C. Rotondo

Mucocutaneous Involvement in Behçet's Disease: How Systemic Treatment Has Changed in the Last Decades and Future Perspectives.

Behçets disease (BD) is a multisystemic disorder of unknown etiology characterized by the “triple symptom complex” consisting of recurrent oral aphthosis, genital ulcers, and chronic relapsing bilateral uveitis. Recurrent mucocutaneous lesions are generally considered the hallmark of the disease, being the most common symptoms presenting at the onset of disease. Although the improvement of knowledge about the pathogenetic mechanism added important changes in the treatment management of BD clinical manifestations, thus avoiding the appearance of serious life-threatening complications which are disease related, the mucocutaneous lesions are still the most nagging clinical manifestations to be treated. In this work we reviewed the current state of knowledge regarding the therapeutic approaches for mucocutaneous lesions of BD mainly based on controlled studies to provide a rational framework for selecting the appropriate therapy for treating these troublesome features of the disease.

No changes in N-terminal pro-brain natriuretic peptide in a longitudinal cohort of patients with systemic sclerosis-associated pulmonary arterial hypertension on therapy with bosentan

The aim of this study was to evaluate N‐terminal pro‐brain natriuretic peptide (NT‐proBNP) in patients with systemic sclerosis (SSc)‐associated pulmonary arterial hypertension (PAH) and changes after therapy with bosentan.

Correlation between serum amyloid-A and serum levels of proinflammatory cytokines in patients with Behçet's disease

Behcets disease (BD) is an inflammatory disorder of unknown aetiology, unanimously recognized as both autoimmune and autoinflammatory disease. Indeed many of its classical manifestations overlap with those of monogenic autoinflammatory disorders. Clinically disease is characterized by multiple organ involvement, in particular by the “triple symptom complex”, consisting of recurrent oral aphthosis, genital ulcers and recurrent bilateral uveitis. The abnormal activation of either innate and adaptive immunity, triggered by some microbial agents in genetically predisposed individuals, with consequent interaction of both T lymphocytes and activated neutrophils would seem to be involved in the disease onset. Therefore multiple cytokines may contribute to the pathological scenario of BD playing a pivotal role in the occurrence of the clinical manifestations.

Intra-articular therapy with tumor necrosis factor-α antagonists: an update

The aim of the study was to review from the present literature the intra-articular (IA) use of the TNF-blocking drugs. A total of 28 papers about this topic were found through a search in PubMed; the first publications date was July 2003. These studies include a total of 214 patients affected by 12 different joint diseases that reported a total of 1046 intra-articular therapies carried out in 10 different joint sites. Infliximab and etanercept were the most widely used medications. The safety of this treatment clearly emerges from our analysis, while more difficult was the evaluation of its efficacy. Nevertheless we deduced an ideal patient profile that may better respond to the IA anti-TNF treatment.

Possible role of adipocytokines in systemic sclerosis–associated small pericardial effusion:

Introduction: Pericardial effusion is a common manifestation of systemic sclerosis, but its pathogenesis has been poorly investigated. Adipokines and interleukins may play a role in the pathophysiology of pericardial effusion. This study aimed at evaluating serum levels of adipokines and interleukins in systemic sclerosis patients with and without pericardial effusion. Methods: A total of 87 systemic sclerosis patients (age 52.6 ± 14 years; disease duration 8.2 ± 6.7 years) were recruited in this study. Demographics, body mass index, and clinical characteristics were recorded in each patient. Pericardial effusion was considered pathologic when ≥50 mL was detected by echocardiography. Serum levels of adiponectin, leptin, resistin, visfatin, tumor necrosis factor-α, interferon-γ, interlueukin-2, interlueukin-10, and interlueukin-17 were measured using Multiplex Immunoassay (Bioplex 200 System). Results: In all, 11 (13%) systemic sclerosis patients had pericardial effusion. Systemic sclerosis patients with and without pericardial effusion did not differ in age, sex, and body mass index. Systemic sclerosis patients with pericardial effusion had significantly higher levels of visfatin (median/interquartile range: 1546 pg/mL (interquartile range: 8590) vs 388 pg/mL (interquartile range: 103), p = 0.03) and interlueukin-17 (1.33 pg/mL (interquartile range: 3.5) vs 0.05 pg/mL (interquartile range: 0.56), p = 0.04), but lower levels of adiponectin (2,845,000 pg/mL (interquartile range: 4,132,900) vs 5,272,100 pg/mL (interquartile range 8,243,600), p = 0.02) than patients without pericardial effusion. Interstitial lung disease, pulmonary arterial hypertension, and “limited” or “diffuse” cutaneous subset did not correlate to adipokines or interleukin levels. Conclusion: Visfatin and adiponectin may play an important role in the pathogenesis of systemic sclerosis–related pericardial effusion. Further longitudinal studies are needed to unravel a possible role of these molecules as biomarkers of pericardial effusion in systemic sclerosis patients.

