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Background:In SSc, ILD is a major cause of morbidity and mortality. High resolution computed tomography (HRCT) is the gold standard for the diagnosis. Predictors of ILD onset are eagerly awaited to improve SSc-ILD management. Pulmonary function test (PFTs) are routinely performed to measure lung function changes.Objectives:Our aim was to investigate the performance of DLCO (diffusing capacity of lung carbon monoxide) and FVC (forced vital capacity) in predicting the development of SSc-ILD.Methods:The longitudinal data of DLCO, FVC and ILD on HRCT of SSc patients from the EUSTAR database were evaluated at baseline (t0), after 12 (±4) (t1) and 24 (±4) (t2) months. Patients with negative HRCT for any sign of ILD both at t0 and t1 were included. Patients who presented or developed pulmonary hypertension during the study period were excluded. At baseline, demographic data, disease duration from Raynaud’s onset, disease subsets, autoantibodies and other laboratory and instrumental data were recorded.Results:474/17805 patients were eligible for the study (403 females, 71 males): 26.0% dcSSc, 58.3% lcSSc, 220 (48.0%) patients with positive anticentromere antibodies (ACA) and 117 (25.4%) with positive antitopoisomerase I antibodies (Topo-I abs). Among all enrolled patients, 46 (9.7%) developed HRCT signs of ILD at t2. Patients with Topo-I abs showed an association with ILD development at t2 (16.7% vs 7.8%, p=0.0031), contrarily ACA positive patients were negatively associated with ILD appearance after 2 years of follow-up (4.4% vs 14.4%, p=0.0001). Positive t2 HRCT patients had a significant lower value of DLCO and FVC at all three assessments when compared to patients with a negative HRCT at t2 (Table 1) and both t0 DLCO and FVC values negatively correlated with ILD development (Table 1). The mean t0 to t1 change (Δ) of DLCO in patients with negative t2 HRTC and positive t2 HRCT were -0.5 (±12.6) and -1.0 (±15.1), respectively. The mean t0 to t1 ΔFVC in patients with negative t2 HRTC and positive t2 HRCT were -0.2 (±10.6) and 0.1 (±11.5), respectively. None of them predicted the appearance of ILD at t2 (ΔDLCO: OR (IC) 0.997 (0.97-1.02), p=0.8024; ΔFVC OR (IC) 1.002 (0.97-1.03), p=0.8664). The data showed an association between t0 DLCO value0 FVC value0 DLCOConclusion:Our data suggest that an impaired baseline DLCO (Table 1.DLCO and FVC values at t0, t1 and t2 values in patients with positive or negative HRCT for ILD at t2 and their statistical differences.Patients without ILD at t2 (mean±SD)Patients with ILD at t2 (mean±SD)OR (95%CL)p-valueDLCO at t079.0 ± 16.669.9 ± 17.40.97 (0.95 - 0.99)0.0006DLCO at t178.4 ± 16.868.9 ± 18.60.97 (0.95 - 0.98)0.0005DLCO at t278.0 ± 17.065.1 ± 19.10.95 (0.93 - 0.97)FVC at t0102.2 ± 17.394.6 ± 16.20.97 (0.96 - 0.99)0.0052FVC at t1101.9 ± 17.994.7 ± 16.50.98 (0.96 - 0.99)0.0092FVC at t2101.6 ± 17.694.5 ± 20.00.98 (0.96 - 1)0.0126Disclosure of Interests:Gemma Lepri: None declared, Cosimo Bruni Speakers bureau: CB reports personal fees from Actelion, personal fees from Eli Lilly, Grant/research support from: CB reports personal fees from Actelion, personal fees from Eli Lilly, grants from European Scleroderma Trial and Research (EUSTAR) group, grants from New Horizon Fellowship, grants from Foundation for Research in Rheumatology (FOREUM), grants from Fondazione Italiana per la Ricerca sull’Artrite (FIRA), outside the submitted work, Lorenzo Tofani: None declared, Alberto Moggi Pignone: None declared, Martina Orlandi: None declared, Tomasetti Sara Speakers bureau: Speaker’s fees for Roche and Boehringer Ingelheim, Mike Hughes: None declared, Francesco Del Galdo: None declared, Rosaria Irace: None declared, Oliver Distler Grant/research support from: OD (last three years) has/had consultancy relationship and/or has received research funding in the area of potential treatments for systemic sclerosis and its complications from (last three years): Abbvie, Acceleron Pharma, Amgen, AnaMar, Arxx Therapeutics, Baecon Discovery, Blade Therapeutics, Bayer, Boehringer Ingelheim, ChemomAb, Corbus Pharmaceuticals, CSL Behring, Galapagos NV, Glenmark Pharmaceuticals, GSK, Horizon (Curzion) Pharmaceuticals, Inventiva, iQvia, Italfarmaco, iQone, Kymera Therapeutics, Lilly, Medac, Medscape, Mitsubishi Tanabe Pharma, MSD, Novartis, Pfizer, Roche, Sanofi, Serodapharm, Topadur, Target Bioscience and UCB. Patent issued “mir-29 for the treatment of systemic sclerosis” (US8247389, EP2331143)., Valeria Riccieri: None declared, Yannick Allanore Speakers bureau: YA received personal fees from Boehringer, Sanofi, Menarini and Medsenic and grants from Alpine with regards to the management of systemic sclerosis, Grant/research support from: YA received personal fees from Boehringer, Sanofi, Menarini and Medsenic and grants from Alpine with regards to the management of systemic sclerosis, Ana Maria Gheorghiu: None declared, Elise Siegert: None declared, Jeska de Vries-Bouwstra: None declared, Eric Hachulla: None declared, Mohammed Tikly: None declared, Nemanja Damjanov: None declared, Francois Spertini: None declared, Luc Mouthon: None declared, Anna-Maria Hoffmann-Vold Speakers bureau: AMHV: received consulting fees from Actelion, ARXX, Bayer, Boehringer Ingelheim, Lilly, Medscape, Merck Sharp & Dohme and Roche; and grants from Boehringer Ingelheim., Consultant of: AMHV: received consulting fees from Actelion, ARXX, Bayer, Boehringer Ingelheim, Lilly, Medscape, Merck Sharp & Dohme and Roche; and grants from Boehringer Ingelheim., Grant/research support from: AMHV: received consulting fees from Actelion, ARXX, Bayer, Boehringer Ingelheim, Lilly, Medscape, Merck Sharp & Dohme and Roche; and grants from Boehringer Ingelheim., Armando Gabrielli: None declared, Serena Guiducci: None declared, Marco Matucci-Cerinic Speakers bureau: has received consulting fees or honorarium from Actelion, Janssen, Inventiva, Bayer, Biogen, Boehringer, CSL Behring, Corbus, Galapagos, Mitsubishi, Samsung, Regeneron, Acceleron, MSD, Chemomab, Lilly, Pfizer, Roche, Grant/research support from: has received consulting fees or honorarium from Actelion, Janssen, Inventiva, Bayer, Biogen, Boehringer, CSL Behring, Corbus, Galapagos, Mitsubishi, Samsung, Regeneron, Acceleron, MSD, Chemomab, Lilly, Pfizer, Roche, Daniel Furst: None declared, Silvia Bellando Randone: None declared

Background:Interstitial lung disease (ILD) is one of the most common complications and one of the main causes of morbidity and mortality in Systemic Sclerosis (SSc). High-resolution computed tomography (HRCT) is the gold standard for the diagnosis of ILD and it allows its quantification. Among semi-quantitative methods, Goh et al proposed a semi-quantitative scoring system to visually quantify ILD extent, with categorical cut-off of 20% to distinguish limited and extensive parenchymal involvement with prognostic implications. More recently, the use of radiomics has allowed the objective quantification of ILD through the use of dedicated software, which calculate different parameters of lung density.Given the exposure to ionizing radiation that the procedure entails, other methods of ILD evaluation are being studied, among which lung ultrasound (LUS) identifies the B-lines as a main feature of ILD. So far, different evidences have proposed the use of LUS for the screening of ILD, even in the early phases of the disease and in subclinical lung involvement.Objectives:the aim of this study is to test the role of LUS in quantifying the severity of SSc-ILD, evaluated with both semi-quantitative visual radiological and quantitative radiomic scores.Methods:Adult SSc patients classified according to the ACR/EULAR 2013 criteria patients were assessed with pulmonary function test (PFTs), lung ultrasound and HRCT over 60 days. CT images were analysed qualitatively (by presence/absence of ILD), semi-quantitatively (categorical Goh score 20% of extent and the continuous extent Goh score made from 5 levels’ assessment– 0 to 100%) and quantitatively [with the densitometric radiomic data obtained through the Horos software - Mean lung attenuation (MLA), Standard Deviation (SD), Kurtosis, Skewness and Lung volume (LV)]. LUS was used to quantify the B-lines detected in each patient by scanning a total of 13 intercostal spaces, on both anterior and posterior chest wall.Results:Among 59 SSc patients (81% women, mean age 48±14 years, 45% anti-Scl70 positive), 23 (39%) presented ILD on HRCT, of which 14 limited and 9 extensive. The mean visual semi-quantitative score was 6%, ranging from 0 to 66%. Our data showed a significantly different number of B-Lines in ILD vs non-ILD patients (median 38 vs 9, p 20% (median 47 vs 9, p=.001) and ILD 20% (median 47 vs 36, p=.78). We observed a significant negative correlation between the number of B-lines and FVC (r=-.472, pConclusion:Our study confirms that LUS represents a useful tool for the identification of SSc-ILD. In addition, we showed that LUS may be useful also for the quantification of the severity of SSc-ILD, by correlating with PFT parameters, radiomics parameters and visual radiological evaluation. Together with the PFTs, LUS could be used to increase the accuracy of the screening and, potentially, of the follow-up of SSc-ILD patients.Disclosure of Interests:Cosimo Bruni: None declared, Lavinia Mattolini: None declared, Lorenzo Tofani: None declared, Luna Gargani Consultant of: GE Healthcare, Philips Healthcare and Caption Health, Nicholas Landini: None declared, Gemma Lepri: None declared, Martina Orlandi: None declared, Serena Guiducci: None declared, Silvia Bellando Randone: None declared, Marco Matucci-Cerinic: None declared

