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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.

ObjectivesThe aim of this study was to adapt the Systemic Sclerosis Quality of Life Questionnaire (SScQoL) into six European cultures and validate it as a common measure of quality of life in systemic sclerosis (SSc).MethodsThis was a seven-country (Germany, France, Italy, Poland, Spain, Sweden and UK) cross-sectional study. A forward–backward translation process was used to adapt the English SScQoL into target languages. SScQoL was completed by patients with SSc, then data were validated against the Rasch model. To correct local response dependency, items were grouped into the following subscales: function, emotion, sleep, social and pain and reanalysed for fit to the model, unidimensionality and cross-cultural equivalence.ResultsThe adaptation of the SScQoL was seamless in all countries except Germany. Cross-cultural validation included 1080 patients with a mean age 58.0 years (SD 13.9) and 87% were women. Local dependency was evident in individual country data. Grouping items into testlets corrected the local dependency in most country specific data. Fit to the model, reliability and unidimensionality was achieved in six-country data after cross-cultural adjustment for Italy in the social subscale. The SScQoL was then calibrated into an interval level scale.ConclusionThe individual SScQoL items have translated well into five languages and overall, the scale maintained its construct validity, working well as a five-subscale questionnaire. Measures of quality of life in SSc can be directly compared across five countries (France, Poland Spain, Sweden and UK). Data from Italy are also comparable with the other five countries although require an adjustment.

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

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

Background Hemodynamic assessment during exercise may unmask an impaired functional reserve of the right ventricle and the pulmonary vasculature in patients with connective tissue disease. We assessed the effect of intravenous sildenafil on the hemodynamic response to exercise in patients with connective tissue disease. Methods In this proof-of-concept study, patients with connective tissue disease and mean pulmonary arterial pressure (mPAP) >20 mm Hg were subjected to a supine exercise hemodynamic evaluation before and after administration of intravenous sildenafil 10 mg. Results Ten patients (four with moderately elevated mPAP 21–24 mm Hg; six with mPAP >25 mm Hg) underwent hemodynamic assessment. All of them showed markedly abnormal exercise hemodynamics. Intravenous sildenafil was well tolerated and had significant hemodynamic effects at rest and during exercise, although without pulmonary selectivity. Sildenafil reduced median total pulmonary resistance during exercise from 6.22 (IQR 4.61–8.54) to 5.24 (3.95–6.96) mm Hg·min·L-1 (p = 0.005) and increased median pulmonary arterial capacitance during exercise from 1.59 (0.93–2.28) to 1.74 (1.12–2.69) mL/mm Hg (p = 0.005). Conclusions In patients with connective tissue disease who have an abnormal hemodynamic response to exercise, intravenous sildenafil improved adaption of the right ventricular-pulmonary vascular unit to exercise independent of resting mPAP. The impact of acute pharmacological interventions on exercise hemodynamics in patients with pulmonary vascular disease warrants further investigation. Trial registration Clinicaltrials.gov NCT01889966.

Hintergrund Medikamentöse Therapiestrategien zur Behandlung der rheumatoiden Arthritis sind entscheidend für den Langzeitverlauf. Sie dienen dem Ziel, durch frühe und konsequente Unterdrückung der Entzündung Gelenkzerstörung zu verhindern und damit die Funktion zu erhalten. Ziel der Arbeit Erarbeitung eines Konsenses für evidenzbasierte Empfehlungen zur Behandlung der rheumatoiden Arthritis mit krankheitsmodifizierenden Medikamenten in Deutschland. Methoden Nach einer systematischen Literatursuche wurde ein strukturierter Konsensprozess durchgeführt. Ergebnisse Sechs übergeordnete Prinzipien und 10 Empfehlungen fassen die Ergebnisse des Konsensprozesses zusammen. Verschiedene Punkte sind gegenüber der Fassung von 2012 neu, so die differenzierte Anpassung des Therapieregimes nach Zeitpunkt und Ausmaß des Ansprechens, das Therapieziel Remission gemessen mithilfe des simplified disease activity index (SDAI) wie auch der potentielle Einsatz zielgerichteter synthetischer DMARDs (tsDMARDs), der JAK-Inhibitoren sowie Empfehlungen zur Deeskalation nach dem Erreichen einer anhaltenden Remission. Wie bisher steht Methotrexat (MTX) im Mittelpunkt der Therapie zu Beginn und als Kombinationspartner im weiteren Verlauf. Die Kombination mehrerer konventioneller synthetischer DMARDs, oder, bei ungünstigen prognostischen Faktoren, der Einsatz von biologischen oder tsDMARDs kommen nach dem Algorithmus bei nicht ausreichendem Ansprechen auf Methotrexat zur Anwendung. Empfehlungen für die Deeskalation der Therapie mit Glukokortikoiden und konsekutiv gegebenenfalls auch DMARDs geben Hilfe für den Umgang mit Patienten, die eine anhaltende Remission erreicht haben. Zusammenfassung Die neue S2-Leitlinie gibt Empfehlungen für die Therapie der RA nach dem Prinzip des ""Treat-to-Target"" (T2T) mit etablierten und neuen krankheitsmodifizierenden Medikamenten (DMARDs), einschließlich der Biologika und JAK-Inhibitoren und macht Vorschläge zur Deeskalation nach Erreichen einer anhaltenden Remission.

