Pamela Polito

Evaluation of right ventricular function performed by 3D-echocardiography in scleroderma patients.

The impairment of the right ventricle (RV) in systemic sclerosis (SSc) is usually related to pulmonary arterial hypertension (PAH). New echocardiographic techniques, such as 3-dimensional echocardiography (3DE) and 2-dimensional speckle tracking (2DSTE), allow an accurate evaluation of the RV function. The aim of this study was to evaluate the RV function using 3DE and 2DSTE in SSc patients with no history of heart disease and no PAH. Forty-five SSc patients, 42 females and 3 males, 28 with limited cutaneous SSc (lcSSc) and 17 with diffuse cutaneous SSc (dcSSc), were studied. Forty-three age- and gender-matched healthy subjects were enrolled as controls. All of them underwent a 3DE and 2DSTE ecocardiographic evaluation of the RV function. Systolic pulmonary arterial pressure (sPAP) and total pulmonary vascular resistance (tPVR) were also estimated by power doppler. RV echocardiographic parameters were compared in the different subsets of SSc patients. A statistical analysis was performed by t-test, ANOVA and multiple logistic regression. RV areas in 2DSTE and volumes in 3DE were higher and RV function parameters were reduced in SSc patients compared with controls. Also sPAP and tVPR were higher, but they did not reach pathological values. Echocardiographic alterations were more pronounced in patients with lcSSc. 3DE and 2DSTE echocardiography allowed us to detect morphological and functional alterations of the RV in a group of SSc patients with no clinical signs of heart disease and no PAH. These patients had significantly higher sPAP and tPVR than healthy controls without reporting values compatible with PAH. These data suggest that RV alterations are related to a pressure overload rather than to an intrinsic myocardial involvement in SSc.

The limited cutaneous form of systemic sclerosis is associated with urinary incontinence: an international multicentre study

Objectives The aim of this study was to explore the association between urinary incontinence (UI) and the main clinical and serological subsets of SSc, to assess risk factors for UI and its impact on quality of life (QoL). Methods UI and QoL were assessed through self-administered questionnaires in 334 patients with SSc from five European tertiary centres. Logistic regressions were performed to test the association between clinical forms, serological status and UI and to adjust for confounders. Further independent predefined SSc risk factors for UI were tested through a multivariable logistic model. Results The prevalence of UI was 63% (95% CI: 60, 68%). lcSSc and ACAs were both significantly associated with UI even after adjusting for age, sex, disability, diabetes, BMI, caffeine consumption, dyspnoea, faecal incontinence, abnormal bowel movement, presence of overlapping rheumatological disease and pulmonary hypertension [adjusted odds ratio (OR) = 2.4; 95% CI: 1.2, 4.7]. ACA and lcSSc doubled the risk of frequent and heavy urinary leaks. Factors independently associated with UI were as follows: lcSSc (OR = 2.2; 95% CI: 1.1, 3.2), ACA (OR = 2.8; 95% CI: 1.4, 5.8), female sex (OR = 10.8; 95% CI: 2.8, 41.3), worsening of dyspnoea (OR = 6.8; 95% CI: 1.2, 36.7), higher HAQ-DI (OR = 3.2; 95% CI: 1.5, 6.7), BMI (OR = 1.1; 95% CI: 1.0, 1.1) and active finger ulceration (OR = 0.3; 95% CI: 0.1, 0.7). Patients suffering from UI had decreased QoL. Conclusion Self-reported UI is frequent in SSc and disproportionally affects the limited cutaneous form of the disease and patients positive for ACA. Trial registration ClinicalTrials.gov, http://clinicaltrials.gov, NCT01971294.

Therapy of scleroderma renal crisis: State of the art

Scleroderma renal crisis (SRC) is an uncommon but still life-threatening manifestation of systemic sclerosis (SSc). The incidence of SRC has decreased in the last few decades, probably due to a widespread use of vasodilators in SSc patients. It is well-recognized that exposure to different drugs can trigger SRC (corticosteroids, cyclosporine) or might prevent its occurrence (iloprost, calcium channel blockers). The prognosis of this life-threatening manifestation has not substantially improved since 1980s, when ACE-inhibitors were introduced in its treatment. ACE-inhibitors remain the mainstay in the therapy of SRC due to their efficacy in controlling malignant hypertension; indeed, the prognosis largely depends on the rapid improvement of the ongoing renal ischemia. Calcium-channel blockers and in third line diuretics and alpha-blockers should be used as additional therapy if blood pressure control remains suboptimal despite maximum tolerated doses of ACE-inhibitors. Given the growing evidence on the role of complement activation and endothelin-1 in the pathogenesis of SRC, recent case-series and case reports have suggested the use of C5-inhibitors and endothelin receptor antagonists in the therapy of SRC, mainly in the refractory cases. Plasma-exchange seems to give some benefits in patients with SRC and microangiopathy or intolerant to ACE-inhibitors. Renal transplantation is the last treatment option and its outcome is similar to that reported in other connective tissue disorders, with a 5-year patient survival rate of about 82%. In this review we summarize the current knowledge in the treatment of SRC.

