06. Vascular

P.224

Are Extremity Telangiectases Related to Severe Disease in Systemic Sclerosis?

Y. Yalcinkaya¹, O. Pehlivan², Z. Erturk¹, U. Gazel¹, A. Korkmaz¹, F. Alibaz-Oner¹, P. Atagunduz¹, H. Direskeneli¹, N. Inanc¹

¹ Marmara University, School of Medicine, Department of Internal Medicine, Division of Rheumatology, Istanbul, Turkey, ² Umraniye Education and Research Hospital, Istanbul, Turkey

Introduction: The number and morphology of telangiectases (T) have been studied in terms of severity and organ involvement in systemic sclerosis (SSc). T are located more frequently on face and trunk than extremities. We aimed to evaluate the impact of the localization of T on different skin areas in addition to number, on disease severity of SSc.

Material and Methods: SSc patients fulfilling ACR/EULAR classification criteria (2013) who had the manifestation T were included. The number of T were calculated by using telangiectasia score (TS)(Shah A.,et al) and localization was classified according to presence of T on extremities or not. Simultaneously; ealy, active and late scleroderma patterns (Cutolo et al.) were determined qualitatively and capillary number (CN) was calculated per linear mm at distal row quantitatively by using nail fold video-capillaroscopy (NVC) in all patients.

Results: In 113 (106 female) SSc patients with T; the mean age was 52±12, the duration of follow-up 57±62 months, Raynaud and non-Raynaud symptom 10±8 and 7±7 years. Limited cutaneous form was found to be in 77 (%68), ANA positivity in 102 (%90) ve anti-Scl70 positivity in 33 (%29) patients. In SSc patients with TS score more than 6 or extremity T; the duration of non-Raynaud symptom was found to be longer (p=0,010 or 0,009), MRSS and activity scores were higher (p=0,004 or 0,012 and p=0,010 or 0,009) and severity scores of general, peripheral vascular involvement and skin were higher (p=0,022 or 0,014, p=0,030 or 0,025 and p=0,006 or 0,02), digital ulcers and flexion contractures were more frequent (p=0,008 or 0,035 and p=0,027 or 0,032), late NVC pattern was more frequent and CN was lower (p=0,001 or 0,003 and p=0,001 or 0,007).

When patients were classified in 3 groups according to TS and presence of extremity T, differences in terms of organ involvement, disease activity and severity scores and NVC findings were summarized in table-1.

Conclusions: Conclusion: Disease duration was shown to be long, disease activity and severity were high and NVC findings were severe in patients with high scores of TS and extremity T. In patients with lower TS the presence of T on extremities was found to be related to severe disease. The number and localization of T was emphasized as they are easy to evaluate in clinical practice and may be useful in determining severe patients with SSc.

P.225

Characteristics and Capillaroscopic Findings of Systemic Sclerosis Patients with Severe Peripheral Vascular Involvement Receiving Specific Vasodilator Treatment

Y. Yalcinkaya, A.U Unal, Z. Erturk, S. Kaymaz, P. Atagunduz, N. Inanc, H. Direskeneli

Marmara University, School of Medicine, Department of Internal Medicine, Division of Rheumatology, Istanbul, Turkey

Introduction: Severity of peripheral vascular involvement (PVI)is known as an important determining cause of morbidity in systemic sclerosis (SSc). Different vasodilating agents have been found to reduce severity and contribute to healing of digital ulcers (DU)in SSc.

Aim: We aimed to evaluate the characteristics and capillaroscopic patterns of the patients with severe PVI under different vasodilator therapeutic regimens.

Material and Methods: The patients were grouped as ‘severe PVI’ (PVT=2,digital pitting scars; PVT=3, digital tip ulcerations and PVT=4, digital gangrene; Medsger) and ‘non-severe PVI’ (PVI=0,no Raynaud’s; PVI=1, Raynaud’s requiring vasodilators). We included patients with severe PVI also who received cyclic iloprost and bosentan and/or sildenafil and compared to non-severe PVI. Nail fold video-capillaroscopy (NVC)was assessed qualitatively (Cutalo et al., early, active and late patterns).

Results: Severe PVI group more frequently had diffuse cutaneous form, contractures, lung disease, anti-Scl70 positivity and high acute phase response and exposed to immunosuppressives (table-1).

Scores of telangiectasia, skin, activity and severity were lower in non-severe group. NVC late pattern was frequent and early pattern was rare in severe PVI groups. Forty-one% (9/22) of patients received second oral agent for PVI. Monotherapy and combination groups had similar scores (table-2).

Conclusions: NVC late pattern was frequent in severe PVI group with long disease duration, exposed to intensive immunosuppresives and received specific vasodilators for PVI. Disease activity and severity were higher in severe PVI group. One third of the severe group required oral combination therapy for PVI. Monotherapy and combination group were similar in terms of severity. NVC is a useful method to monitor digital ischemia and severe organ involvement in SSc.

P.226

Arterial Hypertension in Patients with Systemic Sclerosis

E. Wielosz, M. Majdan, M. Dryglewska, A. Górak

Department of Rheumatology and Connective Tissue Diseases, Medical University, Lublin, POLAND

Introduction: Arterial hypertension is common in systemic connective tissue diseases. The aim of the study was to evaluate the incidence of arterial hypertension (AH) in patients with systemic sclerosis and to present clinical characteristics of the group diagnosed with AH.

Material and Methods: The study included 126 patients (98 women and 28 men) with systemic sclerosis(SSc). The SSc patients were divided into two groups: with arterial hypertension AH(+) - 57 and otherwise AH(-) -69 patients. Sixty patients were diagnosed with diffuse SSc and 66 with limited SSc. Moreover, serological profile, scleroderma renal crisis, involvement of internal organs and mortality were determined. The kidney function was assessed based on the estimated glomerular filtration rate (eGFR) and concentrations of creatinine.

Results: Arterial hypertension was found in 57/126 SSc patients (47%), including 30/57 in the diffuse SSc group and 27/57 in the limited SSc. The patients’ age was statistically significantly higher in the AH(+) SSc group, as compared to the AH(-) SSc group (p=0.007). The incidences of oesophageal involvement (p=0.007), digital ulcerations (p=0.026), overlapping syndromes ( p=0.049) and mortality ( p=0.037) were found to be significantly higher in the AH(+) SSc group. Scleroderma renal crisis was observed in 9 /126 patients (7%). The incidence of chronic kidney disease was higher in the AH(+) SSc group, both of stage 2 (p=0.009) and of stage 3 (p=0.049). The stages 4 and 5 of chronic kidney disease were found only in the group with AH. Moreover, this group was characterized by higher incidences of elevated uric acid (p=0.008).

Conclusions: Arterial hypertension is quite common in patients with systemic sclerosis and is associated with significantly more severe course of disease.

P.227

Abnormal Nailfold Capillaroscopy Pattern is Common in Patients with Connective Tissue Disease and Associated with Organ Involvement

A. Van Roon¹, C.C. Huisman¹, A.M. Van Roon¹, D. Zhang², A.J. Stel³, A.J. Smit¹, H. Bootsma³, D.J. Mulder¹

¹ University of Groningen, University Medical Center Groningen, Internal Medicine, div. Vascular Medicine, Groningen, THE NETHERLANDS, ² Medical Center Leeuwarden, Rheumatology, Leeuwarden, THE NETHERLANDS, ³ University of Groningen, University Medical Center Groningen, Rheumatology and Clinical Immunology, Groningen, THE NETHERLANDS

Introduction: Nailfold capillary microscopy (NCM) has been shown to be associated with disease severity and internal organ involvement in non-consecutive systemic sclerosis (SSc) cohorts. NCM may help in early recognition of connective tissue disease (CTD) but it is unclear to which extent NCM abnormalities occur in several CTD and whether these are associated with organ involvement. The aim is assess NCM in consecutive patients with Raynaud’s phenomenon (RP) and whether these are associated with signs of organ involvement.

Material and Methods: NCM was assessed in consecutive patients with RP (n=759) according to standardized procedures at a dedicated vascular laboratory by trained and experienced technicians. NCM was assessed by widefield videocapillaroscopy. The pattern was classified as normal (n=325), non-specific (n=188) or SSc pattern (early (n=106), active (n=140) or late (n=0) based on the Cutolo patterns). Potential pulmonary involvement was defined as forced vital capacity or diffusion capacity <70%. Gastro-intestinal involvement as scintigraphically (Tc-99M colloid) oesophagus dysmotility. Skin involvement as puffy fingers or sclerodactyly.

Patients were classified as primary RP (normal NCM and negative serology, n=226), early SSc (n=195), SSc (n=40), incomplete Sjögren’s syndrome (iSS, n=5), primary SS (pSS, n=30), incomplete systemic lupus erythematodes (iSLE, n=42), SLE (n=30), mixed CTD (MCTD, n=7), rheumatoid arthritis (RA, n=15) or when not meeting criteria as no classifiable disease (n=169). None were diagnosed with polymyositis or dermatomyositis.

Results: An SSc pattern on NCM was observed in 33% of patients with pSS, 17% SLE, 71% MCTD and 13% RA. Pulmonary, oesophageal and skin involvement was more frequent in secondary RP patients with an SSc pattern, even when analysing only those fulfilling definite criteria for CTD or after exclusion of early SSc and SSc patients. For secondary RP patients, absence of an SSc NCM pattern had a high negative predictive value for pulmonary (92%), oesophageal (91%) and skin (96%) involvement, while positive predictive values were low.

Conclusions: An SSc pattern on NCM is common in CTD patients and is associated with frequent prevalence of organ involvement, even in the absence of (early) SSc. Although this was a retrospective cohort, these data underline the importance of assessing NCM in RP patients to evaluate the risk for organ involvement in CTD other than SSc, already in early disease stages.

P.228

Nailfold Capillary Microscopy and Low Body Mass Index in Raynaud’S Phenomenon Patients

A. Van Roon¹, A. Eman Abdulle¹, A.M. Van Roon¹, A.J. Stel², A.J. Smit¹, H. Bootsma², D.J. Mulder¹

¹ University of Groningen, University Medical Center Groningen, Internal Medicine Div. Vascular Medicine, Groningen, THE NETHERLANDS, ² University of Groningen, University Medical Center Groningen, Rheumatology and Clinical Immunology, Groningen, THE NETHERLANDS

Introduction: Underweight patients develop Raynaud’s phenomenon (RP) more frequently. In a small study, skin temperature and perfusion in RP patients was positively associated with body mass index (BMI). In clinical practice, we frequently observe an abnormal nailfold capillary microscopy (NCM) in underweight subjects with presumably primary RP, from which the implications are unknown. The aim is to study whether being underweight is associated with the presence of more abnormalities on NCM.

Material and Methods: NCM, assessed by videocapillaroscopy, was retrospectively assessed in consecutive patients with suspected RP who had negative serology and did not develop a definite connective tissue disease or organ involvement after a maximum of 5 years follow-up. NCM pattern was classified as normal, non-specific, early, active or late. Weight and height were measured for clinical practice and patients were divided by BMI category: underweight (BMI<18.5 kg/m²), normal weight (BMI 18.5-25 kg/m²), and overweight (BMI >25 kg/m²). Dilated and giant capillaries were counted as well as the total number of capillaries. Patients with a connective tissue disease diagnosis and/or positive serology were excluded.

Results: A total of 352 patients were included (median age 40.6 (24.9-52.9), male/female: 111/241), of which 47 were underweight, 220 normal weight and 85 overweight. Patients who were underweight presented more abnormalities (dilated capillaries, capillary loss or giant capillaries, all p<0.05) on NCM. BMI was negatively associated with NCM pattern, number of dilated capillaries and number of giant capillaries (r=-0.247, r=-0.225 and r=-0.221 respectively, all p<0.001) and positively with the total number of capillaries (r=0.260, p<0.001).

Conclusions: In addition to well-known thermoregulatory abnormalities, clear NCM pattern abnormalities are more frequently observed in underweight patients with primary RP. BMI was negatively associated with the number of dilated capillaries and positively with capillary density. These data potentially suggest that damage to the microvasculature in underweight patients with primary RP may occur independently of the presence or development of a CTD and may be explained by other mechanisms.

P.229

Clinical Characteristics of Critical Limb Ischemia in Systemic Sclerosis

Y. Shirai, Y. Okazaki, M. Kuwana

Nippon Medical School, Tokyo, JAPAN

Introduction: Critical limb ischemia (CLI) is a serious vascular complication in systemic sclerosis (SSc), however, its clinical characteristics and pathogenic process still remain unknown. We investigated outcomes and risk factors of CLI in SSc patients.

Material and Methods: Using a single-center cohort of 333 consecutive cases with SSc who visited our clinic between 2007 and 2015, we retrospectively analyzed clinical and laboratory features of SSc patients who developed CLI. Next, we conducted multivariate analysis to identify risk factors for predicting CLI in 218 SSc cases in whom full serum lipid profiles were available. Finally, using plasma samples from 97 SSc including 11 CLI cases and 19 age- and sex-matched healthy controls (HC), we measured circulating levels angiopoietin-like 3 (ANGPTL3), which regulates both angiogenesis and lipid metabolism, by enzyme immunoassay.

Results: Among 333 patients, we identified 14 CLI cases. All were women, 12 had limited cutaneous SSc, and 12 were anticentromere antibody (ACA) positive. Age at CLI onset was 68 ± 13 years and disease duration was 17 ± 9 years. CLI developed in upper and lower limbs in 4 and 10 cases, respectively. Angiography showed arterial occlusion of forearm, lower leg, or thigh in 13 cases. Four CLI cases underwent percutaneous transluminal angioplasty, but amputation was inevitable. Ten cases required amputation, and 7 of 10 received more than once. In addition, multivariate analysis identified ACA and lower high-density lipoprotein cholesterol (HDL-C) level as independent risk factors for CLI (P = 0.003 and 0.02, respectively), but traditional atherosclerosis risk factors were not associated with CLI. ANGPTL3 levels were significantly higher in SSc than HC and were significantly correlated with HDL-C levels. However, ANGTPL3 levels were not different between CLI and non-CLI cases.

Conclusions: CLI in SSc patients occurred after long disease duration and resulted in poor outcomes. ACA and low HDL-C level were independent risk factors for CLI development. CLI in SSc patients might be a macrovascular disease, which has unique pathogenesis independent of atherosclerosis. Further investigation is warranted.

P.230

Endothelial Dysfunction Markers as Candidates for Disease Activation Biomarkers

R. Sfrent-Cornateanu¹, A.M. Gheorghiu², D. Marta³, R. Oneata², A. Radu², A. Briceag², C. Draganescu², C. Vrancianu², S. Magda⁴, T. Constantinescu⁵, A. Soare², R. Dobrota², I. Ancuta², C. Ciofu², L. Macovei², M. Milicescu², M. Sasu², O. Olteanu², M. Bojinca², V. Stoica², C. Mihai²

¹ Carol Davila University of Medicine and Pharmacy, Dept. Immunology, Bucharest, ROMANIA, ² Cantacuzino Clinical Hospital, Internal Medicine and Rheumatology Department, Bucharest, ROMANIA, ³ Victor Babes National Institute of Research, Bucharest, ROMANIA, ⁴ Cardiology Department, University Emergency Hospital, Bucharest, ROMANIA, ⁵ Marius Nasta National Pneumology Institute, Bucharest, ROMANIA

Introduction: One of the earliest events in the pathogenesis of systemic sclerosis (SSc) is endothelial dysfunction. E- selectin (E-sel), inter-cellular adhesion molecule 1 (ICAM-1), endothelin 1 (ET-1), von Willebrand factor (vWF) and interleukin 6 (IL-6) have been associated with endothelial activation and are also taken into consideration as biomarkers for endothelial dysfunction in SSc.