Objective.Vasculopathy is a key factor in the pathophysiology of systemic sclerosis (SSc) and the main cause for Raynaud phenomenon (RP), digital ulcers (DU), and/or pulmonary arterial hypertension (PAH). It is so far unknown how patients with SSc are treated with vasoactive agents in daily practice. To determine to which extent patients with SSc were treated with different vasoactive agents, we used data from the German Network for Systemic Scleroderma registry.Methods.The data of 3248 patients with SSc were analyzed.Results.Patients were treated with vasoactive drugs in 61.1% of cases (1984/3248). Of these, 47.6% received calcium channel inhibitors, followed by 34.2% treated with angiotensin-converting enzyme (ACE) inhibitors, 21.1% treated with intravenous (IV) prostanoids, 10.1% with pentoxifylline, 8.8% with angiotensin 1 receptor antagonists (AT1RA), 8.7% with endothelin 1 receptor antagonists (ET1RA), 4.1% with phosphodiesterase type 5 (PDE5) inhibitors, and 5.3% with others. Patients with RP received vasoactive therapy in 63.3% of cases, with DU in 70.1%, and with PAH in 78.2% of cases. Logistic regression analysis revealed that patients with PAH were significantly more often treated with PDE5 inhibitors and ET1RA, and those with DU with ET1RA and IV prostanoids. In addition, 41.8% of patients were treated with ACE inhibitors and/or AT1RA. Patients registered after 2009 received significantly more often ET1RA, AT1RA, and IV prostanoids compared with patients registered prior to 2005.Conclusion.These data clearly indicate that many patients with SSc do not yet receive sufficient vasoactive therapy. Further, in recent years, a marked change of treatment regimens can be observed.

Background Interstitial lung disease in systemic sclerosis (SSc-ILD) is a major cause of SSc-related death. Imunosuppressive treatment (IS) is used in patients with SSc for various organ manifestations mainly to ameliorate progression of SSc-ILD. Data on everyday IS prescription patterns and clinical courses of lung function during and after therapy are scarce. Methods We analysed patients fulfilling American College of Rheumatology (ACR)/European League against Rheumatism (EULAR) 2013 criteria for SSc-ILD and at least one report of IS. Types of IS, pulmonary function tests (PFT) and PFT courses during IS treatment were evaluated. Results EUSTAR contains 3778/11,496 patients with SSc-ILD (33%), with IS in 2681/3,778 (71%). Glucocorticoid (GC) monotherapy was prescribed in 30.6% patients with GC combinations plus cyclophosphamide (CYC) (11.9%), azathioprine (AZA) (9.2%), methotrexate (MTX) (8.7%), or mycophenolate mofetil (MMF) (7.3%). Intensive IS (MMF + GC, CYC or CYC + GC) was started in patients with the worst PFTs and ground glass opacifications on imaging. Patients without IS showed slightly less worsening in forced vital capacity (FVC) when starting with FVC 50–75% or >75%. GC showed negative trends when starting with FVC

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

BackgroundValidity of European Scleroderma Study Group (EScSG) activity indexes currently used to assess disease activity in systemic sclerosis (SSc) has been criticised.MethodsThree investigators assigned an activity score on a 0–10 scale for 97 clinical charts. The median score served as gold standard. Two other investigators labelled the disease as inactive/moderately active or active/very active. Univariate–multivariate linear regression analyses were used to define variables predicting the ‘gold standard’, their weight and derive an activity index. The cut-off point of the index best separating active/very active from inactive/moderately active disease was identified by a receiver-operating curve analysis. The index was validated on a second set of 60 charts assessed by three different investigators on a 0–10 scale and defined as inactive/moderately active or active/very active by other two investigators. One hundred and twenty-three were investigated for changes over time in the index and their relationships with those in the summed Medsger severity score (MSS).ResultsA weighted 10-point activity index was identified and validated: Δ-skin=1.5 (Δ=patient assessed worsening during the previous month), modified Rodnan skin score (mRss) >18=1.5, digital ulcers=1.5, tendon friction rubs=2.25, C-reactive protein >1 mg/dL=2.25 and diffusing capacity of the lung for CO (DLCO) % predicted ConclusionsA preliminarily revised SSc activity index has been developed and validated, providing a valuable tool for clinical practice and observational studies.

Objectives: The multisystem manifestations of SSc can greatly impact patients' quality of life. The aim of this study was to identify factors associated with disability in SSc. Methods: SSc patients from the prospective DeSScipher cohort who had completed the scleroderma health assessment questionnaire (SHAQ), a disability score that combines the health assessment questionnaire and five visual analogue scales, were included in this analysis. The effect of factors possibly associated with disability was analysed with multiple linear regressions. Results: The mean SHAQ and HAQ scores of the 944 patients included were 0.87 ( s . d . = 0.66) and 0.92 ( s . d . = 0.78); 59% of the patients were in the mild to moderate difficulty SHAQ category (0 ⩽ SHAQ < 1), 34% in the moderate to severe disability category (1 ⩽ SHAQ < 2) and 7% in the severe to very severe disability category (2 ⩽ SHAQ ⩽ 3). The means of the visual analogue scales scores were in order of magnitude: overall disease severity (37 mm), RP (31 mm), pulmonary symptoms (24 mm), gastrointestinal symptoms (20 mm) and digital ulcers (19 mm). In multiple regression, the main factors associated with high SHAQ scores were the presence of dyspnoea [modified New York Heart Association (NYHA) class IV (regression coefficient B = 0.62), modified NYHA class III (B = 0.53) and modified NYHA class II (B = 0.21; all vs modified NYHA class I)], FM (B = 0.37), muscle weakness (B = 0.27), digital ulcers (B = 0.20) and gastrointestinal symptoms (oesophageal symptoms, B = 0.16; stomach symptoms, B = 0.15; intestinal symptoms, B = 0.15). Conclusion: SSc patients perceive dyspnoea, pain, digital ulcers, muscle weakness and gastrointestinal symptoms as the main factors driving their level of disability, unlike physicians who emphasize objective measures of disability.

Dank der vielen neuen Erkenntnisse uber das Erkrankungsbild der systemischen Sklerose und den Fortschritten in der Diagnostik der vergangenen Jahre kann die Diagnose in immer fruheren Krankheitsstadien gestellt werden. In diesem Artikel mochten wir die Entwicklung der Diagnose- und Klassifikationskriterien uber die letzten Jahrzehnte darstellen, beginnend bei den vorlaufigen ARA-Klassifikationskriterien 1980 uber die Kriterien von LeRoy et al. 1988 und 2001, bis hin zu den neuen ACR/EULAR-Kriterien 2013. Des Weiteren greifen wir die Diskussion uber den sog. Intermediartyp der systemischen Sklerose auf und behandeln die Sonderformen CREST-Syndrom und systemische Sklerose ohne Sklerodermie. Abschliesend blicken wir auf die Entwicklung der Kriterien zur „very early diagnosis“ der systemischen Sklerose (VEDOSS), behandeln die Frage des richtigen Zuweisungszeitpunkts zum Rheumatologen und erlautern mogliche Fruhwarnsymptome in der taglichen Praxis.