Background:Gynaecological problems are often ignored by rheumatologist and have a negative impact on quality of life of RDs patients.Objectives:The aim of this study was to describe gynaecological, reproductive and sexual problems in premenopausal woman with RDs.Methods:A monocentric, cross-sectional observational study was conducted in the Rheumatology Department of Careggi Hospital in Florence. Inclusion criteria: female gender, premenopausal age (and≥18 years old), diagnosis of rheumatic diseases. All patients have been investigated about gynaecological anamnesis and symptoms and subjected to a self-administered validated questionnaire.Results:From May 4 th to November 30th, 2020, 200 patients were enrolled (mean age 39.1± 8.7 years (M±SD)): 58% arthritis, 40% connective tissue disease and 1.5% systemic vasculitis. In the history, spontaneous, full-term birth in 91% and 93% of patients, respectively, was observed and pre-term birth was reported in 8.1%. 63% of patients were breastfed. In family history, menorrhagia, dysmenorrhea, or chronic pelvic pain were reported in 59%, 55 and 7% of patients, respectively. The first menstruation was at 12.3±2.0 years (M±DS) and mostly woman reported menstrual disorders during adolescence (56% experienced dysmenorrhea and 52% menorrhagia). Menstrual disorders and abnormal bleeding were frequently reported also in adulthood: 71% had dysmenorrhea, 38% heavy menstrual cycles and 9% metrorrhagia. Moreover, 26% of patients referred non- menstrual pelvic pain, 19% urinary pain and 18% pain during defecation. Vaginal symptoms were frequently reported: 36% of patients referred vaginal dryness, 29% burning, 19% recurrent vaginal infections and dyspareunia in 39% of patients. Uterine fibroma was present in 23% and endometriosis in 10% of patients. Fertility problems were reported by 10% of patients in a time frame of 7.5±6.4 years and 30% of patients experienced at least one miscarriage; otherwise, 56% of patients have had at least one full-term pregnancy.Conclusion:RDs patients show a high prevalence of various gynaecological problems affecting their quality of life. The management of female RDs patients is a challenge for the clinician and should include an accurate evaluation of the gynaecological aspects (menstruation, fertility, maternity, sexuality) as well as a multidisciplinary teamwork (rheumatologist and gynaecologists).References:[1]Critchley H., Babayev E., Bulun E., et al. Menstruation: Science and society | Elsevier Enhanced Reader. (s.d.). https://doi.org/10.1016/j. American Journal of Obstetrics & Gynecology 2020.06.004[2]Østensen M, Andreoli L, Brucato A,et al. State of the art: Reproduction and pregnancy in rheumatic diseases. Autoimmun Rev. 2015 May;14(5):376-86. doi: 10.1016/j.autrev.2014.12.011. Epub 2014 Dec 30. PMID: 25555818.[3]Marder W, Johnson TRB. Rheumatic diseases and maternal-fetal medicine. Best Pract Res Clin Obstet Gynaecol. 2020 Apr;64:1-2. doi: 10.1016/j.bpobgyn.2019.11.007. Epub 2019 Dec 17. PMID: 31983554.[4]Sammaritano LR, Bermas BL, Chakravarty EE,et al. 2020 American College of Rheumatology Guideline for the Management of Reproductive Health in Rheumatic and Musculoskeletal Diseases. Arthritis Rheumatol. 2020 Apr;72(4):529-556. doi: 10.1002/art.41191. Epub 2020 Feb 23. PMID: 32090480.Disclosure of Interests:None declared

Background:Lung involvement remains the main cause of morbidity and mortality in SSc. In 1 year clinical trials to assess lung involvement, FVC is usually evaluated and changes while the DLCO usually remains unchanged. In longer term observational studies, the DLCO often changes more than the FVC.Objectives:To examine, through a systematic literature review(SLR) and meta-analysis, whether DLCO%pred or FVC%pred (both to be designated solely as DLCO and FVC henceforth), responds more in assessing SSC interstitial lung disease in first year and longer term follow-up(FU).Methods:PubMed, EMBASE and COCHRANE databases were searched for english language articles on SSc published between 1960 and 31st October 2018. Any study that made reference to FVC and DLCO evaluation in SSc and reported their changes over the years was included. Reviewers double extracted articles to obtain agreement on>95% of pre-defined critical outcomes:DLCO and FVC at baseline,1 yr of FU and at the last assessment interstitial lung disease by HRCT of the lungs study design, duration of FU. Other variables included demographics. In all cases I^2 test for heterogeneity was used and a result from 75 to 100% was considered as high heterogeneity.A random effects meta-analysis was used. Differences in the degree of change in FVC and DLCO were tested with t-test without compensation for repeated analysis.Results:1870 articles were screened for eligibility and 21 were selected for the SLR and meta-analysis The analysis used 21 studies to evaluate changes of FVC and DCLO at 1 yr of FU. Only 5 studies were eligible to evaluate changes during longer FU (24.7 months(SD=20.4)). Heterogeneity was high at baseline and FU, (at 1 yr and >1 yr),both for the 21 studies at 1 yr (FVC:I^2 99.74%, 99.78%; DLCO: I^2=99.91%99.92%) and the 5 studies at > 1 year (FVC:I^2 92.86%;DLCO:I^2=99.54%), diminishing the confidence in the results. Table 1 gives the results of the random effects meta-analysis both for 21 and for the 5 studies evaluated. Regarding changes over 1 yr in the 21 studies, change of mean FVC was 2.7 (78.8vs81.5) while change in mean DLCO was 3.07(SE 8.20) (59.7vs 63.4). Considering the 5 studies during long term follow up, change in mean FVC was 2.0(7.36)(81.1vs83.1), and change in mean DLCO was -0.96 (16.95)(55.6vs54.7). Comparing the 1 yr changes in the 21 studies, change in mean FVC was 2.7(5.2)and change in mean DLCO was 3.07(8.2); difference in changes was not statistically significant (p=0.5791). During long term FU (24.7 months), change in mean FVC was 2.0(7.36)and change in mean DLCO was -0.96 (16.95); difference in changes was not statistically different (p=0.4698).Table 1.Results from Random Effect Meta-Analysis21 studies5 studiesFVC % predmean valueSEDLCO % pred mean valueSEFVC % predmean valueSEDLCO % pred mean valueSEBASELINE78.83.4359.75.5281.15.6855.611.591 YEAR FOLLOW UP81.53.8563.46.07---->1 YEAR FOLLOW UP----83.44.6854.712.37Conclusion:Our data are limited by great heterogeneity. Given this limitation, this SLR and meta-analysis indicates that there is no difference in the changes comparing FVC to DLCO at either 1 yr or during longer term follow-up. Corroboration of these results in prospective studies and in registries to make clear, comparable comparisons will be needed.Disclosure of Interests:Silvia Bellando Randone: None declared, Eleonora Cappellini: None declared, Letizia Nidiaci: None declared, Gemma Lepri: None declared, Maria Grazia Lazzaroni: None declared, Corrado Campochiaro Speakers bureau: Novartis, Pfizer, Roche, GSK, SOBI, Gianluca Bagnato: None declared, Domenico Sambataro: None declared, Gianluca Sambataro: None declared, Marco Matucci-Cerinic Grant/research support from: Actelion, MSD, Bristol-Myers Squibb, Speakers bureau: Acetelion, Lilly, Boehringer Ingelheim, Daniel Furst Grant/research support from: AbbVie, Actelion, Amgen, BMS, Corbus Pharmaceuticals, the National Institutes of Health, Novartis, Pfizer, and Roche/Genentech, Consultant of: AbbVie, Actelion, Amgen, BMS, Cytori Therapeutics, Corbus Pharmaceuticals, the National Institutes of Health, Novartis, Pfizer, and Roche/Genentech, Speakers bureau: CMC Connect (McCann Health Company)