Objective: We aimed to determine if these vascular markers may be considered as predictive factors for more severe disease in SSc patients.

Material and Methods: Fifty-four consecutive SSc patients, age [mean (SD)] 52.0 (11.7) years, male gender 6 (11%), diffuse cutaneous subset (dcSSc) 20 (34%), were investigated for vascular markers. Serum E-Sel, ICAM-1, ET-1, vWF and IL-6 and C-reactive protein (CRP) were measured using the ELISA method. An extensive clinical assessment was performed on all patients. Associations between vascular biomarkers and disease characteristics were evaluated by Mann-Whitney U-test and Spearman correlations.

Results: IL-6, E-Sel and ICAM-1 had moderate to good correlations with disease activity (measured by both EScSG activity score 2003 and EUSTAR activity score 2016), patient global disease activity assessment (100mm VAS), SHAQ score, erythrocyte sedimentation rate (ESR) and CRP.

There were significant, negative correlations between lung transfer for carbon monoxide (DLCO) and E-sel, ICAM-1 (both p<0.001) and vWF (p=0.015). ET-1, E-Sel and vWF were all higher in patients with interstitial lung disease (all p<0.02).

Conclusions: We identified significant associations between endothelial dysfunction markers and more severe disease. IL-6, E-Sel and ICAM-1 are good candidates for markers of disease activity.

Acknowledgements: This work was performed as part of the project “Development of a computer-based nailfold videocapillaroscopy (NVC) system for longitudinal evaluation of patients with systemic sclerosis” (QUANTICAP), financed by the UEFISCDI PN-II-PT-PCCA-2013-4-1589 grant.

P.231

Association Between Oxygen Delivery to Tissues and Skin Ulcers in Systemic Sclerosis

A. Sari¹, Y.Z. Sener², M. Oksul², B. Armagan¹, A. Erden¹, L. Kilic¹, A. Akdogan¹

¹ Hacettepe University Faculty of Medicine, Department of Rheumatology, Ankara, TURKEY, ² Hacettepe University Faculty of Medicine, Department of Cardiology, Ankara, TURKEY

Introduction: Skin ulcers (SUs) are common manifestations of vascular disease in systemic sclerosis (Ssc) patients. This study aims to investigate the association between the amount of oxygen delivered to periferal tissues and the development of SUs in SSc patients.

Material and Methods: One hundred and eleven SSc patients (103 female) were recruited consecutively to the study. Transthoracic echocardiography (TTE) was performed for each patient to estimate cardiac output (CO). Arterial oxygen saturation (SaO2) with pulse oximeter in room temperature and serum haemoglobin concentration (Hb) were measured at the time of TTE. The amount of oxygen delivered to tissues (D02) in 1 minute was estimated using the equation D02=CO*(SaO2*1.39*Hb) and adjusted for body weight. Demographic, clinical and laboratory data were retrieved from hospital records. Definition of skin ulcers included both digital ulcers (DUs) and other ulcers (OUs). DUs were described as ulcerations on the skin distal to proksimal interphalangeal joints (PIF) of the digits. Ulcerations outside this area were defined as OUs. Patients were divided into 2 groups according to their history of SUs: no history of SUs (Group 1, n=45), and previous positive history of SUs and/or present active SUs (Group,2 n=66). Chi-square and Mann-Whitney U tests were used for comparing categorical and continuous variables between the groups, respectively.

Results: In all, median age was 52.6 (18.9-76.6) years and median disease duration was 138.0 (1.8-415.2) months. Diffuse disease was present in 30.6% of patients. There were no differences between Group 1 and 2 in terms of age, sex, smoking history, median forced vital capacity, presence of pulmonary hypertension, Sa02 and CO. Group 2 tended to have diffuse disease more frequently (40.9% vs. 15.6%, p<0.01) and longer disease duration (103 vs. 161 months, p<0.01). Median Hb level was significantly lower in Group 2 (13.0 vs. 12.4, p<0.01). When patients with DUs were compared with patients without DUs; SaO2, CO and DO2 did not differ between groups. Median serum haemoglobin was significantly lower in DUs group (12.3 vs. 13.0, p<0.01). There were no difference in patients with and without OUs in terms of SaO2, CO, DO2 and serum haemoglobin levels.

Conclusions: Although the haemoglobin concentration was higher in the non-ulcer group, there was no difference in the amount of delivered oxygen between patients with and without SUs. These findings imply that vasculopathy and/or peripheral artery disease plays a major role in the development of ulcers.

P.232

Raynaud’S Phenomenon and Its Impact on Activities in Daily Life During One Year of Follow-Up in Early Systemic Sclerosis

G. Sandqvist, A. Scheja, M. Wildt, R. Hesselstrand

Department of Clinical Sciences Lund, Section of Rheumatology, Lund University, Lund, SWEDEN

Introduction: Raynaud’s phenomenon (RP) is the clinical expression of an imbalance between vasoconstriction and vasodilating factors and is present in more than 90% of patients with systemic sclerosis (SSc). Attacks are often associated with limitations on daily life activities, impaired health-related quality of life (HRQoL), and anxiety over the development of digital ulcers. Limitations in daily activities resulting from SSc have often been assessed with the Health Assessment Questionnaire (HAQ). However, as the HAQ mainly assesses the activity limitations related to mobility and muscle strength, patient diaries, in which patients record the activities that trigger RP attacks provide valuable complementary information. The aim of this study was to investigate the frequency and duration of RP attacks, and the impact of RP on the activities of daily life in early SSc patients, by means of a patient diary in a one-year follow-up study.

Material and Methods: Fourteen SSc patients who met the 2013 ACR/EULAR criteria for SSc, with a median disease duration of 2 years were enrolled in the study. Every 7 weeks the patients completed a 7-day diary documenting the frequency and duration of RP attacks, the activity causing the attack, and how they handled the attack. The patients’ recorded activities were classified according to the activity and participation domains of the International Classification of Functioning, Disability and Health. The patients also recorded in the diary daily self-assessments of the difficulties with RP using a 0–10 ordinal scale according to the Raynaud’s Condition Score.

Results: Ninety-eight RP weekly diaries were analyzed. The median number of RP attacks varied between 6 and 9 attacks per week, and the median score reflecting the difficulty associated with the attacks varied between 2.0 and 2.9. No difference was found in the number of attacks or the difficulties associated with them between winter, spring and autumn. Fewer attacks and less difficulty were reported in August than in any of the other documented weeks (p<0.05). All patients reported RP attacks associated with domestic activities . Most of the patients reported RP attacks when they were buying groceries, or cutting and handling vegetables, meat or fish. The use of heating devices varied during the follow-up. In February, all patients except one used such devices, while about half of the group used devices during the rest of the year.

Conclusions: Difficulties resulting from RP are present and disabling all year round, which underscores the importance of intense vasoactive therapy and non-pharmacological strategies throughout the year.

P.233

Correlations Between Choroidal Thickness and Skin Blood Perfusion in Systemic Sclerosis Patients, Before and After Iloprost Treatment

A. Sulli¹, B. Ruaro¹, S. Paolino¹, M. Nicolo’², C. Pizzorni¹, C.E. Traverso², C.A. Cutolo²

¹ DiMI, University of Genova, Research Laboratory and Academic Division of Clinical Rheumatology, Genoa, ITALY, ² DINOGMI, University of Genova, Ophthalmology Clinic, Genoa, ITALY

Introduction: Some studies demonstrated choroidal involvement in systemic sclerosis (SSc), and recently optical coherence tomography (OCT) measurement showed significantly thinner choroid thickness (CT) in SSc patients (1-3). Laser speckled contrast analysis (LASCA) evaluates skin blood perfusion (BP) in different areas of the body (4). Iloprost, a prostacycline analogue, is effective in the treatment of microvascular manifestations of SSc (5). The aim of this study was to evaluate possible correlation between CT and skin BP in SSc patients, before and after iloprost treatment.

Material and Methods: Twelve SSc patients according to ACR/EULAR classification criteria (mean age 58±13 years, mean disease duration 5±3 years) underwent ophthalmologic evaluation by OCT and BP evaluation by LASCA, before (T0) and after eight hours of continuous iloprost i.v. infusion (0.5 ng/kg/min) (T1). OCT images were recorded by 3D-2000 OCT (Topcon, Japan), and CT area measurements were manually performed using image J software (6). BP was assessed by LASCA at the level of fingertips, periungueal, whole face, perioral and periorbital area, and the average BP calculated as perfusion units (PU) (4).

Results: BP was found significantly increased after iloprost therapy in all examined skin areas (fingertips 96 vs 119; periungueal 101 vs 120; whole face 178 vs 184, perioral 119 vs 126 and periorbital area 191 vs 199, respectively at T0 and T1, p<0.002). Statistically significant positive correlations were found between BP and CT, before and after iloprost therapy, at periorbital (T0 r=0.55 p=0.022 and T1 r=0.91 p=0.0002), perioral (T0 r=0.75 p=0.002 and T1 r=0.61 p=0.012), whole face (T0 r=0.49 p=0.04 and T1 r=0.47 p=0.05), fingertips (T0 r=0.69 p=0.004 and T1 r=0.63 p=0.01) and periungueal skin areas (T0 r=0.54 p=0.02 and T1 r=0.50 p=0.04). Patients did not show any visual/ocular symptom during and after iloprost infusion. However, statistically significant variation of CT values was observed after iloprost administration (p=0.7).

Conclusions: Despite the small cohort of enrolled patients, this study demonstrates a correlation between skin BP and CT in SSc patients. The results also confirm that LASCA may be a tool to monitor BP changes during microvascular targeted treatments.

References. 1. Farkas TG, et al Am J Ophthalmol 1972;74:875–886. 2. Serup L, et al Ophthalmic Res 1987;19:303–308. 3. Ingegnoli F, et al Microvasc Res 2015;97:31–36. 4. Ruaro B, et al Ann Rheum Dis 2014;73:1181–5. 5. Scorza R, et al Clin Exp Rheumatol 2001; 19:503–8. 6. Yamashita T, et al Invest Ophthalmol Vis Sci 2012;53:1102–1107.

P.234

Correlation Between Capillaroscopy Patterns of Microangiophaty and Skin Involvement in Systemic Sclerosis

B. Ruaro, A. Sulli, C. Pizzorni, S. Paolino, M. Ghio, E. Alessandri, M. Cutolo

Research Laboratory and Academic Division of Clinical Rheumatology, Department of Internal Medicine, University of Genoa, Genoa, ITALY

Introduction: Systemic sclerosis (SSc) is characterized by microvascular damage and skin impairment (1-3). Peripheral microangiopathy may be easily recognized and scored by nailfold videocapillaroscopy (NVC) (1-2). The modified Rodnan skin score (mRSS) is the validated method to assess the severity of skin impairment, and high frequency skin ultrasound (US) is a relatively new technique to measure dermal thickness (DT) (4-6). Furthermore, plicometer skin test (PST) is another method to evaluated cutaneous involvement in SSc patients (7). The aim of this study was to identify possible correlations between capillaroscopic patterns of nailfold microangiopathy and the microangiopathy evolution score (MES) and cutaneous involvement evaluated by US, mRSS and PST in SSc patients.

Material and Methods: Sixty-seven SSc patients (mean age 65±10SD years, mean disease duration 8±7 years) were enrolled after informed consent. All subjects were assessed by mRSS, US and PST to evaluate the DT in the seventeen skin areas of the body usually evaluated by mRSS (zygoma, fingers, hands, dorsum of hands, forearms, arms, chest, abdomen, thighs, legs, feet) (3,4). NVC was used to assess the proper pattern of microangiopathy and to calculate the microangiopathy evolution score (MES) (1,2). Statistical evaluation was performed by non-parametric tests.

Results: All methods demonstrated a progressively higher DT in patients with “Early”, vs. “Active” and vs “Late” pattern of nailfold microangiopathy (p<0.004), and a positive correlation was observed with MES (r=0.70 p<0.001). A positive correlation was also observed in SSc patients between the three method to evaluate DT (PST vs mRSS r=0.97, p<0.0001; PST vs US r=0.54, p<0.0001; US vs mRSS r=0.54, p<0.0001).

Conclusions: This study demonstrates a relationship between microangiopathy impairment and skin damage In SSc patients. This results also confirms that the degree of microangiophaty damage evaluated by capilaroscopy might be a mirror of other clinical aspects of systemic sclerosis.

References. 1. Cutolo et al. J Rheumatol 2000; 27;155.60. 2. Sulli A, et al. Ann Rheum Dis 2008;67:885-7. 3. Krieg T, et al. Rheumatology 2009; 48: iii14–iii18. 4. Moore TL, et al. Rheumatology 2003;42:1559-63. 5. Sulli A, et al. Ann Rheum Dis. 2014;69:1140-3. 6.Ruaro B, et al. Microvasc Res. 2017;115:28-33. 7. Parodi MN, et al. Br JRheumatol. 1997;36:244-50.

P.235

On-Demand Sildenafil as a Treatment for Raynaud’S Phenomenon: a Series of N-of-1 Trials

M. Roustit¹, J. Giai², O. Gaget³, M. Mouhib³, A. Lotito³, C. Khouri³, S. Blaise⁴, C. Seinturier⁴, F. Subtil², B. Imbert⁴, P.H. Carpentier⁴, S. Vohra⁵, J.L. Cracowski¹

¹ Univ. & CHU Grenoble-Alpes, Inserm HP2 UMR 1042, Grenoble, FRANCE, ² Université de Lyon, CNRS UMR 5558; Hospices Civils de Lyon, Lyon, FRANCE, ³ CHU Grenoble Alpes, Inserm CIC1406, Grenoble, FRANCE, ⁴ CHU Grenoble Alpes, Vascular Medicine Department, Grenoble, FRANCE, ⁵ University of Alberta, Edmonton, CANADA

Introduction: Continuous treatment of Raynaud’s phenomenon (RP) with Phosphodiesterase-5 inhibitors has shown moderate efficacy (1). Moreover, patients with RP may not be willing to take a long-term treatment; as RP attacks are usually triggered by exposure to cold, “as required” single doses before/during exposure may be a good alternative. The objective of the present study is to assess the efficacy and safety of an on demand sildenafil treatment in RP.

Material and Methods: A series of randomized, double-blind, N-of-1 trials was conducted in patients with primary or secondary RP. Each trial consisted in repeated cycles of 1-week treatment periods with placebo, sildenafil 40 mg or sildenafil 80 mg taken as required, with a maximum of two doses daily. Mixed models were used and parameters were estimated in a Bayesian framework to determine individual and aggregated probabilities of efficacy on the Raynaud’s Condition Score (RCS), the frequency, and the duration of RP attacks. Skin blood flow in response to cooling was assessed with Laser Speckle Contrast Imaging.

Results: Thirty-eight patients completed two to five treatment cycles (secondary RP, n=12). On aggregated data, the probability that sildenafil 40 mg is more effective than placebo on RCS, frequency, and duration of attacks is 90.6%, 92.9%, and 96.7%, respectively. For sildenafil 80 mg, the probability of superiority over placebo for these outcomes is 62.6%, 91.4%, and 97%, respectively. Inter-individual effect size was highly heterogeneous, with adjusted relative risks ranging from 0.27 to 2.9. Overall, sildenafil was associated with significantly more adverse events than placebo. We observed a dose-dependent effect of sildenafil on skin blood flow during cooling.

Conclusions: On demand sildenafil has a greater probability of efficacy than placebo in patients with RP. Individual data show highly heterogeneous response, highlighting the need for personalized treatment for these patients.