Aufgrund der verbesserten diagnostischen Moglichkeiten der letzten Jahrzehnte kann heute die Erkrankung der systemischen Sklerose (SSc) in immer fruheren Erkrankungsstadien diagnostiziert werden. Mit der Fruhdiagnose der Erkrankung ergeben sich fur den Rheumatologen gleichzeitig neue Herausforderungen im klinischen Alltag. In diesem Artikel wird das therapeutische Management der systemischen Sklerose mit einem Schwerpunkt auf die Fruhstadien der Erkrankung erlautert. Diagnostik und Therapie fruher Symptome, wie dem Raynaud-Phanomen, „puffy fingers“, digitalen Ulzerationen, Calcinosis cutis sowie einer fruhen kardiopulmonalen, nephrologischen oder gastrointestinalen Beteiligung, werden diskutiert. Abschliesend werden Moglichkeiten und Grenzen der fruhen immunmodulatorischen Therapie und autologen Stammzelltransplantation fur Patienten mit einem rasch progressiven und schweren Verlauf der Erkrankung besprochen.

Raynaud’s phenomenon (RP) can occur as benign, usually primary, RP. By contrast, complex RP is mainly secondary and can be caused by severe, chronic diseases such as systemic sclerosis. This article mainly reviews treatment opportunities for secondary RP, but also refers to primary RP wherever evidence is at hand. The main focus is on drugs recommended by expert panels or research consortia, such as the European League Against Rheumatism Scleroderma Trials and Research (EUSTAR) group. In addition, this review intends to provide a comprehensive overview of the different therapeutic approaches that have been tested in RP to date, some with more impact versus others with less impact. Thereby, conclusions about the pathogenesis of RP can be drawn, which can guide future clinical trials and research.

Objectives Myocardial manifestations of systemic sclerosis are mainly due to fibrotic remodeling. We report on two cases, where an endocardial and myocardial inflammation may be a relevant component of cardiac disease. Case series Case 1 presented with fulminant tricuspid failure in the absence of pulmonary hypertension and with newly developing systemic sclerosis. Myocardial biopsy and MRI supported endocardial and myocardial inflammation. Treatment with cyclophosphamide resulted in stabilization of cardiac function and normalization of cardiac enzymes. The patient died due to infectious complications. Case 2, also newly developed systemic sclerosis, presented with renal crisis and pulmonary alveolitis. Elevated cardiac troponin T persisted in the presence of cyclophosphamide treatment, subsequent MRI suggested myocardial inflammation. After stepping up treatment by addition of rituximab cardiac enzymes normalized and cardiac function stabilized. Conclusion We hypothesize that low-grade endocardial and myocardial inflammation may be more relevant in systemic sclerosis than appreciated previously.

Seit Beginn der Ara der biologischen Praparate weis man, dass Tuberkulose eine potenziell lebensbedrohliche Komplikation bei der Behandlung von Patienten mit rheumatischen Erkrankungen darstellt. Nationale und internationale Gesellschaften haben Empfehlungen fur das Tuberkulosescreening herausgegeben und fur die Behandlung von Tuberkuloserisikopatienten. Aufgrund der relativen Seltenheit offener Tuberkulose bei Patienten mit rheumatischen Erkrankungen ist die Erfahrung einzelner Rheumatologen mit dieser Komplikation begrenzt. Daher haben wir die Tuberkulosefalle in unserem Rheumazentrum (mit Behandlung von uber 1500 stationaren und 8000 ambulanten Fallen pro Jahr) von 2006–2011 ausgewertet, um mehr als 10 Jahre nach Beginn der ersten Anwendung von Biologika auserhalb kontrollierter klinischer Studien ein lebensnahes Bild zu erhalten. Wir fanden 4 Falle, anhand derer sich die Schwierigkeiten von Diagnose und Therapie zeigen.

Objective: Qualitative capillaroscopy patterns in juvenile- and adult-onset systemic sclerosis (SSc) were studied in adulthood using data from the EULAR Scleroderma Trials and Research (EUSTAR) database. Methods: Data collected between June 2004 and April 2013 were examined with focus on capillaroscopy. In this retrospective exploratory study, series of patients with juvenile-onset SSc were matched with series of adult-onset SSc having the same gender and autoantibody profile. Results: 30 of 123 patients with juvenile-onset and 2108 of 7133 with adult-onset SSc had data on capillaroscopy. Juvenile-onset SSc showed scleroderma pattern more frequently than adult-onset SSc (93.3% and 88%). The OR was 2.44 and 95% Cl 0.57-10.41. An active scleroderma pattern was present in 58% of juvenile- and 61% of adult-onset SSc. The OR was 0.91 and 95% Cl 0.28-2.93. The late scleroderma pattern was present in 61% of juvenile- and 55.5% of adult-onset SSc. The OR was 1.06 and 95% Cl 0.34-3.56. Conclusion: This is the first exploratory study on the comparison of capillaroscopy between juvenile- and adult-onset SSc in adulthood. Juvenile-onset SSc had an increase prevalence of sderoderma pattern, but a similar distribution of the three patterns was suggested. Further studies are needed to define this issue. (C) 2015 Elsevier Inc. All rights reserved.

