A. Cordeiro

Anti-fibrotic nintedanib—a new opportunity for systemic sclerosis patients?

Systemic sclerosis is a connective tissue disease characterized by progressive skin thickening and a wide spectrum of internal organ involvement. Pathogenesis includes vasculopathy, inflammation, and fibrosis. Although immunosuppressants such as cyclophosphamide and mycophenolate mofetil have shown some benefit in interstitial lung disease management, it is still a major cause of morbi-mortality in these patients. Therefore, there is a current need for new therapies. Here, we report a 65-year-old female patient with limited cutaneous systemic sclerosis, anti-topoisomerase-positive and extensive lung disease. The patient developed progressive lung fibrosis under several immunosuppressants and was started on nintedanib, with clinical and functional stabilization. Nintedanib is a tyrosine-kinase inhibitor that blocks several profibrotic pathways, inhibiting proliferation and migration of fibroblasts and decreasing the synthesis of extracellular matrix proteins. It is approved for idiopathic lung fibrosis and has demonstrated good results in inhibiting migration and proliferation of systemic sclerosis dermal fibroblasts, constituting a promising agent for systemic sclerosis-associated lung fibrosis.

AB0607 Pulmonary embolism in systemic sclerosis – one year follow up

Background Risk of pulmonary embolism (PE) in systemic sclerosis (SSc) has been estimated between 2.51–3.47 fold higher when compared to non-SSc patients (pts). Proinflammatory state, vasculopathy and vascular injury may contribute to a prothrombotic state in SSc and increased risk for venous thromboembolism. Objectives Calculate frequency and identify possible risk factors for PE among SSc pts;analyse efficacy of longterm anticoagulation (ACO) in these pts. Methods We conducted a retrospective analysis of 110 pts with SSc followed in our Rheumatology department and selected those who performed lung ventilation/perfusion scintigraphy (V/Q scan) or CT pulmonary angiography due to worsening dyspnea/fatigue or isolated reduction of the carbon monoxide diffusing capacity (DLCO). We collected demographic features, comorbidities, age at SSc diagnosis, anti-nuclear antibody specificities, dyspnea according to New York Heart Association (NYHA) classes and results of cardiopulmonary exams. PE and related variables were assessed at baseline and after 12 months of ACO. Results PE was diagnosed in 12 out of 29 (41.4%) SSc pts that met inclusion criteria, with the majority presenting bilateral peripheral multisegmental defects. Most were females (91.7%), mean age of 59.4 (±12.7) years (yrs). Two thirds were diagnosed with limited SSc with mean disease duration of 13.3 (±12.9) yrs. Mean time between SSc and PE diagnosis was 8.5±8.2 yrs, although one third of the pts was diagnosed within the first year of SSc diagnosis. One patient was taking oral contraceptives and none had thrombophilia, previous surgery or cancer. One third was classified as having NYHA class≥3, with a mean N-terminal pro-brain natriuretic peptide (NTproBNP) of 1108pg/mL (19 to 8069). Six pts had concomitant interstitial lung disease (ILD) and 8 had an estimated pulmonary artery systolic pressure (PASP)≥35 mmHg (6 of them had concomitant ILD). From these only 2 had pulmonary hypertension confirmed by right heart catheterization and 1 died. When comparing SSc pts with and without PE, Scl70 positivity was more common in pts with PE (p=0.041). No significant associations were found between PE and several cardiovascular risk factors. From the 12 pts with PE, 10 were on longterm ACO:5 on rivaroxaban, 4 on warfarin and 1 on apixaban. Clinical reassessment after 12 months of ACO is shown in figure 1. Conclusions Our results suggest that PE is frequent in SSc and must be considered in the differential diagnosis of worsening fatigue and dyspnea and/or reduction of DLCO/PASP increase. PE may occur more frequently in Scl70 positive pts and early in disease course, probably due to vasculopathy and vascular injury being more prominent in the early phase of the disease. Although there is no consensus regarding the optimal ACO, the diseases vasculopathy seems to be an important contributor, potentially preventing improvement in perfusion defects, regardless of the anticoagulant used. Disclosure of Interest None declared

AB0636 Interstitial Lung Disease in Scleroderma Portuguese Patients: Table 1.