AB0618 A unique ultrasound pattern of adipose tissue in systemic sclerosis patients: a comparison with rheumatoid arthritis patients and healthy controls. two sides of adipose tissue involvement in systemic chronic inflammatory diseases

Background Systemic sclerosis (SSc) and rheumatoid arthritis (RA) are both chronic and systemic inflammatory diseases, involving connective tissue. The adipose tissue is acknowledged as an immune organ that secretes numerous inflammatory signals and it is supposed playing an important role in up-regulation of inflammatory status. A few data are published on altered white adipose tissue (WFT) distribution in patients (pts) with RA. None data are available about WFT distribution in SSc pts Objectives We aimed to characterize the subcutaneous adipose tissue (total (sWFT); superficial (SsWFT); inner (IsWFT)) and visceral adipose tissue (vWTF) thickness, evaluated by ultrasound (US) of abdominal adipose tissue, in SSc pts, with different body mass index classes (BMI), comparing with RA pts and healthy controls (HC). Methods 42 SSc pts, 57 RA pts and 12 HC were recruited in this study. WFT measurements were assessed, using US (7.5 MHz probe), along the xiphoumbilican line: sWFT thickness (distance between the inner edge of the skin at the outer edge of the alba line (AL)), SsWFT (lobular upper zone of sWFT), IsWFT (sWFT- SsWFT); vWFT thickness (distance between the inner edge of the AL and the peritoneal line). Results No subject enrolled had metabolic syndrome. RA pts had thicker vWFT (15.6±7.6mm) than SSc pts (10.8±5.8mm) or HC (10.1±3.8mm) (p=0.001). In particular, the upper-weigh RA pts had vWFT 88% thicker than upper-weight HC and the RA obese pts had vWFT 87% thicker than obese HC. While, the upper-weight SSc pts had vWFT 22% thicker than upper-weight HC, and the SSc obese pts had vWFT 16% thicker than obese HC. Positive correlations were found between all WFT measures and BMI in RA pts and HC (p≤0,05). In SSc pts we found lack of correlation between SsWFT and BMI (r=0.232; p=0.145). Of note, only in SSc pts we observed different US WFT patterns (fig. 1a, fig. 1b) characterized by rearrangement of normal sWFT structure (HC fig. 1c and RA pts fig. 1d). These structural rearrangements consisted in the absence of adipose lobules, replaced by hypoechoic – anechoic areas (fig.1a) (attributable to edema), or by hyperechoic lines and spots (fig.1b) (attributable to fibrotic replacement of subcutaneous abdominal fat), independently by SSc diffuse or SSc limited skin subset. Conclusions In SSc and RA the WFT is abnormal. The WFT in RA seems be altered just for dimension and distribution, in particular the vWFT is overexpressed; it might be due to vWFT hyperactivity induced by inflammatory status. In SSc, the WFT is altered in the structure of sWFT. A direct involvement of sWFT in pathologic mechanism of SSc is supposed. An edema phase and a fibrotic phase of abdominal sWFT can be hypothesized, independently by skin involvement. If these findings will be confirmed by fat histological analysis, the US of WFT might be an important tool for the clinicians to identified the earlier stage and/or the active phase (edema) of SSc, in order to support physicians in the decision making about the treatment management. Disclosure of Interest None declared