Osteonecrosis of the lunate bone, also known as Kienbock’s disease, is a very rare disease of unknown cause. Until today, only six cases of osteonecrosis of the lunate bone in patients with systemic sclerosis (SSc) have been reported in the literature. It is unknown whether these few cases reflect only a coincidence of two rare diseases or whether osteonecrosis of the lunate bone is a potential currently underestimated disease-associated feature of SSc. In this study, we report the clinical course of nine SSc patients with magnetic resonance imaging proven osteonecrosis of the lunate bone and discuss associated disease characteristics and potential underlying pathophysiological mechanisms. Overall, our observations suggest that osteonecrosis of the lunate bone is a frequent and so far under-recognized manifestation of SSc which might be linked to SSc-related vasculopathy. It is important to distinguish osteonecrosis of the lunate bone from wrist arthritis in SSc patients because the clinical treatment is different. In general, the clinical progression of osteonecrosis of the lunate bone seems to be slow in SSc patients. As most of the patients have only minor complaints, watchful waiting in combination with analgesic therapy seems to be a feasible treatment approach in most patients whether an operative intervention might be necessary in rapid progressive cases.

Rheumatoid arthritis is a common autoimmune disease primarily manifesting as chronic synovitis, subsequently leading to a change in joint integrity. Progressive disability and systemic complications are strongly associated with a decreased quality of life. To maintain function and health in patients with rheumatoid arthritis, early, aggressive and guided immunosuppressive therapy is required to induce clinical remission. Antirheumatic drugs are capable of controlling synovial inflammation and are therefore named ‘disease-modifying antirheumatic drugs’ (DMARDs). This article aims to bridge the beginning of DMARD therapy with agents such as methotrexate, leflunomide, sulfasalazine, injectable gold and (hydroxy)chloroquine with biological therapies, and with the new era of kinase inhibitors. Mechanisms of action, as well as advantages and disadvantages of DMARDs, are discussed with respect to the current literature and current recommendations.

Introduction The objective of this cross-sectional and retrospective cohort study was (1) to determine the usefulness of intima-media thickness (IMT) in contrast to plaque assessment, (2) to examine the value of additive femoral artery sonography and (3) to identify potential risk factors for atherosclerosis and incident cardiovascular events in systemic sclerosis (SSc) and systemic lupus erythematosus (SLE) patients. Methods In this study, 90 SSc and 100 SLE patients were examined by duplexsonography. IMT was measured in common carotid and common femoral arteries, plaques were assessed in common, internal and external carotid and common, proximal superficial and deep femoral arteries. Different definitions of pathological IMT (pIMT) were compared with the presence of plaque. Results were evaluated in relation to traditional and non-traditional risk factors for baseline atherosclerosis (logistic regression) and their predictive value for cardiovascular events during follow-up (cox regression). Results Definite atherosclerosis occurred frequently without signs of subclinical atherosclerosis in both diseases: pIMT >0.9 mm was present in only 17/59 (28.9%) SSc and 13/49 (26.5%) SLE patients with already present atherosclerotic plaques. Using age-adjusted pIMT definitions, this rate was even lower (5.1-10.3% in SSc, 14.3-26.5% in SLE). Plaques were located only at the carotid or only at the femoral arteries in 26 (13.7%) and 24 (12.6%) patients, respectively. Age and nicotine pack-years were independently associated with atherosclerotic plaques in SLE and SSc patients, as well as the cumulative prednisolone dose in SSc subgroup, and ssDNA positive SLE patients had a lower risk for atherosclerotic plaque. During follow-up (available for 129/190 (67.9%) patients, 650 person-years), cardiovascular events occurred more often in patients with coronary heart disease (adjusted-hazards ratio (HR) 10.19, 95% confidence interval (CI) 3.04 to 34.17, P