Background:In SSc, skin involvement of the face is frequent and extremely disabling, resulting in limited mouth opening, an altered dentition, difficulty in teeth care, as well as having a strong impact on the emotional and psychological well-being, thus impairing quality of life.Objectives:to evaluate the efficacy of a self-treatment protocol (created by AMURR A Multidisciplinary Association of Rheumatological Rehabilitation) for face and tempomandibular joints (TMJs) rehabilitation with two devices used in the dental field.Methods:40 SSc patients (37 female and 3 male) with a mouth opening ≤ 40 mm, were recruited and randomized in two groups of treatment: Group 1 (20 patients: mean age 50,650 yrs ± 13,937 SD, mean disease duraton 10,45 yrs ± 7,877 SD, opening mouth 32,250 mm ± 5,590 SD) treated with a home self-treatment protocol consisting of 23 exercises carried out at home in front of a mirror, 22/23 exercises were performed once a day, one of these using a device to obtain uniform stretching of the buccal rhyme, another one usingused three times a day to reduce tension of muscles of the TMJs, facilitating the mouth opening; group 2 (20 patients: mean age 58,05 yrs ± 18,103 SD, mean disease duration 17,4 yrs ± 15,017 SD, opening mouth 34,950 mm ± 5,753) without physical rehabilitation, only drugs as treatments of SSc and its complications. All patients underwent a baseline (T0) and 45 days (T1) clinimetric assessment by self-assessment of quality of life with SF-36 (Short-Form 36 Health Survey), of the degree of disability of the mouth with MHISS (of the Mouth Handicap in Systemic Sclerosis scale), Muscle pain evaluated by numerical rating scale (NRS) of the temporomandibular joint with TMD (Temporo mandibular Disorders), evaluation of mouth opening and ROM of the cervical spine. Statistical analysis was performed using the t-test or the Mann-Whitney test for assessing changes in all measurement scales between treatment groups.Results:The protocol of home physiotherapy exercises resulted in a statistically significant improvement in the treated group compared to group 2 both for mouth opening (T0: 32,250 ± 5,590, T1: 35,650 ± 6,046) vs (T0: 34,950 ± 5,753 T1: 34,300 ± 6,001) (pConclusion:The use of the home exercises protocol associated with the two devices has shown a significant improvement of the disability linked to skin involvement of the face. This highlights the fundamental role that home rehabilitation self therapy has in practice. These data will need to be confirmed in a larger cohort of patientsDisclosure of Interests:Mauro Passalacqua: None declared, Cristian Foggi: None declared, Nicola Mauro: None declared, Lorenzo Tofani: None declared, Serena Guiducci: None declared, Cosimo Bruni Speakers bureau: Actelion, Eli Lilly, Gemma Lepri: None declared, Jelena Blagojevic: None declared, Khadija El Aoufy: None declared, Ginevra Fiori: None declared, Francesca Bartoli: None declared, Susanna Maddali Bongi: None declared, Marco Mitola: None declared, Marco Gizduloch: None declared, Marco Matucci-Cerinic Grant/research support from: Actelion, MSD, Bristol-Myers Squibb, Speakers bureau: Acetelion, Lilly, Boehringer Ingelheim, Silvia Bellando Randone: None declared

Background:in SSc, PAH has a high morbidity and mortality burden. Therefore, screening and early detection are pivotal to achieve an early diagnosis of PAH.Objectives:to search the literature for all screening modalities for SSc-PAH in reference to right heart catheterization as diagnostic gold standard.Methods:papers from 2 previously published SLRs [22 fromGlaude et al(1) – from inception to 19/06/2012 - and 22 fromYoung et al 2018– from 20/06/2012 to 02/10/2017] were included. The articles’ database was integrated with a systematic search on Pubmed, EMBASE, Web of Science for papers published from 03/10/2017 to 31/12/2018. A total of 199 papers were reviewed and 32 were finally extracted. Bias risk was assessed through QUADAS2 tool.Results:167 papers were excluded from data extraction mainly for PAH screening non as main focus or for non-including SSc patients. The 32 papers extracted presented a low bias risk according to QUADAS2. Screening methods reported were:Echocardiographic parameters in 31/32 studies, in particular systolic pulmonary arterial pressure (sPAP) in 22 papers; 40 mmHg was the most frequently used cut-off (in 12/22 papers); sPAP was part of a composite algorithm in 9/22 papers. Among others, tricuspid regurgitation velocity (TRV) was used in 6/31 (as part of composite 5/6) and right atrial pressure (RAP) in 3/31 papers.Pulmonary function tests parameters in 22/32 papers, with % predicted Lung diffusion for carbon oxyde (DLco) in 21 papers, with a 50% cut-off in 11/21 and as part of composite algorithm in 13/21 studies. Moreover, walked distance at six minutes walking test was a screening parameter in 3/32 papers.Serum biomarkers in 12/32 papers, with anti-centromere antibodies (6/12), NT-proBNP (6/12) and uric acid (5/12) being the most frequently reported.Clinical parameters in 15/32 papers, with unexplained dyspnoea in 9/15 and telangiectasias in 5/15 papers.Composite algorithms were used in 18/32 manuscripts: among them, DETECT (5/18), ESC/ERS 2009 (4/18) or 2015 (3/18) guidelines, ASIG (2/18) e ITINER-air (1/18). In different cohorts, DETECT and ASIG showed higher sensitivity and negative predictive value than ESC/ERS 2009.Conclusion:in the literature, the screening of SSc-PAH is largely investigated by echocardiographic parameters. In particular, sPAP and TRV, both as single items or part of a composite algorithm, including also serum biomarkers, clinical and functional parameters, are the most frequent parameters evaluated.(supported by an Actelion Pharmaceuticals unrestricted research grant)References:[1]Gladue H, et al. Screening and diagnostic modalities for connective tissue disease-associated pulmonary arterial hypertension: a systematic review. Semin Arthritis Rheum. 2014 Feb;43(4):536-41.[2]Young A, et al. Update of screening and diagnostic modalities for connective tissue disease-associated pulmonary arterial hypertension. Semin Arthritis Rheum. 2019 Jun;48(6):1059-1067.Acknowledgments:(supported by an Actelion Pharmaceuticals unrestricted research grant)Disclosure of Interests:Cosimo Bruni Speakers bureau: Actelion, Eli Lilly, Giacomo De Luca Speakers bureau: SOBI, Novartis, Celgene, Pfizer, MSD, Maria Grazia Lazzaroni: None declared, Elisabetta Zanatta: None declared, Gemma Lepri: None declared, Marco Matucci-Cerinic Grant/research support from: Actelion, MSD, Bristol-Myers Squibb, Speakers bureau: Acetelion, Lilly, Boehringer Ingelheim

Background:Interstitial lung disease (ILD) and pulmonary arterial hypertension carry a negative impact on SSc prognosis. Chest CT is the gold standard in assessing ILD and helps in evaluating associated vascular involvement.Objectives:As qualitative analysis of CT scans is limited by low reproducibility and time constraints, we aimed at evaluating parenchymal and vascular features in SSc-ILD by quantitative analysis (QA) of CT scans and testing the relationship with clinical-functional data.Methods:We prospectively enrolled 80 patients who underwent PFTs and chest CT scan spirometry gated at TLC on the same day. Clinical, lung functional and diffusion data, as well as disability indexes were collected. CT images were analyzed by a computational platform for texture analysis of ILD patterns (CALIPER), through Imbio LTA. It quantified the extent of normal pattern (NP %), ground glass opacities (GG %), reticulation (RET %), honeycombing (HC %), total ILD extent (ILD EXT %) and hyperlucent (HL %). Low density areas, representing emphysematous area, were also quantified (LDA %). For lung vessel analysis, a software program developed by the Ludwig Boltzmann Institute for Lung Vascular Research was used. This software determined total, arterial, and venous vascular volumes (TV, AV, VV), and relative volumes (TV%, AV%, VV%), as well as density and number for total, arterial and venous vessels.Results:43/80 patients/CT scans were eligible for both software analyses, while 36/43 for arterial and venous separation. TV% and total vessel density were correlated positively with mRSS and negatively with %FVC (r=-0.537 and r=-0.382) and %TLC (r=-0.511 and r=-0.648), while vessel tortuosity correlated positively with %DLco. This was confirmed when separately analyzing arterial vessels, while VV% negatively correlated with %FVC, %TLC and %DLco. There was a positive correlation between %ILD patterns and %vascular volumes, being significant for TV%-AV%, total vessels and arterial density. Conversely, %ILD patterns were negatively correlated with VV and number of veins detected, despite positive correlation between VV% and ILD_EXT%. When clustering patients according to %FVC and %DLco with 80% normal cutoff, %FVC allowed clustering according to significantly different ILD patterns extents and vascular features, while %DLCO for vascular features only. Moreover, the consecutive addition of functional impairment and worsening of ILD (from both normal %FVC and %Dlco, to %DLco impairment only to both %FVC and %Dlco impairment), there was a significant increase in %TV, % AV and %VV, with the exception of decrease in %VV and venous density in patients with double impairment versus DLco single impairment.Conclusion:This is the first study showing in SSc a direct correlation between ILD and the increase in lung vascular volume, which is characterized by increase in arterial volume and density and reduction in venous volume and number. These results might be explained by the reduction of pulmonary volume due to fibrosis. However, also a para-physiological mechanism of redistribution of blood flow in lung areas, less involved by ILD, might be considered. Further studies on lung vessel quantification and distribution are ongoing.Disclosure of Interests:Cosimo Bruni Speakers bureau: Actelion, Eli Lilly, Mariaelena Occhipinti Consultant of: Imbio, Gianna Camiciottoli: None declared, Maurizio Bartolucci: None declared, Michael Pienn: None declared, Gemma Lepri: None declared, Alessio Fabbrizzi: None declared, Alessandra Tottoli: None declared, Giuglia Ciardi: None declared, Dilia Giuggioli: None declared, Giovanna CUOMO: None declared, Francesco Masini: None declared, Horst Olschewski: None declared, Federico Lavorini: None declared, Linda Calistri: None declared, Marco Matucci-Cerinic Grant/research support from: Actelion, MSD, Bristol-Myers Squibb, Speakers bureau: Acetelion, Lilly, Boehringer Ingelheim