AB0250 The adipose tissue as predictive factor of disease activity in rheumatoid arthritis patients: evaluation of body fat composition by bioelectrical impedance analysis and ultrasonography

Background Adipose tissue (AT) is an endocrine organ able to secrete the “adipokine” molecules that contribute to the low-grade inflammatory state in obese subjects and to the local inflammation that affects joints and bone (1,2). High-grade inflammation, in course of RA, leads to an altered body composition (3,4), characterized by the increasing of fat mass and the decreasing of lean mass, mostly not associated to body mass index (BMI) variations (3,5). The BMI is not able to differentiate visceral (VTH) and subcutaneous (STH) fat tissue and to distinguish between muscle mass and fat mass body composition (BC) (6,7). Alternative methods proposed for assessment of visceral fat deposition, are bioelectrical impedance analysis (BIA) and ultrasonography (US). Objectives The aim of the study is to investigate if BC, assessed by BIA and US, correlates with disease activity (assessed by the Disease Activity Score using 28 joint counts – DAS28) and affects the response to the therapy (DAS 28 variation from first evaluation). Methods 87 consecutive RA patients (pts) (72 women and 15 men; aged 52.4±13.2 years; disease duration of 10.7±8.6 years), treated with DMARDs and/or biologics (bDMARDs), were recruited during their regular visit. The inclusion criteria were the 1987 American College of Rheumatology (ACR) or ACR/EULAR 2010 classification criteria. The pts underwent to anthropometric measures (BMI); abdominal US to assess STH and VTH and derived computing of peritoneal circumference (PC); and BIA to the indices of body composition (fat-free mass index (FFMI) and fat mass index (FMI). Results We observed increasing values of BMI, FMI, VTH (fig. 1) and CP with the worsening of disease activity phases, evaluated by DAS 28. In particular, pts with DAS28≥5.1 had highest BMI (30,9±2; p=0,036), FMI (11,5±1,6; p=0,05), CP (92,7±12,5 cm; p=0,035) and VTH (24,8±5,8 mm; p=0,046) than pts in less severe disease activity. By linear regression analysis the predictor of higher DAS28 is the BMI (p=0,028). As regard the drug response, the predictors of DAS 28 improvement are higher FFMI (p=0,044) and lower BMI (p=0,015), independently by bDMARDs or DMARDs treatment. A trend to higher FMI and US AT measures was observed in female with high disease activity, in particular in menopause pts. Conclusions An altered fat distribution is observed in active RA phases; in particular, the FMI increasing is attributable just to visceral AT (VTH and CP). An inflammatory hyperactivity of visceral adiposity could be supposed in RA. The body composition, in addition to BMI, seems to predict the disease activity and drug response in RA patients. The evaluation of VTH by US could be useful to not overestimate the disease activity; instead the BIA could be a useful tool to support the clinicians in a more aggressive treatment management. References Nat Clin Pract Rheumatol 2007; 3(12):716–24. J Mol Endocrinol 2009; 43(1):11–8. Mediators Inflamm 2013; 2013:710928. Arthritis Care Res (Hoboken) 2012; 64(10):1471–9. Nat Rev Rheumatol 2010; 6(8):445–51. Curr Opin Clin Nutr Metab Care 2003; 6(4):387–93. Ann Rheum Dis 2007; 66(10):1316–21. Disclosure of Interest None declared

SAT0217 Axon Reflex Vasodilatation of Digital Arteries in Systemic Sclerosis Patients, Evaluated by Laser-Doppler Fluxmetry