Prevalence and disease-specific risk factors for Lower Urinary Tract symptoms in Systemic Sclerosis: an international multi-centric study

To determine the prevalence of lower urinary tract symptoms (LUTS) in systemic sclerosis (SSc), to find specific risk factors, and to assess their impact on quality of life (QoL).

Long-term improvement in activities of daily living in women with systemic sclerosis attending occupational therapy

Introduction Systemic sclerosis often affects hand function, leading to severe disability in many subjects. There is little data available on the effects of occupational therapy in systemic sclerosis in current literature. The aim of our study was therefore to evaluate the effects of a cycle of occupational therapy on performing activities of daily living in a group of women with systemic sclerosis. Method Twenty women with systemic sclerosis were included in the study: 10 followed a cycle of occupational therapy; 10 were enrolled as controls. An occupational therapy cycle consisted of six meetings of 90 minutes each over a 3-week period. All women were evaluated by the Health Assessment Questionnaire and Evaluation of Daily Activity Questionnaire at baseline and after 24 weeks. The use of devices and alternative strategies was also assessed. Results We observed a significant reduction in the Health Assessment Questionnaire and Evaluation of Daily Activity Questionnaire scores in occupational therapy subjects after 6 months compared to controls. There was also evidence of significant improvement in four dimensions of the Evaluation of Daily Activity Questionnaire: eating; indoor mobility; outdoor mobility; and communication. The number of devices in the occupational therapy group increased significantly. Conclusion Our findings suggest a relevant role for occupational therapy in improving activities of daily living in women with systemic sclerosis. The use of strategies learned during occupational therapy sessions allows for long-lasting beneficial effects.

SAT0194 IL-6 Serum Levels and Coronary Microvascular Dysfunction in Patients with Systemic Sclerosis

Background Functional impairment of coronary microcirculation is thought to be a pathway in the development of cardiac involvement in systemic sclerosis (SSc). The underlying mechanism is not fully understood. A reduction of coronary flow reserve (CFR) suggests a coronary microvascular dysfunction (CMD) and predicts adverse outcomes in several cardiovascular diseases. Interleukin-6 (IL-6) is involved in the pathogenesis of SSc and it is a marker of immune activation. High serum levels of IL-6 are correlated with the severity of skin lesions, pulmonary fibrosis and pulmonary hypertension, but the role of IL-6 in the development of cardiomyopathy in SSc is yet not clear. Objectives To assess the relationship between CFR values and IL-6 serum levels in SSc. Methods Forty SSc patients (32 female and 8 male, aged 55±11 years), classified according to the 2013 ACR/EULAR criteria, were enrolled. Disease activity was evaluated by EUSTAR score. Twenty-three patients were affected by diffuse cutaneous form and 17 by limited form. All patients had no clinical evidence of heart disease. Coronary flow velocity in the left anterior descending coronary artery was detected by transthoracic Doppler echocardiography at rest and during adenosine infusion. CFR was the ratio of hyperaemic diastolic flow velocity (DFV) to resting DFV. A CFR ≤2.5 was considered abnormal and marker of CMD. Serum levels of IL-6 and of cardiac biomarkers (pro-BNP and troponin I) were evaluated in all patients. Results CFR was reduced in 21 patients (52.5%). The average value was 2.08±0.29. Serum levels of IL-6 (n.v. <2.5 pg/mL), pro-BNP (n.v. <125 ng/L) and troponin I (n.v. <0.0017 μg/L) were increased respectively in 50%, 45% and 27.5% of cases. No significant correlation between CFR and subsets of SSc was found. Higher EUSTAR score were correlated with reduced CFR (p=0.037) and high values of IL-6 (p=0.002). A significant correlation between the increase levels of IL-6 and the reduction of CFR (p=0.039) was found. Conclusions Our results showed that high serum levels of IL-6 are associated with CMD independently from the severity of SSc. A positive correlation between IL-6, EUSTAR score and the impairment of CFR in SSc patients may be suggest an implication of IL-6 in the cardiac pathogenesis of SSc. The evaluation of serum IL-6 might represent a tool for the prediction of CMD, suggesting a role in the increased cardiovascular risk in patients with SSc. Moreover they could open new possibilities for the treatment of SSc cardiomyopathy. Disclosure of Interest None declared

FRI0585 Nailfold Videocapillaroscopy: An Open Window on Coronary Microvascular Dysfunction in Systemic Sclerosis

