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DeSScipher is the first European multicentre study on management of systemic sclerosis (SSc), and its observational trial 1 (OT1) evaluated the efficacy of different drugs for digital ulcer (DU) prevention and healing. The aim of this study was to assess current use of vasoactive/vasodilating agents for SSc-related DU in the expert centres by analysing the baseline data of the DeSScipher OT1.Baseline characteristics of patients enrolled in the OT1 and data regarding DU were analysed.The most commonly used drugs, in both patients with and without DU, were calcium channel blockers (CCBs) (71.6%), followed by intravenous iloprost (20.8%), endothelin receptor antagonists (ERAs) (20.4%) and phosphodiesterase 5 (PDE-5) inhibitors (16.5%). Of patients, 32.6% with DU and 12.8% without DU received two drugs (p 0.001), while 11.5% with DU and 1.9% without DU were treated with a combination of three or more agents (p 0.001). Sixty-five percent of the patients with recurrent DU were treated with bosentan and/or sildenafil. However, 64 out of 277 patients with current DU (23.1%) and 101 (23.6%) patients with recurrent DU were on CCBs alone.Our study shows that CCBs are still the most commonly used agents for DU management in SSc. The proportion of patients on combination therapy was low, even in patients with recurrent DU: almost one out of four patients with current and recurrent DU was on CCBs alone. Prospective analysis is planned to investigate the efficacy of different drugs/drug combinations on DU healing and prevention. Key Points • The analysis of DeSScipher, the first European multicentre study on management of SSc, has shown that the most commonly used vasoactive/vasodilating drugs for DU were CCBs, followed by intravenous Iloprost, ERAs and PDE-5 inhibitors. • More than half of the patients with recurrent DU received bosentan and/or sildenafil. • However, the proportion of patients on combination therapy of more than one vasoactive/vasodilating drug was low and almost one out of four patients with current and recurrent DU was on CCBs alone.

Lower limb ulcers may represent real clinical challenge in patients with systemic sclerosis (SSc). They are often multifactorial, long-lasting and difficult to treat. In addition to microangiopathy, macrovascular arterial and venous involvement may overlap and cause ulcer formation. Other local factors, as calcinosis and hyperkeratosis can contribute. Several types of lesions with different aetiology may occur, even in the same patient. Systematic clinical evaluation and diagnostic work-up are mandatory for proper ulcer classification that is essential for their management, since diverse lesions may require different treatment.

In systemic sclerosis (SSc), the use of corticosteroids (CS) is controversial due to their association with scleroderma renal crisis (SRC). However, patients with very early and early disease, characterised by main inflammatory component, may benefit from CS therapy. The aim of this review is to discuss pros and cons of CS treatment in SSc, providing current evidence about the use of CS in SSc. Moreover, we discuss also the underlying pathogenetic mechanisms that may be the background for the potential harms and efficacy of CS in SSc.

Idiopathic inflammatory myopathies (IIMs) encompass a heterogeneous group of rare autoimmune diseases characterised by muscle weakness and inflammation, but in antisynthetase syndrome arthritis and interstitial lung disease are more frequent and often inaugurate the disease. Clinical practice guidelines (CPGs) have been proposed for IIMs, but they are sparse and heterogeneous. This work aimed at identifying: i) current available CPGs for IIMs, ii) patients ’ and clinicians’ unmet needs not covered by CPGs. It has been performed in the framework of the European Reference Network on rare and complex connective tissue and musculoskeletal diseases (ReCONNET), a network of centre of expertise and patients funded by the European Union’s Health Programme. Fourteen original CPGs were identified, notably recommending that: i) extra-muscular involvements should be assessed; ii) corticosteroids and methotrexate or azathioprine are first-line therapies of IIMs. ii) IVIG is a treatment of resistant-DM that may be also used in other resistant-IIMs; iii) physical therapy and sun protection (in DM patients) are part of the treatment; v) tumour screening for patients with DM include imaging of chest, abdomen, pelvis and breast (in woman) along with colonoscopy (in patients over 50 years); vi) disease activity and damages should be monitor using standardised and validated tools. Yet, only half of these CPGs were evidence-based. Crucial unmet needs were identified both by patients and clinicians. In particular, there was a lack of large multidisciplinary working group and of patients ’ preferences. The following fields were not or inappropriately targeted: diagnosis; management of extra-muscular involvements other than skin; co-morbidities and severe manifestations.

Objectives SSc is a chronic autoimmune disease characterized by inflammation of the skin and multiple internal organs. Articular involvement is one of the main features of SSc, and typical hallmarks of SpA have been found in SSc patients. The aim of the present study was to estimate the prevalence of entheseal and synovio-entheseal complex (SEC) alterations in a cohort of SSc patients. Methods One hundred SSc patients and 25 healthy subjects were included in this cross-sectional study. The enthesis sites of lateral epicondylar common extensor tendons (CET) and the enthesis of the Glasgow Ultrasound Enthesis Scoring System were evaluated. SEC involvement was evaluated only at CET enthesis. Results In SSc, the Glasgow Ultrasound Enthesis Scoring System score was significantly higher (median 4.0, interquartile range 2.0–7.0) than in controls (median 1.0, interquartile range 0.0–3.0) (P < 0.0001). CET enthesis of SSc patients showed more frequent US B-mode alterations than that of controls (χ2 = 11.47, P = 0.0007 for size; χ2 = 13.79, P = 0.0002 for cortical irregularity, χ2 = 5.24, P = 0.022 for calcification/enthesophytes). Power Doppler US signal at CET enthesis was significantly more frequent in SSc patients than in healthy controls (χ2 = 9.11, P = 0.0025), as was the concomitant SEC involvement (χ2 = 8.52, P = 0.0035). Conclusion These data show that SSc patients frequently present US features of enthesopathy. Moreover, CET enthesopathy was correlated with SEC inflammation, suggesting that entheseal inflammation in SSc may share the same micro-anatomical targets as found in SpA.