Background Systemic sclerosis (SSc) is a rheumatic disorder characterized by inflammation and fibrosis involving the skin as well as internal organs, including the lung. Objectives This study was conducted to characterize SSc patients with ILD and determine predictor features for the presence of ILD. Methods A retrospective evaluation of SSc patients from our Rheumatology department was undertaken. ILD was defined according to imaging findings in high-resolution CT (HRCT) combined with functional parameters. Demographic features, auto-antibodies, spirometry, diffusion capacity for carbon monoxide (DLCO) measurement, echocardiography and 6-minute walk test were compared between groups with and without ILD using parametric tests and non-parametric tests. Predictor factors were established by logistic regression analyses. Results One hundred and three SSc patients with current mean age of 60.2±14.1y and mean disease duration of 10.0±9.6y were evaluated. Thirty-four (35.8%) patients were diagnosed with ILD, of whom 13 had limited cutaneous SSc, 14 had diffuse cutaneous SSc, 2 sine sclerodema and 5 overlap syndroms. ANA was positive in 100% cases, anti-Scl70 was found in 55% and anti-centromere antibody positivity was found in 15% of patients. HRCT revealed diffuse parenchymal lung disease involvement >20% in 18 (53%) cases, with the majority showing a predominant honeycombing pattern. Spirometry showed a restrictive pattern in 8 patients and 1 had obstruction. The DLCOsb was abnormal in 7 patients. Three patients had pulmonary hypertension confirmed by right heart catheterization, 2 patients classified as group 1 and 3 and 1 patient of group 5. About 63% of ILD patients were ever treated with corticosteroids and 27% with cyclophosphamide, which were the most common drugs used. Two patients were also treated with rituximab. In this ILD-group, 5 deaths were recorded, 2 due to cancer, 1 abdominal sepsis, 1 pulmonary hypertension and 1 of unknown cause. Comparison of these ILD patients with non-ILD patients revealed some significantly differences (Table 1).Table 1. Statistically significant distinctions between patients with and without ILD ILD patients (n=34) No-ILD patients (n=61) P Current mean age (years) 61.8±14.5 58.6±13.2 0.330 Mean disease duration (years) 11.6±9.8 9.2±9.3 0.250 Anti-centromere antibody (%) 5 (15) 48 (79) <0.001 Anti-Scl70 antibody (%) 18 (55) 4 (7) <0.001 Diffuse cutaneous disease (%) 14 (41) 5 (8) <0.001 Digital ulcers (%) 19 (54) 11 (18) <0.001 NYHA Functional Classification (%) 23 (67) 30 (49) 0.017 Tricuspid regurgitation (%) 26 (84) 24 (45) 0.001 DLCOsb <60 (%) 7 (64) 0 (0) 0.056 Hypoxemia at rest (%) 8 (27) 4 (7) 0.013 Gastrointestinal involvement (%) 10 (48) 9 (24) 0.060 Death (%) 5 (16) 1 (2) 0.020 Multivariate analysis showed that digital ulcers (OR=31.6, 95% CI 3.09 to 321.91), Anti-Scl70 antibody positivity (OR=10.1, 95% CI 1.19 to 85.74) and anti-centromere antibody negativity (OR=0.08, 95% CI 0.01 to 0.83) were independently associated with the presence of ILD. Conclusions This study is one of the first studies carried out in Portugal regarding lung involvement in SSc. About one third of the patients had ILD, whose main characteristics are in accordance with other European cohorts. We confirmed that anti-SCL70 positivity, presence of digital ulcers as well as the absence of anti-centromere antibody is independently associated with ILD Disclosure of Interest None declared

OP0129 Nailfold Capillaroscopy in Rheumatology Practice - A Single Center Experience