Background Systemic sclerosis (SSc) is a heterogeneous multisystem connective tissue disease, usually subdivided into the main SSc subsets, e.g. limited (lcSSc), diffuse SSc (dcSSc) and SSc overlap syndromes. However, some patients present with symptoms suggestive of, but not conclusive for a diagnosis of definite SSc. This subset has been referred to as undifferentiated or very early SSc. It was defined as positive RP together with at least one further feature of SSc and/or detectable SSc-specific autoantibodies. Objectives Methods Up to date, more than 3400 patients have been registered within the German network for systemic scleroderma. Disease progress after initial patient registration and further follow-up visits was analysed to determine, whether clinical features in patients with undifferentiated SSc change over time into definite SSc. Results Among 3473 registered patients, 8.1% (282/3473) were diagnosed with undifferentiated SSc. Of these, 87.5% were female with a mean age at onset of 59.9±1.5years. A significant difference was detectable comparing patients with undifferentiated SSc and lcSSc (54.8±0.5years; p 34.0% of undifferentiated SSc patients suffered from sicca symptoms, followed by 31.2% with gastrointestinal (GI) involvement, 30.5% with musculoskeletal involvement, 14.5% with lung fibrosis, 6.0% with heart involvement, 5.0% with pulmonary arterial hypertension (PAH) and 0.4% with renal crisis. Musculoskeletal involvement, sicca symptoms and heart involvement were found in a similar percentage in patients with undifferentiated and lcSSc. Lung fibrosis, PAH and GI involvement occurred significantly less in patients with undifferentiated SSc compared to lcSSc. Within a mean follow-up time of 3.6years, the majority of the patients classified initially as undifferentiated SSc, remained within this subset (76.6%), while only 16.3% converted into lcSSc. 4.6% were classified as dcSSc and 3.2% as SSc overlap syndromes. Conclusions Patients classified as undifferentiated SSc, develop clinical features suggestive of SSc at a significantly older age than other subsets (i.e. 5–10 years). During follow up progression into a limited, diffuse or SSc overlap syndrome subset was observed, however, the majority of undifferentiated SSc patients remained stable and did not develop definite SSc. 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 Patient reported outcome measures (PROM) are required as key outcomes in disease modifying therapeutic trials in systemic sclerosis (SSc) and could also improve the clinical care of patients with SSc. A PROM tool for clinical trials and practice in SSc, covering the different features of this multi-organ autoimmune disease, is lacking. Objectives To develop and validate a brief, disease-specific, patient-derived, composite disease impact score for scientific and clinical use in SSc. Methods This multi-center project involves SSc patients and experts from 11 European countries. Firstly, using the nominal group technique, patients with SSc selected the health dimensions where the disease has the most significant impact. The dimensions were subsequently given numeric priority by an international group of SSc patients. The dimensions with the top 10 median ranks, as ranked by the patients, were used to construct the ScleroID questionnaire using numeric rating scales. Further, the dimensions are currently weighted by distributing 100 points among the dimensions by a larger cohort of patients from all participating countries. The calculation of the score will be based on the ranking of the weights. Results 24 SSc patients selected 17 health dimensions in the nominal group exercise. The prioritization cohort included 108 SSc patients from 11 centers (female:male 82:25, limited:diffuse SSc subset 53:54). The top 10 health dimensions which were ranked most relevant by the patients were Raynaud9s phenomenon, hand function, upper and lower gastrointestinal tract symptoms, pain, fatigue, limitation of life choices and activities, body mobility, breathlessness and digital ulcers (Figure 1). Conclusions The EULAR ScleroID score is a novel tool under development designed for use in clinical practice and clinical trials to display the disease impact of SSc. Further validation of this new instrument will be performed as soon as the weighting procedure is completed. Acknowledgement Contributing patients: Yanne Perriault, Susanne Tuppeck, Helene Kambourakis, Elisabeth Scheel, Stephan Houbertz, Anna Vegh, Beata Garay Toth, Barbara Zappitello, Grazia Tassini, Silvia Sandulescu, Ana Marcela Badea, Stefana Dumitru, Rachida Amrouch, Alicia Garcia Oliva, Begona Maria Gorricho Corta, Heleen Lever, Johanna Berglind, Mervat Gaafar, Natalie Perruchoud, Alice Martins Correia, Richard Dodds, Nicola Whitehill. Disclosure of Interest R. Dobrota: None declared, M. Becker: None declared, K. Fligelstone: None declared, J. Fransen: None declared, A. Kennedy: None declared, Y. Allanore Grant/research support from: Bristol-Myers Squibb, Roche/Genentech, Inventiva, Pfizer, Sanofi, and Servier, Consultant for: Actelion, Bayer, Roche/Genentech, Inventiva, Medac, Pfizer, Sanofi, Servier, and UCB, P. Carreira: None declared, L. Czirijak: None declared, C. Denton: None declared, R. Hesselstrand: None declared, G. Sandqvist: None declared, O. Kowal-Bielecka: None declared, M. Matucci-Cerinic: None declared, C. Mihai: None declared, A. Gheorghiu: None declared, U. Muller-Ladner: None declared, M. Frerix: None declared, T. Heiberg: None declared, O. Distler Grant/research support from: Bayer, Sanofi, Ergonex, Boehringer Ingelheim, Actelion, Pfizer, Consultant for: 4 D Science, Actelion, Active Biotec, Bayer, BiogenIdec, BMS, Boehringer Ingelheim, EpiPharm, Ergonex, espeRare foundation, Genentech/Roche, GSK, Inventiva, Lilly, medac, MedImmune, Pharmacyclics, Pfizer, Serodapharm, Sinoxa

Background Systemic sclerosis (SSc) can greatly impact the patients9 quality of life due to the multisystem manifestations. The health assessment questionnaire (HAQ) is one of the most commonly used measures of disability in musculoskeletal disorders and was extended to form the scleroderma HAQ (SHAQ), a more disease-specific disability scale that incorporates the HAQ and the 5 SHAQ-visual analogue scales (VAS) into one score. Objectives This study aims to identify predictors of disability in SSc by means of the SHAQ. Methods Patients from the DeSScipher cohort were included in the analysis if they had at least one complete SHAQ recorded, fulfilled either the 1980 ACR or the 2013 ACR/EULAR criteria for SSc and were above 18 years of age. Multiple linear regression analysis was used to assess the combined effect of factors possibly associated with disability. Variables included in the model were defined a priori. Results 813 patients had one complete SHAQ recorded between June 2013 and January 2016 (34.1% of all patients followed in the DeSScipher cohort). Of these, 12% fulfilled only the 2013 ACR/EULAR criteria, 2% fulfilled only the 1980 ACR criteria and 86% fulfilled both, the median age was 58 years (IQR 49–67) and 15% were male. 26% of the patients were in the diffuse SSc subset, 56% in the limited and 18% had SSc sine sclerosis. The patients had a median SHAQ score of 0.79 (IQR 0.28–1.31) and a median HAQ score of 0.88 (IQR 0.25–1.5). The medians of the five VASs included in the SHAQ were (in order of the VAS magnitude): overall disease severity (30, IQR 10–51), Raynaud9s phenomenon (21, IQR 3–50), pulmonary symptoms (10, IQR 1–40), gastrointestinal symptoms (6, IQR 1–31) and digital ulcers (2, IQR 1–30). 60% of the patients were in the lowest SHAQ category (score of 0 to 1) which is regarded as “mild to moderate difficulty”, 34% in the category regarded as “moderate to severe disability” (score of 1 to 2) and 6% in the category regarded as “severe to very severe disability” (score of 2 to 3). In multiple linear regression, the main factors associated with high SHAQ scores were dyspnoea (NYHA-stage 4 (β=0.67), 3 (β=0.59) and 2 (β=0.18; all vs. stage 1), fibromyalgia (β=0.42), muscle weakness (β=0.25), current digital ulcers (β=0.20) and gastrointestinal symptoms (oesophageal symptoms, β=0.18; stomach symptoms, β=0.14; intestinal symptoms, β=0.14; figure). Conclusions Patients perceive dyspnoea, pain, digital ulcers, muscle weakness and gastrointestinal symptoms as the main factors driving their level of disability. 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 centres: Moscow(78), Padova(31), Istanbul(133), Wuppertal(192), Monserrato(142), Roma(94), Cologne(44), Cluj-Napoca(16), Ancona(34), Iasi(162), Frankfurt(124). Disclosure of Interest None declared