Background:Interstitial lung disease (ILD) is the leading cause of mortality in patients with Systemic Sclerosis (SSc). Forced Vital Capacity (FVC) is a major indicator of severity in SSc ILD. The ELF serum test and its constituent biomarkers (HA, PIIINP and TIMP-1) have shown to correlate with FVC in two large, independent multicentre cohorts of 457 patients, but also showed a correlation with age.Objectives:Here we aimed to investigate the relationship of the ELF biomarkers and age in a large population of healthy controls and to identify a combined clinical and biomarkers model to stratify for risk of ILD progression in a multicentre longitudinal cohort of patients with SSc.Methods:ELF score was measured in sera from 925 healthy controls in one centre and 869 longitudinal samples from 254 SSc patients from 6 centres across 4 European countries. Clinical data were recorded according to EUSTAR Minimal Essential dataset. FVC% change over time was estimated by Mixed-effects modelling. Patients were then divided in two groups: progressors, with a %FVC drop > 3%/year (according to published MCID) and a group of patients with stable or improving FVC. Lasso penalised regression was carried out with biomarkers and the available clinical and demographic variables at patient’s first visit as potential predictors. The resulting linear predictor was used to derive two thresholds, one for optimal sensitivity (rule-out) and one for optimal specificity (rule-in). Patients within thresholds were further selected according to the ratio of TIMP-1: PIIINP (Figure 1).Results:HA was the only ELF biomarker that correlated significantly with age in the healthy control cohort. Therefore, we defined by linear regression a “residual HA” which accounted for age. TIMP1, PIIINP and residual HA were then considered as distinct biomarkers in the analysis of the SSc cohort. 189 SSc patients with 785 time-points had complete datasets and were included in the analysis. Median follow up was 33 months (IQR 18-48). One-hundred and forty patients (74%) were classified as non progressors, 94 (50%) with no change or improving FVC and 46 (24%) with FVC drop Conclusion:Building on the face and content validity of the biomarkers included in the ELF score, here we identify an easy to assess combined clinical and biomarker model to stratify patients for their risk of ILD progression. Despite its derivation from a large multicentre cohort, independent validation will determine the clinical value of Scleroscore as a stratification tool for risk of progression of SSc ILD.Disclosure of Interests:Michelle Hutchinson: None declared, Giuseppina Abignano: None declared, Jelena Blagojevic: None declared, Silvia Laura Bosello: None declared, Yannick Allanore Grant/research support from: Alpine, Boehringer Ingelheim, Genentech/Roche, Medsenic, and Sanofi, Christopher Denton Consultant of: Corbus, Actelion, GlaxoSmithKline, Bayer, Sanofi, Galapagos, Inventiva, Boehringer Ingelheim, Roche, CSL Behring, Acceleron, Horizon, Arxx Therapeutics, Grant/research support from: Corbus, Actelion, GlaxoSmithKline, Bayer, Sanofi, Galapagos, Inventiva, Boehringer Ingelheim, Roche, CSL Behring, Acceleron, Horizon, Arxx Therapeutics, Oliver Distler Consultant of: 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, Grant/research support from: 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, Paul Emery Consultant of: Lilly, Abbvie, Roche, Grant/research support from: Lilly, Marco Matucci-Cerinic Consultant of: Chemomab, Lilly, Abbvie, Actelion, Francesco Del Galdo Speakers bureau: Astra-Zeneca, Boehringer Ingelheim, Actelion, Consultant of: Astra-Zeneca, Mitsubishi-Tanabe, Capella Biosciences, Chemomab, Actelion, Boehringer-Ingelheim, Grant/research support from: Capella Biosciences, Chemomab, Kymab, Mitsubishi-Tanabe

Background:In March this year, most of the routine activities were cancelled during the streaming of the pandemic in Italy. This prompted a pragmatic reorganization of the traditional care model of nursing and medicine, to quickly give an efficient clinical response. During the first phase of the pandemic, outpatient visits dropped by more than 60%, forcefully shifting to telemedicine to assure continuity of care despite the lockdown.Objectives:The aim of the present work was to describe the strategy adopted during and immediately after the lockdown to assure the follow up of patients and the maintenance of their treatment in an outpatient “virtual” telemedicine clinic dedicated to RDs.Methods:the patient flow to a rheumatology division during the lockdown was evaluated retrospectively from March to September 2020 in accordance with local restrictions, and three periods are described.Results:653/913 (71.5%), 542/542 (100%) and 1.048/1.048 (100%) infusion activities scheduled were performed at the centre for daily infusion and pre-infusion assessment, respectively during the 1st, 2nd and 3rd period. In the outpatient clinic during the 1st period, 96.96% of the cases was shifted to Telemedicine, which decreased to 52.45% in the 2nd period; while in the 3rd period, 97.6% of the performances were carried out at the clinic. Diagnostic procedures, such as ultrasound, capillaroscopy, and joint injection were generally postponed during the 1st period, reduced drastically during the 2nd and performed regularly during 3rd period. Ulcer treatment and the Clinical Trial Unit never stopped their activity. The flow of the activity of the outpatient clinic and the day hospital is represented as monthly trends in graph 1 (See Graph 1).Conclusion:Our data show the feasibility of Telemedicine in a lockdown condition. Shifting stable patients to Telemedicine has the potentiality to minimize the risk of contagion and allow continuity of care. In the future, the use of Telemedicine for specific clinical uses might assure patient assistance also in non-pandemic conditions.References:[1]Rawaf S, Allen LN, Stigler FL et al. Lessons on the COVID-19 pandemic, for and by primary care professionals worldwide. Eur J Gen Pract. 2020 Dec;26(1):129-133. doi: 10.1080/13814788.2020.1820479. PMID: 32985278.[2]McDougall JA, Ferucci ED, Glover J, et al. Telerheumatology: A Systematic Review. Arthritis Care Res (Hoboken). 2017 Oct;69(10):1546-1557. doi: 10.1002/acr.23153. Epub 2017 Aug 22. PMID: 27863164; PMCID: PMC5436947.[3]Romão VC, Cordeiro I, Macieira C, Oliveira-Ramos F, Romeu JC, Rosa CM, Saavedra MJ, Saraiva F, Vieira-Sousa E, Fonseca JE. Rheumatology practice amidst the COVID-19 pandemic: a pragmatic view. RMD Open. 2020 Jun;6(2):e001314. doi: 10.1136/rmdopen-2020-001314. PMID: 32584782; PMCID: PMC7425193.Characters from table content including title and footnotes:Graph 1.Monthly trend for telemedicine and visits during the SARS Cov2 emergencyAcknowledgements:The project (Telereuma) has been supported by an unrestricted grant of Biogen, BMS, and Novartis.Disclosure of Interests:None declared

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

In systemic sclerosis (SSc), different types of cutaneous lesions (calcinosis, ulcers and gangrene) may be observed. Digital ulcers are defined as the loss of tissue occurring on fingers. With the arrival of new vasodilator and vasoactive drugs, DU became a topic of copious number of publications. Although a lot of efforts have been made to clarify their pathogenesis, to improve their healing and to prevent their occurrence, up to now no classification of DU has been universally accepted by the clinicians and by the scientific community.

Digital loss is the most serious and fearful complication of digital ulcers (DUs) in systemic sclerosis (SSc). It may occur as a consequence of gangrene that leads to an autoamputation or to surgical amputation or as a result of amputation performed for other reasons, as severe osteomyelitis.

Background At early stages, SSc lung involvement is characterised by Ground Glass Opacities (GGO) at High Resolution Computed Tomography (HRCT). However, HRCT scan is not able to provide functional information and to discriminate between an “active inflammatory” and an “established fibrotic” GGO. 18Fluoro-Deoxy-d-Glucose (18F-FDG) Positron Emission Tomography/Computed Tomography (PET/CT) is able to detect metabolic activity picking up inflammation and provides both morphologic and metabolic data. Objectives The aim of this study was to evaluate, if 18F-FDG PET/CT scan may identify the inflammatory component of GGO in SSc interstitial lung disease. Methods Seven patients with SSc (1 male and 6 females; mean age 59.56 y±9.15 SD; median disease duration 5 years, 2–11 who underwent 18F-FDG PET/CT scan because of cancer screening, were retrospectively analysed. HRCT images analysis led to classification of pulmonary segments as “negative” (normal morphology) and ”positive” (GGO). Furthermore, the “Warrick score” was used as a staging tool for SSc-ILD. Mean Standardised Uptake Value (mSUV) of segmental parechima was normalised (nmSUV) by comparison with the values of selected control subjets. Results No SSc patient was affected by cancer. Three patients had a Warrick Score >0, while 4 patients did not had any lung involvement (Warrick Score=0). The 3 patients with a Warrick Score >0 had also skin involvement with a median mRSS 6 (2–7) and pathological lung FDG uptake. In “positive” segments of SSc patients, nmSUV was significantly higher than in the lung segments of the control population (mean estimation 1.53; C.I. 1.42–1.65, p 0, the nmSUV was significantly higher than in segments of the control population (mean estimation 1.29; C.I. 1.22–1.37, p 0. “Negative” lung segments of patients with Warrick Score >0 showed a 32% higher 18F-FDG uptake than “negative” lung segments of patients with Warrick Score=0. (C.I. 0.17–0.48, p Conclusions Morphologically “positive” GGO segments show an increased 18F-FDG uptake suggesting the existence of a metabolically active (inflammatory) GGO. However, in patients with GGO, negative lung segments showed a higher nmSUV than negative lung segments in patients without GGO. This may suggest that PET/CT may disclose an underlying inflammatory process, which cannot yet be evidenced by HRCT. Further studies on a larger population are warranted to confirm these data and possibly provide a prognostic significance of PET/CT positivity in SSc patients. Disclosure of Interest None declared