Background Nailfold capillaroscopy (NCP) is an easy, non-invasive and useful tool for the diagnosis and follow-up of Systemic Sclerosis (SSc) and other systemic rheumatic diseases. Objectives To present our single center experience with NCP, describing the main reasons for NCP request, and the major abnormalities detected in capillaroscopy. Methods Retrospective analysis of patients submitted to NCP assessment, from January 2013 to December 2015 in our center. We collected reasons for NCP request, demographic and clinical data, autoimmunity profile and NCP results. Results A total of 221 NPC, corresponding to 197 patients, 167 females (84.8%) and 30 males (15.2%) aged from 9 to 90 years were reviewed. One hundred and thirty eight (62.4%) patients had no definitive diagnosis, 53 patients (24%) had SSc, 7 (3.2%) had mixed connective tissue disease, 3 (1.4%) had dermatomyositis/polymyositis (DM/PM), and 3 (1.4%) antiphospholipid syndrome (APS). Raynauds phenomenon (RP) alone was the most frequent reason for requesting NCP (33% of the cases), and combined with ANA positivity accounted for another 30.8% of the requests. RP was present in 73.3% of the patients, acrocyanosis in 16.3%, livedo reticularis and puffy hands accounted for 8.6% each one. Anti-nuclear antibodies (ANA) were positive in 59.7%, anti-centromere antibodies were present in 21.3%, anti-topoisomerase I and SSA/SSB in 5.1% of the cases. One hundred and fifty nine (71.9%) NCP were considered abnormal. The most frequent specific disease pattern was the early one (Cuttolo) in 15%. The most frequent findings were: capillary tortuosity in 112 (71.8%) cases, capillary dilatations in 95 (60.9%), and hemorrhages in 85 (54.5%). NCP was abnormal in 79.4% of patients with RP and ANA, 41.2% of them displaying specific findings of rheumatic diseases (Table 1). In SSc patients the late and the early pattern (Cuttolo) were the most frequent, present in 15 and 13 NCP, respectively. Concerning specific NCP findings capillary dilatations (81%), hemorrhages (73.6%) and megacapillaries (71.7%) were the most frequent (Table 2). Of the 138 cases without definitive diagnosis, 61. 6% had abnormal NCP, although mostly with non-specific patterns (50%). In 10 (7.2%) patients NCP helped to establish the diagnosis: VEDOSS (Very Early Diagnosis of Systemic Sclerosis) in 6, antiphospholipid syndrome in 3 and DM in one case. Conclusions In our experience, NCP was helpful for the diagnosis of rheumatic systemic disease. Specific NCP findings were more frequent in patients with RP + ANA positivity, suggesting that this combination is associated with more disease incidence. Patients with isolated RF had less pathologic NCP findings than those with isolated. ANA positivity. The prospective follow up of those patients with abnormal NCP and no definitive diagnosis will help to establish the predictive value of observed alterations. References Cutolo M, Pizzorni C, Sulli A. Capillaroscopy. Best Pract Res Clin Rheumatol. 2005 Jun;19(3):437–52 Disclosure of Interest None declared

SAT0237 Nailfold Capillaroscopy Findings in Scleroderma Patients – Prognostic Implications