Background The Systemic Sclerosis Quality of Life (SScQoL) questionnaire is a 29-item tool developed in UK to measure needs-based patient-reported quality of life in people with systemic sclerosis (SSc). Objectives To undertake a cross-cultural adaptation and validation of the SScQoL in six European countries. Methods This was a cross-sectional study involving six European countries: Germany, France, Italy, Spain, Sweden and UK. Adult patients with a definite diagnosis of SSc, who were willing and able to complete the SScQoL were eligible. The English SScQoL was adapted into the five European languages using a forward-backward translation process. 1 The translated SScQoL was completed by patients and the data was analysed using Rasch models. Where local response dependency was evident, items were grouped into subscales (function, emotion, sleep, social and pain) and re-analysed to test the scaling properties and cross-cultural equivalence, thus allowing calibration of the SScQoL into an interval scale. Results The adaptation of the SScQoL into European languages was seamless except in Germany, where patients reported problems in deciding yes/no responses for some items. Cross-cultural validation included 849 patients (mean age =57.9 years, SD =13.9), 87% of whom were women. All country-specific data except Germany had good fit to the Rasch model after correcting for local dependency. See table 1. After excluding Germany from the analysis, the scale was validated and calibrated with cross-cultural adjustment for Italy in the social subscale. Conclusions The SScQoL translated versions can be used as a valid common measure in France, Spain, Sweden, UK and Italy; the latter with adjustments in the social subscale. The German version requires further work. References Beaton DE, et al. Guidelines for the process of cross-cultural adaptation of self-report measures. Spine. 2000;25(24):3186–91. Disclosure of Interest None declared

Severe axial and peripheral involvement in HLA-B27-negative psoriatic arthritis (PsA) remains very rare. In 2011, an 82-year-old woman who had had PsA since 1973 was referred to our department. She had plaque psoriasis at elbows, knees, and scalp since 1972, and the first diagnosis of PsA was in 1973. In 1974, she received 15 injections with gold-sodium thiomalate, but this was terminated because of lack of efficacy. In 1978, …

Objectives. To assess the prevalence and risk factors of ulnar artery occlusion (UAO) in an unselected SSc patient cohort and to determine whether UAO is associated with digital ulcers (DUs). Methods. A total of 79 SSc patients and 40 ‘healthy’ controls underwent colour duplex sonography of the radial and ulnar artery to compare blood flow velocity, resistive indices (RIs) and presence of occlusion and were followed for a mean of 53 months. Results. In both, radial and ulnar arteries, peak systolic velocity (PSV) and end-diastolic velocity (EDV) were significantly lower and RI higher in SSc patients compared with controls (PSVrad: 40.1 vs 48.6 cm/s; PSVuln 38.2 vs 56.6 cm/s; EDVrad 3.8 vs 10.4 cm/s; EDVuln 3.0 vs 13.0 cm/s; RIrad 0.91 vs 0.82; RIuln 0.92 vs 0.80; all P < 0.01). Seventeen (21.5%) SSc patients had UAO (11 patients bilateral) compared with none in the control subjects. Patients with UAO had a significantly longer disease duration (170 vs 66 months, P < 0.001). At baseline, the prevalence of DU was not different in upper extremities with UAO [8/28 (28.6%)] compared with upper extremities without UAO [36/129 (27.9%)]. However, during follow-up new or recurrent DU occurred more often in upper extremities with UAO than in those without UAO [14/28 (50%) vs 24/113 (21.2%); relative risk (RR) = 2.4; 95% CI 1.4, 3.7; P = 0.002]. Conclusion. Blood flow is significantly decreased in radial and ulnar arteries in SSc. UAO is frequent and an important risk factor for the development of DUs in patients with SSc.

Background Interstitial lung disease (ILD) represents one of the most frequent causes of death in systemic sclerosis (SSc) patients. Yet, there are no approved drugs for treatment of SSc-ILD, consensus of management is difficult, and evidence-based data facilitating a treatment algorithm for everyday practice are lacking. Objectives To describe immunosuppressive treatment and prescription patterns in patients with SSc-ILD. Methods The European League against Rheumatism – Scleroderma Trial and Research (EUSTAR) database was established in 2004 to collect annually data on specialized care of patients with SSc. Based on this database, the FP7 DeSScipher project consisting of several observational trials was initiated, of which one focuses on ILD. The EUSTAR database was analyzed with respect to immunosuppressive therapy. Results Out of a cohort of 11,496 SSc patients, we identified 3,778 adult patients fulfilling the ACR or according to available data the new ACR-EULAR criteria, additionally showing signs of ILD (either on plain X-ray or high resolution computed tomography) with at least one report on immunosuppressive treatment. Mean age was 55.5±13.4 years, with 83.6% females and a mean SSc disease duration of 8.5±7.9 years. Mean mRSS was 10.6±8.7, 44.4% had diffuse skin involvement, 46.9% the limited SSc subtype, and 7.5% sclerodactyly only. Compared to the 2,681 (71%) patients who had at least one episode of immunosuppressive therapy the 1,097 (29%) patients without use of immunosuppressants ever were on average 5 years older, had longer disease duration (3.2 years), more often limited skin involvement, higher DLCO and FVC values.The immunosuppressants most frequently used were prednisolone (pred) (58.8%), cyclophosphamide (cyc) (19.1%), azathioprine (aza) (15.0%), methotrexate (mtx) (14.7%), and mycophenolate mofetil (mmf) (13.1%), all others were prescribed in less than 3%. With regard to highest treatment intensity ever received, similar proportions of patients got monotherapies (34.0%) and combinations of two drugs (32.4%), while triple therapy was comparably rare with 4.1%. When comparing patient characteristics at treatment start of the most frequent regimens, differences compared to the “never IS” group and between treatment arms become apparent (table 1). Conclusions “Everyday” use of immunosuppressants is frequent in SSc-ILD patients showing a wide variety of single and combined substances with distinct patient patterns between treatment regimens. However, prospective studies are still necessary to define indications and outcomes. The EU-funded international FP7 DeSScipher research project was initiated to achieve this goal, comprising 5 prospective observational trials addressing the most frequent medical problems in SSc patients. Acknowledgements This study was supported by the Seventh Framework Program of European Commission as part of the DeSScipher Project (grant agreement No. 305495). Disclosure of Interest D. Huscher: None declared, S. Adler: None declared, E. Siegert: None declared, Y. Allanore: None declared, L. Czirjak: None declared, F. Del Galdo: None declared, C. P. Denton Grant/research support from: Actelion, CSL Behring, Novartis, Consultant for: Actelion, GSK, Bayer, Inventiva, Takeda, O. Distler Grant/research support from: or consultant fees: 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., I. Foeldvari: None declared, M. Frerix: None declared, M. Matucci-Cerinic: None declared, U. Mueller-Ladner: None declared, I. H. Tarner Grant/research support from: and speaker9s honoraria from Abbvie, Actelion, BMS, Chugai, Pfizer, Roche and UCB, G. Valentini: None declared, U. A. Walker Consultant for: manufacturer of Ilaris, G. Riemekasten: None declared