Objective.To evaluate pathogenesis and clinical features of lower limb ulcers in systemic sclerosis (SSc) and to propose a classification that could be used in clinical practice.Methods.Charts of 60 patients with SSc who had lower limb cutaneous lesions were reviewed. All patients had videocapillaroscopy and arterial and venous lower limb color Doppler ultrasonography (US). Arteriography was performed if occlusive peripheral arterial disease was suspected.Results.The 554 lesions were classified as hyperkeratosis, ulcers, and gangrenes. There were 341 (61.6%) hyperkeratoses, 208 (37.5%) ulcers, and 5 (0.9%) gangrenes. Ulcers were divided into pure ulcers, ulcers associated with hyperkeratosis, and ulcers secondary to calcinosis. Involvement of arterial and venous macrocirculation as determined by color Doppler US was observed in 17 (18.3%) and 18 (30%) patients, respectively. Seventeen out of 37 patients with pure ulcers (45.9%) presented neither venous insufficiency nor hemodynamically significant macrovascular arterial disease. In these patients, pure ulcers were most likely caused by isolated SSc-related microvascular involvement (pure microvascular ulcers). The only significant risk factor for development of pure microvascular ulcers in the multivariate analysis was the history of lower limb ulcers (OR 26.67, 95% CI 2.75–259.28; p < 0.001).Conclusion.Results of our study indicate that lower limb ulcers in SSc often have a multifactorial pathogenesis that may be difficult to manage. Further studies are needed to validate the proposed classification and to assess the most appropriate management of lower limb ulcers in SSc.

The aim of this study was to evaluate in systemic sclerosis (SSc) retrospectively the effect of Bosentan and Sildenafil and their combination on Raynaud’s phenomenon (RP), function, and capillaroscopic patterns. One hundred and twenty-three SSc patients (mean age ± sd, 57.69 ± 14.07 years) were retrospectively evaluated and divided into two groups according to American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification score: group 1 score < 10, group 2 score > 10. Each group was divided into three subgroups according to treatment: Bosentan, Sildenafil, and Bosentan + Sildenafil. Nailfold videocapillaroscopy (NVC), Scleroderma Health Assessment Questionnaire (SHAQ) and Raynaud Condition Score (RCS) were performed at baseline and after 3 and 6 months. In Bosentan (29 patients: 12, group 1; 17, group 2), NVC changed significantly in both groups, after 3 and 6 months (p = 0.00439, group 1; p = 0.00035, group 2). In group 1, the “active” and the “late” patterns reduced, and the “aspecific” increased. In group 2, there was a reduction of late patterns, a worsening of SHAQ (p < 0.005) and an improvement of RCS (p = 0.00014). In Sildenafil (63 patients: 35, group 1; 28, group 2), after 3 months, NVC patterns changed significantly in both groups(p = 0.042 group 1, p = 0.00089 group 2). In group 1, the late and early patterns increased, and the aspecific decreased. In group 2, a significant change of NVC pattern was observed also after 6 months (p = 0.00089): the late pattern increased while the active one reduced. After 6 months, SHAQ was significantly reduced in group 1 (p = 0.00027) and in group 2 (p = 0.0043). RCS improved in both groups (p = 0.0042, group 1; p = 0.0016, group 2). Combination therapy (Bosentan + Sildenafil) (31 patients: 14, group 1; 17, group 2) induced significant changes on NVC only in group 1 after 3 (p = 0.00256) and 6 months (p = 0.000349) with a reduction of the late and active patterns and an increase of the early pattern. In both groups, after 6 months, SHAQ (p < 0.05, group 1; p = 0.00049, group 2) and RCS significantly reduced (group 1, p = 0.00024; group 2, p = 0.0021). Patients treated with Bosentan + Sildenafil show a significant improvement of RCS and NVC. This combination therapy may exert a vascular activity achieving an amelioration of the structure of microvasculature in SSc.

Interstitial lung disease (ILD) is the leading cause of systemic sclerosis (SSc) related morbidity and mortality. LL-37 peptide is the only cathelicidin of the human antimicrobial peptide family with antimicrobial effects and immunomodulatory activity. LL-37 has anti-fibrotic effects and anti-apoptotic effects on SSc dermal fibroblasts. The aim of the study was to investigate the circulating levels of LL-37 in SSc patients and its association with clinical, laboratory, and instrumental parameters. Fifty-eight SSc patients (30 with and 28 without pulmonary involvement) and 28 healthy controls were enrolled in the study. Pulmonary involvement was defined when ILD was found at HRCT (ground glass, reticular, and honeycombing pattern). Circulating LL-37 levels were measured with ELISA test. In SSc patients with ILD serum, LL-37 concentrations were remarkably lower (1.36 mg/ml) than those in SSc patients without ILD (4.62 ng/ml, p = 0.035) and controls (5.53 ng/ml, p = 0.009). In SSc patients without ILD, serum LL-37 levels were not different from controls (p = 0.812). No significant association or correlation was found between LL-37 levels and any other clinical, serological, or instrumental features. Serum LL-37 levels are significantly lower in patients with SSc ILD. Our results may suggest that lower LL-37 levels may be associated with the development of ILD. Whether circulating levels of LL-37 might be used as an indirect marker of ILD remains to be determined in larger SSc cohorts.

Background SSc patients suffer from Raynaud9s phenomenon, hand skin hardening and scarring, digital ulcers, esophagus/gastric dysmotility, dysphagia and mucosal dryness. These symptoms significantly reduce patient9s life autonomy and impair the capacity to handle their therapy usually made by different modalities of administration: oral, topical, inhalation, intramuscular, subcutaneous, intravenous, and rectal. Objectives to investigate the methods of administration used by SSc patients, their preferred methods, their compliance to pharmacological therapy, and the difficulties that are encountered by the patients during pharmacotherapy. Methods 2 questionnaires were prepared on an ad hoc basis. The first given to patients, the second to be filled out by the patient9s physician. The first questionnaire comprised 25 questions to investigate the problems encountered by patients when taking their medications by correlating these with two validated activities indices: SHAQ-DI (activities of daily living) and the COCHIN scale (hand activities). The second questionnaire collected demographic and important SSc-related clinical information (eg.age, sex, disease duration, symptoms). 80 Ssc patients completed the questionnaires, maintaining anonymity. A “difficulty index” was also filled out, where: 0 = no difficulty to 4 = impossible to use or too difficult to use. Results In particular, the dimension of the pills is problematic, and has identified a paradoxical situation because large pills are difficult to swallow (41,25% patients who use pills) but at the same time small pills are difficult to pinch with the fingers (62,25% patients who use pills). Conclusions SSc patients experience significant problems in maintaining adherence to treatments due to difficulties in the use of blisters and bottles with children proof stoppers. Pills still remain the most preferred method of treatment. In conclusion, patients unanimously wished to avoid the use of blisters, defintively preferring bottles without the children proof stopper to make the treatment easier and provide a more independent life. Disclosure of Interest None declared