Background Cardiac involvement is an important determinant of prognosis in systemic sclerosis (SSc). The identification of patients with high risk has a great importance and coronary microvascular dysfunction (CMD) predicts major adverse outcomes in several cardiovascular diseases (1). Nailfold video capillaroscopy (NVC) represents an essential tool in the classification criteria for SSc and the best method to analyse microvascular abnormalities in these patients. Objectives To assess the relationship between nailfold capillaroscopy-derived scores and coronary flow reserve (CFR), a marker of CMD, in SSc. Methods Twenty-three patients (20 F, 3 M, aged 59±12 years), 13 with diffuse and 12 with limited form of SSc, without clinical evidence of heart disease, and 23 healthy controls were enrolled. All patients underwent NVC. According to Sulli et al. the capillaroscopic parameters considered were: presence of enlarged and giant capillaries, haemorrhages, loss of capillaries (avascular score), microvascular disarray, and capillary ramifications. For each field was adopted a semiquantitative rating scale to score each capillary abnormality (1). Coronary flow velocity in the left anterior descending coronary artery was detected by transthoracic Doppler echocardiography (TDE) at rest and during adenosine infusion. CFR was the ratio of hyperaemic diastolic flow velocity (DFV) to resting DFV. A CFR≤2.5 was considered abnormal and marker of CMD. Results CFR was lower in patients with SSc than in healthy controls (2.2±0.8 vs 3.6±0.6, p<0.0001). The prevalence of CMD was higher in patients than in controls (65% vs 4%, p<0.0001). CFR was inversely related to avascular score (Figure A) and capillary ramification (r=-0.473, p=0.02). In patients with CMD (CFR≤2.5) avascular score was higher (0.78±0.06 vs 0.22±0.1, p=0.02) (Figure B). No relationship with other NVC scores was found. An exploratory receiver-operator characteristic analysis identified avascular score>0.27 (AUC 0.80, p=0.01) as the best discriminating threshold for CMD (Sensitivity 73%, Specificity 75%, NPV 60%, PPV 84%; OR 2.93, p=0.02). Conclusions Our study showes that microvascular abnormalities at NVC correlate with CMD in SSc. The evaluation of NVC in SSc might represent a tool for the prediction of coronary microvascular dysfunction, by considering the systemic microvascular derangement at the capillary nailfold. References Pepine CJ et al. JACC 2010. Sulli A et all. Ann Rheum Dis 2008. Disclosure of Interest None declared

AB0616 RO/SSA Autoantibodies in A Cohort of 552 Scleroderma Patients

Background Autoantibodies to Ro/SSA antigens have been demonstrated in 15-38% of patients with Systemic sclerosis (SSc) but their association with clinical manifestation and other serological patterns is not clear (1,2,3). Objectives The aim of our study was to verify the prevalence of anti-SSA pattern in our cohort of patients with SSc. We also analyzed the clinical features of these patients, particularly the organ involvement. Methods The retrospective review involved patients with SSc admitted to the Rheumatology Unit (University of Padova) from 1983 to 2013. By our data-base we obtained the demographic characteristics of patients, the antinuclear antibodies (ANA) specificity and the prevalence of the main visceral involvement. ANA were assayed by counter-immunoelectrophoresis (CIE). Lung involvement (ILD) was diagnosed if DLCO was <70% of predicted and forced vital capacity was <75% of predicted, or interstitial disease was note on chest radiogram or on HRTC. Heart involvment was defined in the presence of conduction defects or arhytmias on ECG and/or left ventricular diastolic dysfunction on echocardiogram. Pulmonary arterial hypertension (PAH) was estimated by Doppler echocardiogram (>45 mm Hg). Scleroderma renal crisis was defined by rapidly progressive renal failure and malignant arterial hypertension. Results Our cohort consisted of 552 SSc patients, 71 males (13%) and 481 (87%) females, with mean age at diagnosis of 46.9±14.1 yrs; 155 patients (28%) were affected by diffuse and 397 (72%) by limited cutaneous form of SSc. ANA were positive in all patients. Anti-SSA pattern was found in 23 cases (4.2%); it was associated to anti-topoisomerase I in 15 (65.2%) and to anti-centromere in 8 (34.8%). Patients with anti-SSA pattern were 19 women and 4 men, with mean age at diagnosis of 49.6±12.9 yrs; 14 had the diffuse (60.9%) and 9 the limited cutaneous form (39.1%) of SSc. ILD was diagnosed in 14 cases (60.9%), cardiomyopathy in 4 (17.4%), PAH in 2 (8.7%). No patient developed scleroderma renal crisis. The frequency of organ involvement was similar to that of the entire cohort of SSc patients, except for scleroderma renal crisis. Conclusions The prevalence of anti-SSA pattern in our cohort of SSc patients was lower than that reported by other Authors, probably because the assay method (CIE) was more specific but less sensitive than others. Anti-SSA autoantibody does not seem to affect the clinical features, in particular the visceral involvement. This conclusion is in agreement with Parker et al. (1) and Fujimoto et al. (2), while Hudson et al. report a higher frequency of ILD in patients with anti-SSA pattern (3). References Parker JC, Burlingame RW, Bunn CC. J Autoimmune Dis. 2009; 6;6:2. Fujimoto M, Shimozuma M, Yazawa N et al. Ann Rheum Dis. 1997; 56:667-70. Hudson M, Pope J, Mahler M et al. Arthritis Res Ther. 2012, 14:R50. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.5134