ClinicalTrials.gov Identifier: NCT02050360

1. Roustit M, Blaise S, Allanore Y, Carpentier PH, Caglayan E, Cracowski J-L. Phosphodiesterase-5 inhibitors for the treatment of secondary Raynaud’s phenomenon: systematic review and meta-analysis of randomised trials. Ann. Rheum. Dis. 2013;72(10):1696–1699.

P.236

Nailfold Videocapillaroscopy Patterns in Scleroderma Spectrum Disorders

V. Rodrigues Bernardino, M. Fernandes, Ac. Rodrigues

Autoimmune Diseases Unit, Hospital Curry Cabral - Centro Hospitalar Lisboa Central, Lisbon, PORTUGAL

Introduction: Nailfold videocapillaroscopy (NVC) is a non-invasive technique used to investigate skin microcirculation, having a significant role in the diagnosis of scleroderma spectrum disorders (SSDs). This group includes Systemic Sclerosis (SSc), Localized Scleroderma (LC), Overlap Syndromes (OS), Mixed Connective Tissue Disease (MCTD) and Scleroderma Mimicking Syndromes (SMS). Capillary abnormalities such as enlarged or giant capillaries, microhaemorrhages, a decline in capillary density and neoangiogenesis usually configure a scleroderma pattern. The latter can further be divided in early, active and late patterns.

Material and Methods: NVC was performed with a Videocap biomicroscope using well established classification criteria. NVC images and reports from all patients evaluated from January 2011 to current date were retrospectively analyzed. Comparisons were made using the Chi square tests; p values of < 0,05 were considered statistically significant.

Results: From 2011 to the present date, 203 NVC were performed to patients with SSDs, from which 186 women and 17 man. Mean age was 48 [±17] years. Raynaud’s Phenomenon (RP) was present in 92% of patients. SSc was the main diagnosis (n = 128: limited cutaneous (n = 98), diffuse cutaneous (n = 29), scleroderma sine scleroderma (n = 1)), followed by MCTD (n = 52), OS (n = 14), LC (n = 7) and SMS (n = 2). NVC results revealed scleroderma pattern (SP+) in 80% of patients (n = 163: early (n = 46), active (n = 82), late (n = 35)), non-scleroderma pattern (SP-) in 18% (n = 36), unspecific or normal in 2% (n = 4). In the SP- group, RP was absent in 14%. Significant statistic correlation was found between RP in SSDs and SP+ (p = 0,045), SSc and SP+ (p = 0,005), LC and SP-; no relation was established between DMTC and SP+ (p = 0,129) or OS and SP+ (p = 0,736).

Conclusions: Scleroderma pattern in NVC is a hallmark of SSDs, and statistical correlation was established between RP and SP+, as well as SSc and SP+. In MCTD, OS and LC no specific NVC pattern was identified, as vascular damage may not be as pronounced in these disorders.

P.237

Nailfold Videocapillaroscopy Scleroderma Pattern in Patients without Connective Tissue Disorders

V. Rodrigues Bernardino, M. Fernandes, Ac. Rodrigues

Autoimmune Diseases Unit, Hospital Curry Cabral, Centro Hospitalar Lisboa Central, Lisbon, PORTUGAL

Introduction: Nailfold videocapillaroscopy (NVC) is a non-invasive technique used to investigate skin microcirculation. This technique allows the distinction between primary and secondary Raynaud Phenomenon (RP) and it has a significant role in the diagnosis of scleroderma spectrum disorders (SSDs). Capillary abnormalities as enlarged or giant capillaries, microhaemorrhages, a decline in capillary density, and neoangiogenesis are usually the patterns that configure a scleroderma disorder.

Material and Methods: NC were performed with a Videocap biomicroscope using well established classification criteria. NC images and reports from all patients evaluated from January 2013 to current date were retrospectively analyzed.

Results: 18 NVC were identified as having scleroderma pattern and negative immunological results, which corresponded to 14 patients, 7 man and 7 women. Mean age was 36 [±18] years. RP was present in 93% of patients, but none of them had related connective tissue diseases (CTD). Relevant clinical aspects included livedo reticularis (n = 1) and erythema pernio (n = 3). No signs indicative of peripheral and visceral involvement or other elements of SSc were found. Risk factors for RP included tobacco (n = 2). RP treatment was based on Nifedipin (n = 5) and Bosentan (n = 1). Scleroderma patterns were divided according to Cutolo et al classification into early (n = 15), active (n = 4) and late (n = 0). In 3 patients, the NVC was repeated over time, with stable results and no clinical deterioration.

Conclusions: Scleroderma pattern in NVC is a hallmark of SSDs. However, patients with no CTD known disease can also present scleroderma patterns. These results suggest that either a CTD is yet to evolve in our patients or that other non-CTD related situations can mimic scleroderma patterns. The latter must be clarified to avoid clinical misinterpretations. A larger observational study must be carried on.

P.238

Leptin and Adiponectin Levels in Systemic Sclerosis Patients: Correlation with Manifestations of Vascular Damage

L. Gigante, E. De Lorenzis, G. B. Canestrari, G. Natalello, B. Tolusso, C. Di Mario, G. Ferraccioli, E. Gremese, S. L. Bosello

Institute of Rheumatology - Università Cattolica del Sacro Cuore, Rome, ITALY

Introduction: Adipocytokines are implicated in the development of fibrosis, vasculopathy and immune abnormalities through a variety of biological effects, but their role in systemic sclerosis (SSc) is not completely investigated. Two of the most abundant circulating adipokines, leptin and adiponectin, have a role in the development of endothelial dysfunction.

In addition to its metabolic actions, adiponectin has anti-inflammatory properties, while leptin mediates actions in endothelial cells, such as angiogenesis, vasodilation, NO production and upregulates various mediators of vascular inflammation.

In this study we investigated leptin and adiponectin levels and their ratio in SSc patients according to disease subtypes and clinical characteristics.

Material and Methods: Leptin and adiponectin levels were evaluated in 100 SSc patients by ELISA. Data regarding BMI, cardiovascular risk factors, disease subtype, organ involvement, vascular manifestations and nailfold capillaroscopy were available for the entire cohort. Inflammatory markers (ESR; CRP and IL-6) were also tested.

Results: In our cohort, as expected, adiponectin levels inversely correlate with IL-6 levels (R= -0.4, p<0.001), while directly correlate with capillary density on nailfold capillaroscopy (R=0.3, p=0.03). Patients with avascular areas on nailfold capillaroscopy presented lower levels of adiponectin (5.3±3.9 μg/ml) compared to patients without avascular areas (7.3±3.4 µ/ml), p=0.005. The antinflammatory and endothelium protective role of adiponectin emerged also when we considered the lung involvement: in fact patients with DLCO>50% presented higher levels of adiponectin (7.0±3.9 microgr/ml) compared to patients with DLCO<50% (5.8±3.8 microgr/ml), p=0.05.

Leptin levels directly correlate with vascular density on nailfold capillaroscopy (R=0.3, p=0.02), confirming the role of leptin in endothelial omeostasis. Furthermore patients with avascular areas presented lower leptin levels (15.5 ±13.0 ng/ml) compared to patients without avascular areas on capillaroscopy (31.1±28.4ng/ml), p=0.003. Leptin levels were lower in patients with active digital ulcers (9.3±6.6 ng/ml), compared to patients without ulcers (9.3±6.6 ng/ml), p=0.01. Considering the cardiopulmonary involvement, leptin levels inversely correlate with pulmonary arterial pressure on echocardiography (R=-0.24, p=0.02). Finally leptin levels inversely correlate with skin score (R=-0.3, p=0.009) and patients with early disease presented lower leptin levels (15.1±13.2 ng/ml) compared to patients with long lasting disease (29.9±28.7ng/ml), p=0.006.

Conclusions: These two cytokines are dysregulated in systemic sclerosis, in fact their reduction is associated with manifestations of vascular damage in scleroderma disease, suggesting a possible role of leptin and adiponectin in the impaired angiogenesis and in the development of vascular damage in scleroderma patients.

P.239

Survival in Systemic Sclerosis-Associated Digital Ulcers. Meta-Analyses and Systematic Review of the Literature

P. Meunier¹, L. Dequidt², T. Barnetche¹, E. Lazaro³, P. Duffau³, C. Richez¹, L. Couzi⁴, M.E. Truchetet¹, J. Seneschal²

¹ Rheumatology Department, University Hospital of Bordeaux, Bordeaux, FRANCE, ² Dermatology Department, University Hospital of Bordeaux, FRANCE, ³ Internal Medicine Department and Clinical Immunology, University Hospital of Bordeaux, Bordeaux, FRANCE, ⁴ Nephrology Department, University Hospital of Bordeaux, FRANCE

Introduction: Systemic sclerosis (SSc) is a chronic autoimmune disorder associated with high morbidity and mortality. Survival can be threatened in certain forms of SSc and determining prognosis criteria is crucial. Digital ulcers (DUs) are a common and disabling manifestation of SSc. The aim of this meta-analysis was to assess the association between the presence of DUs and mortality in SSc.

Material and Methods: We performed a systematic review and meta-analysis in the Pubmed and Scopus databases from January 1960 to May 2017. To optimize our research strategy, we achieved two research strategies using different keywords: « systemic sclerosis » and « digital ulcers » (strategy A); « systemic sclerosis » and « mortality » (strategy B). Articles were read independently by two reviewers. All studies, in which survival for SSc-associated DUs was reported, were included in the analysis. If not estimated, a risk ratio (RR) for mortality was estimated for each study. Pooled RR were calculated.

Results: 59 studies were examined for full text, and after the exclusion and inclusion criteria were applied, 10 articles were finally included in the analysis. SSc patients with DUs had an increased pooled mortality risk, (RR, 95% CI) at 1.53 (1.23-1.90).

Conclusions: Our meta-analysis revealed a higher mortality in SSc patients associated DUs. They could define a subgroup of patients with a worse prognosis. Having DUs may be a predictive factor to develop organ involvement such as pulmonary or cardiovascular events that could be associated with poor survival. This work suggests that early diagnosis and management are recommended in patients with SSc associated with DUs for a better outcome of survival. So developing DUs could be a red flag indicating severe form of SSc and should encourage to identify organ-involvement and result in a specific management.

P.240

Reliability of Simple Capillaroscopic Definitions to Describe Capillary Morphology in Rheumatic Diseases

K. Melsens^{1, 2}, M. Cutolo³, A.L. Herrick⁴, I. Foeldvari⁵, E. Deschepper⁶, F. De Keyser^1,2, O. Distler⁷, F. Ingegnoli⁸, Y. Mostmans^9,10, U. Müller-Ladner¹¹, C. Pizzorni³, V. Riccieri¹², B. Ruaro³, A. Sulli³, A. Trombetta³, A. Vanhaecke^1,2, V. Smith^1,2

¹ Department of Rheumatology, Ghent University Hospital, Ghent, BELGIUM, ² Department of Internal Medicine, Ghent University, Ghent, BELGIUM, ³ Research Laboratory and Academic Division of Clinical Rheumatology, Department of Internal Medicine, University of Genoa, Genoa, ITALY, ⁴ Centre for Musculoskeletal Research, The University of Manchester, Manchester Academic Health Science Centre, Manchester, UNITED KINGDOM,⁵ Hamburg Centre for Pediatric and Adolescent Rheumatology, Centre for Treatment of Scleroderma and Uveitis in Childhood, Hamburg, GERMANY, ⁶ Biostatistics Unit, Department of Public Health, Ghent University, Ghent, BELGIUM, ⁷ Department of Rheumatology, University Hospital Zurich, Zurich, SWITZERLAND, ⁸ Division of Rheumatology, Istituto Gaetano Pini, Department of Clinical Sciences & Community Health, University of Milan, Milan, ITALY, ⁹ Department of Dermatology, Vrije Universiteit Brussel (VUB), Universitair Ziekenhuis Brussel (UZ Brussel), Department of, Brussels, BELGIUM, ¹⁰ Department of Immunology and Allergology (CIA), Centre Hospitalier Universitaire (CHU) Brugmann, Université Libre de Bru, Brussels, BELGIUM, ¹¹ Rheumatology and Clinical Immunology, University of Giessen/Kerckhoff-Klinik, Bad-Nauheim, GERMANY, ¹² Department of Internal Medicine and Medical Specialities, University Sapienza Rome, Rome, ITALY

Introduction: The European League Against Rheumatism (EULAR) study group on microcirculation in rheumatic diseases has previously proposed simple definitions for interpretation of capillaroscopic morphology of single capillaries, which resulted in moderate reliability. This study has the aim to further optimize these definitions.

Material and Methods: To fine-tune the existing definitions (normal—hairpin, tortuous or crossing; abnormal—not hairpin, not tortuous and not crossing), convexity of the capillary head was added as a condition to be evaluated as normal (see figure). Thirty images with good visibility of single capillaries were selected by the golden standard team and presented to the attendees of the seventh EULAR Course on capillaroscopy, held in Genoa 2016. Attendees (n = 119) were asked to categorize themselves into one of the following levels of expertise in capillaroscopy: no experience (novices), n = 69; less than 5 years of experience, n = 41 and more than 5 years of experience, n = 9. Also, 5 independent experts (AH, FI, AS, MC and VS) evaluated the capillaries. Inter-rater agreement was assessed by calculation of the Cohen’s kappa between each rater pair of all possible combinations of attendees and the gold standard (GS) and then averaged to provide the Light kappa. In addition, the Cohen’s kappa scores between each attendee and the GS were averaged to obtain a mean index of reliability of the attendees to the GS.

Results: The resulting Light kappa based on 30 capillaries was 0.78 for all EULAR course attendees and 0.82 for the 5 independent experts. More specifically, the Light kappa was 0.84 for experienced attendees, 0.78 for moderate experienced attendees and 0.77 for novices. The mean Cohen’s kappa coefficient of all attendees to the GS was 0.81 (95% CI: 0.79-0.83). The mean Cohen’s kappa between each attendee and the GS was 0.83 (95% CI: 0.78-0.88) for experienced attendees, 0.81 (95% CI: 0.77-0.85) for moderate experienced attendees and 0.80 (95% CI: 0.77-0.83) for novices. The mean Cohen’s kappa between each expert in capillaroscopy and the GS was 0.81 (95% CI: 0.71-0.92).

Conclusions: This multicentre, international study, conducted at the seventh EULAR course on capillaroscopy, showed excellent reliability of optimized simple capillaroscopic definitions for describing morphology of capillaries by rheumatologists with varying levels of expertise. Further large-scale validation with random selection of single capillaries is needed to validate these findings.

P.241

Ultrasonic- Assisted Wound Debridement Compared with Autolitic Debridement for Scleroderma Ulcers: a Retrospective Clinical Study in a Heterogeneous Population of Systemic Sclerosis Patients

A. Marcoccia, C. Salvucci, T. D’Alesio, T. Nuzzo, M.G. Modesti

Sandro Pertini Hospital-Unit of Ischemic Microcirculatory Diseases and Scleroderma Ulcers, Roma, ITALY

Introduction: Ultrasonic-assisted wound debridement (UAWD) is a new method that uses acoustic energy to selective remove devitalized tissue from the wound bed to promote wound healing. Digital ulcers (DUs) usually develop in a large number of Systemic Sclerosis (SSc) patients and are very painful and difficult to treat.The aim of the present study was to evaluate the effectiveness of UAWD on the healing of Scleroderma DUs, the procedural pain as a Visuale Analogic Scale (VAS 0-10), the needs of antimicrobic treatment compared to the conventional autolitic debridement.