Background Nailfold capillaroscopy (NCP) is a useful tool for the diagnosis and follow-up of systemic rheumatic diseases and represents one of the best methods to evaluate microvascular abnormalities. Objectives To characterize NCP findings of patients with Systemic Sclerosis (SSc), and understand how NCP associates with the presence of digital ulcers, gastrointestinal involvement, pulmonary arterial hypertension (PAH) and interstitial lung disease (ILD). Methods NCP findings of adult patients with SSc followed-up in our center were reviewed. Demographic and clinical features were collected. Nonparametric tests were used to determine potential associations between capillaroscopy findings/patterns and the presence of digital ulcers, gastrointestinal involvement, PAH and ILD. Results In total, 52 out of 103 patients with SSc had at least one NCP result available. Forty five were female (86.5%) and seven male (13.5%), the age was 56.6 ±13.2 years and disease duration 10.9 ±10.5 years. Thirty one (59.6%) had limited cutaneous SSc, seven (13.5%) diffuse cutaneous SSc, ten (19,2%) VEDOSS, three (5.8%) overlap syndromes and one (1.9%) SSc sine scleroderma. (table 1). The most frequent NCP findings were hemorrhages (54.7%) megacapillaries (54.7%), and capillary dilatations (52.8%). We found that digital ulcers were significantly associated with the existence of avascular areas (p=0.02), and with neoangiogenesis (p=0.03) in univariate analysis, but were not associated with any capillaroscopy pattern. Looking to interstitial lung disease, there is a trend for association with the presence of avascular areas (p=0.056). Only one patient had PAH confirmed by right heart catheterization. In this case NCP showed giant capillaries, neoangiogenesis and avascular areas. There was also a trend for association between avascular areas and higher values of NT pro BNP (p=0.078). Gastrointestinal involvement was not significantly associated with NCP findings (table 2).Table 1. Distribution of patients according to NCP and disease subtypes Diffuse cutaneous Limited cutaneous Overlap syndrome VEDOSS Sine scleroderma (n=7) (n=31) (n=3) (n=10) (n=1) Early pattern n (%) 0 (0) 9 (29) 1 (33) 6 (60) 0 (0) Active pattern n (%) 1 (14.2) 5 (16.1) 1 (33) 2 (20) 0 (0) Late pattern n (%) 3 (42.9) 7 (22.6) 0 (0) 0 (0) 0 (0) Nonspecific n (%) 3 (42.9) 8 (25.8) 1 (33) 1 (10) 1 (100) Normal NCP n (%) 0 (0) 2 (6.5) 0 (0) 1 (11) 0 (0) Conclusions In our study the presence of avascular areas and neoangiogenesis in NCP was significantly associated with the existence of digital ulcers. Also, ILD and higher values of NT-proBNP were more common in patients who present avascular areas. These results suggest that abnormalities detected in the NCP might help predict organ involvement, although long term follow up and greater numbers of patients are needed in order to confirm the prognostic value of NCP findings. References Mannarino E, Pasqualini L, Fedeli F, Scricciolo V, Innocente S. Nailfold capillaroscopy in the screening and diagnosis of Raynauds phenomenon. Angiology 1994; 45: 37–42 Disclosure of Interest None declared

AB1056 Nailfold Capillaroscopy in Suspected Connective Tissue Disease Without Raynaud's Phenomenon: Table 1.

Background The diagnostic1 and prognostic2 value of nailfold capillaroscopy (NCP) in patients with Raynauds phenomenon (RP) is well-established. However, its role in the assessment of patients without RP is still unclear. Objectives We aimed to assess the diagnostic role of NCP in suspected connective tissue disease (sCTD) without RP. Methods We included all patients with CTD or sCTD submitted to NCP assessment from January 2013 to December 2014. Clinical features were recorded, as well as the presence of antinuclear antibodies (ANA) and extractable nuclear antigens (ENA). NCP results were appraised according to capillary density, presence of dilatations, megacapillaries, hemorrhages, tortuosity, neovascularization and avascular areas. We classified NCP results as normal, nonspecific findings (NSF) and scleroderma pattern (SSP)3. Patients with sCTD were compared according to the presence/absence of RP, ANA/ENA and NCP findings. Results We included 112 patients: 95 (84.8%) female, with a mean age of 48±18 years. The most frequent CTDs were systemic sclerosis (SSc, n=33, 29.5%) and mixed CTD (n=6, 5.4%). Fifty-eight (51.8%) patients had sCTD – 37 (62.5%) had RP, 26 (55.3%) were ANA positive and 46 (86.8%) were ENA negative. Thirty-three (56.9%) had NSF; one sCTD patient exhibited SSP. Dilatations were present in 27 (51.9%), tortuosity in 40 (76.9%), hemorrhages in 22 (43.2%) and neovascularization in 8 (15.4%) individuals. Patients with and without RP were not different considering clinical features, ANA/ENA positivity and NCP findings (Table 1). The presence/absence of ANA and NCP findings were also not associated with distinct clinical features. Table 1. Comparison of patients with and without RP Features RP, n (%) or m (SD) No RP, n (%) or m (SD) p value Sex (female) 33 (89.2) 16 (76.2) 0.2621 Age (years) 45.3 (20.0) 38.9 (19.7) 0.3023 Puffy hands 2 (5.4) 1 (4.8) – ANA positivity 16 (55.3) 10 (58.8) 0.7682 ENA (n=53) 4 (n=34,11.8) 4 (n=19,21.1) 0.0602 Dilatations 13 (35.1) 5 (23.8) 0.5562 Tortuosity 17 (45.9) 9 (42.9) >1.02 Hemorrhages 10 (27.0) 5 (23.8) >1.02 Neovascularization 5 (13.5) 1 (4.8) 0.4022 NCP (NSF) 23 (62.2) 10 (47.6) 0.3631 Nonparametric statistical analysis using Chi-square (1) or Fishers Exact test (2) for categorical variables and Mann-Whitney U test (3) for numerical variables (confidence interval 95%). Conclusions RP, ANA positivity and the presence of nonspecific findings in NCP were not discriminant in the short-term assessment of this patient group. Long term follow-up is needed in order to better understand the diagnostic and prognostic role of these NCP findings in both patients with and without RP. References Mannarino E, et al. Nailfold capillaroscopy in the screening and diagnosis of Raynauds phenomenon. Angiology 1994; 45: 37–42. Blockmans D, et al. Predictive value of nailfold capillaroscopy in the diagnosis of connective tissue diseases. Clin Rheumatol 1996; 15: 148–53. Cutolo M, et al. Nailfold videocapillaroscopy assessment of microvascular damage in systemic sclerosis. J Rheumatol 2000; 27: 155–60. Disclosure of Interest None declared