In systemic sclerosis (SSc), Raynaud's phenomenon is the earliest clinical manifestation paralleled by nailfold capillaroscopic alterations that may occur months or even years before the onset of fibrosis.1 This evidence suggests a crucial role of microangiopathy characterised by a progressive loss of capillaries with the formation of avascular areas.1 ,2 Consequent chronic tissue hypoxia leads to skin ulcers and gangrene that heavily burden patients’ quality of life.1 ,2 Vascular endothelial growth factor-A (VEGF-A) is overexpressed in SSc skin, and increased circulating levels of VEGF-A correlate with the severity of nailfold capillary loss.2–4 It has been demonstrated that the VEGF-A primary transcript can be alternatively spliced in its terminal exon, producing two distinct mRNA splice variants that are translated to the proangiogenic VEGF165 and antiangiogenic VEGF165b isoforms.5 These two isoforms bind to the tyrosine kinase receptor VEGFR-2 with the same affinity, but binding of VEGF165b results in an insufficient tyrosine phosphorylation/activation of VEGFR-2 and incomplete or transient downstream signalling, which lead to an impaired angiogenic response.5 ,6 Recently, we have provided the first evidence that dermal expression and plasma levels of VEGF165b are raised in SSc patients, and VEGF165b overexpression prevents SSc dermal microvascular endothelial …

Systemic sclerosis (SSc) is a challenge for the rheumatologist as it is easy to diagnose when it is evolved to skin fibrosis with obliterative vasculopathy and organ involvement but its diagnosis remains very difficult in the very early/early phase of the disease because the American College of Rheumatology (ACR) and LeRoy criteria, which are currently those largely used to classify SSc, were shown to be not sensitive enough to reach a very early or an early diagnosis of SSc.1–4 Therefore, the SSc diagnosis may be delayed for several years following the onset of Raynaud's phenomenon (RP) and even after the onset of the first non-RP symptom. This reality implies that the diagnosis, and consequently the therapy, are delayed until skin involvement and/or internal organ involvement are evident5–8 and, in too many cases, already irreversible.6 The fact that organ involvement may be present from the earliest stages of SSc corroborates the necessity of a very early or at least an early diagnosis of SSc to try to identify therapy which might achieve disease remission. Moreover, the rheumatologist is also facing today the problem to position the patient in the SSc evolution from its very early to the early and to the established phase. Previously, several attempts have been made to define the early phase of SSc7 and recently even the concept of very early SSc has been widely accepted and investigated.8 RP, despite its lack of specificity, has been proposed as a pivotal sign in a previous attempt to define criteria for the diagnosis of ‘early’ SSc9 and has been also considered as the main ‘sentinel’ sign10 for the identification of ‘very early …

BackgroundThe oesophagus is the first gastrointestinal (GI) tract involved in systemic sclerosis (SSc), followed by the anorectum.ObjectiveEvaluation of oesophageal and anorectal involvement and their correlations in patients with very early diagnosis of SSc (VEDOSS).Patients and methods59 patients with VEDOSS, evaluated with oesophageal and anorectal manometry and investigated with lung function tests and chest HRCT. Demographic data, oesophageal and anorectal symptoms, Raynaud's phenomenon, autoantibodies, videocapillaroscopy patterns, puffy fingers and digital ulcers were recorded for all patients.ResultsIn 4 patients oesophageal manometry and in 17 patients anorectal manometry was not performed because of scarce tolerance. Oesophageal peristalsis was absent in 14 patients; its pressure and speed were significantly lower in 41 patients (p80% showed only an abnormal peristalsis (ConclusionsIn patients with VEDOSS, oesophageal and anorectal disorders are frequently detected, showing that very early SSc is characterised by GI involvement.

Background PANDAS (Pediatric Autoimmune Neuropsychiatric Disorders associated with Streptococcal Infections) identifies a subgroup of pts with unusually abrupt and dramatic TIC/OCD onset GAS infection related. PANS “Pediatric acute-onset neuropsychiatric syndrome” is a term proposed to describe a clinically distinct presentation of OCD/TIC with post infectious origin. Differently from PANDAS, in PANS other agents may trigger the disease, including Mycoplasma pneumonia, Influenza viruses, Epstein Barr virus, Borrelia Burgdorferi, Herpes simplex and Varicella viruses. Clinical presentation is characterized by an abrupt dramatic onset of OCD and additional neuropsychiatric symptoms nor explained by known neurologic or medical disorders1. Objectives To describe clinical features of 23 Italian children with OCD/TIC diagnosed as PANS in comparison to our PANDAS group. Methods Between May 2009 through January 2016 we recruited 23 pts (13 M, 10 F) with OCD/TIC starting before puberty. The mean age at onset 77 mnths±35.6SD. Results 19 (86.4%) were full-term born, 3 (13.6%) from Caesarean section (no information in 1 adopted child). 8/21 (38.1%) had familiars with OCD/tics or other neurologic diseases (2 pts without data). At onset, clinical signs were OCD in 3 (13%), OCD and motor tics in 7 (30.4%), motor tics in 5 (21.7%), vocal tics in 1 (4.3%), motor/vocal tics in 5 (21.7%), motor/vocal tics and OCD in 2 (8.7%), Mean age at diagnosis 106.8 months±36.9 SD. Antistreptolysin O and antiDNaseB titers were negative in all pts. In all EBV, Mycoplasma pneumoniae, CMV, Borrelia Burgdorferi were tested: 2 pts had history of tick bite and Borrelia Burgorferi Ab+, 6 pts Mycoplasma pneumoniae Ab+, 1 EBV Ab+; in 2 pts a VZV infectionAb+ was found. In 1 child Rotavirus infection was suspected and 12 had a viral pharyngitis before OCD/Tics onset. All underwent neuropsychiatric evaluation, none had deficit of psychological development; in all autoimmunity (ANA; antiDNA and ENA Ab) was negative as well as cerebral MR and EEG. All received antibiotic therapy according to the specific infection: pts with Mycoplasma macrolide, pts with VZV antiviral, pts with Borrelia amoxicillina. All showed benefit during and after the treatment. Pts, with no specific agent, received amoxicillina and benzathine benzylpenicillin with benefit after a more prolonged period than PANDAS pts. Conclusions Our data show that PANS as PANDAS prediliges males with higher familiar predisposition in PANS. The age at onset is comparable to PANDAS, while OCD are more common and severe than in PANDAS. All pts had an infectious event, as PANDAS pts, but the trigger agent was different from GAS, and all responded to the specific therapy. PANDAS and PANS mainly differs from the trigger agent. The knowledge of PANS and PANDAS is mandatory to early recognize children at the disease onset avoiding to delay the diagnosis and the beginning of therapy. Acknowledgement 1Chang K et al. Clinical evaluation of Youth with pediatric acute onset neuropsychiatric syndrome (PANS): recommendations from the 2013 PANS Consensus Conference. J Child Adolescent Psychopharmacology 2015:25:3–13 Disclosure of Interest None declared

Background VEDOSS project relied on a specific set of inclusion criteria identifying patients in very early stage of systemic sclerosis (SSc) to be submitted to a tight follow up and unravel factors linked to the progression of the disease. The components of the ELF score (PIIINP, TIMP-1 and HA) have been shown to correlate with severity of skin and lung fibrosis in SSc. Objectives Our aim was to analyze the concentrations of ELF components in a subset of patients enrolled in the VEDOSS study and determine their potential diagnostic value. Methods Sera from 114 patients enrolled into the VEDOSS data base and 67 SSc controls fulfilling ACR/EULAR 2013 criteria (subsets: 33 diffuse; 34 limited) were obtained from 2 centres. Serum concentrations of ELF components were determined on Siemens Advia Centaur platform. Logistic regression analysis of the results was performed employing classification of SSc as state variable. Results Among the 114 patients enrolled from VEDOSS, 30 subjects had primary Raynaud9s phenomenon (PRP); 54 had Raynaud9s phenomenon (RP) and at least one of the following “red flags” (risk factors) for SSc: (Puffy fingers, ANA, SSc specific autoantibodies or SSc-specific capillaroscopic pattern) without fulfilling 2013 ACR/EULAR criteria (score 9) despite having no evidence of skin involvement nor interstitial lung disease at lung high resolution CT or pulmonary arterial hypertension, left ventricular systolic impairment or renal involvement. All serum biomarkers concentrations correlated with age (p Conclusions Our data indicate that the SSc score is a simple serum test based model that can be used in patients with RP to aid in the very early diagnosis of SSc. Furthermore, the identification of VEDOSS patients with a high SSc score test and already classified as SSc even in the absence of internal organ involvement can be used in intervention trials aimed to prevent further disease progression. Disclosure of Interest None declared

Background “Pet Therapy”, better defined as Animal-assisted Intervention (AAI), is based on the interaction between animal and human being and is a tool which may complement and support traditional therapies. It can be used on patients affected by different diseases, improving their quality of life from behavioral, physical and psychosocial point of view. Objectives The aim of our study was to evaluate the effect of AAI in improving quality of life and compliance to standard pharmacological treatment in a cohort of Systemic Sclerosis (SSc) patients. Methods 42 SSc patients attending at Scleroderma Unit and undergoing iloprost intravenous infusion were divided in three groups: 1) 14 SSc patients (mean age 60.4±8.6 yrs) submitted to 20 AAI sessions with a professional team (doctor, nurse, couple of animal-handler); 2)control (C1) 14 SSc patients (mean age 63.4±5.3 yrs) engaged in alternative social activity as create a cookbook; 3)control (C0) 14 SSc patients (mean age 62.3±6.8 yrs) without any alternative activity. All patients underwent psychological evaluation at baseline (t0) and at the end of project of AAI (t1); moreover the following test (italian standardized version) was performed at the beginning (s0) and at the end (s1) of each single session: General Anxiety State-Trait Anxiety Inventory (STAI-T), Beck Depression Inventory (BDI), Social Interaction Anxiety Scale (SIAS), Eysenck Personality Questionnaire-Revised (EPQ-R), the Social Phobia Scale (SPS), the Toronto Alexythymia Scale (TAS-20), the Thought Control Questionnaire (TCQ), the Visual Analog Scale (VAS), the State-anxiety (STAI-S). Results At the end of each session, AAI group showed a decrease of the anxiety state level while it was higher in the two control groups ( p s p s Conclusions In agreement with literature [1], our work showed that AAI might be a crucial tool to support the traditional therapies thanks to the creation of a different relationship between patient and doctor. This may allow a better compliance to the therapy in a chronic disease like SSc, where patient9s compliance is usually low. References Matuszek S. Animal-facilitated therapy in various patient populations: systematic literature review. Holist Nurs Pract. 2010 Jul-Aug;24(4):187–203. Disclosure of Interest None declared