Material and Methods: We conducted a retrospective study on 140 SSc patients referred to our center due to DUs, whose onset was longer than 12 weeks. The cohort was very heterogenous, showing a different time of disease onset, different size and localization of DUs, different systemic therapy, different drugs and/or different dosage of drugs, according to the different caring rheumatological centers. Sixty-eight SSc patients (A Group) underwent both UAWD (using the appliance surgysonic wound-Esacrom) and conventional therapy, while 72 SSc patients (B Group) were treated with conventional wound therapy and autolytic debridement. The effectiveness endpoint were the reduction of median time of complete wound healing, the significant reduction of procedural pain on VAS 0-10 and the significant reduction of rate of antibiotic treatment.

Results: All the treated DUs had a chronic course, incurred from more than 12 weeks ( range 15-53 in A Groups; 13-47 in B group. DUs of A group were completely healed in a median time of 19 weeks (ranged 6-28), in comparison of the B Group median healing time of 23 weeks ( ranged 12 - 39). The infection and the procedural pain ratings were significantly reduced in A Group versus B Group ( P<0.05). Only 12 patients of the A group needed antibiotic treatment versus 31 patients in the B group . All patients in the A Group showed good compliance to UAWD reporting a slight and bearable procedural pain (VAS < 3). In B group the procedural pain VAS was > 5.

Conclusions: The use of UAWD in the treatment of SSc DUs appears to be effectiveness and complementary to traditional treatment (autolysis, enzymatic) on healing. it showed to significantly reduce infectious complications and good compliance to treatment, by reducing procedural pain and antibiotic needs in comparison to conventional treatment alone. UAWD seems a very promising treatment for SSc DUs but further investigations are needed

P.242

Combination of Capillaroscopic and Ultrasonographic Evaluations in Systemic Sclerosis: Results of a Cross-Sectional Study

A. Lescoat^{1, 2}, G. Coiffier³, M. de Carlan¹, C. Cazalets¹, A. Ballerie¹, C. Droicourt^{4, 5}, A. Perdriger³, P. Jégo^{1, 2}

¹ Department of Internal Medicine, CHU Rennes, University of Rennes 1, Rennes, FRANCE, ² INSERM, U1085, Research Institute in Health, Environment and Occupation / IRSET, Rennes, FRANCE, ³ Department of Rheumatology, CHU Rennes, University of Rennes 1, Rennes, FRANCE, ⁴ Department of Dermatology, CHU Rennes, University of Rennes 1, Rennes, FRANCE, ⁵ INSERM CIC1414, UPRES EA 7449 REPERES (Pharmacoepidemiology and access to health care), Rennes, FRANCE

Introduction: Macrovascular involvement is under-evaluated in systemic sclerosis (SSc). The relevance of macrovascular features as reliable severity markers of the the vasculopathy is still controversial in SSc. The objective of this study was to compare microvascular damages on nailfold capillaroscopy (NC) with macrovascular manifestations evaluated by hand power doppler ultrasonography (PDUS) in SSc patients, and to assess the associations of these damages with the main digital manifestations of the disease: digital ulcers (DU), pitting scars, acro-osteolysis and calcinosis.

Material and Methods: NC, hand X-Rays and PDUS were systematically performed in 64 unselected SSc patients. PDUS evaluation with assessment of ulnar artery occlusion (UAO) and finger pulp blood flow (FPBF) was performed blinded for the results of X-Rays and NC.

Results: UAO and pathologic FPBF were associated with severe capillary loss (<4 capillaries/mm) on NC (respectively OR=4.04 (1.23-13.29); p<0.05 and OR=3.38 (1.03-11.05); p<0.05). UAO was significantly associated with Cutolo’s late NC pattern (OR=3.80 (1.31-11.01); p<0.05). DU history was associated with UAO (OR=10.71 (3.36-34.13); p<0.0001), pathologic FPBF (OR=7.67 (2.52-23.28); p<0.0001), late pattern (OR=6.33 (2.03-19.68; p=0.001) and severe capillary loss (OR=8.52 (2.15-33.78); p=0.001). Acro-osteolysis was also associated with UAO (OR=15.83 (3.95-63.54); p<0.0001), pathologic FPBF (5.52 (1.71-17.90) p=0.003), late NC pattern (OR=6.86 (2.18-21.53); p=0.001) and severe capillary loss (OR=7.20 (2.16-24.02), p=0.001). Calcinosis on X-rays were associated with late NC pattern (OR=5.41 (1.82-16.12); p=0.002), severe capillary loss (OR=12.69 (3.14-51.26); p<0.0001) and UAO (OR=3.19 (1.14-8.92); p=0.025) but not with pathologic FPBF. Combination of UAO and severe capillary loss in a same patient was especially associated with DU history (OR=18.60 (2.24-154.34); p=0.001) and acro-osteolysis (OR=10.83 (2.56-45.88); p=0.001).

Conclusions: The combination of macro and microvascular evaluations by PDUS and NC may help to detect patients with a more severe vasculopathy. As PDUS is a widely available non-invasive tool, used in daily practice by an increasing number of rheumatologists, it may therefore prove to be relevant to detect patients with a more severe vasculopathy in daily practice. Recent clinical trials, evaluating therapeutic measures supposed to prevent new DU occurrence have failed to reach their primary outcome. Therefore, both macro and microvascular evaluations of the hand may help to better identify patients at high risk of ischeamic digital complications. The relevance of PDUS as a daily evaluation tool is still to be determined. The impact of therapeutic measures (i.e. vasodilator treatments) on PDUS parameters (UAO, FPBF) also needs to be evaluated.

P.243

Association of Skin Pigmentation Disorders with Vascular Involvement in Systemic Sclerosis: Analysis of a Cohort of 239 Patients

V. Leroy¹, P. Henrot², T. Barnetche², M. Cario-Andre³, P. Manicki², A.S. Darrigade¹, C. Richez², M.S. Doutre¹, E. Lazaro⁴, D. Barcat⁵, J.P. Vernhes⁶, J. Constans⁷, A. Taieb¹, M.E. Truchetet², J. Seneschal¹

¹ Department of dermatology, Hôpital Saint-André, CHU de Bordeaux, Bordeaux, FRANCE, ² Department of Rheumatology, Hôpital Pellegrin, CHU de Bordeaux, Bordeaux, FRANCE, ³ Inserm U1035, BMGIC, University of Bordeaux, Bordeaux, FRANCE, ⁴ Department of Internal Medicine, Hôpital Haut-Levêque, CHU de Bordeaux, Pessac, FRANCE, ⁵ Department of Internal Medicine, Hôpital Robert Boulin, Libourne, FRANCE, ⁶ Department of Rheumatology, Hôpital Robert Boulin, Libourne, FRANCE, ⁷ Department of Vascular Medicine, Hôpital Saint-André, CHU de Bordeaux, Bordeaux, FRANCE

Introduction: Systemic Sclerosis (SSc) could be associated with skin pigmentation disorders. However, little is known regarding the relation between skin pigmentation abnormalities and the course of the disease.

Our objective was to assess the association between pigmentation disorders and systemic involvements in SSc patients.

Material and Methods: This is a single-center retrospective study on a cohort of SSc patients. Five patterns of skin pigmentation disorders were defined: diffuse hyperpigmentation, sun-exposed areas hyperpigmentation, face/neck/upper chest hypopigmentation, acral hypopigmentation and diffuse hypopigmentation.

Results: 239 patients were included: 61 men and 178 women, mean age: 59.7 years old (SD 12.85 years). 88 (36.8%) patients had skin pigmentation disorders, with the following repartition among them: diffuse and sun-exposed hyperpigmentation in 38.6% (n=34) and 27.3% (n=24) respectively, face/neck/chest hypopigmentation in 10.2% (n=9), diffuse hypopigmentation in 12.5% (n=11) and acral hypopigmentation in 17% (n=15). Hyperpigmentation, and particularly diffuse hyperpigmentation, were associated with diffuse SSc (p=0.003 and 0.001), increased modified Rodnan’s skin score (mRSS) (p=0.037 and 0.001) and early Raynaud involvement (p<10-4 and p=0.002). Diffuse hypopigmentation was also associated with diffuse SSc (p=0.024) and increased mRSS (p=0.001). Hypopigmentation and diffuse hyperpigmentation were associated with vascular involvement (associating pulmonary arterial hypertension, digital ulcers and/or renal crisis; p=0.005 and 0.009), and more precisely with digital ulcers (p=0.01 and p=0.005).

Conclusions: Our study demonstrates significant association between pigmentation disorders and vascular involvement in SSc. Screening for skin pigmentation disorders could be useful in the management of SSc patients: both as a diagnostic tool and during follow-up to identify patients with high risk to develop vascular involvement.

P.244

Evaluation of Nailfold Capillaroscopic Pattern and Capillary Density in 318 Patients with Connective Tissue Diseases

G. Kumánovics, G. Nagy, L. Czirják

University of Pécs, Pécs, HUNGARY

Introduction: Nailfold capillaroscopy widely used to investigate patients with systemic sclerosis (SSc), but not in other connective tissue diseases (CTD).

To characterize both capillary morphology and measure capillary density in patients with different CTDs. Cases with and without RP were compared. Characteristics of patients with overlap syndrome features were also described.

Material and Methods: 318 patients with different CTDs and 25 healthy controls were enrolled. Capillary density and diagnostic parameters described by Cutulo including mean microangiopathy evaluation score (MES) and its components were also calculated. Presence of RP was investigated by a questionnaire. Overlap syndromes were defined as cases fulfilling a classification criteria of at least two distinct CTDs.

Results: The median capillary density of 89 patients with systemic sclerosis (SSc) was 6.66(5.2;7.94) and median MES was 1.97(1.19;3.13). In 73 cases with SLE the median capillary density was 8.23(7.4;8.94), the median MES was 1.00 (0.56;1.47). 28.8% of SLE patients had SSc capillary pattern (early, active or late pattern), all except two of them had RP. SLE-RP patients had significantly lower capillary density compared to SLE-non-RP patients (7.97 [7.19;8.72]vs. 8.92 (8.19;9.34), p<0.05). Median giant capillary point was significantly higher in the RP-SLE subgroup (0.06[0.00;0.28]vs. 0.00 [0.00;0.00] p<0.001) compared to cases without RP. The median capillary density of the 56 patients with Sjogren’s syndrome was 8.63 (7.38;9.44). SS overlap patients (n=41) had significantly lower capillary density compared to SS cases without overlap syndrome (9.13 [8.59;9.91] vs. 8.09 [7.19;9.25], p<0.05). Thirty patients had inflammatory myositis. The median capillary density in the myositis group was 8.22 (7.00;8.59). The 11 myositis-RP patients had significantly lower capillary density compared to ones without RP (6.89 [5.47;8.31] vs. 8.41 [7.59; 8.63], p<0.05). 52 patients fulfilled rheumatoid arthritis criteria (RA), 33 of them presented RP. 30.8% of all RA patients showed SSc capillary pattern, 87.5% of them had RP. Patients in RA-RP group had significantly lower capillary density (8.16 [7.25;9.06] vs. 9.38 [9.03;9.84] p<0.001) and significantly higher dilatation, giant capillary and hemorrhage point.

Conclusions: In patients with SLE and RA a higher percentage of SSc capillary pattern was observed than previously described. The capillary microscopic pattern is influenced by the coexistence or lack of RP in most of CTDs. Lower capillary density was observed in the presence of RP in SLE and RA compared to non-RP SLE and non-RP RA patients. Abnormalities of capillary density and morphology can also be observed in cases with SLE and RA without having RP.

P.245

Comparative Efficacy of Treatments for Secondary Raynaud’S Phenomenon: a Systematic Review and Network Meta-Analysis of Randomized Trials

C. Khouri¹, M. Lepelley², S. Blaise¹, Y. Allanore³, Al. Herrick⁴, Jl. Cracowski¹, M. Roustit¹

¹ Univ. Grenoble-Alpes, Inserm HP2 UMR 1042, CHU Grenoble Alpes, Grenoble, France, Grenoble, FRANCE, ² Pharmacovigilance Department, CHU Grenoble Alpes, Grenoble, France., Grenoble, FRANCE, ³ Université Paris Descartes Sorbonne Paris Cité, Inserm U1016 and CNRS UMR8104, Institut Cochin, Paris, France., Paris, FRANCE, ⁴ University of Manchester, Salford Royal Hospital NHS Foundation Trust, Salford Royal Hospital, Stott Lane, Manchester, Manchester, UNITED KINGDOM

Introduction: Recent guidelines from the European League against Rheumatism (EULAR) recommend oral calcium channel blockers (CCBs) as first-line therapy for Raynaud’s phenomenon (RP) secondary to systemic sclerosis (SSc), and phosphodiesterase type 5 (PDE-5) inhibitors in patients with severe RP and/or those who do not respond to CCBs. Intravenous prostacyclin (IV PGI2) analogues are indicated in some cases, and other treatments might also show some efficacy. Yet, there are few randomized, pairwise comparisons between all these treatments. We aimed at performing a systematic review of RCTs and at combining direct and indirect comparisons in a network meta-analysis to assess the effect size of the different treatments on SSc-related RP.

Material and Methods: This systematic review complies with the PRISMA statement guideline, and the full protocol is available online (PROSPERO registry, CRD42017057518). Eligible studies were double-blind, parallel or crossover randomized trials assessing any pharmacological treatment for RP in patients with SSc. The outcomes were the frequency and duration of RP attacks, and its severity (assessed through the Raynaud’s Condition Score or any other severity score). Data were abstracted and analyzed using the standardized mean difference (SMD). We performed a random-effects network meta-analysis using the graph theoretical method.

Results: Fifty-six studies enrolling 3757 patients (90.8% of whom had secondary RP) were included in quantitative analysis. IV PGI2 analogues, PDE-5 inhibitors and CCBs were the only drug classes to significantly decrease both RP frequency and severity. On frequency, the effect size was comparable between CCBs and PDE-5 inhibitors [0.29 (95% CI 0.05, 0.53) and 0.32 (95% CI 0.07, 0.57), respectively], and about twice larger for IV PGI2 analogues [0.67 (95% CI 0.34, 1.00)]. Differences were smaller on severity: SMD=0.32 (95% CI 0.10, 0.54) for PDE-5 inhibitors, 0.44 (95% CI 0.20, 0.67) for CCBs, and 0.49 (95% CI 0.19, 0.78) for IV PGI2 analogues. Only PDE-5 inhibitors showed a significant effect on the duration of RP attacks, SMD=0.27 (95% CI 0.03, 0.51). The results from two studies could not be obtained despite repeated requests (NCT01090492 and NCT00528242).

Conclusions: Network meta-analysis of double-blind, randomized controlled trials showed the highest efficacy for IV PGI2 analogues. Among oral treatments, PDE-5 inhibitors and CCBs had comparable efficacy, which is in line with the recently updated EULAR recommendations. However, the effect size is modest, and the lack of standardization of outcome measures is a limitation.

P.246

Whole Body Distribution and Clinical Associations of Telangiectasia in Systemic Sclerosis: a Cross-Sectional Study

M. Jouvray¹, D. Launay¹, S. Dubucquoi², V. Sobanski¹, C. Podevin³, M. Lambert¹, S. Morell-Dubois¹, P.Y. Hatron¹, E. Hachulla¹, J. Giovannelli³

¹ CHU Lille - département de médecine interne et immunologie clinique, Lille, FRANCE, ² CHU Lille - institut d’Immunologie, Lille, FRANCE, ³ Centre de Référence des Maladies Autoimmunes et Systémiques Rares du Nord et Nord-Ouest de France (CeRAINO), Lille, FRANCE

Introduction: Telangiectasia (TA), one of the diagnostic criteria for systemic sclerosis (SSc), could be a clinical marker for the severity of vasculopathy, including pulmonary arterial hypertension (PAH). We designed a cross-sectional study: (i) to describe the whole-body distribution of TA, (ii) to assess the associations between the whole-body number of TA and the characteristics of patients, (iii) to determine whether the number of TA may be useful to discriminate SSc-PAH patients.