Background The Enhanced Liver Fibrosis (ELF) test is a serum test including the serum concentrations of amino-terminal pro-peptide of procollagen type III (PIIINP), tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) and hyaluronic acid (HA). A recent single centre study showed that ELF score and its components are markers of overall fibrosis in systemic sclerosis (SSc) mainly reflecting skin and lung involvement (1). Objectives To determine the value of ELF score and its single analytes in an independent multicentre cohort of SSc patients. Methods 254 SSc patients from 6 European Rheumatology Centres were included in this study. Clinical data were collected at time of sampling. Serum samples were collected and stored according to EUSTAR biobanking recommendations (2). Sera were analysed employing a high-throughput in vitro diagnostic (Siemens Alpha-Centaur). Statistical analysis was performed with SPSS software V.24. Results The 254 SSc patients had a mean age 55.8±13.8 years, and included 209 females and 80 patients with diffuse cutaneous SSc (dcSSc). ELF score was overall higher in males than in females (p=0.0236) as well as in dcSSc compared to limited cutaneous SSc patients (p=0.0015). ELF score and the single markers significantly correlated with the degree of skin involvement (mRSS) and inversely correlated with FVC%, TLC% and DLCO%. Concordantly all markers significantly correlated with skin and lung severity as assessed by the Medsger9s scale (Table 1). TIMP-1 and PIIINP levels were higher in patients with lung fibrosis assessed by chest HRCT scan (p=0.0126 and p=0.0308 respectively). Significant correlation (p Conclusions The value of ELF score as independent marker of skin and lung involvement is confirmed in a second independent multicentre cohort of SSc patients. A longitudinal study paired with analysis of large cohort of healthy controls is currently on going to identify a SSc specific test with the highest predictive value for skin and lung progression independently of age and gender. References Abignano G et al. Ann Rheum Dis. 2014. Beyer C et al. Ann Rheum Dis. 2011. Disclosure of Interest None declared

Background A consensus on DU definition in SSc has been recently reached (1),while for their evaluation,classification and categorisation it is still missing. Objectives To identify in SSc a set of essential items for DU evaluation, to assess if the existing DU classification (2) was useful and feasible in clinical practice, and to investigate if the DU categorisation (3) was preferred to the simple division of DU in recurrent and not recurrent. Methods The DU Desscipher items that reached >60% of completion rate were administered to EUSTAR centres via online survey.These items were: DU distal to the proximal interphalangeal joints, recurrent DU, DU history, infection, gangrene, amputation, total number of DU, number of new DU, number of healed DU, number of DU defined as loss of tissue, number of DU due to calcinosis and number of DU due to digital pitting scars (DPS).Questions about feasibility and usefulness of the existing DU classification (DU due to DPS, to loss of tissue, derived from calcinosis and gangrene) (2) and newly proposed DU categorisation (episodic, recurrent and chronic) (3) were also administered. Results All Desscipher and 82/194 EUSTAR centres (42.3%) completed the questionnaire.Out of 27 items selected for the Desscipher study, those scored by>70% of participants as essential and feasible for DU evaluation in clinical practice were only the following: number of DU defined as a loss of tissue (level of agreement 91.1%), recurrent DU (84%) and number of new DU (74.4%).For 64.6% of the centres,the classification of DU was considered useful and feasible in clinical practice.Moreover, 80.3% of the centres preferred the categorization of DU in episodic,recurrent and chronic. Conclusions For clinical practice, EUSTAR centres identified only three essential items for DU evaluation and considered useful and feasible the proposed classification and categorisation of DU.The set of items needs to be further validated by Delphi voting in order to implement its use in clinical practice while further implementation of DU classification and categorisation is warranted. References Suliman Y et al.Preliminary musculoskeletal ultrasound (MSUS) ulcer definition does not correlate with visual observation in systemic sclerosis (SSc) patients. J. Scleroderma Relat. Disord.2017(in press). 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. Matucci-Cerinic M et al.Elucidating the burden of recurrent and chronic digital ulcers in systemic sclerosis: long-term results from the DUO Registry. Ann Rheum Dis. 2016;75:1770–6. Disclosure of Interest None declared

Background Systemic sclerosis (SSc) is characterized by endothelial cell (EC) apoptosis, impaired angiogenesis and peripheral microvasculopathy. Soluble α-Klotho (sKl) is a pleiotropic molecule with multiple effects on ECs, including antioxidant and vasculoprotective activities. On the EC surface, sKl interacts with vascular endothelial growth factor (VEGF) receptor-2 (VEGFR-2) and transient receptor potential canonical-1 (TRPC-1) cation channel to control EC homeostasis. Here, we investigated whether sKl might act as a protective factor to improve angiogenesis in dermal microvascular endothelial cells (MVECs) from SSc patients (SSc-MVECs). Methods Wound healing assay was performed on healthy dermal MVECs (H-MVECs) challenged with sera from healthy controls or SSc patients with or without the addition of sKl. Capillary morphogenesis on Matrigel was assessed in H-MVECs and SSc-MVECs at basal conditions and treated with sKl, as well as in H-MVECs challenged with healthy or SSc sera in presence or absence of sKl. The expression of α-Klotho, VEGF165b, VEGFR-2, TRPC-1, Ki67 and active caspase-3 in H-MVECs and SSc-MVECs was investigated by western blotting. Immunostaining for α-Klotho was performed in H-MVECs and SSc-MVECs, and in healthy and SSc skin sections. Results Treatment with sKl effectively counteracted the inihibitory effects of SSc sera on wound healing ability and angiogenic performance of H-MVECs. The addition of sKl significantly improved angiogenesis and maintained over time capillary-like tube formation in vitro by SSc-MVECs. Stimulation of SSc-MVECs with sKl resulted in the upregulation of the proliferation marker Ki67 in parallel with the downregulation of proapoptotic active caspase-3. The expression of α-Klotho was significantly lower in SSc-MVECs than in H-MVECs. The expression of TRPC-1 was also significantly decreased, while that of VEGFR-2 and VEGF165b was significantly increased, in SSc-MVECs compared with H-MVECs. Challenge with sKl either significantly increased TRPC-1 or decreased VEGF165b in SSc-MVECs. Ex vivo analyses revealed that α-Klotho immunostaining was almost absent in the dermal microvascular network of SSc skin compared with control skin. Conclusions Our findings provide the first evidence that α-Klotho is significantly decreased in the microvasculature in SSc skin and that sKl administration may effectively improve SSc-MVEC functions in vitro by acting as a powerful proangiogenic factor.