Background Serum surfact protein D (SP-D) levels are elevated in systemic sclerosis interstitial lung disease (SSc-ILD) (1). Gastroesophageal reflux disease (GERD) is suggested to be a risk factor for SSc-ILD (2). However, previous studies did not analyze SP-D by subgroups of SSc-ILD patients with and without GERD. Objectives Aim of our study was to evaluate SP-D as a biomarker of severity of SSc-ILD in the presence or absence of GERD. Methods 56 SSc patients underwent chest computertomography and lung function test to evaluate ILD, and gastroesophagoscopy for confirmation/exclusion of GERD. Extend of lung fibrosis >20%, presence of ground-glass opacity (GGO) and honey combing (HC) were compared between SSc-ILD patients with and without GERD by chi-square test. Serum samples were analyzed for SP-D by Enzyme Linked Immunosorbent Assay. Correlations were evaluated by Spearman rank correlation test. Kruskal-Wallis test or Mann–Whitney U test were used to compare SP-D levels between different patient groups (values in ng/ml, mean±SD). Results 49 patients (87.5%) were female, mean age was 46.5±14.4 years. 43 patients had limited and 13 patients diffuse cutaneous involvement. 27 patients had coexistent ILD and GERD (group 1), 16 patients had ILD but no GERD (group 2) and 13 patients had no ILD or GERD (group 3). All patients with GERD by gastroesophagoscopy had signs of ILD by computer tomography. SSc-ILD patients with vs without GERD had statistically significant more often an extend of lung fibrosis >20% (20/37 (74.1%) vs 6/16 (37.5%, p=0.018) and tendentially more often GGO (19/27 (70.4%) vs 7/16 (43.75%), p=0.084), but there was no difference in presence of HC. The levels of SP-D were not significant different between male and female (286±97 vs 227±170, p=0.169) neither between diffuse and limited cutaneous SSc patients (291±198 vs 218±150, p=0.218). In addition, SP-D did not correlate with age (r=0.221, p=0.102) or disease duration (r=-0.164, p=0.226). SP-D levels were higher in group 1 compared to group 2 and group 3 (316±156 ng/ml vs 237±134 ng/ml va 62±19 ng/ml, p SP-D levels were highly correlated with the extend of lung fibrosis (r=0.783, p Conclusions ILD-SSc patients with GERD have a more severe lung involvement and higher SP-D levels then ILD-SSc patients without GERD. Moreover, SP-D levels are much lower in SSc patients without ILD or GERD. Thus, our results suggest that GERD is linked with extend of lung fibrosis and may contribute to GGO, as SP-D was a valuable biomarker to monitor the severity of SSc-ILD. References Kumanovics et al.: Comprehensive investigation of novel serum markers of pulmonary fibrosis associated with systemic sclerosis and dermato/polymyositis. Clin Exp Rheumatol. 2008. Christmann et al.: Gastroesophageal reflux incites interstitial lung disease in systemic sclerosis: clinical, radiologic, histopathologic, and treatment evidence. Semin Arthritis Rheum. 2010. Disclosure of Interest None declared

Background Due to lack of adequate clinical research data, drug treatment of the rare disease systemic sclerosis (SSc) is commonly off-label. The international EC-funded research project DeSScipher (acronym for “to decipher the optimal management of systemic sclerosis”) was designed to increase the evidence-based treatment strategies for SSc patients and subsequently to improve their long-term quality-of-life. Objectives The primary objective is to compare the outcomes of different treatments with respect to efficacy and safety of currently used off-label drugs from the early to the advanced phases of the main SSc-associated organ dysfunctions in a routine rheumatology in- and outpatient setting. Methods Five prospective observational trials (OTs), carried out within the EULAR Scleroderma Trials and Research (EUSTAR) group, have been designed to analyze current treatment approaches of early functionally relevant manifestations such as digital ulcers (OT1) and hand arthritis (OT2) to the morbidity and mortality-driving manifestations such as interstitial lung disease (OT3), pulmonary hypertension (OT4) and severe heart disease (OT5). The study protocols are accessible at clinicaltrials.gov Identifiers NCT01836263, NCT01834157, NCT01858259, NCT01840748, NCT01829126. Results Between April 2013 and January 2015, 1781 SSc patients have been screened at 27 contributing EUSTAR centers. 1577 (89%) patients have been enrolled into at least one of the five OTs. In particular, 1179, 127, 981, 237 and 716 patients have been enrolled into OT1-5, respectively (3240 in total; a given patient could be enrolled into multiple OTs), which represents a baseline patient recruitment rate of 79% of the target number of 4098 patients (accordingly 226%, 79%, 59%, 25% and 91% of the required number of 522, 160, 1670, 960, 786 patients for OT1-5, respectively). The completion of 1-year (OT3, OT5) and 2-year follow-up visits (OT1, OT2, OT4) are pending. Conclusions DeSScipher is currently the largest prospective observational research project ever for SSc. While patient recruitment is still ongoing, preliminary results of the five OTs are expected in late 2015 and the final results depending on the completion of follow-up visits are expected between 2017 and 2018. Acknowledgements 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: Wuppertal (member N°192), Lille (93), Bad Bramstedt (187), Moscow (78), Assiut (168), Moscow (190), Bucharest (100), Monserrato (142), Iasi (162), Cluj-Napoca (16), Frankfurt (124), Salford/Manchester (80), Tubingen (56), Ancona (34), Zagreb (51) and Roma (94). Disclosure of Interest None declared