Material and Methods: Patients were included in our National Referral Centre for Rare Systemic And Autoimmune Diseases if they fulfilled the 2013 ACR / EULAR criteria for SSc. They were excluded if they had received laser treatment. The whole-body number and distribution of TA were recorded at inclusion. The associations with patients’ characteristics were studied using univariate and multivariate linear regressions.

Results: 106 patients were enrolled, including 12 with PAH. The median (interquartile range) number of TA/patient was 30 (82.7). Their distribution was: 37.2% on the face, 33.2% on the upper limbs including 26.4% on the hands, 28.1% on the trunk including 17.1% for the upper part of the trunk, and 1.5% on the lower limbs. Using multivariate model, the whole-body number of TA was independently associated with PAH (p=0.038), pulmonary embolism (p=0.012), decreased glomerular filtration rate (p=0.038), increased soluble Endoglin (p=0.039) and male gender (p=0.033). The ROC analyses assessing the ability of TA to discriminate the presence of PAH revealed that the area under the curve was significant for the number of TA on the whole body (0.77 (0.57; 0.88)), on the hands and face (0.81 (0.57; 0.91)) and on the hands alone (0.77 (0.57; 0.89)).

Conclusions: In SSc-patients, TA were predominantly located on the face, hands and the upper part of the trunk. They may reflect the vasculopathy of SSc and could be a useful clinical biomarker for vascular disease, particularly for PAH, the most severe vascular complications of the disease.

P.247

Safety and Effectiveness of Hyperbaric Oxygen Therapy for Systemic Sclerosis Ulcers

S. Armstrong^1,2, A. Evans³, Z. Ahmad^1,2, S. Johnson^1,2,4

¹ Mount Sinai Hospital - Toronto Scleroderma Program, Toronto, CANADA, ² University of Toronto - Department of Medicine, Toronto, CANADA, ³ University of Toronto - Department of Anaesthesia, Toronto, CANADA, ⁴ University of Toronto - Institute of Health Policy, Management and Evaluation, Toronto, CANADA

Introduction: Vascular complications of systemic sclerosis (SSc, scleroderma) can result in ulcers in the distal extremities, which limit function and are often refractory to conventional treatments. Hyperbaric oxygen therapy (HBOT) has been used in the treatment of non-healing wounds, but its utility in patients with SSc is uncertain. The primary objective of this study was to evaluate the safety of HBOT for SSc ulcers. We secondarily evaluated the effectiveness of HBOT for SSc ulcers, and patient selection criteria for treatment of SSc ulcer patients with HBOT.

Material and Methods: We conducted a cohort study of SSc patients who were evaluated for treatment with HBOT in the Toronto Scleroderma Program and the Toronto General Hospital Hyperbaric Unit between 2002 and 2015. HBOT treatments involved 30-50 sessions in a monoplace or multiplace chamber with compression to a maximum depth of 2.5 atm and breathing oxygen for a total of 90 minutes 5 days per week. Ulcers were defined as lesions with a visually discernable depth and loss of epithelial continuity. Reasons for declining access to HBOT, adverse events and effectiveness in ulcer healing were evaluated. An ulcer was categorized as healed if it achieved epithelial continuity or National Pressure Ulcer Advisory Panel (NPUAP) stage X (stable necrotic tissue core or eschar). Transcutaneous oxygen tension criteria for evaluating ‘healability’ in diabetic foot ulcers were applied as none have been validated for the SSc.

Results: 2261 subjects were reviewed to identify 36 HBOT treated ulcers in 10 SSc subjects. They had a mean ± SD age of 58.0 ± 13.9 years. Eighty-seven percent were female. Ulcer locations included fingertip (n=10 (28%)), hand-PIP/DIP (n=11 (31%)), hand-MCP (n=2 (6%)) and lower extremity (n=10 (28%)). Thirteen SSc subjects did not receive HBOT due to reasons that included lack of achieving “healable” response to oxygen on transcutaneous oximetry and technical limitations in sensor placement options (n=4), presence of moderate - severe pulmonary arterial hypertension (n=2) and confinement anxiety (n=1). Of the HBOT treated subjects, adverse events included brief episodes of otic barotrauma (n=2) and nausea (n=2). Twenty-three ulcers (64%) improved after HBOT.

Conclusions: HBOT may be an effective option for SSc patients with non-healing ulcers. Therapy was generally well-tolerated, with no significant adverse events although transient self-limiting otic barotrauma was reported. Patient selection criteria specific to the SSc population may need to be developed as the presence of pulmonary arterial hypertension is considered a contraindication to HBOT.

P.248

Venous Thromboembolism in Systemic Sclerosis: Prevalence, Risk Factors and Impact on Survival

S. Johnson^1,2,3,4, N. Hakami^1,2,3,5, Z. Ahmad^1,3, D. Wijeysundera^4,6,7

¹ Mount Sinai Hospital - Toronto Scleroderma Program, Toronto, CANADA, ² Toronto Western Hospital - Toronto Scleroderma Program, Toronto, CANADA, ³ University of Toronto - Department of Medicine, Toronto, CANADA, ⁴ University of Toronto - Institute of Health Policy, Management and Evaluation, Toronto, CANADA, ⁵ Ministry of Health - King Fahad Central Hospital, Jizan, SAUDI ARABIA, ⁶ Toronto General Hospital - Department of Anesthesia and Pain Management, Toronto, CANADA, ⁷ University of Toronto - Department of Anesthesia, Toronto, CANADA

Introduction: Whether systemic sclerosis (SSc) confers increased risk of venous thromboembolism (VTE) is uncertain. We evaluated the incidence, risk factors and impact of VTE on SSc survival.

Material and Methods: A cohort study of SSc subjects who fulfilled the ACR–EULAR classification criteria between 1970-2017 was conducted. Deep vein thrombosis was defined as thrombus on extremity ultrasound. Pulmonary embolism was defined as thrombus on thorax CT angiogram. Risk factors for VTE and time to all-cause mortality were evaluated.

Results: Of the 1181 subjects, 40 (3.4%) experienced VTE events. The cumulative incidence of VTE was 2.7 (95% CI 1.9, 3.7) per 1000 patient-years. PAH (OR 3.77 (96%CI 1.83,8.17), peripheral arterial disease (OR 5.31 (95%CI 1.99,12.92), ScL70 (OR 2.45 95%CI 1.07,5.30), and anticardiolipin antibodies (OR 5.70 (95%CI 1.16,21.2) were predictors of VTE. There were 440 deaths. There was no difference in survival between those with and without VTE (HR 1.16 (95%CI 0.70,1.91). ILD (HR 1.54 (95%CI 1.27,1.88) and PAH (HR 1.35 (95%CI 1.10,1 .65) were predictors of mortality.

Conclusions: The risk of VTE in SSc is comparable to the general population. The presence of PAH, peripheral arterial disease, ScL70 and anticardiolipin antibodies are risk factors for VTE. VTE does not independently predict SSc survival.

P.249

A Feasibility Study of a Novel Light Treatment for Digital Ulcers in Systemic Sclerosis

M. Hughes¹, T. Moore¹, J. Manning¹, J. Wilkinson², S. Watson³, P. Samraj⁴, G. Dinsdale¹, C. Roberts⁵, A. Herrick¹, A. Murray¹

¹ Centre for Musculoskeletal Research, The University of Manchester, Salford Royal NHS Foundation Trust, Manchester Aca, Manchester, UNITED KINGDOM, ² Research and Development, Salford Royal NHS Foundation Trust, Salford, UNITED KINGDOM, ³ Medical Physics Department and University of Manchester, Salford Royal NHS Foundation Trust, Manchester, UNITED KINGDOM, ⁴ Medical Physics Department, Salford Royal NHS Foundation Trust, Salford, UNITED KINGDOM, ⁵ Centre for Biostatistics, Institute of Population Health, School of Medicine, The University of Manchester, Manchester, UNITED KINGDOM

Introduction: Locally acting, well-tolerated treatments for digital ulcers (DUs) in patients with systemic sclerosis (SSc) are needed. We aimed to investigate the safety, feasibility, and tolerability of a novel light treatment, and to tentatively assess treatment efficacy for SSc-DUs.

Material and Methods: A custom built device was constructed consisting of infrared, red and violet light-emitting diodes. Treatment was administered twice weekly for three weeks, with follow-up at weeks 4 and 8. Any safety concerns were documented at each visit.

Patient opinion on the time to deliver, feasibility (‘not feasible’, ‘indifferent’, ‘feasible’) and pain visual analogue score (VAS) (0-100, 100 most severe) with light treatment was collected. Patient and clinician DU VAS (0-100, 100 most severe) were documented. An independent assessor graded the change in DU appearance from photographs (-2 [much worse] to +2 [much better]). DU laser Doppler (perfusion) imaging was performed immediately before and after treatment, at the DU centre and surrounding tissue.

Results: 14 DUs in 8 patients (7 female and 1 male) were studied. The mean (SD) age of patients was 48.5 (15.2) years. Raynaud’s phenomenon (RP) duration was 16.1 (11.7) years and disease duration (from first non-RP clinical manifestation) was 11.9 (7.6) years. Two patients had severe finger contractures. The majority of patients had a history of severe digital vascular disease, including previous intravenous vasodilator therapy (n=6). Almost all patients (n=7) were receiving treatment with vasodilatory drug therapy.

Eight patients with 14 digital ulcers were recruited. 46 light treatments were administered, with no adverse events. All patients believed that light treatment was “feasible” and “took just the right amount of time”, with a low associated mean pain VAS of 1·6 (SD 5·2). Severity of DUs as judged by patients and clinicians improved during the study (mean change in VAS –7·1 and –5·2, respectively; both p=<0·001). According to independent assessment, mean change in appearance of DUs per week was 0·14 (95% CI 0 ·0–0·3) (p=0·01).

There was a significant increase in the relative (compared with baseline) mean perfusion after (compared with before) light treatment, in particular at the DU centre (0·32, 95% CI 0·13–0·52; p=0·0013).

Conclusions: Light treatment for DUs is safe, feasible and well tolerated. There was an early suggestion of treatment efficacy, with a significant improvement in DUs during the course of the study, and a local increase in DU perfusion with light treatment. Future research is warranted to develop light-based treatment as a locally acting therapy for SSc-DUs.

P.250

A Study Examining the Reliability of Digital Ulcer Definitions as Proposed by the Uk Scleroderma Study Group: Challenges and Insights for Future Clinical Trial Design

M. Hughes¹, M. Bhushan², K. Chakravarty³, C. Denton³, S. Dubey⁴, S. Guiducci⁵, L. Muir⁶, V. Ong³, L. Parker³, J. Pauling⁷, A. Prabu⁸, J. Ravenscroft⁹, C. Rogers¹⁰, C. Roberts¹¹, A. Tracey¹, A. Herrick¹

¹ Centre for Musculoskeletal Research, The University of Manchester, Salford Royal NHS Foundation Trust, Manchester, UNITED KINGDOM, ² Department of Dermatology, Blackpool Teaching Hospitals NHS Foundation Trust, Blackpool, UNITED KINGDOM, ³ Centre for Rheumatology and Connective Tissue Diseases, Royal Free Hospital, London, UNITED KINGDOM, ⁴ University of Florence, Florence, ITALY, ⁵ Department of hand surgery, Salford Royal NHS Foundation Trust, Salford, UNITED KINGDOM, ⁶ University Hospitals Coventry and Warwickshire NHS Trust, Coventry, UNITED KINGDOM, ⁷ Department of Pharmacy and Pharmacology, University of Bath, Bath, UNITED KINGDOM, ⁸ Rheumatology Department, City Hospital, Sandwell and West Birmingham Hospitals NHS Trust, Birmingham, UNITED KINGDOM, ⁹ Member of Working Group, contact via Professor Herrick, The University of Manchester, Manchester, UNITED KINGDOM, ¹⁰ The University of Manchester, Manchester, UNITED KINGDOM, ¹¹ Centre for Biostatistics, Institute of Population Health, School of Medicine, The University of Manchester, Manchester, UNITED KINGDOM

Introduction: The reliability of clinician grading of systemic sclerosis (SSc)-digital ulcers (DUs) has been reported to be poor to moderate at best, which is a major concern in clinical trial design. The aim of this study was to examine the reliability of new proposed UK Scleroderma Study Group (UKSSG) DU definitions (‘no ulcer’, ‘healed ulcer’ and ‘DU’) amongst UK clinicians with an interest in SSc. A secondary aim was to examine the performance of the definitions to be used in the context of ‘preventative studies’ (i.e. no ulcer vs healed ulcer/DU) and ‘treatment studies’ (i.e. no ulcer/healed ulcer vs DU).

Material and Methods: Raters graded through a custom-built web-based interface 90 (80 unique and 10 repeat) images of a range of digital lesions collected from patients with SSc. Lesions were graded on an ordinal scale of severity: ‘no ulcer’, ‘healed ulcer’, or ‘DU’. Reliability was assessed using a weighted kappa coefficient, with bootstrapping to generate estimates of confidence intervals. Data was dichotomised by adjoining adjacent categories for application in future ‘preventative’ and ‘treatment’ studies for DUs.

Results: Twenty-three clinicians: 18 rheumatologists, 3 dermatologists, one hand surgeon and one specialist rheumatology nurse, completed the study. A total of 2070 (1840 unique + 230 repeat) image gradings were obtained. For intra-rater reliability, across all images the overall weighted kappa coefficient was high (0.71) and was moderate (0.55) when averaged across individual raters.

Intra-rater reliability (kappa) was high for both the dichotomised analyses of ‘preventative’ (0.70, 95% CI = 0.62 – 0.79) and ‘treatment’ (0.77, 95% CI = 0.67 – 0.86) analysis. Inter-rater reliability was fair for the dichotomised analyses of ‘preventative’ (0.25, 95% CI = 0.19 – 0.31) and moderate for ‘treatment’ (0.41, 95% CI = 0.33 – 0.49) analysis.

Conclusions: Although our proposed DU definitions had high intra-rater reliability, the overall inter-rater reliability was poor. Our study further highlights the challenges of DU assessment by clinicians with an interest in SSc, and also provides a number of useful insights for the design of future clinical trials. Further research is warranted to improve the reliability of DU definition/rating as an outcome measure in clinical trials, including examining the role for objective measurement techniques, and the development of DU patient reported outcome measures.

P.251

Study of Quantitative Videocapilaroscopy in Systemic Sclerosis

A. Guillen-Del-Castillo¹, A. Selva¹, E.L. Callejas-Moraga¹, C. Tolosa-Vilella², S. Alonso-Vila¹, I. Sanz-Pérez¹, V. Fonollosa-Pla¹, C.P. Simeón-Aznar¹

¹ Hospital Universitari Vall D’Hebron, Universitat Autònoma de Barcelona, Barcelona, SPAIN, ² Corporació Sanitària Universitària Parc Taulí, Sabadell, SPAIN

Introduction: Systemic sclerosis (SSc) is an autoimmune disease characterized by a microvascular dysfunction. The aim of this study was to analyse the alterations of the capillary nailfold bed and describe their correlation with clinical variables.

Material and Methods: 134 SSc patients according to LeRoy and Medsger diagnostic criteria from the Hospital Universitari Vall d’Hebron were selected. Patients underwent an echocardiogram, pulmonary function test and nailfold videocapillaroscopy (NVC) within a 3 months period. NVC features were quantitatively measured. SPSS 20.0 were used for statistical analysis. A P-value < 0.05 was considered as significant.