Infliximab (IFX) is an anti-tumor necrosis factor-alpha antibody used to treat inflammatory joint diseases. Infusion reactions (IR) can occur during and after intravenous administration and often require discontinuation of IFX therapy. This retrospective study aimed at evaluating the incidence of IR in patients with joint inflammatory diseases receiving IFX with and without premedication. Clinical charts of rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis patients receiving IFX from January 2002 to December 2014 were reviewed. Patients receiving only one premedication protocol over time were enrolled and clustered based on the type of premedication as follows: group 1 received no premedication; group 2 received paracetamol, esomeprazole, hydrocortisone, and chlorpheniramine maleate; group 3 received paracetamol, hydoxyzine, ranitidine, and 6-methylprednisolone. Adverse events were recorded during the infusion, in the following hours and at control visits. The charts of 105 patients treated with IFX were selected. IR were observed in 23/51 patients of group 1, in 7/35 patients of group 2, and none of 19 patients in group 3. IR incidence was significantly lower in the second (p = 0.021) and third (p

Interstitial lung disease (ILD) is a key prognostic factor in connective tissue disorders (CTDs). The aim of our study was to assess the changes in pulmonary functional tests (PFTs) in various CTDs, including anti-synthetase syndrome (SYN), systemic sclerosis (SSc) and mixed connective tissue disorder (MCTD), following the use of rituximab therapy.A multicentre retrospective analysis of patients with ILD secondary to SYN (n=15), MCTD (n=6) and SSc (n=23). PFTs were performed at baseline and at 1 and 2 years of follow-up. The primary outcome was the change in forced vital capacity (FVC) at 1 year.In the SYN population, median FVC changed from 53.0% (42.0-90.0) at baseline to 51.4% (45.6-85.0) at 1 year and 63.0 (50-88) (p=0.6) at 2 years (p=0.14). In SSc, FVC changed from 81.0% (66.0-104.0) at baseline to 89.0% (65.0-113.0) at 1 year (p=0.1) and 74.5 (50-91) at 2 years (p=0.07). In the MCTD population, FVC changed from 64.5% (63.0-68.0) at baseline to 63.0% (59.0-71.0) at 1 year (p=0.6) and 61 (59-71) after 2 years (p=0.8). DLCO showed a trend for improvement in the SYN population (p=0.06 at 1 year and 0.2 at years) while changes remain non-significant in the SSc and MCTD patients. In SYN patients, the percentage of responders at 1 year for FVC (33.3%) was greater than in SSc (9.5%) (p=0.07) and MCTD (17%) (p=0.45). RTX showed a satisfactory safety profile.A trend of improvement of PFTs was observed in SYN patients although not reaching significance, while SSc and MCTD patients were stabilised.

Computer operators are at risk to develop health disorders related to prolonged computer use. We assessed the occupational risk factors for computer-related health disorders and evaluated health conditions of 939 Serbian computer operators. Musculoskeletal (55.8%), ocular (27.3%) and mental disorders (7.1%) were reported most frequently. Risk factors for health disorders, in both male and female populations, were age; overtime work; negative working atmosphere; awkward posture at work; the presence of vibrations, noise, dust and chemical pollution in the workplace. Negative working atmosphere, body mass index > 30, total job tenure and duration of exposed employment were risk factors for developing health disorders only in males, while smoking was a risk factor only in the female population. Our study showed high prevalence of muscu-loskeletal and ocular disorders in Serbian computer operators. More effective preventive measures are necessary to improve computer operators ‘ health.

Pulmonary arterial hypertension (PAH) is an important cause of death in systemic sclerosis (SSc), despite the improvement of therapies. An early diagnosis and the use of drugs interfering with the main pathogenic pathways of PAH is pivotal for the improvement of prognosis in primary PAH and PAH secondary to autoimmune rheumatic diseases, mainly SSc. Lately, new specific therapies have been developed targeting prostacyclin, endothelin, and nitric oxide pathways, the major pathogenic pathways leading to endothelial dysfunction in PAH. Epoprostenol improved life expectancy of patients with primary and secondary PAH, but its continuous intravenous administration requires experienced centers. More stable analogues of prostacyclin, administrated by intravenous (iloprost, treprostinil), subcutaneous, inhalatory (treprostinil, iloprost), and oral route (Beraprost) have shown efficacy in PAH. Bosentan, the first oral endothelin receptor antagonist (with affinity for endothelin A and B receptors) improves exercise function and survival in PAH, both primary and secondary to autoimmune rheumatic diseases. This is confirmed also for Sitaxsentan and Ambrisentan, selective A receptor antagonists. Because of its short half-life and systemic side effects, short-term NO inhalation is used only in short-term management of PAH in critically ill adults. Inhibitors of NO degradation, such as sildenafil, a phosphodiesterase (PDE) type 5 inhibitor, improved functional and hemodynamic parameters without significant side effects. Vardenafil and taladafil, longer-acting PDE inhibitors, also have vascular pulmonary selectivity. All these drugs may be used in combination, to maximize their clinical benefit not only in patients unresponsive to single drugs, but also potentially as initial therapy of PAH.

Increased evidence suggests an accelerated macrovascular disease in systemic sclerosis (SSc). Brachial artery flow-mediated vasodilation (FMD) and carotid intima-media thickness (IMT) are two indicators of subclinic cardiovascular disease and are frequently used as surrogate measures of subclinic atherosclerosis. The aim of this study was to evaluate macrovascular involvement in SSc. We studied 35 SSc patients (6 males and 29 females; 11 with diffuse and 24 with limited disease) and 20 healthy controls. Brachial artery FMD was assessed by method described by Celermajer in all patients and 13 control subjects. IMT was measured using high-resolution B-mode ultrasonography in patients and controls. Traditional risk factors for atherosclerosis (hypertension, dyslipidemia, and smoke) were also assessed. FMD was significantly impaired (3.41% +/- 4.56% versus 7.66% +/- 4.24%; P < 0.037) and IMT was significantly elevated compared with healthy controls (0.93 +/- 0.29 mm versus 0.77 +/- 0.13 mm; P < 0.005). FMD was not significantly different in SSc with increased IMT compared with those with normal IMT). No correlation was found between risk factors for atherosclerosis and the impairment of FMD or IMT in SSc patients. The impairment of endothelial function and structural changes of large vessels are evident in SSc, but do not seem associated with traditional risk factors for atherosclerosis. Prospective studies including also clinical outcomes are needed to assess the features and significance of macrovacular involvement in SSc.

Systemic sclerosis (SSc) is characterized by microvascular and macrovascular alterations. The D allele of the ACE I/D polymorphism is known to be associated with an increased incidence of atherosclerosis and has been recently proposed as associated with increased risk of SSc. This study evaluates the relationship between intima-media thickness (IMT), ankle-brachial pressure measurements (ABPI) and ACE I/D polymorphism in SSc patients.According to the presence of ACE D allele (analysed by PCR), 53 SSc patients (47 females and 6 males; median age was 60.4 +/- 10.68 yrs; range 40-75 yrs) were divided in carriers of the D allele (DD + ID) (n = 46) and carriers of the I allele (II) (n = 7). In these patients, IMT and ABPI [calculated as the posterior tibial artery pressure (mmHg) divided by the brachial pressure] were obtained. Forty-three healthy controls (40 women and 13 men; median age 56.3 +/- 10.23; range 40-70 yrs) of the same ethnicity were recruited.SSc patients had IMT significantly higher than controls (0.85 +/- 0.03 vs 0. 68 +/- 0.01; P0.03). No significant differences (P0.3) in ABPI values between patients (1.018 +/- 0.10) and controls (1.091 +/- 0.11) were found. SSc patients with ACE DD and ID genotype showed an IMT significantly greater (0.89 +/- 0.03) than those carrying the II genotype (0.61 +/- 0.01) (P0.04). ABPI was not different among ACE gene genotypes.Our findings confirm an increased prevalence of macrovascular disease in SSc patients and show that IMT is greater in patients carrying the ACE DD and ID genotype in comparison with II homozygotes. This suggests that, in SSc, the presence of ACE D allele may predispose to an involvement of the macrovascular system.

