogenesis of SSc intimal hyperplasia.

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