Background Systemic sclerosis (SSc) is a connective disease characterized by severe microvessels vasculopathy. The important role of endothelial dysfunction in SSc pathogenesis is widely demonstrated, but the SSc related autonomic nervous system impairment is controversial and rarely described. The dysregulation of axon reflex vasodilatation of fingertip microvessels in SSc has been reported in some studies, but the functional involvement of digital arteries in SSc patients had never been investigated. Objectives We aimed at evaluating the blood flux changes mediated by axon reflex response upon heating stimulus in SSc patients. Methods 87 SSc patients (SSc pt) and 22 healthy controls (HC) were recruited in this study. The SSc patients were aged 52,7±16,2 yrs, with disease duration of 8,23±7,8 yrs. The LD Flowmetry (Periflux System 5000, Perimed) with 4 LD heating probes was used to measure the skin blood flux of the middle phalanx of the 2nd, 3rd, 4th and 5th fingers of the left hand. The skin fingers flux was recorded at pre-heating period with probes temperature fixed at 34 °C (PHF) and after 5 min heating at 44 °C (IHF). Therefore, the heating test assesses the variation of digital artery flux in response to local heating stress at 44 °C. The ratio IHF/PHF evaluates the axon reflex mediated vasodilatation (ARMV). The results are expressed as average across 4 fingers at each time. The flux was expressed in perfusion unit (PU) and HC and SSc patients responses were compared by the t-student test. Statistic significance was set at p≤0,05. The data analysis was performed using IBM SPSS statistic 20. Results The ARMV was significantly reduced in SSc patients (2,2±1,4) in comparison with HC (4,8±2,7, p=0,0001). IHF was lower in SSc patients (118,6±54,3) than HC (168±78, p=0,001). Dividing the SSc pts group by the presence of pitting scars (PS), digital ulcers (DU) and digital necrosis (DN), we observed a lower IHF in SSc pts with PS (103,2±48,6) than in SSc pts without (138,1±56, p=0,003), and in SSc pts with DU (97,8±47,6) than in SSc pts without (160,27±120,1, p=0,002). Moreover, SSc pts with ND showed a lower ARMV (1,8±1) than SSc pts without (2,6±1,5, p=0,006), and a lower IHF (98,3±49,1 vs 133,2±54,5, p=0,004). The age, sex, concomitant therapy with Ca-antagonist or Bosentan or cardioaspirin did not influence the digital artery flux. Conclusions This study provided evidence that a functional impairment of DA occurs in SSc, and it worsens with increasing severity of vascular clinical manifestations. Disclosure of Interest None declared

SAT0212 Pericardial Effusion Related To Systemic Sclerosis: A Possible Contribution of The Serum Levels of Adipokines and Interleukines