Background Vitamin D (vitD) is known for its essential role in calcium homeostasis and bone health. It is now considered as a potent neurosteroid hormone, with a pivotal role on the brain development and normal brain function. VitD ligand-receptor, a receptor that mediates the majority of vitamin D biological actions, has been found throughout the body including the central nervous system (CNS). Vitamin D deficiency is commonly observed in patients with severe mental illness such as schizophrenia. PANDAS is an autoimmune disorder characterized by obsessive-compulsive symptoms and/or tics triggered by group-A beta-hemolytic Streptococcus infections with relapsing/remitting course due to recurrence of infections itself. Despite the action of 25-hydroxyvitamin D [25(OH)D] on immune and CNS system, to our knowledge, no studies have been performed in patients with PANDAS. Objectives To evaluate 25(OH)D levels in a large cohort of children and adolescents with PANDAS 2. To compare the results with a healthy control group. Methods We measured plasma 25(OH)D levels in one hundred seventy-nine patients with PANDAS (49 females, 132 males, mean age at diagnosis 101.4 ±30.1 months) and an age, sex, and body mass index-matched control group of 179 subjects. Results Patients with PANDAS showed a higher percentage of reduced 25(OH)-vitamin D levels ( vs. 82.5%; p vs. 24.8±7.3 ng/mL, p vs. 32.5±8.7) period. Yet, serum 25(OH)-vitamin D levels correlated with the number of streptococcal infections before the diagnosis (p Conclusions PANDAS patients have reduced 25(OH)D values that seem to be associated with streptococcal infections, and the probability of its recurrences. So, reduced 25(OH)D levels may be a cause significantly important in PANDAS etiopathogenesis. A regular supplementation of VitD in PANDAS patients is recommended as it should improve the course of the disease and prevent or reduce the recurrences of infections and the relapses of neurological symptoms. This hypothesis should be further explored in future studies. Disclosure of Interest None declared

Background Iloprost (ILO) is a synthetic analogue of prostacyclin PGI 2 with a potent vasodilator action, an anti-proliferative effect on smooth muscle cells and inhibition of platelet aggregation. ILO is employed intravenously for the control of Raynaud Phenomenon and digital ulcers. Up to now, no agreement has been reached on the regimen (dosage and frequency) to be used in SSc patients. Objectives To identify the most common side effects that are developed during ILO infusion in SSc. Methods 81 SSc patients, classified according to ACR EULAR criteria, derived from two Italian centers, were submitted to ILO infusion: patients were subclassified according to the edematous or fibrotic/atrophic phase of the disease. ILO was infused (6–8 hour infusion, dose ranging from 0.5 to 1.0 ng/kg/ min) (1) with a progressive increase of the dosage up to the achievement of patient9s tolerance: the infusion on pump was started at 5 ml/hour and increased every half an hour up to 20 ml/hour (a dose of 4 mcg/h which corresponds to 1ng/kg)according to patients tolerance and appearance of side effects. Results Out of 81 patients, 16 were in the edematous phase with puffy fingers (digital edema). In this cohort, 5 individuals (31.2%) developed diarrhea and 9 (56.2%) developed hypotension during the infusion. When the drug was withdrawn patients had an immediate amelioration but when ILO was restarted, they again developed diarrhea or hypotension that led to definitive interruption of the treatment. Moreover, 10/16 patients (62.5%) experienced significant and painful digital swelling which led to the tapering of the infusion dosage below 10 ml/hr (which corresponds to 0.5 ng/kg per min); out of 10 patients, only one could continue the treatment while the other 9 had to be withdrawn due to the maintenance of the intense digital pain due to vasodilation. Finally, 11 patients (68.7%) reported flushing and 7 (43.7%) headache, but they were always controlled with the reduction of the infusion below 10 ml/hr. Out of 81 patients, 65 were in the atrophic/ fibrotic phase: 10 patients (15.3%) developed diarrhea and 24 pts (37%) hypotension that led to temporary withdrawal: when ILO was restarted and kept below 10 ml /hr, no side effects were experienced. In 23 cases (35.3%) flushing and in 8 cases (12.3%) headache were experienced, but were well controlled with infusion reduction below 10 ml/hr. Conclusions ILO was well tolerated in SSc patients characterized by fibrotic phase, where side effects could be managed by reducing/modulating the infusion rate. In edematous patients, ILO infusion should be decided in case where the severity of Raynaud9s phenomenon or the presence of digital ulcers strongly suggests its use. References Wigley FM, et a Intravenous iloprost infusion in patients with Raynaud phenomenon secondary to systemic sclerosis. A multicenter, placebo-controlled, double-blind study Ann Intern Med. 1994;120:199–206 Disclosure of Interest None declared

Background Kawasaki disease (KD) is an acute multisystemic vasculitis, affecting primarily infants and children, and it is the most common cause of acquired heart disease in Western countries. The exact pathogenesis of KD has not been clearly identified, but infections caused by one or more pathogens are strongly suspected as major cause of the disease. Our previous study demonstrated that KD patients have highly reduced 25(OH)-vitamin D levels in comparison with healthy controls and also with other immunological disorders, suggesting a hypothetical role of vitamin D deficiency in the development of coronary artery damage in KD, and low vitamin D levels might contribute to the severity of chronic vascular abnormalities. Specific polymorphisms of vitamin D receptor ( VDR ) gene have recently been associated with different biologic response to vitamin D itself. Objectives 1.To analyze the possible associations of these polymorphisms in a series of Italian children affected by KD. 2. To evaluate a possible influence of VDR polymorphism in enhancing the risk of the disease. Methods We recruited 50 Italian infants and children affected by typical KD (38 males, 12 females), age ranging from 2 through to 62 months. Genomic DNA was extracted from peripheral blood leukocytes to analyze VDR polymorphisms by PCR-based sequencing ( CDX2 in the promoter region) and PCR-based enzymatic digestions ( FokI in exon 2, BsmI and ApaI in intron 8, and TaqI in exon 9). An Italian population of 2221 unrelated individuals without KD or other immunological disorders was used as healthy controls. The distribution of polymorphism genotypes and alleles was evaluated in patients vs healthy controls. Results The distribution of all Cdx2, FokI, BsmI, ApaI , and TaqI polymorphisms (both as genotypes or alleles) did not show significant differences between affected subjects and healthy controls. Conclusions In conclusion, this pilot study evidence that VDR polymorphisms seem not to have any influence in determining the risk of KD. Anyway, future larger studies are needed to unravel the exact relationship between VDR genotype and KD development and/or clinical characteristics. Disclosure of Interest None declared

Background JIA is the most common chronic arthritis of childhood. Vitamin D is a potential immuno-modulator in many conditions, including autoimmune diseases. Its influence in JIA is still unclear. Specific polymorphisms of vitamin D receptor gene ( VDR ) have recently been associated with different biologic responses to vitamin D itself. Objectives 90 Italian children, adolescents and young adults with poli- or oligoarticular onset of JIA were studied. VDR polymorphisms were analysed by PCR-based sequencing ( CDX2 in the promoter region) and PCR-based enzymatic digestions ( FokI in exon 2, BsmI and ApaI in intron 8, and TaqI in exon 9) in the genomic DNA from blood of patients. 2221 healthy Italian unrelated individuals have been used as controls for VDR polymorphism frequencies. Distribution of VDR polymorphisms has been evaluated in patients vs controls, in patients with active and inactive disease, and in patients with poli- or oligoarticular JIA. Methods The distribution of FokI , BsmI , and TaqI polymorphisms did not show any significant difference between subjects with JIA and controls. Conversely, significant statistical differences in the distribution of CDX2 and ApaI genotypes were found, respectively with the CDX2 GG genotype (Yates-corrected chi-square 6.56; Odds ratio=1.80; p =0.0104) and the TT ApaI genotype (Yates-corrected chi-square 20.97; Odds ratio=2.67; p =0.0000), both more frequent in JIA than in controls. Also the G allele of CDX2 (Yates-corrected chi-square 6.12; Odds ratio=1.60; p =0.0134) and the T allele of ApaI (Yates-corrected chi-square 19.69; Odds ratio=2.05; p =0.0000) was more frequent in JIA. No statistical differences were found for all the analysed VDR polymorphisms, between the poliarticular vs oligoarticular forms. No significant association was found between VDR polymorphisms and active or inactive forms of JIA, neither with osteopenic or normal bone mineral density status. Conclusions Pathogenetic mechanisms influencing the predisposition to JIA are poorly elucidated and autoimmune dysfunctions are strongly suspected. This genetic study found a significantly higher frequency of the GG genotype of VDR CDX2 polymorphism and TT genotype of VDR ApaI polymorphism in patients with JIA. The CDX2 polymorphism is located in the promoter region of the VDR gene and has been associated with VDR mRNA expression, while the ApaI polymorphism has been associated with the stability of VDR mRNA. Therefore, we can speculate that CDX2 GG genotype and ApaI TT genotype can both influence the expression of the VDR protein, presumably resulting in a reduced receptor activity with subsequent decreased response to vitamin D and potential immunity deregulation, favouring the development of JIA. Conversely, VDR polymorphisms seem not to have any influence for patients9 active or non-active status, both for the oligoarticular and poliarticular form of the disease. Disclosure of Interest None declared