Introduction The vascular and nervous systems have several anatomic and molecular mechanism similarities. Emerging evidence suggests that proteins involved in transmitting axonal guidance cues, including members of class III semaphorin (Sema3) family, play a critical role in blood vessel guidance during physiological and pathological vascular 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 whether in systemic sclerosis (SSc) Plexin-D1/Sema3E axis could be involved in the dysregulation of vascular tone control and angiogenesis. Methods Sema3E levels were measured by quantitative colorimetric sandwich ELISA in serum samples from 48 SSc patients, 45 subjects with primary Raynaud's phenomenon (pRP) and 48 age-matched and sex-matched healthy controls. Immunofluorescence staining on skin sections from 14 SSc patients and 12 healthy subjects was performed to evaluate Sema3E and Plexin-D1 expression. Western blotting was used to assess Plexin-D1/Sema3E axis in human SSc and healthy dermal microvascular endothelial cells (SSc-MVECs and H-MVECs, respectively) at basal condition and after stimulation with recombinant human vascular endothelial growth factor (VEGF), SSc and healthy sera. Capillary morphogenesis on Matrigel was performed on H-MVECs treated with healthy, pRP or SSc sera in the presence of Sema3E and Plexin-D1 soluble peptides. Results Serum Sema3E levels were significantly higher both in pRP subjects and SSc patients than in controls. In SSc, Sema3E levels were significantly increased in patients with early nailfold videocapillaroscopy (NVC) pattern compared to active/late patterns and pRP, and in patients without digital ulcers versus those with ulcers. In SSc skin, Sema3E expression was strongly increased in the microvascular endothelium. Cultured SSc-MVECs showed higher levels of phosphorylated Plexin-D1 and Sema3E expression than H-MVECs, and stimulation with SSc sera increased phosphorylated Plexin-D1 and Sema3E in H-MVECs. The addition of Sema3E-binding Plexin-D1 soluble peptide significantly attenuated the antiangiogenic effect of SSc sera on H-MVECs. Conclusions Our findings suggest that Plexin-D1/Sema3E axis is triggered in SSc endothelium and may have a role in the dysregulation of angiogenesis and vascular tone control by inducing neuro-vascular mechanism alterations clinically evident in particular in the early disease phases.

Objective To retrospectively analyse the features of calcinosis in a cohort of SSc patients. Methods Charts of SSc patients attending the Ulcer Unit of the Rheumatology Department, University of Florence and presenting a clinical suspicion of calcinosis were considered in the study. Data on clinical history, including recent skin changes, and clinical examination of all areas with suspected calcinosis, radiological imaging of the calcinotic area, demographics and SSc-related organ involvement and pain measured by a visual analogue scale were recorded. Results In 52 of 112 SSc patients, a total of 316 calcinoses were recorded and were divided into visible and palpable {154 [47.4%], clustered according to their macroscopic features as mousse [49 (31.8%)] and stone [: 105 (68.2%)]} and non-visible but palpable {: 162 [52.6%]: net [5 (3%)], plate [22 (13.8%)] and stone [135 (83.2%)]}. The X-ray-based classification of all calcinoses, both visible and non-visible, was as follows: stone, 289 (91.4%); net, 12 (3.8%) and plate, 15 (4.8%). Skin ulcers complicated 154 of 316 calcinoses (48.7%). Mousse calcinosis was associated with pulmonary arterial hypertension, the stone subset was suggestive of pulmonary involvement and justified further investigation and the net subset was the slowest to heal. Conclusion Our data indicate that calcinosis may be classified in SSc as mousse, stone, net and plate according to its clinical and X-ray features. This classification awaits validation for a possible use in clinical practice and to support early treatment and prevention of complications.

Systemic sclerosis (SSc) is a severe autoimmune disease that involves skin and internal organs. Clinical manifestations of SSc are very heterogeneous and derive from microvascular, inflammatory and fibrotic tissue changes. Besides the skin, lung, gastrointestinal tract, heart and kidneys are mainly affected. Over the last years, a progress in the treatment was made, especially in the field of renal involvement and pulmonary hypertension, but prognosis of the disease remains still bad. More efforts are needed to improve the management of organ impairment by early detection and prompt treatment, in order to prevent the development of severe complications.

Objectives In systemic sclerosis (SSc), vascular involvement is characterised by vascular endothelial growth factor (VEGF)-A/VEGF receptor (VEGFR) system disturbances. Neuropilin-1 (NRP1), a receptor for both class-3 semaphorins (Sema3s) and VEGF-A, is required for optimal VEGF-A/VEGFR-2 signalling. Here, we investigated the possible involvement of Sema3A/NRP1 axis in SSc. Methods Circulating Sema3A and soluble NRP1 (sNRP1) were measured in patients with SSc and controls. NRP1 and Sema3A expression in skin biopsies was evaluated by immunofluorescence and western blotting. NRP1 expression was assessed in SSc and healthy dermal microvascular endothelial cells (SSc-MVECs and H-MVECs), and in SSc and control endothelial progenitor cell (EPC)-derived endothelial cells (ECs). The possible impact of transcription factor Friend leukaemia integration 1 (Fli1) deficiency on endothelial NRP1 expression was investigated by gene silencing. The binding of Fli1 to NRP1 gene promoter was evaluated using chromatin immunoprecipitation. Capillary morphogenesis was performed on Matrigel. Results Decreased sNRP1 levels in SSc were associated with active and late nailfold videocapillaroscopy patterns and digital ulcers. No difference in Sema3A was found between patients and controls. NRP1 was significantly decreased in SSc-MVECs both ex vivo and in vitro. NRP1 and Fli1 significantly decreased in H-MVECs challenged with SSc sera, while they were not different in SSc and control EPC-derived ECs. Fli1 occupied the NRP1 gene promoter and Fli1 gene silencing reduced NRP1 expression in H-MVECs. NRP1 gene silencing in H-MVECs resulted in a significantly impaired angiogenic capacity comparable to that of cells treated with SSc sera. Conclusion In SSc, NRP1 deficiency may be an additional factor in the perturbed VEGF-A/VEGFR-2 system contributing to peripheral microvasculopathy and defective angiogenesis.