AB0704 Pulmonary Embolism in Oligosymptomatic Systemic Sclerosis Patients

Background Systemic Sclerosis (SSc) patients were recently described to have a higher risk of pulmonary embolism (PE) than healthy individuals1. Portuguese expert consensus2 recommends screening for PE when respiratory distress cannot be explained by the presence of cardiovascular or pulmonary interstitial involvement (ILD). Objectives We present our 5-year experience with PE in SSc patients. Methods We included all adult SSc patients submitted to lung ventilation/perfusion scintigraphy (V/Q scan) or CT pulmonary angiography (AngioCT) due to worsening dyspnea/fatigue or isolated reduction of the carbon monoxide diffusing capacity (DLCO), from January 2010 to December 2014. We collected demographic data, functional class according to the World Health Organization (WHO-FC) classification, comorbidities, risk factors for PE and results from AngioCT and V/Q scans. A descriptive statistical analysis was performed. Results Eighteen patients were included: 15 females, with a mean age of 55±14 years and median disease duration 2 (IQR 2.5) years. Nine patients were diagnosed with PE, 8 of which by V/Q scan and 1 using AngioCT. Eight patients had bilateral peripheral multisegmental PE and 1 unisegmental PE. Five PE patients had a WHO-FC of 1-2. Three of the remaining 4 patients with WHO-FC >2 had concomitant extensive ILD, and one patient had pulmonary hypertension. No patient had thrombophilia, previous surgery or cancer. The frequency of hypertension, diabetes, smoking, obesity and dyslipidemia was similar to patients without PE. Anti-topoisomerase positive SSc patients (Anti-topo+) were slightly overrepresented in the PE group (5 vs 2 Anti-topo+ patients without PE). Other disease imunophenotypes were equally distributed between subgroups. Conclusions Oligosymptomatic PE is common in SSc patients. Traditional procoagulant risk factors do not account for this increased risk. Disease-specific risk factors, such as vascular endothelial dysfunction, may be involved. The impact of PE in disease prognosis is yet unknown. References Chung WS, Lin CL, Sung FC, Hsu WH, Yang WT, Lu CC, Kao CH. Systemic sclerosis increases the risks of deep vein thrombosis and pulmonary thromboembolism: a nationwide cohort study. Rheumatology (Oxford). 2014 Sep;53(9):1639-45. doi: 10.1093/rheumatology/keu133. Epub 2014 Apr 8. Grupo de Estudos de Doenças Reumáticas Sistémicas (GEDRESIS). Manual Prático de Esclerose Sistémica. Sociedade Portuguesa de Reumatologia; 2014. Disclosure of Interest None declared