Background Raynaud9s Phenomenon (RP) is often the first sign of Systemic Sclerosis (SSc) vasculopathy and several drugs (calcium channel blockers, prostanoids, Endothelin 1 receptor antagonists, phosphodiesterase-5 inhibitors are commonly used to reduce frequency and severity of RP attacks. Objectives The aim of our study was to evaluate retrospectively the efficacy of different vasoactive therapeutic regimens, particularly of Bosentan and Sildenafil, on the quality of life and apillaroscopic patterns in SSc patients. Methods 123 SSc patients (mean age sd: 57.69±14.07 years) were retrospectively evaluated. Patients were arbitrarily divided into 2 groups according to ACR/EULAR classification score: group 1 with score ≤10, group 2 with score >10. Each group was then divided into 3 subgroups according to different vasoactive treatment: Bosentan, Sildenafil, and Bosentan plus Sildenafil. Nailfold videocapillaroscopy (NVC) was performed at baseline and after 3 and 6 months as well as SHAQ (Scleroderma Health Assessment Questionnaire) and RCS (Raynaud Condition Score). Results 29 patients were on Bosentan (12 patients of group 1; 17 of group 2), 63 patients on Sildenafil (35 patients of group 1; 28 of group 2) and 31 patients on combination of Bosentan plus Sildenafil (14 patients of group 1; 17 of group 2). Patients on Bosentan: The capillaroscopic pattern changed significantly, both after 3 months (p=0,00439 group 1, p=0,00076 group 2) and after 6 months (p=0,00439 group 1, p=0,00035 group 2) of treatment, if compared to baseline, in both groups. In group 1 , both the “active” that the “late” patterns were reduced while the “aspecific” pattern increased. In group 2 , there was a reduction of percentage of “late” pattern. In group 1, SHAQ and RCS did not change while in group 2 SHAQ worsened significantly (p Patients on Sildenafil: After 3 months of treatment, in both groups the NVC patterns changed significantly (p=0.042 group 1, p=0,00089 group 2). In particular, in group 1 the “late” and “early” patterns increased while the “asepcific” pattern decreased. In group 2, a significant change of NVC pattern was observed also after six months of treatment (p=0,00089), in particular the “late” pattern increased while the “active” pattern reduced. After 6 months SHAQ significantly reduced both in group 1 (p=0,00027), that in group 2 (p=0,0043). RCS improved in both groups (p=0,0042 group 1, p=0,0016 group 2). Patients on combination therapy (Bosentan+Sildenafil): Only in group 1, combination therapy induced significant changes on NVC patterns both after three months (p=0,00256) and after 6 months of treatment (p=0,000349). In particular, a progressive reduction of the “late” “active” patterns was observed, while the “early” pattern increased. In group 2 no pattern modification was observed. In both groups, after 6 months SHAQ was significantly reduced (p Conclusions SSc patients treated with Bosentan/Sildenafil combination had a significant improvement of the microvascular involvement when compared to Bosentan and Sildenafil alone. The combination achieved a modification of the NVC pattern thus fostering microvascular de-remodelling. Disclosure of Interest None declared

Background Kawasaki disease (KD) is an acute febrile systemic vasculitisin childhood that is associated with inflammatory cytokines, in which the vascular inflammation results in damage to the coronary arteries. Vitamin D plays an important role in the regulation of immunity, and several studies demonstrate that its active form 25(OH)VIT exhibits anti-inflammatory activities and modulate the inflammatory response in the systemic vasculitis. Objectives 1. To assess serum levels of 25(OH)VITD in children with KD, and 2. to evaluate the possible relationship between 25(OH)VITD deficiency and coronary artery damage in these patients. Methods We evaluated 25(OH)VITD serum levels in 60patients with KD (18 females, 42 males, mean age at KD diagnosis 23.8±15.4 years). These patients were compared with a sex- and age-matched control group. In all patients 25(OH)VITD serum levels were measured in the acute phase of the illness before IVIG treatment. All patients received timely the current treatment for KD, IVIG 2 g/kg and aspirin (30-50 mg/kg). Among the 60 pts 3 developed coronary artery aneurysms (diameter >5 mm Results KD patients showed significantly reduced 25(OH)VITD levels (8.90±2.24 mg/dl) in comparison to controls (21.70±4.35 mg/dl; p Conclusions 25(OH)VITD might have a role in the development of coronary damage. Yet, low 25(OH)VITD levels might contribute to the chronic course and severity of coronary aneurysms in the KD. Future larger studies are needed to explore the relationship between serum 25(OH)VITDlevels and KD cardiac damage. References Kudo K, Hasegawa S, Suzuki Y, Hirano R, Wakiguchi H, Kittaka S, Ichiyama T.1α,25-Dihydroxyvitamin D(3) inhibits vascular cellular adhesion molecule-1 expression and interleukin-8 production in human coronary arterial endothelial cellsJ Steroid BiochemMolBiol 2012;132:290-4. Suzuki Y, Ichiyama T, Ohsaki A, Hasegawa S, Shiraishi M, Furukawa S.Anti-inflammatory effect of 1alpha,25-dihydroxyvitamin D(3) in human coronary arterial endothelial cells: Implication for the treatment of Kawasaki disease.J Steroid BiochemMol Biol. 2009;113:134-8. Disclosure of Interest None declared

Background The treatment of ILD remains a challenge for the rheumatologist. Recent studies suggested a potential short-term benefit of rituximab (RTX) on connective tissue diseases developing ILD. Objectives To compare RTX effects on ILD in patients with systemic sclerosis (SSc), mixed connective tissue disorder (MCTD) and anti-synthetase (SYN). Methods Multicentre retrospective assessment of the effects of RTX on ILD comparing three patient populations: SSc (n=23), MCTD (n=6) and SYN (n=15). All underwent high-resolution computed tomography (HRCT) at baseline and lung function tests (LFTs) at baseline and at 1 and 2 years of follow-up. The primary outcomes were the mean change in predicted forced vital capacity (FVC) value and the percentage of responders defined by an increase in FVC of 10% or greater. Results In SYN patients, although the change of FVC from baseline to 2 years was not statistically significant, a trend of improvement was observed (table 1). In SSc, discrepancies were observed with a trend of improvement at 1 year but a decline at 2 years. In MCTD, FVC remained table at 1 and 2 years of follow-up. In SYN patients, the percentage of responders for FVC was greater than in SSc (33.3% vs 9.5%) (p=0.1) and than in MCTD patients (33.3% vs 16.7%) (p=0.15). At baseline, SSc and MCTD patients had a higher FVC when compared to SYN population (table 1) and this finding may partially explain the major percentage of responders in SYN than in SSc. The percentage of responders in DLCO (gain ≥15%) was similar in SYN and SSc populations (27.3% and 23.8% respectively). Some patients received DMARDs and/or immunosuppressive treatment previously or/and concurrently to RTX; although this did not influence our findings, these treatments may influence the effects of RTX. RTX showed a satisfactory safety profile. Conclusions Our data obtained in routine care provide for the first time outcomes in LFTs after 2 years of follow-up. The main results show a good safety profile supporting future development. We also observed a promising trend of improvement in the SYN group and indicate that the drug may provide a stabilization of the involvement of the lung in SSc and MCTD. Future trials on homogenous groups of patients are warranted to determine how rituximab may be positioned in the treatment of CTD-ILD, but the SYN group should be prioritized. Acknowledgements EULAR scintific travel bursary Disclosure of Interest G. Lepri: None declared, J. Avouac: None declared, P. Airo: None declared, F. Anguita Santos: None declared, S. Bellando Randone: None declared, J. Blagojevic: None declared, O. Distler Grant/research support from: received research funding from, 4D Science, Actelion, Active Biotec, Bayer-Schering, Biogen, Biovitrium, BMS, Boehringer Ingelheim Pharma, EpiPharm, Ergonex, GSK, Inventiva, Medac, Novartis, Pfizer, Pharmacyclics, Roche/Genentech, Sanofi/Genzyme, Serodapharm, Sinoxa and United BioSource Corporation., F. J. Garcia Hernandez: None declared, J. A. Gonzalez Nieto: None declared, S. Guiducci: None declared, S. Jordan: None declared, V. Limaye: None declared, B. Maurer: None declared, V. Riccieri: None declared, A. Selva-O9Calaghan: None declared, M. Matucci Cerinic: None declared, Y. Allanore Grant/research support from: received research funding in relationship with the treatment of systemic sclerosis from Actelion, Bayer, Biogen Idec, BMS, Genentech/Roche, Inventive, Medac, Pfizer, Sanofi/Genzyme, Servier and UCB