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 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 In SSc, the management of DU is a problem in clinical practice, therefore their prevention is highly warranted. Sildenafil, iloprost, calcium channel blockers (CCB), ACE inhibitors (ACEi) and bosentan, alone or in combination, are used for DU prevention without unanimous agreement. Objectives DeSScipher (“to decipher the optimal management of SSc”) is an EC-funded FP7 research project that consists of five observational trials (OT) addressing different aspects of SSc. The aim of OT1 was to evaluate the efficacy of vasoactive and vasodilating drugs or a combination therapy for the management of DU in SSc. Methods Longitudinal data were collected for up to 24 months by 28 DeSScipher centres. In SSc patients, the efficacy of sildenafil, bosentan, sildenafil+bosentan, iloprost or CCB /ACEi for the prevention of new DU was evaluated. Clinical features, ulcer type and other drugs were also recorded. Time without new DU, proportion of patients without new DU, risk of developing new DU and the mean number of new DU per patient were evaluated at 6 months follow-up. Results In OT1, 1394 patients were enrolled. The history of DU was a significant risk factor for developing new DU (OR=3.146; (95%CI:1.19–8.31), p=0.021), therefore analysis was focused on secondary prevention (prevention of new DU in patients with DU history). 473/1394 (33.9%) had a history of DU and 268/473 (56.7%) had follow up data (58.2% limited and 41.8% diffuse SSc subset). 47/268 (17.5%) were on Bosentan, 33/268 (12.3%) on Sildenafil, 40/268 (14.9%) on Iloprost, 31/268 (11.6%) on Sildenafil and Bosentan combination and 117/268 (43.7%) on CCB/ACEi alone. In patients with history of DU in the last 24 weeks, the treatment with CCB/ACEi alone was associated with 7 fold increased risk of developing new DU compared to all other treatment arms (OR =7.313; 95%CI:1.248–42.85, p=0.027). Patients on concomitant immunosuppressive treatment had a trend towards faster DU recurrence. Conclusions History of DU in the past 24 weeks should prompt a more aggressive preventive strategy other than therapy with CCB/ACEi alone due to its lower efficacy to prevent DU recurrence compared to the other treatment options. Acknowledgement The DeSScipher project was funded by the European Community9s Framework Programme 7 (FP7-HEALTH-2012.2.4.4–2 - Observational trials in rare diseases) under grant agreement N° 305495. We acknowledge the contribution of the following EUSTAR centers: Ancona (member N°34), Assiut (168), Bad Bramstedt (187), Belgrade (55), Bucharest (100), Cluj-Napoca (16), Erlangen (106), Frankfurt (124), Hamburg (64), Iasi (162), Istanbul (21), Istanbul (133), Koln (44), Monserrato (142), Moscow (78), Moscow (190), Padua (31), Rome (94), Salford/Manchester (80), Tubingen (56), Wuppertal (192). Disclosure of Interest None declared

Background The ELF test and its components (PIIINP, TIMP-1 and HA) have been shown to correlate with skin, lung and overall fibrosis and not with any vascular manifestation of Systemic Sclerosis (SSc) 1 . On the contrary, NT-proBNP has been suggested to be useful for stratification of SSc patients, especially to identify those at risk of pulmonary hypertension 2 . Objectives Aims of this study were: a) to validate ELF score and its single analytes on an independent cohort of scleroderma patients; b) to evaluate whether NT-proBNP could provide additional value to the development of an SSc-specific algorithm. Methods 250 sera from SSc patients from a single UK centre were analysed employing a high-throughput in vitro diagnostic of a routine NHS pathology lab to measure ELF score, its analytes and NT-proBNP levels. All patients fulfilled 2013 ACR/EULAR classification criteria for SSc. Clinical, laboratory and instrumental data were collected at time of sampling. Statistical analysis was performed using SPSS. P Results Multivariate analysis of ELF score (including the variables found statistically significant in univariate analysis) identified age, mRSS and DLCO% as independently associated with ELF score (p Conclusions Our findings validate the value of ELF score in a second independent cohort of 250 SSc sera and suggest that NT-proBNP has a complementary value correlating with other aspects of the disease such as PAH and heart severity. Longitudinal multicentres studies are warranted to determine the sensitivity to change and the predictive value of these biomarkers in SSc patients and to build up a new combined scleroderma specific algorithm including markers of fibrosis and vasculopathy. References Abignano G et al. Ann Rheum Dis 2014 Avouac J et al. Arthritis Care Res 2015 Disclosure of Interest None declared

Objective.Cardiac involvement means a poor prognosis in systemic sclerosis (SSc). Conduction defects and arrhythmias are frequent in patients with SSc, and may result in sudden cardiac death. We tested whether electrophysiologic studies and implantation of cardioverter defibrillators are recommended when ventricular arrhythmias are present.Method.A cardioverter defibrillator was implanted in 10 patients with SSc who had heart involvement.Result.After 36 months, analysis of the device showed several episodes of ventricular tachycardia in 3 patients, which were promptly reverted by electrical shock delivery.Conclusion.In patients with SSc who are affected by ventricular arrhythmias, the implantation of a cardioverter defibrillator may prevent sudden cardiac death.

Autoimmune diseases are characterized by enhanced atherosclerosis. Humoral immune responses to mycobacterial HSP-65, human HSP-60, and to oxLDL have been established in a number of human autoimmune diseases and are considered to be associated with atherosclerosis. The aim of this study was to evaluate carotid artery intima-media thickness (IMT) in patients having systemic sclerosis (SSc) and to find out whether early atherosclerosis is associated with these autoantibodies. Forty-four patients having SSc underwent clinical evaluation and carotid artery IMT measurement. Several autoantibodies were tested among patients and a control group. The antibodies against human HSP-60 were measured by antihuman (IgG/IgM) HSP-60 ELISA kit. IgGs and IgMs antimycobacterial HSP-65 were determined using an ELISA with mycobacterial recombinant HSP-65 antigens. Similarly, anti-oxLDL antibodies were measured by an ELISA kit. Abnormal IMT levels were significantly more common in SSc patients compared with control subjects. Age was found as the sole most significant clinical parameter associated with carotid artery IMT in SSc. Disease duration, type of SSc, lung function tests, and cardiovascular risk factors were not associated with IMT in these patients. Levels of HSP-60, HSP-65, and oxLDL autoantibodies were similar among patients compared with controls, and in patients having "positive" IgM anti-HSP-65, higher IMT values were found. Abnormal carotid IMT is more prevalent in SSc than in normal subjects. Age rather than other clinical parameters is associated with early atherosclerotic changes in SSc. Autoantibodies to oxLDL, HSP-60, and HSP-65 are not elevated in SSc and there is only a borderline association with carotid artery IMT.