Results: Female was the predominant gender (84.3%). Limited cutaneous subtype was the most prevalent (65.7%), following by diffuse cutaneous SSc (20.9%). More than 90% of patients met the ACR/EULAR 2013 classification criteria. The age (±standard deviation) at NVC was 38.5 (±15.7) years. Anti-centromere antibodies (ACA) were present in 36.6% of patients. Regarding organ involvement, 58 (43.3%) patients suffered from interstitial lung disease (ILD) and 11 (8.2%) pulmonary hypertension (PH). The forced vital capacity (FVC) was 80.8 (±20.1) % and diffusion capacity for carbon monoxide (DLCO) was 66.2 (±23.7) %. The tricuspid regurgitation velocity (TRV) was 2.8 (±0.3) m/s and the right ventricular systolic pressure 30.7 (±12.0) mmHg. SSc-ILD patients presented lower capillary density 4.86 /mm compared with 5.88 /mm in patients with no ILD (P = 0.005), and also more number of capillaries with neoangiogenesis 0.56 /mm compared with 0.31 /mm (P = 0.005). Multivariate linear regression analysis to establish the associations with FVC found a relationship between the number of capillaries with neoangiogenesis and lower FVC values (P < 0.001), as well as male gender and the identification of ILD on high resolution CT. For each capillary with neoangiogenesis visualized on average per 1 mm, FVC was 7.3% reduced. Number of abnormal capillaries were also related to reduced FVC (P = 0.049). Multivariate linear regression analysis showed associations between diminished DLCO values and reduced number of enlarged capillaries and increased number of giant capillaries, along with ILD on high resolution CT, lower FVC, PH confirmed by right heart catheterization, TRV >2.9m/s or other PH signs in the echocardiography. In this way, for each enlarged capillary per 1 mm, the DLCO was 7.8% higher. On the contrary, for each giant capillary per 1 mm, the DLCO was 11.8% diminished.

Conclusions: This work suggests that microvascular alterations may play a role as a pathogenic link with the lung SSc involvement.

P.252

Endothelial Dysfunction and Corticosteroid Therapy in Patients with Scleroderma

J.J. Gonzalez¹, P. Garcia De La Peña¹, O. Carrion², A. Abdelkader²

¹ Rheumatology Department. Hm Sanchinarro, Madrid, Spain, ² Angiology And Vascular Surgery Department. Hm Sanchinarro, Madrid, SPAIN

Introduction: Objectives: To study whether patients with systemic sclerosis (SSc) have an increased cardiovascular risk (CVR), measured on the basis of analytical, angiodinamic and / or vascular lesions on carotid ultrasound.

Material and Methods: Epidemiological and analytical data were collected. Vascular echographic protocol included assessment of carotid GIM, atheromatous plaques, and flow-mediated vasodilation (VDMF in%) was determined as the ratio between the difference in the diameter of the brachial artery minus the basal diameter, divided by the basal diameter. Endothelial dysfunction (ED) was considered for VDMF <10% and severe ED if <5%.

Results: 70 adult patients with SSc diagnosis (ACR 2013 criteria) were included. 94% were women, mean age 50.2 ± 12.5 years (range 19-76), and mean evolution time of 3.0 ± 4.4 years (range 0-20).

The distribution by subgroups was: limited SSc (48%), diffuse SSc (34%), pre-SSc (4’2%), sine scleroderma SSc (2.8%), MCTD (4.2%). Mean BMI 24.5 (SD ± 5). Mean SSRm 9.3 ± 7.0 (range 0-42). 32% had ulcers, 15.7% ILD and 2.5% PAH.

The capillaroscopy pattern was normal in 4.2%, non-specific in 28.8%, active in 27.3%, early in 19.7% and late in 19.7%.

Hypovitaminosis D was observed in 59% of the sample: insufficiency (<30ng / mL) in 32% of the sample, and deficit (<20 ng / mL) in 27%.

Fifty percent received corticosteroids at the time of inclusion, 75% had doses below 10 mg / day, and 65% had a duration of more than one year.

As for ultrasound findings, 39% had pathological IMT (> 0.9 mm), 23% had atheroma plaques (being bilateral in 40% of cases). The ABI had pathological values (<0.9) in 17% of the patients.

84% of the sample had ED data, being severe in 49% of subjects (VDMF <5%).

In the bivariate statistical analysis, the presence of ED was associated with corticoid intake (OR 6,12, 95% CI: 1.44-25.92, p = 0.014). In the multivariate model, the probability of ED (OR = 8.78, 95% CI: 1.52-50.78, p = 0.015) was shown to be very important for corticosteroid therapy, an independent effect of SSRm and the RCV SCORE index.

Conclusions: - The vast majority of the sample had endothelial dysfunction (84%), being severe in half of the patients.

- Steroid treatment greatly increases the likelihood of ED (up to 8 times).

- Although low doses of EC in general are used in SSc, it has been demonstrated that it also has implications for RCV.

P.253

Subclinical Atheromatosis and Vitamin D Deficiency in Patients with Scleroderma

J.J. Gonzalez¹, P. García De La Peña¹, O. Carrión², A. Abdelkader²

¹ Rheumatology Department. Hm Sanchinarro, Madrid, SPAIN, ² Angiology And Vascular Surgery. Hm Sanchinarro, Madrid, SPAIN

Introduction:

Objectives

To study whether patients with SSc have an increased cardiovascular risk (CVR), measured on the basis of analytical, angiodinamic and/or vascular lesions on carotid ultrasound.

The carotid IMT is a marker of cardiovascular morbidity and mortality, allowing measurement and monitoring of atherosclerosis in asymptomatic individuals, being surrogate markers of future coronary disease, stroke and general death in the general population and in inflammatory rheumatologic diseases.

Material and Methods: Epidemiological and analytical data were collected.

Vascular ultrasound protocol included assessment of carotid intima-media thickness (IMT), presence of atheromatous plaques, and exploration of peripheral arteriopathy using the ankle arm index (ABI).

Results: Seventy adult patients with ES diagnosis were included. 94% of the women had a mean age of 50.2 ± 12.5 years, and an average evolution time of 3.0 ± 4.4 years.

The distribution by subgroups was: limited SSc (48%), diffuse SSc (34%), pre-SSc (4’2%), sine SSc (2.8%), MCTD (5’7%) and overlap syndrome 4’2%). The mean SSRm was 9.3 ± 7.0 (range 0-42).

The IMT presented pathological values (> 0.9 mm) in 39% of the sample, 23% had atheroma plaques. Subclinical atheromatosis affected 41.4% (patients without CV events, pathological IMT and / or atheroma plaques). The ABI had pathological values (<0.9) in 17% of the patients.

In the bivariate analysis, the pathological GIM was related to the presence of ACA antibodies (OR = 3.80, 95% CI: 1.15-12.52, p = 0.028) and with the SCORE index of CVR (OR = 2.93, 95% CI: 1.12-7, 64, p = 0.028); And the presence of atherosclerotic plaques was associated with increased SSRm score (OR 1.09, 95% CI 1.00-1.19, p = 0.046), and the highest CVR SCORE index (OR 3.90, 95% CI: 1.31-11.56, p = 0.014.

In the multivariate analysis, the serum vitamin D concentration showed a protective effect on IMT (OR = 0.94, 95% CI 0.89-0.99, p value = 0.025); And the main determinant of atheromatous plaques is the SCORE index, since the increase of one unit in SCORE index multiplies by 4 the probability of presenting plaques (OR = 4.06, 95% CI: 1.31-12.60 ; P = 0.015).

Conclusions: • 40% had pathological IMT values, showing association with positive ACA and the SCORE risk index.

• The serum concentration of 25-OH-vitamin D showed a protective effect on IMT. Sixty percent of the sample had vitamin D deficiency.

• The presence of atheromatous plaques (23% of patients) was associated with higher SSRm indexes and SCORE index.

P.254

Intravenous Epoprostenol as Treatment for Digital Vasculopathy Associated with the Scleroderma Spectrum of Diseases

H. Farber, S. Law, R. Simms

Boston University School of Medicine, Boston, USA

Introduction: Intravenous prostanoid therapy is often recommended for severe systemic sclerosis-related digital vasculopathy. However, evidence supporting this recommendation is very limited. In this study, we evaluated the safety and efficacy of intravenous epoprostenol as treatment of scleroderma spectrum digital vasculopathy

Material and Methods: Using an ICD-9 code search, we identified patients at Boston University Medical Center with systemic sclerosis who had received intravenous epoprostenol as treatment for scleroderma spectrum digital vasculopathy between October 1, 2003 and September 1, 2015. Charts were reviewed and abstracted for this retrospective case series.

Results: We identified 35 patients who fulfilled these criteria (scleroderma spectrum digital ischemia/vasculopathy treated with intravenous epoprostenol); there were 47 total encounters. In 31 of these encounters, there was documentation in the record of improvement: decrease in pain, increased perfusion of digits assessed by warmth or color, and/or decreased number of digital ulcer number or size. In 16 of these encounters, there was no conclusive documentation in the record of improvement; however, there were no episodes of deterioration with intravenous epoprostenol. Intravenous epoprostenol infusion was well-tolerated with few adverse effects.

Conclusions: Intravenous epoprostenol infusion as treatment for scleroderma spectrum digital vasculopathy is effective and safe. Scleroderma spectrum digital vasculopathy improved with intravenous epoprostenol infusion in the majority of treatments. Further studies are needed to develop standardized measures of response/effectiveness and standardized drug protocols.

P.255

The Role of Naildfold Capillarascopy in the Study of Raynaud’S Phenomenon - Experience in a Medical Center in Argentina

S. Scarafia, M.A. Cusa

Instituto de Asistencia Reumatologica Integral (I.A.R.I), Buenos Aires, ARGENTINA

Introduction: Raynaud’s Phenomenon (RP) is a disorder of the microvasculature, characterized by episodic attacks of digital colour change,triggered by exposure to cold or emotional stress. Only 12.6% is secondary to rheumatic disease. It’s mainly associated to Systemic Sclerosis and Dermatomyositis, though it’s also observed in Systemic Lupus Erythematosis, Mixed Connective Tissue Disease, Primary Sjogren Syndrome, Rheumatoid Arthritis, Vasculitis and Antiphospholipid Syndrome. Naifold Capillaroscopy (NC) is a noninvasive, easy and safety diagnostic technique, designed to evaluate small vessels of the microcirculation in the nailfold, useful for the early detection of vascular disorders. Aim: To estimate the sensitivity and specificity of NC for the diagnosis of RP secondary to rheumatic disease.

Material and Methods: Diagnosis test study. We included patients who underwent NC from March 2016 to April 2017 at I.A.R.I. We recorded age, sex, evolution time of the RF, comorbidities and physical exam. Patients with RP secondary to rheumatic disease, occupational and envoirmental exposure were excluded. All NC were performed by the same physician with an electronic microscope (50X-200X). We considered normal or abnormal capillaroscopy according to EULAR’s definition. The rheumatologyst’s diagnosis was the gold standard. The categorical variables were expressed with percentage and the quantitative variables as mean (SD) or median (IQR) according to distribution. Data was analized with SPPS program.

Results: We included 53 patients, 96.2% women (n:51), median age 43 years old (IQR 32-58), median RP evolution time 12 months (IQR 6-24), normal physical exam 71.7%, smoker 13.2%, ex-smoker 11.3%, positive ANA 37.7%. 75.5% of the capillaroscopies were normal, SD pattern was observed in 17% of the patients. The RP was associated with rheumatic disease in 16 patients (30.2%), Limited Systemic Sclerosis 31.25%, Difuse Systemic Sclerosis 25%, Primary Sjogren Syndrome and Systemic Lupus Erythematosis 12.5% respectively, Mixed Connective Tissue Disease 6.25%, Antiphospholipid Syndrome 6.25%. NC sensitivity 59%and specificity 97% for diagnosis of the RP associated to rheumatic disease. Intra observer agreement kappa:0.89 ICC 95% 0.75-1.

Conclusions: NC is useful diagnosis tool with high specificity to differentiate the primary RP from the associated with rheumatic disease.

P.256

Differential Diagnosis of Necrotic Digital Ulcers Managed in the Last 7 Years in An Internal Medicine Unit: a Propos 14 Patients

G. Chalhoub

Central regional Hospital of MERCY, Ars Laquenexy, FRANCE

Introduction: Digital necrotic ulcers represent a serious situation that requires rapid and effective management in order to avoid and or to limit amputation which will represent a permanent handicap for the patients.

We were interested in sharing our experience regarding the most common causes of necrotic digital ulcers encountered in our internal medicine unit over the past7years.

Material and Methods: This is a retrospective study from 2010 to 2017, including14 cases with digital necrosis (9 women & 5 men). The average age was50.14 years. All patients had necrotic digital ulcers of1or more finger and or toe.

2cases presented with long term fever. 2 with a history of scleroderma, 8were active smokers, 3patients with history of drug abuse, 2cancer patients(1woman treated with PACLITAXEL for ovarian cancer and1patient with recent lung cancer).

1 case presented with superior vena cava syndrome(SVCS). 1Heroine addict initially hospitalized for panuveitis and1 presented an atrial fibrillation (AF).

Arterial/venous echodoppler of limbs, supra aortic trunks and CT angiogram+cardiac ultrasound were performed in all patients.

Antinuclear antibodies were significant in 5patients(1positive anti-Ku & anti Scl70 in 3cases). Anti-neutrophil cytoplasmic antibodies(ANCA)in1patient. Thrombophilia was negative in all patients.

Results: Scleroderma was confirmed in 3women, 1of whom presented a severe mesenteric infarction.

The embolic nature confirmed in 4cases(in3 cases, the necrosis was due to injections of crushed Buprenorphine tablets, 1of them presented a severe endocarditis- N°4 had abdominal aorta thrombosis due to AF).

Wegener’s graulomatosis was confirmed in 1patient and BUERGER disease in 2 smocker patients. Syphilis was confirmed in homosexual patient. The paraneoplastic nature was found in the bronchial cancer patient and in the SVCS patient which was related to a lung cancer. PACLITAXEL was incriminated in the patient of ovarian cancer.

Heparin was used in all patients. ILOMEDINE was initiated in many patients(Scleroderma, PACLITAXE & paraneoplastic causes) and BOSENTAN in 2 patients with Scleroderma.

Surgery was performed(angioplasty and thrombectomy in3patients, amputation in4 patients and intestinal resection in1patient).

The cutaneous outcome was generally favorable in most patients with Scleroderma, paraneoplastic cases due to initiation of chemotherapy and in the AF. Rapid death occurred in patients with endocarditis and syphilis.

Conclusions: The causes of digital necrosis remain diversified. It should be identified in order to start the specific treatment as soon as possible. Heparin therapy remains the treatment of choice. The amputation in advanced cases is mandatory in order to avoid sepsis.

The combination of ILOMEDINE and BOSENTAN remains effective in scleroderma and may limit the need of amputation.

P.257

A Cohort Study of Macrovascular Involvement in Patients with Systemic Sclerosis

C. Caimmi¹, S. De Marchi², G. Astorino¹, E. Bertoldo¹, P. Caramaschi¹, M. Rossini¹

¹ Rheumatology Unit, University of Verona, Verona, ITALY, ² Angiology Unit, University of Verona, Verona, ITALY

Introduction: It is well known that systemic sclerosis (SSc) affects microvessels, but data on macrovascular involvement are still lacking or debatable. Aim of this study was to estimate the prevalence of atherosclerotic plaques and their possible determinants in a large cohort of SSc patients.

Material and Methods: One-hundred and four outpatients with SSc were enrolled. Data about disease characteristics and cardiovascular risk factors (diabetes, hypertension, dyslipidemia, smoke) were collected and patients underwent a full ecocolorDoppler ultrasonography of arteries of the neck and lower limbs (LL).