Background PANDAS is defined by neuropsychiatric symptoms, mainly obsessive-compulsive disorder (OCD) or tics, temporally associated with group A β-hemolytic Streptococcus (GAS) infections, showing acute prepubertal onset and relapsing/remitting course. Objectives To describe the clinical features of a cohort of 242 Italian pts with OCD and/or tics related to a previously confirmed GAS infection. Methods Between May 2009 and January 2015 we recruited 242 pts (185 males, 76.45%) with OCD and/or tics starting before puberty associated with a previous upper airway infection (impetigo in 2 cases). GAS infection was confirmed in all patients. Their mean age at onset was 77.64 months ±30.1 SD. Results Two hundred and twenty-three children (93.31%) were full-term born after a regular pregnancy, and 52 (37.68%) from Caesarean section (though for 4 adopted children there were no information); 101/236 (42.8%) had familiars with OCD/tics or other neurologic diseases (for 6 patients there were no familial history data). Sport activity was evaluated in only 149 out of 242 patients, and was performed by 122/149 (81.88%). Clinical signs were motor tics in 109/242 (45.04%), vocal tics in 6/242 (2.48%), motor/vocal tics in 28/242 (3.31%), motor/vocal tics and OCD in 18/242 (7.44%), OCD in 16/242 (6.61%), OCD and motor tics in 61/242 (25.21%), OCD and vocal tics in 4/242 (1.65%). At the first evaluation the mean age was 102.70 months ±35.12 SD. Brain MRI was performed resulting within normal limits in 110/242 patients. Pharyngeal swab was positive in 34/242 (14.05%). A nti-streptolysin O titer was 550 in 129/242 (53.31%), while in the remaining 28/242 (11.57%) this titer was in progress or not evaluated. Anti-DNase B titer was >650 IU/ml in 76/242 (31.4%) and 75% in 58/242 (23.97%), and not-valuable in 47/242 (19.42%). Conclusions Our preliminary data in the largest pediatric population with PANDAS ever studied until now show male predominance and familiar recurrence rate over 40%. Clinical onset occurs at a mean age of 8.5±2.9 years with motor tics in 45% of cases. Increased anti-DNase B titer is found in over 30% of patients. Benzathine benzylpenicillin has resulted effective in 3/4 of cases with complete or partial remission of symptoms. Disclosure of Interest None declared

Background and objectives The vascular and nervous systems have several anatomic and molecular mechanism similarities. Emerging evidence suggests that proteins involved in transmitting axonal guidance cues, including class III semaphorin families, also play a critical role in blood vessel guidance during physiological and pathological vessel development. Sema3E is a natural antiangiogenic molecule that causes filopodial retraction in endothelial cells, inhibiting cell adhesion by disrupting integrin-mediated adhesive structures. The aim of the present study was to investigate if Plexin-D1/Sema3E axis could be involved in the dysregulation of vascular tone control (RF) in SSc. Materials and methods Sema3E levels were measured by quantitative colorimetric sandwich ELISA in serum samples from 45 subjects with primary Raynaud’s phenomenon (pRP), 48 SSc patients and 48 age- and sex-matched healthy controls. Western blot was used to evaluate Plexin-D1/Sema3E axis in human SSc and healthy dermal microvascular endothelial cells (SSc-MVEC and H-MVEC, respectively) at basal condition, and after stimulation with recombinant human vascular endothelial growth factor (VEGF), SSc and healthy sera (both n = 3). Immunofluorescence staining on skin sections from 14 SSc patients and 12 healthy subjects was performed in order to evaluate Sema3E and Plexin-D1 expression. Results Serum Sema3E levels were significantly higher both in pRP subjects and SSc patients than in sera controls. In SSc, Sema3E levels were significantly increased in patients with early nailfold videocapillascopy pattern (NVC) compared to active/late pattern and pRP, and in patients without ulcers compared to those with digital ulcers. SSc-MVEC showed higher levels of phosphorylated Plexin-D1 and Sema3E expression compared with H-MVEC, and stimulation with SSc sera increased the expression of phosphorylated Plexin-D1 and Sema3E in H-MVEC. In SSc, Sema3E expression was increased in the dermis, particularly in the vascular endothelium. Conclusions Our findings suggest that Plexin-D1/Sema3E axis is triggered in SSc and may have a role in the dysregulation of vascular tone control by inducing neuro-vascular mechanism alterations clinically evident in particular in the early disease phases.

Background The interest in the association between 25(OH) D and Systemic Lupus Erythematosus (SLE) started in the last decade when VIT D status was related to low bone mass in these patients. Several studies have shown that the majority of SLE patients have 25(OH) D deficiency, highlighting the possible association between SLE and 25(OH) D. While VIT D deficit in SLE may be related to lack of sun exposure, several studies report a positive association between SLE activity and 25(OH) D deficiency.VIT D seems to be important in decreasing the risk of cancer, autoimmune, infectious and cardiovascular diseases. This effect may be related to VIT D regulation of immune function. In vitro studies have detected that vitamin D metabolites up-regulate the anti-inflammatory and down-regulate pro-inflammatory cytokines, and enhance the T-reg production. While numerous studies have been performed in adulthood SLE, a few data are available in juvenile onset SLE (JSLE), despite reduced bone mass and increased fracture risk are well recognized as one of the major health problems in these patients. Therefore, VIT D status should have a role in reducing bone mass in JSLE Objectives The purpose of this study was: 1. To assess serum 25(OH) D levels in children, adolescents, and young adults with JSLE; 2. To identify the risk factors for vitamin D deficiency in this population Methods Fifty-five consecutive patients with JSLE (37 F, 9 M, mean age 18.9±6.3 yrs) entered the study. In all DXA scans at the lumbar spine, serum calcium and phosphate, bone alkaline phosphatase (BSAP), parathyroid hormone (PTH), and 25-hydroxyvitamin D (25(OH) D) were assessed the same day Results JSLE patients showed significantly reduced 25(OH) D levels than controls (p Conclusions JSLE patients have a significant lower 25(OH) D levels than controls, and subjects with active disease have significant reduced 25(OH) D levels in comparison to those with inactive disease, and have a higher risk of developing 25(OH) D deficiency. Our results seem support a role of 25 (OH) D deficiency in the bone growth of JSLE patients. So, vitamin D might be an additional factor to improve the normalization of bone mass and quality in subjects with JSLE References Attar SM, Siddiqui AM. Vitamin d deficiency in patients with systemic lupus erythematosus. Oman Med J. 2013, 28:42-7. Adorini L, Penna G. Control of autoimmune diseases by the vitamin D endocrine system. Nat Clin Pract Rheumatol. 2008,4:404-12 Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.3645

Background PANDAS is a pathological condition, starting before puberty, characterized by rapid onset of OCD and/or tics, temporally related with immune-mediated response to GABHS infection Objectives To describe the clinical features of 87 Italian patients with sudden occurrence of OCD and/or tics related to a previously GABHS infection Methods Between May 2009- January 2014 we observed 87 patients (66 M, 21 F, mean age: 77.9±28.3 months) with OCD and/or tics associated with a previous GABHS infection. Demographic, familiar data, and specific laboratory data (thyroid function, ANA, anti-dsDNA, anti-ENA, anti-cardiolipin, LAC, and anti-tissue transglutaminase antibodies) were assessed. All underwent EEG, echocardiography and neuropsychiatric consultation; 55/87 brain MRI Results 80/87 (93.0%) were full-term, 19/87 (22.1%) after Caesarean section, 41/86 (47,6%) had familiars with OCD/tics or other neurologic diseases. 74/87 (87.7%) did regular physical activity. In all, clinical onset was dramatically acute and occurred at a mean age of 77.9±28.3 months (range 24-160). 40/87 (46.0%) started with motor tics; 5 (5.7%) with OCD; 6 (6.9%) with motor/vocal tics; 29 (33,3%) with motor tics and OCD, and 6 (6.9%) with motor/vocal tics and OCD. At first evaluation 12/87 (13.8%) had motor/vocal tics, 35/87 (40.2%) only motor tics, 1/87 (1.1%) vocal tics, 23/87 (26.4%) motor tics and OCD, 8/87 (9.2%) motor/vocal tics and OCD, 4/87 (4.6%) OCD, and 3/87 (3.4%) had no apparent symptom. 33/87 had no clinically-evident infectious episode before clinical onset, 53/87 (61.3%) a previously-established pharyngitis, otitis and/or upper airway infection; 1/87 had a previous impetigo.Mean age at diagnosis was 104.8±32.5 months. Inflammatory parameters were negative in all, at onset and at our first clinical evaluation. Brain MRI, EEG, thyroid tests, and coeliac disease screening were normal in all. Their subsequent histories were mostly alternating between remission and exacerbation. Anti-streptolysin O titer was evaluated in 79 patients: it was less than 250 IU in 14 (17.7%), between 250 and 550 IU in 37 (46.8%), and over 550 IU in 28 (35.4%). Anti-DNase titre was evaluated in 56 patients, resulting increased (over 650 U) in 26 (46.4%). ANA was positive at low titre in 2 patients, while other autoimmunity tests were completely negative. All received benzathine benzylpenicillin while amoxicillin was given for 10 days in the case of a concurrent demonstrated streptococcal infection. Sertraline was used in 4, haloperidol in 6. Psychotherapy was required in most patients. 60/82 patients (73.2%) displayed complete/partial remission of neurological symptoms; the follow-up of 5 patients is in progress Conclusions Our preliminary data show that PANDAS is mainly observed in males (75.9%) with familiar recurrence of different motor disturbances in 47.6% of cases, clinical onset occurs at a mean age of 6.4±2.3 years with the coexistence of OCD and motor tics in most cases, and an increased anti-DNase titre is found in 46.4% of patients. In addition, benzathine benzylpenicillin has resulted effective in all cases with complete/partial remission of symptoms Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.3560