Background Patients affected by systemic sclerosis (SSc) develop functional and structural microcirculatory dysfunction, which leads to skin fibrosis initially affecting distal extremity. Recent studies have tested the possibility of evaluating the skin microcirculation of the entire hand and its spatial heterogeneity by means of optical Near-Infrared Spectroscopic (NIRS) of blood HbO2 saturation (stO 2 ). The NIRS-sensitive camera is a non-invasive tissue oxygenation measurement system based on near infrared light. The camera reports and approximates value of stO 2 in superficial tissue. Processing software of the NIRS-camera generates 2D imaging maps automatically in real time. Objectives To test whether NIRS hand imaging may evaluate microcirculatory dysfunction in SSc Methods Forty-two SSc patients (90% women, mean age 55.1±15.6 years) and 18 sex and age-matched healthy controls (86% women, mean age 54.3±14.5 years, p=.89) underwent evaluation of the hand microcirculation by NIRS 2D imaging. A blood pressure cuff was applied to the forearm and 3-min ischemia was induced. Images were acquired at basal conditions at each 10 seconds during 3 minutes of ischemia and during reperfusion condition. Four regions of interest (ROI) were positioned on each fingertip, from the second to the fifth finger. Results A significant difference was found between controls and SSc in basal stO 2 (84.4±9.9 vs 75.9±12.5%, p 2 (65.6±10.2 vs 54.4±10.9%, p 2 (92.4±3.9 vs 86.8±6.6%, p 2 (247±42 vs 277±60 msec, p 2 compared to patients without (78.8±11.7 vs 69.3±12.7, p Conclusions Data show that NIRS hand imaging is a simple, automated promising tool to non-invasively assess the skin microcirculation of the entire hand, which can complement information deriving from nailfold capillaroscopy. Acknowledgements We thank Mr. Gennaro D9Angelo for his technical support. 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 SSc is a vasculopathy characterised by dysregulation of angiogenesis and vascular tone control leading to severe ischemia and loss of capillaries. In the complex system of interconnection between blood vessels and nerves there is an emerging evidence suggesting that proteins involved in transmitting axonal guidance cues, such as class III semaphorins, play a role in the regulation of vascular development. Sema3E has been shown to repel endothelial cells, modulating the cytoskeleton and focal adhesion structures leading to cellular apoptosis. Objectives To investigate if soluble Sema3E could be involved in the dysregulation of vascular tone control in primary Raynaud9s phenomenon (pRP) and in secondary RP investigating (Very Early Diagnosis of Systemic Sclerosis) VEDOSS and SSc patients. Methods Sema3E serum levels were measured by quantitative colorimetric sandwich ELISA in 102 pRP serum samples without autoantibodies positivity and without nailfold videocapillaroscopy (NVC) alterations, 100 SSc, 48 VEDOSS patients and 104 age- and sex-matched healthy controls. SSc and VEDOSS patients were evaluated for internal organ damage. Sema3E levels were expressed as median and range and compared by Mann-Whitney U test. p≤0.05 were considered statistically significant. Results Sema3E levels were significantly increased in pRP (median 1.00 ng/mL, range 0.00-5.84 ng/mL), VEDOSS (median 0.79 ng/mL, range 0.00-1.45 ng/mL) and SSc patients (median 0.85 ng/mL; range 0.00-18.01 ng/mL) versus healthy controls (median 0.55 ng/mL; range 0.00-1.47 ng/mL) (p Conclusions Our data show that Sema3E sera levels are significantly increased in pRP, VEDOSS and SSc patients. Circulating Sema3E levels are higher in SSc patients without digital ulcers and with early NVC pattern. In particular, Sema3E may be involved in the early modifications of neuro-vascular mechanisms leading to dysregulation of vascular tone control. 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

We have previously suggested a model for the eukaryotic genome based on the structure of the bacterial nucleoid where active RNA polymerases cluster to loop the intervening DNA. This organization of polymerases into clusters--which we call transcription 'factories'--has important consequences. For example, in the nucleus of a HeLa cell the concentration of soluble RNA polymerase II is approximately 1 mM, but the local concentration in a factory is 1000-fold higher. Because a promoter can diffuse approximately 100 nm in 15 s, one lying near a factory is likely to initiate; moreover, when released at termination, it will still lie near a factory, and the movement and modifications (e.g. acetylation) accompanying elongation will leave it in an 'open' conformation. Another promoter out in a long loop is less likely to initiate, because the promoter concentration falls off with the cube of the distance from the factory. Moreover, a long tether will buffer it from transcription-induced movement, making it prone to deacetylation, deposition of HP1 (heterochromatin protein 1), and incorporation into heterochromatin. The context around a promoter will then be self-sustaining: productive collisions of an active promoter with the factory will attract factors increasing the frequency of initiation, and the longer an inactive promoter remains inactive, the more it becomes embedded in heterochromatin. We review here the evidence that different factories may specialize in the transcription of different groups of genes.

Musculoskeletal ultrasonography is a routine diagnostic tool in rheumatological practice. The technique has only recently been used to evaluate articular and periarticular structures. In systemic sclerosis, different aspects of hand and wrist involvement have now been described, offering hope for the transfer of ultrasonography for this condition to the clinic.

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 and objectives Systemic Sclerosis (SSc) is an autoimmune connective tissue disease characterised by impairs angiogenesis, alterations of microcirculation, senescence and apoptosis of endothelial cells (ECs). A recent study demonstrated that soluble Klotho (sKl) protein interacts with the vascular endothelial growth factor receptor 2 (VEGFR-2) and with transient receptor potential canonical-1 (TRPC-1) by forming a complex on the surface of endothelial cells. This heterotrimeric complex is internalised in response to vascular endothelial growth factor (VEGF) stimulation, thus regulating VEGFR-2/TRPC-1–mediated Ca 2+ influx, to maintain endothelial biological homeostasis. The aim of this study was to evaluate, if soluble Klotho might act as protective humoral factor on SSc Microvascular Endothelial Cells (MVECs) by inhibiting cellular senescence and inducing angiogenesis. Materials and methods Wound healing capacity was performed in healthy and SSc-MVECs under standard conditions and after sKl stimulation. Angiogenesis was evaluated by in vitro capillary morphogenesis on Matrigel in healthy and SSc-MVECs at basal condition, upon challenge with sKl, SSc and healthy sera, and sKl in combination with SSc and healthy sera. Western blot was performed in order to evaluate TRPC-1 and VEGFR-2 expression level in SSc and healthy MVECs at basal condition, after stimulation with sKl, SSc sera (n = 5), healthy sera (n = 5), and with sKl in combination with SSc and healthy sera before and after wound injury. Results Wound healing capacity significantly increased in healthy and SSc-MVECs after sKl challenge in respect to basal condition. Angiogenesis was significantly higher in SSc-MVECs upon challenge with sKl compared to both basal SSc and healthy MVEC. Moreover, angiogenesis was significantly increased in healthy MVECs challenged with SSc sera in combination with sKl respect to MVECs with SSc sera alone. TRPC-1 and VEGFR-2 expression level significantly increased under injury in both healthy and SSc-MVECs cultured with sKl respect to basal condition. Conclusions Our findings suggest that, under vascular injury conditions, sKl increases the wound healing ability and induces blood vessels formation in SSc-MVECs.

Background In systemic sclerosis (SSc) vascular involvement is a primary event characterized by vascular tone dysfunction and increased circulating levels of vascular endothelial growth factor (VEGF). Neuropilin-1 (NRP1) is a receptor for both class-3 semaphorin (sema) family of axon guidance molecules and VEGF. NRP1 is required for optimal VEGF/VEGFR-2 signaling, and NRP1-deficient mice exhibit vascular defects including disorganized blood vessels, lack of normal branching and missing capillary networks. Sema3a controls physiological and pathological angiogenesis. Objectives In the present study, we investigated the possible involvement of sema3a/NRP1 axis in SSc and its correlation to nailfold videocapillaroscopy (NVC) patterns and digital ulcers. Methods Soluble NRP1 (sNRP1) and sema3a levels were measured by quantitative colorimetric sandwich ELISA in serum samples from SSc patients (n=49) and age- and sex-matched healthy controls (n=39). Patients were classified according to NVC patterns (early, active and late). NRP1 and sema3a protein expression was evaluated by immunofluorescence and western blot in skin biopsies from SSc patients (n=10) and healthy controls (n=8). NRP1 expression was also evaluated in human dermal microvascular endothelial cells from SSc patients (SSc-MVECs) and healthy controls (H-MVECs) at basal level, and in H-MVECs after stimulation for 24 hours with recombinant human VEGF165 (10 ng/ml), SSc sera (n=3) and healthy sera (n=3). Results Circulating sNRP1 levels were significantly reduced in SSc patients (median 0.22 ng/ml) compared with healthy controls (median 0.69 ng/ml) (p=0.005). In particular, sNRP1 levels were significantly lower in either SSc patients with active or late NVC patterns than in controls (both p Conclusions NRP1 expression is significantly decreased in SSc, and lower sNRP1 levels correlate with the severity of nailfold capillary modifications and presence of digital ulcers. NRP1 might play a role in the vascular damage and in the impairment of the angiogenic process in SSc. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.3662

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