Results: mean age was 62 (13) years and 17 (16.3%) patients were male. Seventy patients (67.3%) had a limited subset and the mean disease duration was 12.7 (6.8) years. A previous history of digital ulcers was found in 27 cases (26.0%). Thirty-eight patients (36.5%) were on ongoing or previous treatment with immunosuppressive drugs.

Regarding cardiovascular risk factors, 22 (21.2%) had hypertension, 7 (6.7%) diabetes, 52 (50%) dyslipidemia and 45 (43.3%) were active or past smokers. Fifty-seven (54.2%) patients had plaques at carotids, 1 (1%) at LL and 37 (35.9) at UL. Prevalences were higher in older patients, as expected.

Patients with carotid plaques were older (p<0.001), with hypertension (p=0.057), a limited disease subset (p=0.005), a more severe disease accordingly to Medsger severity score (0.048), worse renal function (p=0.012), higher glucose blood levels (p=<0.001), homocysteinemia (p=0.006) and ESR (p=0.004) and less often on immunosuppresors (p=0.048) but more often on steroids (p=0.050). Patients with LL plaques were older (p<0.001), male (p=0.003), treated with statins (p=0.056), with a worse renal function (p=0.001), higher glucose blood levels (p=0.038) and homocysteinemia (p=0.006).

In multivariate analysis with all variables with a p<0.010 in univariate, patients with carotid plaques were found to be older (p=0.003) and with a limited disease subset (p=0.012; OR 5.6, CI95% 1.5 to 21.5). These data were confirmed even after correcting also for other well-known risk factors for atherosclerosis. No variables were found to be statistically different between patients with and without LL plaques.

Conclusions: in this study we performed one of the most complete evaluation of macrovascular involvement in one of the most numerous cohort of SSc patients present in literature. The prevalence of carotid and LL plaques did not seem to be higher in SSc patients as compared to what reported in healthy subjects. Intriguing is that patients with limited disease have an increased risk of having carotid plaques even after correcting for possible confounders.

P.258

Severe Systemic Sclerosis and Nailfold Microangiopathy

M. Boonstra, D.C. Noordhoek, T.W.J. Huizinga, L.J.J. Beaart-Van De Voorde, J.K. De Vries-Bouwstra

Leiden University Medical Center, Leiden, THE NETHERLANDS

Introduction: Microangiopathy in Systemic Sclerosis (SSc), as visualized by nailfold capillary microscopy (NCM), is a dynamic and sequential process. Uncontrolled case-reports and a case-serie report possible improvement of nailfold microangiopathy after hematopoietic stem cell transplantation (HSCT). We aimed to evaluate differences in nailfold microvasculature in patients with severe SSc treated with HSCT and those treated otherwise.

Material and Methods: Recent and prior to treatment nailfold capillaroscopy images of patients with severe SSc were scored by two trained observers, blinded for treatment. Severe SSc was defined as fulfilling criteria of the ASTIS trial: A) disease duration < 4 years, modified Rodnan skin score (mRSS) >15 and carbon monoxide diffusing capacity (DLCO) and/or forced vital capacity (FVC) < 80% and evidence of interstitial lung disease OR B) disease duration < 2 years, mRSS > 20, ESR > 25 mm/1st hour and/or Hb <11 g/dl. Scoring included categorical scores (0=no changes to 3=> 66% alterations per millimetre) for capillary loss, neoangiogenesis, haemorrhages, dilatations, giants, disorganisation, together with a qualitative pattern and a VAS score for overall severity of microangiopathy. We here present preliminary results based on the scores of one observer.

Results: 27 HSCT and 21 controls (n=14 cyclophosphamide, n=7 other) were included. At follow-up nailfold microscopy of HSCT subject significantly displayed less giants (p=<0.05; no giants: HSCT 58% [n=15] vs. control 30% [n=6]), less disorganisation (p=0.02; >66% disorganisation: HSCT 7% (n=2) vs. control 45% [n=9]) and less often an SSc pattern (p=0.02; HSCT 44% [n=12] vs. control 80% [n=16]). The VAS score for overall severity of microangiopathy was significantly better in the HSCT group (p=0.033; median 32 [IQR 17-61]) vs. control 60 [IQR 36-71]).

Change in microangiopathy relative to baseline could be assessed in 21 patients (HSCT n=11, control n=10). Categorical scores for capillary loss (p=0.008; δcapillary loss category: HSCT -1 [IQR -1 to -1] vs. control 0 [IQR -0.5 to 1] ), dilatation (p=0.007; δdilatation category: HSCT -2[IQR -2 to -1] vs. control 0 [IQR -1 to 0]) and VAS scores (p=0.016; median δVAS -58 [IQR -63 to -19] in HSCT vs. -5 [IQR -24 to 8] in controls) improved significantly more in the HSCT group compared to controls.

Conclusions: Microangiopathy in severe SSc patients after HSCT is less severe and shows more improvement over time compared to severe SSc patients treated otherwise. In specific, improvement seems to be characterized by normalization of the capillary diameter and capillary density.

P.259

Correlation Between Healing Time and Blood Perfusion by Laser Speckle Contrast Analysis in Patients with Systemic Sclerosis

S. Barsotti^1,2, A. D’Ascanio¹, V. Venturini¹, L. Amanzi¹, S. Bilia¹, M. Mosca¹, A. Della Rossa¹

¹ Rheumatology Unit - Azienda Ospedaliero-Universitaria Pisana, Pisa, ITALY, ² Department of Medical Biotechnology - University of Siena, Siena, ITALY

Introduction: Digital ulcers (DUs) are a major manifestation of Systemic sclerosis and a proxy of disease severity(SSc). Furthermore DUs affect strongly daily quality of life of SSc patients. Laser speckle contrast analysis (LASCA) is a novel technique that can analyze blood perfusion (BP) in the fingers and in DU areas. The objective of the present study was to evaluate BP in patients with SSc and DUs and correlate these values with treatments and time to healing.

Material and Methods: During calendar year 2016-2017, we enrolled 24 consecutive SSc patients (2 male, 22 female; 16 patients with limited cutaneous SSc-lcSSc and 8 with diffuse cutaneous SSc-dcSSc, mean age 55.2±16.8 years) referred at our outpatient clinic for DUs at fingertips. BP was assessed at the first evaluation in the fingers affected by DU, unaffected fingers, DU area, peri-ulcer area and the same area of unaffected fingers. DUs were defined infected on clinical grounds (swelling, severe pain, erythema, essudation). Treatment with major vasoactive drugs (iloprost, bosentan, sildenafil) and time to DU healing under standard local treatment were collected. Statistical analysis was made by Statview-software.

Results: BP was lower in patients with dcSSc as compared to lcSSc in the finger affected by DUs (48.8±28.5 vs 90.2±44.8 p=0.038) and in unaffected fingers (52.2±21.1 vs 81.9±35.3 p=0.048). Analyzing the entire group the mean healing time was not correlated to BP in DU area or fingers.

Infected DUs showed higher BP as compared to non-infected DUs (198±112 vs 108.8±60.4) and required a longer healing time (165.5±75.7 vs 103.5±53.8 days p=0.045). In non-infected DUs (n=18), the mean healing time was longer in patients with lower BP in DUs area (r=-0.496 p=0.05) and peri-ulcer area (r=-0.488 p=0.011) while in infected DUs no correlation between BP and healing time was noticed.

Patients treated with bosentan and iloprost presented higher BP in the unaffected fingers (respectively p=0.002 and p=0.001) compared to untreated patients. However, no BP changes in DU area/fingers were observed. Sildenafil was not associated with significant differences in BP.

Conclusions: Our study suggests a potential usefulness of LASCA in the assessment of DUs in SSc patients. BP values could help in identifying difficult to heal lesions, either due to a markedly reduced perfusion (lower BP) or to the presence of an infection (higher than expected BP).

Additional data are needed to better define the role of BP as a guide to treatment, ulcer management and prevention in routine clinical practice.

P.260

Raynaud’S Phenomenon in Patients with Systemic Sclerosis Treated with Prostanoids

Z. Bagautdinova¹, I. Gaisin²

¹ V.A. Nasonova Research Institute of Rheumatology, Moscow, RUSSIA, ² Izhevsk State Medical Academy, Izhevsk, RUSSIA

Introduction: Description of the Raynaud’s phenomenon (RP) in patients with systemic sclerosis (SSc) with a long three-year observation and treatment with prostanoids.

Material and Methods: 25 RP patients (pts) held clinical-instrumental and serological studies – LDH, creatine phosphokinase, CRP, biomarkers – interleukins 1, 4, 6, 8, TNF-α, γ-IF, complement (C3, C4), interview HAQ, SF-36. 5 pts were treated by intravenous iloprost 25 µg for 3-5 days every 3-6 months, 11 pts received intravenous alprostadil 20 µg for 10 days every 6-12 months. 9 pts had alprostadil-switch-to-iloprost or iloprost-switch-to-alprostadil regimen due to prostanoids side effects.

Results: More than 50% of pts reported signs of RP, on average, for 4.3 years earlier, than symptoms of systemic sclerosis. Time since onset of RP was behind the beginning of SSc for 2.3 years. 8 (32%) pts had diffuse SSc, 17 (68%) pts had limited SSc. SSc activity identified in 15 patients (5.46±2.04 points). The total index of severity was 9.96±7.04.

All pts with active SSc had normal levels of complement (C3, C4) and CRP. Before treatment with alprostadil, the level of ESR was increased. LDH was elevated before iloprost treatment. All pts had normal creatine phosphokinase. The levels of proinflammatory IL-6 and CRP were associated with SSc activity.

Three of five pts (60%) were classified as good responders to iloprost treatment and four of eleven pts (36%) – to alprostadil. Iloprost and alprostadil reduced the frequency of RP attacs by ~ 1.2/day and daily duration of RP attacs. Treatment with alprostadil decreased numbness. After a 36-month follow-up, all 5 iloprost pts and all 2 alprostadil pts had healed up digital ulcers (DU). A trend towards a significant decrease in HAQ was observed in iloprost group compared to alprostadil. According to SF-36 questionnaire, pain and physical condition of all pts limited daily role activities.

Increased IL-1 and IL-8 levels were indicative of disease activity and required the correction of the DMARDs-therapy.

Conclusions: Treatment of RP in SSc with intravenous iloprost is effective in healing of DU, in reducing the frequency and duration of RP attacks, in improvement of quality of life according to HAQ.

Alprostadil may be recommended to RP pts with non-infectious DU without risk of phalanxs amputation. Prostanoids in treatment of RP pts with DU is effective and appears to be promising in prevention of new ulcers.

P.261

Association Between Bone Density and Microarchitecture and Micro- and Macro-Vascular Impairments At the Hand in Systemic Sclerosis

L. Atlan¹, N. Ibrahim², A. Valery³, C. Bazzi⁴, F. Rollin², G. Bens⁵, M. Marot¹, E. Esteve⁵, E. Lespessailles²

¹ Department of Rheumatology, university hospital center of Tours, Tours, FRANCE, ² Department of Rheumatology, Regional Hospital Center of Orléans, Orléans, FRANCE, ³ Department of Medical Information, Regional Hospital Center of Orléans, Orléans, FRANCE, ⁴ Department of Vascular Medicine, Regional Hospital Center of Orléans, Orléans, FRANCE, ⁵ Department of Dermatology, Regional Hospital Center of Orléans, Orléans, FRANCE

Introduction: Osteoporosis and atherosclerosis have both epidemiological and biological linkages. In systemic sclerosis (SSc), patients have a vascular involvement but also an increased risk of osteoporosis. The main objective was to investigate the link between bone density and micro-architecture alteration, measured by High-Resolution peripheral Quantitative Computed Tomography (HR-pQCT), and both macro-vascular disease, analyzed by digito-brachial pressure index (DBI) and micro-vascular parameters by the Cutolo score at the sclerodermic hand.

Material and Methods: We performed a monocentric cross-sectional study in female patients with SSc. Macrovascular assessment was realized by DBI at the 2nd and 4th finger measured on laser-doppler, considered pathological if DBI less than or equal to 0.7. Microvascular involvement was analyzed by Cutolo score on nailfold videocapillaroscopy, considered severe if pattern > I. Volumetric Bone Mineral Density (vBMD) and bone microarchitecture were measured by HR-pQCT at the distal radius.

Results: 33 SSc patients were included. In univariate analysis, low values of cortical vBMD were significantly associated with a DBI less than or equal to 0.7 at the second finger (p = 0.004), a DBI less than or equal to 0.7 in the fourth finger (p = 0.002) and a Cutolo pattern > I (p = 0.008). In multivariate analysis, low cortical vBMD was associated with a DBI less than or equal to 0.7 at the 4th finger, the age and a score of Cutolo pattern > I (adjusted R²=0.58; p=<0.001). Low cortical thickness was associated with a DBI less than or equal to 0.7 at the fourth finger, Cutolo pattern > I and age (adjusted R² = 0.49, p=<0.001). Low trabecular thickness was associated with a DBI less than or equal to 0.7 at the fourth finger (adjusted R² = 0.29, p = 0.001).

Conclusions: Our study findings showed an association between the severity of microvessels and macrovessels damage and altered microarchitectural indices at the radius in SSc confirming the link between vessels and bone that has been evidenced in previous studies. Longitudinal studies in larger group of patients with SSc might contribute to allow future preventive and therapeutic advice against osteoporosis in SSc patients with microvessels or macrovessels alterations.

P.262

Capillaroscopic Findings in Patients with Incomplete Crest Syndrome: Preliminary Results

C. Pomirleanu ^{1, 2}, R. Paiu², E. Ancuta³, R. Chirieac⁴, C. Ancuta^{1, 2}

¹ University of Medicine and Pharmacy Grigore T Popa, Iasi, ROMANIA, ² Clinical Rehabilitation Hospital, Rheumatology Department, Iasi, ROMANIA, ³ Elena Doamna Clinical Hospital, Iasi, ROMANIA, ⁴ SANOCARE Medical and Research Center, Iasi, ROMANIA

Introduction: telangiectasia) is widely acknowledged as the limited cutaneous Systemic Sclerosis (SSc) subtype, an entity with distinct pathobiological, clinical and therapeutic strategies.

As peripheral vasculopathy remains an essential event in SSc, the main objective of our study was to evaluate microvascular abnormalities by nailfold videocapillaroscopy (NVC) in CREST syndrome.

Material and Methods: Cross-sectional case-study in five patients classified as having incomplete CREST syndrome (without sclerodactyly) attending our outpatient rheumatology department (EUSTAR 162 center).

All subjects were evaluated according to a standardized protocol including demographics, and SSc-related variables (disease duration, Raynaud and non-Raynaud clinical features, antibody profile, disease activity and severity).

NVC assessment of microvascular damage was performed by the same trained examiner using an Optilia 200x capillaroscope, (i) tracking morphological alterations such as the distribution and orientation of capillary, shape, density and size, inter-capillary distance, haemorrhages, hemosiderin deposits, avascular areas and neoangiogenesis; and (ii) classifying as “early”, “active” or “late” pattern.

Results: We analyzed four female and one male, aged between 49 and 74 years, calcinosis, esophageal dismotility and telangiectasia were reported in two out of five SSc, Raynaud’s phenomenon in all cases, while sclerodactyly was not found; all patients had ANA positivity with anti-centromere B protein specificity.

The most common capillaroscopic findings described in our cases were: mild vascular architectural disorganization, moderate loss of capillaries (4-5/mm), frequent giant capillaries, hemosiderin deposits, as well as mild ramified/bushy capillaries. All changes were compatible with an active scleroderma pattern, as shown in figure 1a.

Moreover, we systematically identified the same significant structural anomalies of the capillaries, respectively a specific morphological aspect of a giant capillary with the diameter between 76-195 micron (figure 1b).