Background Heart disease in patients with systemic sclerosis (SSc) can cause manifestations such as cardiac blocks (CBs), ventricular arrhythmias (VA), and congestive heart failure (CHF) which may require a pacemaker/defibrillator implant, are the cause of death or sudden death (SD) in about 20% of patients and can be referred to as severe heart disease (SHD). The European League against Rheumatism – Scleroderma Trial and Research (EUSTAR) database provides an unique opportunity to address this topic. The results of such analysis are instrumental for the DeSScipher project, an EU funded project devoted to decipher the optimal management of SSc . Objectives To investigate the prevalence of each SHD manifestation and their associations with demographic, serological, clinical and therapeutic aspects in a large series of adult SSc patients. Methods Seven EUSTAR-DeSScipher centers provided clinical charts at study entry including all the items of SHD. The prevalence of any and each SHD manifestation was calculated. The associations with demographic, serological, clinical features and treatment with vasodilators, i.e. calcium channel blockers (CCBs) and /or ACE inhibitors (ACEi), were investigated by univariate analysis and confirmed by multivariate logistic regression analysis. Results At July 6th 2012, 1119 SSc patients from the 7 EUSTAR centers had no missing data (995 females, 164 males; median age 53.6 years, range 14-86). Out of them, 211 patients (19%) had at least 1 SHD manifestation, 152 patients had CBs (14%), 71 had VA (6%), 132 had CHF (12%), and 27 received a pacemaker/defibrillator implant (2%). CBs were the only SHD manifestation in 100 patients, VA in 31, and CHF in 80. No association was found between SHD and clinical (diffuse or limited) and serological (ACA or anti-Scl-70) subset. No association was found between either CHF or pacemaker/defibrillator implant and any other disease feature. In multiple logistic regression analysis, CBs were associated with bibasilar lung fibrosis at chest X-Ray (OR=2.6; 95%CI=1-6.4; p=0.04), while VA were associated with increased CPK levels (OR=11; 95%CI=1-117; p=0.02) and, unexpectedly, current CCB use (OR 10; 95%CI 1.4-76.1; p=0.02). Conclusions This is the first study devoted to investigate SHD in a large series of carefully assessed SSc patients. SHD was detected in about 19% of the cases, CBs in 14%, VA in 6%, CHF in 12%. Pacemaker/defibrillator implant was needed in 2.4%. These data highlight the importance of an accurate heart assessment in SSc patients. Moreover, the associations between VA and CPK elevation and current CCB use should stimulate the clinician to avoid these drugs in patients with myositis/myocarditis. Acknowledgements 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 Disclosure of Interest S. Vettori Grant/research support from: Roche, Consultant for: Phadia Thermofisher, Pfizer, Abbvie, G. Cuomo: None declared, V. Jaeger: None declared, M. Frerix: None declared, E. Siegert: None declared, V. Lorand: None declared, S. Jordan: None declared, G. Riemekasten: None declared, Y. Allanore: None declared, L. Czirjak: None declared, I. Tarner: None declared, O. Distler Grant/research support 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, Consultant for: 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, C. Denton: None declared, M. Matucci-Cerinic: None declared, F. Del Galdo: None declared, U. Walker: None declared, U. Mueller-Ladner: None declared, G. Valentini: None declared

Background Cardiac troponins (cTn) are widely used as biomarkers for the diagnosis and quantitation of cardiac injury (1). Autoantibodies against cTn, especially against cTnI (anti-cTnI), have been recently described in association with cardiac dysfunction (2). However, their clinical significance is still unclear. Systemic sclerosis (SSc) is a chronic autoimmune connective tissue disease that is associated with heart involvement, although often clinically occult (3,4). Objectives Hence, the value of elevated cTn levels and a possible autoimmune response against cTnI as biomarkers in patients with SSc were the aims of this study. Methods Out of our monocentric SSc cohort we retrospectively identified 113 of 190 patients in whom routine laboratory assessment including high-sensitive cTnT was performed. Stored biosamples, available for 60/113 patients (53.1%), were used to assess auto-cTnI titres as previously described (5). A 2x2 table, using chi-square test, compared the results of cTnT and anti-cTnI. If available, cardiac magnetic-resonance-imaging (cMRI) data were retrospectively evaluated to assess early myocardial gadolinium enhancement (T1 ratio, as a marker for hyperemia and capillary leakage) as well as edema (T2 ratio). Results Out of 113 patients with available results for cTNT, 41 patients (36.3%) had a positive and 72 (63.7%) a negative result. Biosamples were available for 21 cTNT positive and 39 cTNT negative patients. Anti-cTnI were detected in 17 samples (28.3%): in 8 (38.1%) cTNT positive compared to 9 (23.1%) cTNT negative patients (p=0.218). Anti-cTnI-titres were 1:40 in 7, 1:80 in 6 and 1:160 in 4 samples. cMRI data were available for three anti-cTnI positive patients (all diffuse cutaneous subtype). All of them had a distinct change in the T1 ratio (6.4-8.9), not in the T2 ratio. Late enhancement (gold standard for the detection of myocarditis) was present in one patient (6). Conclusions The preliminary results of this pilot study suggest that cTnT levels are elevated in about one third of SSc patients, and anti-cTnI are present in about a third of cTNT positive patients. Additionally, anti-cTnI can be detected in about a quarter of cTNT negative patients. Whether cTNT and/or anti-cTnI autoantibodies might serve as new biomarkers in SSc heart disease need to be evaluated in further prospective trials. References Kaya Z Clin. Immunol. 134,80–88(2010). Kaya Z Circulation Research 110,145–158(2012). Allanore Y Curr Opin Rheumatol 20,697–702(2008). Meune C Arch Cardiovasc Dis 103,46–52(2010). Leuschner F Eur. Heart J. 29, 1949–1955(2008). Desai CS Curr Opin Rheumatol 23,545–554(2011). Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.3595