Background The main hallmark of systemic sclerosis (SSc) is vasculopathy characterised by dysregulation of angiogenesis and vascular tone leading to loss of capillaries. The vascular and nervous system have several anatomic similarities that extend to level of the molecular mechanisms. Emerging evidence suggests that proteins involved in transmitting axonal guidance cues, including class III semaphorin families, also play a critical role in blood vessel guidance during physiological and pathological vessel development. Sema3E acts through its receptor plexin-D1 to control endothelial cell positioning and patterning of the developing vasculature. Sema3E is a natural antiangiogenic molecule that causes filopodial retraction in endothelial cells inhibiting cell adhesion by disrupting integrin-mediated adhesive structures. Objectives The aim of the present study was to investigate if plexin-D1/Sema3E axis could be involved in dysregulated vascular tone control (RF) characteristic of SSc. Methods Sema3E levels were measured by quantitative colorimetric sandwich ELISA in serum samples from 45 subjects with primary Raynaud's phenomenon (PRF) without ANA, Scl70, ACA positivity, 48 SSc patients and 48 age- and sex-matched healthy controls. Patients were classified according to nailfold videocapillaroscopy (NVC) patterns (early, active and late). Sema3E levels were expressed as median and range and compared by Mann-Whitney U test. Differences were considered significant for p values less than 0.05. Western blot was used to evaluate plexin-D1/Sema3E axis in human dermal microvascular endothelial cells from healthy subjects (H-MVECs) at basal condition and after stimulation with recombinant human VEGF165 (10 ng/ml), lcSSc sera (n=3) and healthy sera (n=3) for 24h. Results Sema3E sera levels were significantly higher both in PRF subjects (median 0.54 ng/ml) and SSc patients (median 0.67 ng/ml) respect to healthy controls (median 0.19 ng/ml) (both p

Background Great interest is devoted today to patients with very early diagnosis of systemic sclerosis (VEDOSS), characterized by the presence of Raynaud phenomenon (RP), puffy fingers, Antinuclear antibodies (ANA), plus the presence of disease related autoantibodies (anti-centromere – ACA – and antiTopoisomerase I – ATA) and/or nailfold videocapillaroscopy (NVC) scleroderma pattern [1,2]. In established SSc, NVC is today considered an outcome measure [3]. Objectives To describe microvascular modifications in VEDOSS patients and to retrospectively evaluate te effectiveness of NVC in monitoring the evolution of microvascular disease. Methods Patients with RP attending our outpatient clinics from March 2010 to October 2013 were enrolled. Autoantibodies were tested and NVC was performed at baseline and at follow-up an optical probe equipped with 200x lens. Giant capillaries, micro-haemorrhages, capillary loss and ramified/bushy capillaries were searched in NVC images and then clustered/scored according to the medium value of the alteration, as following: 0% present, score 0; from 0% to 33%, score 1; from 33% to 66%, score 2; over 66%, score 3 [4]. Scores given to each parameter were summed and compared between baseline and follow-up assessment: a decrease of the total score of at least 2 points was considered as improvement, an increase of at least 2 points as worsening, otherwise as stable. Results 167 patients were enrolled (18 males, mean age 51±15 years, 10±8 years since RP onset), with ANA positive in 96/167 (57.5%), ACA and ATA in 41/167 (24.5%) and 17/167 (10.2%) respectively. On NVC, giant capillaries were found in 62/167 (37.1%), haemorrhages in 72/167 (43.1%), loss of capillaries in 2/167 (1.2%) and ramified/bushy capillaries in 10/167 (5.9%). At baseline, giant capillaries and haemorrhages were associated with ANA plus ACA/ATA positivity ( p Conclusions NVC confirms its ability in detecting capillary modification in VEDOSS patients, as well as its effectiveness in monitoring microvascular disease evolution in time. References Avouac J, Fransen J, Walker UA et al. Preliminary criteria for the very early diagnosis of systemic sclerosis: results of a Delphi Consensus Study from EULAR Scleroderma Trials and Research Group, Ann Rheum Dis 2011Mar;70:476-81. Minier T, Guiducci S, Bellando-Randone S et al. Preliminary analysis of the Very Early Diagnosis of Systemic Sclerosis (VEDOSS) EUSTAR multicentre study: evidence for puffy fingers as a pivotal sign for suspicion of systemic sclerosis. Ann Rheum Dis.2013 Aug 12. Cutolo M, Sulli A, Pizzorni C et al. Capillaroscopy as an Outcome Measure for Clinical Trials on the Peripheral Vasculopathy in SSc-Is It Useful? Int J Rheumatol 2010. Sulli A, Secchi ME, Pizzorni C, Cutolo M.Scoring the nailfold microvascular changes during the capillroscopic analysis in systemic sclerosis patients.Ann Rheum Dis.2008 Jun;67(6):885-7.Epub 2007 Nov 23 Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.2957

Background Stressful Life Events (SLEs) may play a role in the etiopathogenesis of autoimmune diseases, especially during childhood ( early SLEs) and in the year prior to the onset of the disease ( recent SLEs). Such a deleterious effect of stressful events seems to be mediated by the inadequate responsiveness to stressors and to chronic inflammation due to a dysregulation of the Hypothalamic-Pituitary-Adrenal axis (HPA axis). Few studies have addressed the relationship between SLEs and SSc and none of them evaluated the effect of both early and recent life events. Objectives The aims of the present study were to explore the multiple effects of stress on SSc onset and course, and to evaluate the impact of pain perception and health-related quality of life on patients with SSc. Methods 110 consecutive SSc patients were enrolled. The assessment included a face-to-face interview and the administration of self-reported questionnaires evaluating pain perception and quality of life (Short Form (36) Health Survey (SF-36), Brief Pain Inventory (BPI), Childhood Experience of Care and Abuse Questionnaire and Florence Psychiatric Interview). Clinical status was assessed by modified Rodnan Skin Score and Raynaud Condition Score, nailfold videocapillaroscopy and instrumental examination of internal organs. Results Compared to a group of matched controls (n=110), a higher proportion of patients reported at least one Stressful Life Events (56.3% vs 34.5%, p early life events were more frequently reported by SSc patients, even though a significantly difference was obtained only for “loss of mother” and for “sexual abuse” (13.6% vs 5.4%, p recent life events compared to patients without a significant clinical worsening (54.0% vs 26.0% p Conclusions Early SLEs can be considered potential risk factors for the onset of SSc. The occurrence of recent SLEs may have a role in the course of the disease, being linked to a significant clinical worsening. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.4998

Objectives Evaluation of the presence of digital lesions [1] in patients with diagnosis of very early systemic sclerosis (VEDOSS) [2] and of their correlation with clinical, laboratory and imaging parameters. Methods 110 VEDOSS patients were investigated for presence of digital pitting scar, calcinosis, digital ulcers (DUs), necrosis or gangrene, nailfold videocapillaroscopic abnormalities, disease specific autoantibodies (anti-centromere and anti-topoisomerase I) and internal organ involvement (chest HRCT, pulmonary function tests with DLCO evaluation, oesophagealmanometry, Holter ECG, cardiac Doppler US, renal arteries Doppler US) [3]. Results 4 patients reported a history of digital pitting scars, 16 patients presented active DU and 14/16 also reported a history of previous DUs. Other 9 patients reported a history of DUs only. Both the history and the presence of DUs showed statistically significant correlation with esophageal manometry only (analyzed through IBM SPSS Statistics version 19, using Spearman’s Rho test:ρ=0,681 &ρ=0,633 respectively, p Image/graph Conclusions DUs are already present in VEDOSS patients and correlate with esophageal involvement [4]. DU may be considered as a sentinel sign for the presence of early organ involvement, meaning the evolution from thevery early to the early phase of systemic sclerosis [5]. References Amanzi L et al. Digital ulcers in scleroderma:staging, characteristics and sub-setting through observation of 1614 digital lesions. Rheumatology (Oxford).2010 ;49:1374-82. Avouac J et al, “Preliminary criteria for the very early diagnosis of systemic sclerosis: results of a Delphi Consensus Study from EULAR Scleroderma Trials and Research Group”, Ann Rheum Dis. 2011 Mar;70:476-81. Czirjak L, Matucci Cerinic M: Beyond Raynaud’s phenomenon hides a very early systemic sclerosis: the assessment of organ involvement is always mandatory. Rheumatology 2011;50:250-1 Lepri G et al: Evidence for Esophageal and anorectal involvement in patients with very early diagnosis of systemic sclerosis (VEDOSS):report from a single EUSTAR centre. (Submitted) Matucci Cerinic M et al: Very early versus early disease: the evolving definition of the many faces of Systemic Sclerosis Ann Rheum Dis; 2012 Nov 23 Disclosure of Interest : None Declared

Background SSc affects gastrointestinal tract in more than 80% of patients. Esophageal involvement is the most common manifestation with a prevalence ranging between 50 and 90%. Objectives Evaluation of esophageal involvement and detection of its predictor factors in very early SSc patients. Methods 56 patients (55 females), mean age 49,2±14 years, with very early SSc were evaluated with esophageal manometry. The demographic data, esophageal symptoms (dysphagia, typical GERD symptoms), Raynaud phenomenon (presence/absence, duration), autoantibody profile (anticentromere antibodies [ACA], antinuclear antibodies [ANA], anti-Scl70 antibodies [Scl70]), videocapillaroscopy patterns (Normal, Early, Active, Late), puffy fingers, digital ulcers were recorded for all patients. Results Esophageal body dysmotility (abnormal mean pressure of peristalsis or absence of peristalsis) was present in 49 patients (94,2%), and was associated with a hypotensive lower esophageal sphincter (LES) in 26 (53,1%). Esophageal symptoms were present in 26 patients (50%).Puffy fingers were present in 22 patients (42,3%) and were associated with a smaller area of LES ( p-value: 0.011) . In 4 patients esophageal manometry was not performed because of scarce tolerance of the procedure. Conclusions Esophageal disorders are frequently seen in very early SSc patients in particular in patients with puffy fingers. Disclosure of Interest None Declared