Conclusions: The association between limited SSc phenotype CREST and abnormal giant capillaries described in patients without sclerodactyly raised the question whether other factors outside the classical ones are involved in peripheral vasculopathy.

Further research is required in order to clarify the pathobiological and clinical significance of specific giant capillaries described in CREST without sclerodactyly.

P.263

Subclinical Atherosclerosis is Lower in Patients with Systemic Sclerosis Than in Patients with Rheumatoid Arthritis

M. Aguilar-Zamora¹, L. Montolio-Chiva¹, M. Robustillo-Villarino¹, D. Ybáñez-García¹, È. Valls-Pascual¹, À. Martínez-Ferrer¹, E. Rodilla-Sala², J.J. Alegre-Sancho¹

¹ Rheumatology Department, Hospital Universitari Dr. Peset, Valencia, SPAIN, ² Internal Medicine Department, Hospital de Sagunt, Sagunt, Valencia, SPAIN

Introduction: Subclinical atherosclerosis (AS) and vascular complications (VC) are higher in patients with Systemic Sclerosis (SSc) than in healthy population. A major intrahospital mortality because of VC in patients with SSc as to those with Rheumatoid Arthritis (RA) and Systemic Lupus Erythematosus (SLE) has also been described.

Objectives: To compare the presence of subclinical AS among patients with SSc, RA and a population of healthy people.

Material and Methods: Transverse study including patients diagnosed with SSc and RA. Patients with previous VC, renal failure and/or diabetes were excluded. The control group were volunteers from the same geographical area. We gathered demographic variables (age,gender,BMI), smoking status, blood pressure and analytical variables (cholesterol, atherogenic index[AI]). The extracranial branches of carotid artery were explored by ultrasonography (US) using an ESAOTE MyLab XV70 with a 7-12 MHz linear transducer and an automated program measuring intima-media thickness (IMT) through radiofrequency (RFQIMT). The presence of atheroma plaques as per the Mannheim consensus was registered. Statistical analysis: IBM-SPSS Statistics v22.0 package.

Results: 266 patients were included, 23,7% (85) SSc and 50,4% (181) RA. The control group was conformed by 93 healthy individuals. Women proportion, arterial hypertension and age were greater in RA and SSc patients than in healthy subjects (p<0,001); but smoking status was higher in healthy subjects (p<0,001). BMI was lower in patients with SSc than RA (p=0,046) and the healthy group (p=0,008). No differences were found between groups in the rest of variables. Results of the vascular study, grouped by diagnosis, is shown in the table below.

A major prevalence of atheroma plaque and pathologic US was seen in RA patients than in SSc patients (p=0,002 and p=0,007, respectively) and healthy subjects (p=0,005 and p=0,001, respectively), whereas no differences between SSc and healthy subjects were seen within these results. Patients with SSc, however, showed higher mean IMT values than healthy subjects (p=0,047) but less than patients with RA (p<0,001), with a higher percentage of patients with IMT>0,9 than healthy subjects (p=0,005) in the bivariate analysis. However, this association was lost in the multivariate analysis, and these differences might be due to age and arterial hypertension differences between groups.

Conclusions: RA is a more atherogenic disease than SSc, probably because of its higher inflammatory load. Higher mortality by VC in SSc could be attributed to a major multiorganic affection of the disease. In our serie we didn’t find a higher prevalence of subclinical AS in patients with SSc than in healthy subjects.

P.264

Capillaroscopy and Macrovascular Disease in Patients with Systemic Sclerosis

M. Aguilar-Zamora¹, L. Montolio-Chiva¹, M. Robustillo-Villarino¹, D. Ybáñez-García¹, È. Valls-Pascual, À. Martínez-Ferrer¹, J.A. Román-Ivorra², J.J. Alegre-Sancho¹

¹ Rheumatology Department, Hospital Universitari Dr. Peset, Valencia, SPAIN, ² Rheumatology Department, Hospital Universitari i Politècnic La Fe, Valencia, SPAIN

Introduction: Subclinical atherosclerosis (AS) and vascular complications (VC) are higher in patients with Systemic Sclerosis (SSc) than in healthy population. However, the relationship between macrovascular and microvascular damage has not been adequately studied by specific techniques such as capillaroscopy.

Objectives: To explore the possible relation between several macrovascular disease variables (carotid doppler ultrasound, ankle-brachial index [ABI]) and capillaroscopy findings in patients with SSc.

Material and Methods: Transverse descriptive study with analytical components. Study population: 115 SSc patients. Variables: 1) clinical variables; 2) capillaroscopy study: findings of scleroderma pattern (megacapillaries, haemorrhages and avascular areas) and classification of evolving patterns according to Cutolo et al.; 3) vascular study: ankle-brachial index (ABI) and carotid doppler ultrasound (ESAOTE MyLab XV70, 7-12 MHz linear transducer, software RFQIMT) measuring intima-media thickness (IMT) and presence of atheroma plaques (Mannheim Consensus). A vascular surgeon measured ABI, and the doppler ultrasound was done by a highly experienced rheumatologist, blind to the rest of findings, in a term of 3 months. Statistical analysis: IBM-SPSS Statistics v22.0 package.

Results: 115 patients where included consecutively, of which finally 108 were studied: mean age 60.16 years (SD ±15.16), 99 women (91.7%), mean SSc evolution time 11.45 years (SD ±8.84); LcSSc (50%), SSc without scleroderma (18.5%), DcSSc (16.7%), overlap syndrome (9.3%), pre-SSc (5.6%). The mean right side IMT was 0,579 mm (SD ± 0,126), and the left side 0,657 mm (SD ± 0,158); 33,3% had atheroma plaques. In total, 37% had a pathological carotid ultrasound, and 39,8% had macrovascular damage (atheroma plaque and/or IMT > 0,9 mm and/or ABI< 0,9). In the capillaroscopy study, megacapillaries, haemorrhages and avascular areas were found in a 82,4%, 74,1% and 56,5% of patients, respectively. When re-classifying the findings according to Cutolo et al, 31,5% of patients showed an early pattern, 37% an active pattern and a 22,2 % a late SSc pattern. In the bivariate analysis, the existence of macrovascular affection showed an association with a capillary pattern with more avascular areas and fewer megacapillaries. Statistically, this association was significant between the presence of avascular areas and the macrovascular damage (χ2= 4,412; p-valor = 0,036) and the pathological carotid ultrasound (χ2= 4,107; p-valor = 0,043) variables. A tendency towards an association between these last two macrovascular variables and capillaroscopy patterns of major microvascular damage was seen.

Conclusions: Nailfold capillaroscopy might be a useful tool to predict the presence of AS and macro vascular damage in patients with SSc.

P.265

Factors Related with the Development of Atherosclerosis in Patients with Systemic Sclerosis

M. Aguilar-Zamora¹, L. Montolio-Chiva¹, M. Robustillo-Villarino¹, D. Ybáñez-García¹, È. Valls-Pascual¹, À. Martínez-Ferrer¹, J.A. Román-Ivorra², J.J. Alegre-Sancho¹

¹ Hospital Universitari Dr. Peset, Valencia, SPAIN, ² Hospital Universitari i Politècnic La Fe, Valencia, SPAIN

Introduction: Subclinical atherosclerosis (AS) and vascular complications (VC) are higher in patients with Systemic Sclerosis (SSc), and this has been related to nontraditional vascular risk factors (VRF).

Objective: To identify VRF independently related to the existence of macrovascular affection (carotid ultrasound, ankle-braquial index [ABI]) in patients with SSc.

Material and Methods: Transverse descriptive study with analytical components. Study population: 115 SSc patients. Variables: 1) clinical variables; 2) questionnaires and indices: global VAS, HAQ and SF-36, CHFS (Cochin Hand Function Scale) and MHISS (Mouth Handicap In Systemic Sclerosis scale), HOMA and SCORE; 3) Analytical variables: hemogram, classic vascular risk biomarkers, activity/inflammation biological markers, autoantibodies, hemostasis/vascular disease markers; 4) vascular study: ABI and carotid doppler ultrasound (ESAOTE MyLab XV70, 7-12 MHz linear transducer, software RFQIMT) measuring intima-media thickness (IMT) and the presence of atheroma plaques (Mannheim Consensus); 5) Other variables. A vascular surgeon measured ABI, and the doppler ultrasound was done by a highly experienced rheumatologist, blind to the rest of findings, in a term of 3 months. Statistical analysis: IBM-SPSS Statistics v22.0 package.

Results: 115 patients where included consecutively, of which finally 108 were studied: mean age 60.16 years (SD ±15.16), 99 women (91.7%), mean SSc evolution time 11.45 years (SD ±8.84); LcSSc (50%), SSc without scleroderma (18.5%), DcSSc (16.7%), overlap syndrome (9.3%), pre-SSc (5.6%). AS risk factors: 38.9% hypertension, 46.3% dyslipidemia, 6.3% diabetes. Overall, 37% had a pathological carotid ultrasound, and 39.8% macrovascular damage (atheroma plaque and/or IMT > 0.9 mm and/or ITB <0.9). The bivariate analysis showed a relation between macrovascular disease and several traditional and nontraditional (related to the disease) VRF. In the multivariate analysis, age, HTA, DL, systolic pressure, glycaemia, renal function, VC history, SCORE values, SF36, duration of the SSc, coexistence of an inflammatory disease, diastolic dysfunction of the LV, ESR, D-dimer values, estimated PsAP values, and the use of different drugs (statins, ACEI, ARBs, endothelin receptor antagonists, rituximab) maintained a significant relationship with the different macrovascular disease variables.

Conclusions: Macrovascular disease in patients with SSc is associated with traditional VRF (age, HTA and DL) as well as VRF related to SSc (prolonged duration, greater inflammatory load, elevated PsAP values, diastolic dysfunction of LV). An strict control of blood pressure values and the use of statins should be part of the regular protocol for treating selected and elderly patients.

P.266

Study of the Role of IL-6 in the Development of Atherosclerosis in Patients with Systemic Sclerosis

M. Aguilar-Zamora¹, L. Montolio-Chiva¹, M. Robustillo-Villarino¹, D. Ybáñez-García¹, È. Valls-Pascual¹, À. Martínez-Ferrer¹, J.A. Román-Ivorra², J.J. Alegre-Sancho¹

¹ Rheumatology Department, Hospital Universitari Dr. Peset, Valencia, SPAIN, ² Rheumatology Department, Hospital Universitari i Politècnic La Fe, Valencia, SPAIN

Introduction: Background: IL-6 is one of the cytokines with greater presence in Systemic Sclerosis (SSc) and also one of the key cytokines in the development of atherosclerosis (AS). A study by Schiopu E, et al (Rheumatology 2014) showed a relationship between IL-6 and carotid AS. However, the results were not confirmed in a multivariate analysis and wheter these results are replicable in different populations from different geographical areas has not been tested.

Objectives: To assess the relation between plasma IL-6 and AS findings in patients with SSc.

Material and Methods: Transverse descriptive study with analytical components. Study population: a cohort of 115 patients with SSc. Variables: 1) clinical variables; 2) determination of serum IL-6 (IMMULITE 2000; Siemens Healthcare Diagnostics, UK); 4) vascular study: ankle-brachial index [ABI] and carotid doppler ultrasound (ESAOTE MyLab XV70, 7-12 MHz linear transducer, software RFQIMT) measuring intima-media thickness (IMT) and presence of atheroma plaques (Mannheim Consensus). A vascular surgeon measured ABI, and the doppler ultrasound was done by a highly experienced rheumatologist, blind to the rest of findings, in a term of 3 months. Statistical analysis: IBM-SPSS Statistics v22.0 package.

Results: 115 patients where included consecutively, of which finally 108 were studied: mean age 60.16 years (SD ±15.16), 99 women (91.7%), mean SSc evolution time 11.45 years (SD ±8.84); LcSSc (50%), SSc without scleroderma (18.5%), DcSSc (16.7%), overlap syndrome (9.3%), pre-SSc (5.6%). AS risk factors: 38.9% hypertension, 46.3% dyslipidemia, 6.3% diabetes. Mean concentrations of serum IL-6 were 4.34 pg/mL (SD ± 5). Mean right IMT was 0.579 mm (SD ± 0.126), and left 0.657 mm (SD ± 0.158); 33.3% had atheroma plaque. In total, 37% had a pathological carotid ultrasound and 39.8% macrovascular damage (atheroma plaque and/or IMT> 0.9 mm and/or ABI< 0.9). In the bivariate analysis, serum IL-6 was associated to the IMT as well as the presence of atheroma plaque (p-value = 0.002).This association was maintained when jointly considering an ABI< 0.9 (p-value = 0.003). Serum IL-6 was also related to the difference in systolic arterial pressure between both arms (r-Pearson = 0.236; p-value = 0.022). In the multivariate analysis, the number of atheroma plaques and the macrovascular damage variable maintained statistical significance in the different models.

Conclusions: Serum IL-6 concentrations are independently related to the presence of AS and macrovascular disease in patients with SSc. Blocking the action of IL-6 by means of specific therapies could be a therapeutic option which could reduce macrovascular damage in patients with SSc.

P.267

Implications of Capillaroscopic Patterns on Clinical Manifestations and Prognosis in the Spanish Registry of Systemic Sclerosis Patients (RESCLE)

M. Rodero-Roldán

Hospital General de La Defensa, Zaragoza, SPAIN

Introduction:

A growing body of evidence supports the role of microvasculopathy as the promary pathogenic event mediated by autoinmunity; the alterations in the microvasculopathy can be evaluated by capillaroscopy (CP). It still has not been proven if CP is useful to identify the subgroup of scleroderma (SSc) patients with the highest morbidity-mortality, but in recent years some authors found association between some SSc pattern in CP and different manifestations.

In this study, the RESCLE observers investigate the prognostic value of specific capillaroscopy patterns (CPP) in SSc, and the clinical characteristics and prognosis according to capillaroscopic pattern, both globally and by SSc subsets.

Material and Methods: Cross-sectional study on CPP in the multicentric patients registry from the RESCLE. We studied a cohort of 988 patients who were classified in 4 subsets using a modified Leroy and Medsger classification: "prescleroderma", limited cutaneous SSc (lcSSc), diffuse cutaneous SSc (dcSSc), and SSc sine scleroderma (sineSSc). The capillaroscopy followed the patterns described by Maricq: active pattern (AP) and slow pattern (SP). We collected epidemiologic, clinical, laboratory and other tests, and we studied the associations by CPP.

Results: Out of 988 patients, 604 patients (61,13%) had SP and 384 (38,86%) had AP; 89% were women and the mean age at diagnosis was 51,9 (±15,2). AP was associated with dcSSc (p<0,001) and shorter time until diagnosis (p 0,002). In the global series we found association between AP and digital ulcers (DU)(p 0,0033), diffuse interstitial lung disease (dILD)(p <0,001), and scleroderma renal crisis (SRC)(p <0,001), while SP was associated with malignancy (p,044). Association was found between anti-centromere antibodies and SP(p 0,009), and between anti-topoisomerase and AP (p 0,005).

Lower global series and dcSSc subset survival were associated with AP (p 0,047 and p 0,038, respectively). In the global series and dcSSc subset the SSc-related mortality was associated with AP (p 0,012 and p 0,002, respectively), while the not SSc-related mortality was associated with SP (p 0,012 and p 0,002, respectively). Multivariate analysis of the global series confirmed the AP as risk marker for dcSSc (p 0,000), and SP for malignancy (p 0,044); while in dcSSC subset the AP is a risk marker for mortality(p 0,002).

Conclusion: AP was associated with several clinical manifestations (dILD, SRC, DU), while SP was associated with malignancy. In both the global series and dcSSc subset,AP was related with lower survival, stating the implication of the CPP as a risk marker