Background Pericardial effusion (PE) is a common clinical manifestation in systemic sclerosis (SSc). Few data are available about its pathogenesis. The role of adipokines and interleukins produced by the adipose tissue and the immune system in PE related to SSc had never been investigated. Objectives This study aimed at evaluating the differences in serum levels of adipokines and interleukins (IL) in systemic sclerosis (SSc) patients with and without PE. Methods A total of 87 outpatients (84 female, mean age of 52,6±14,2 ys, and disease duration of 8,2±6,7 ys), who fulfilled the ACR/EULAR 2013 SSc classification criteria, were recruited in this study. The anthropometric measures, as body mass index (BMI), demographic, clinical and laboratoristic characteristics and SSc related manifestations were assessed in each patient. The presence of PE was evaluated by means of echocardiographic techniques (the presence of fluid ≥5 cc was considered pathologic). Sera levels of adiponectin, leptin, resistin, visfatin, tumor necrosis factor α (TNF-α), interferon g (INF-g), IL-2, IL-10 and IL-17 were measured in SSc patients, using Multiplex Immunoassay (Bioplex 200 System), by means of two kits (Bioplex ProTM Cytokine/Chemokine and Growth Factor Assay e Bioplex Pro Diabetes Assay). The data normality was verified using Kolmogorov-Smirnov Test; the comparisons between SSc patients groups were evaluated by Mann-Whitney U test and t-student test, where appropiate. Statistic significance was set at p≤0,05. The results are expressed as median and interquartile range (IQR) or means±1standard deviation. The data analysis were assessed using IBM SPSS statistic 20. Results 11 SSc patients had PE. The SSc patients groups (with and without PE) did not differ in age, sex and BMI. 11 SSc patients were obese (BMI≥30) (2 with PE and 9 without PE). We found significant differences between SSc patients with PE and without PE in sera levels of visfatin (1546,9 (8590,9) vs 388,8 (103); p=0,036), adiponectin (2845000 (4132900,0) vs 5272100,0 (8243600,0); p=0,027) and IL-17 (1,33 (3,5) vs 0,05 (0,56); p=0,45). Moreover higher adiponectin/leptin ratio was found in patients with PE than SSc patients without PE (569,2 (1415,3) vs 166,9 (504,9) p=0,032). The presence of interstitial lung disease, pulmonary arterial hypertension, limited or diffuse skin subset, the different nail fold videocapillaroscopy pattern and the modified Rodnan skin score did not influenced the serum levels of adipokines and IL. In the SSc patients with PE there is no differences in visfatin and adiponectin serum level and adiponectine/leptin ratio between patients that are in menopause and those who are not. Conclusions The visfatin and adiponectin could play an important role in pathogetic mechanism in pericardial effusion related to SSc. Further study are necessary to unravel a role of visfatin and adiponectin as biomarkers of SSc and a role of the adipose tissue and innate immune system in PE related to SSc pathology. Disclosure of Interest None declared

SAT0216 Chest Ultrasound Signs of Interstitial Lung Disease in Systemic Sclerosis Patients: A Comparison between High Resolution Chest Computed Tomography Findings

Background Interstitial lung disease (ILD) is a typical clinical manifestation in Systemic Sclerosis (SSc). The high resolution chest computed tomography (HRCT) is the gold standard to evaluate and grade ILD. The presence of fibrotic tissue in the lung, or other structures beside the air, allows obtaining specific sonography images (such as ultrasound lung comet, higher pleural line thickness, irregular pleural margins and subpleural cysts) by chest ultrasound. In previous studies it was demonstrated that the ultrasound comets number increases in SSc patients. Objectives We aimed at correlating the specific lung sonography signs with ground glass and honeycombing pattern detected by chest HRCT. Methods A total of 60 SSc outpatients (54 female, mean age 56,2 ± 13,8 ys and disease duration of 9,57±8,7 ys), who fulfilled ACR/EULAR 2013 SSc classification criteria, were recruited. All patients underwent chest HRCT and US examination. The US examination was performed with 7,5 Mhz probe and conducted with patients in sitting position from paraspinal line to anterior axillary line, for each intercostals space. The presence of typical ultrasound signs as lung comets (pathological if >35), higher pleural line thickness (pathological if >2mm), irregular pleural margins, subpleural cysts and pleural effusion was detected. The sensitivity, specificity and accuracy of US patterns (compared to chest HRTC) were evaluated by ROC analysis. Statistic significance was set at p<0.05. All results are expressed as mean ± 1 standard deviation. Results 23 patients had the CT honeycombing pattern, of which 92% had the US irregular pleural margins, 70% had US higher pleural line thickness and sub-pleural cysts, just 54% had US lung comets. 16 patients had the CT ground glass pattern, of these in 94% the US irregular pleural margins, in 87% US lung comets, in 60% US higher pleural line thickness were found. As regard the CT ground glass pattern the US sign with the highest specificity (91%), sensibility (85,7%) and accuracy (88%) was the lung comets; while regarding the CT honeycombing pattern the US sign with the highest specificity (92%), sensibility (69,6%) and accuracy (82%). Conclusions The lung US is a good diagnostic technique for its repeatability, low cost and risklessness. Although HRCT remains the best imaging technique to assess the ILD, in SSC the lung US could be a useful tool to detect the presence or the evolution of ILD and to improve the timing of HRTC without exposing the patients to high radiation doses over time. Disclosure of Interest None declared