Search

Objective To evaluate differences in nailfold videocapillaroscopy (NVC) findings between SSc patients with and without a diagnosis of pulmonary arterial hypertension (PAH). Methods One hundred and ten SSc patients were enrolled in this cross-sectional, case–control, multicentre study. Patients were divided into cases (SSc-PAH confirmed by right heart catheterization) and controls (SSc-nonPAH with low probability of PAH). NVC patterns (early, active and late) and morphological parameters (microvascular density, non-specific abnormalities, giant capillaries, micro-haemorrhages, avascular areas) were considered using a semiquantitative scoring system. Results SSc-PAH patients showed higher frequencies of late pattern (P  < 0.01), non-specific abnormalities (P  < 0.01), lower capillary density (P  < 0.01), higher avascular areas (P  < 0.01) and a higher mean NVC score (P  < 0.01). Contrarily, the early/active pattern (P  < 0.01) and a higher rate of micro-haemorrhages (P  = 0.04) were more frequent in non-PAH patients. By a multivariate analysis, SSc-PAH patients, compared with non-PAH, had more non-specific abnormalities [27/55, 49.1% vs 10/55, 18.2%; adjusted odd ratio (OR) 16.89; 95% CI: 3.06, 93.16], a lower capillary density (grade 3, 20/55, 36.4% vs 5/55, 9.1%; adjusted OR 38.33; 95% CI: 2.34, 367.80) and avascular areas (18/55, 32.7% vs 10/55, 18.2%; adjusted OR 16.90; 95% CI: 2.64, 44.35). A correlation was found between the mean pulmonary arterial pressure and avascular areas (P  < 0.01), capillary density (P  < 0.01) and non-specific abnormalities (P  < 0.01). A clinical model including the NVC variables may be able to predict a diagnosis of PAH. Conclusion Our results indicate that the distinctive peripheral microcirculatory injury of SSc, i.e. capillary loss and morphological abnormalities, appear more severe and pronounced in patients with SSc-PAH. [ABSTRACT FROM AUTHOR]

Objective To evaluate the evidence concerning systemic pharmacological treatments for SSc digital ulcers (DUs) to inform the development of evidence-based treatment guidelines. Methods A systematic literature review of seven databases was performed to identify all original research studies of adult patients with SSc DUs. Randomized controlled trials (RCTs) and prospective longitudinal observational studies (OBSs) were eligible for inclusion. Data were extracted, applying the patient, intervention, comparison, outcome framework, and risk of bias (RoB) was assessed. Due to study heterogeneity, narrative summaries were used to present data. Results Forty-seven studies that evaluated the treatment efficacy or safety of pharmacological therapies were identified among 4250 references. Data from 18 RCTs of 1927 patients and 29 OBSs of 661 patients, at various RoB (total 2588 patients) showed that i.v. iloprost, phosphodiesterase-5 inhibitors and atorvastatin are effective for the treatment of active DUs. Bosentan reduced the rate of future DUs in two RCTs (moderate RoB) and eight OBSs at low to high RoB. Two small studies (moderate RoB) indicate that Janus kinase inhibitors may be effective for the treatment of active DUs, otherwise there are no data to support the use of immunosuppression or anti-platelet agents in the management of DUs. Conclusion There are several systemic treatments, across four medication classes, that are effective therapies for the management of SSc DUs. However, a lack of robust data means it is not possible to define the optimal treatment regimen for SSc DUs. The relatively low quality of evidence available has highlighted further areas of research need. [ABSTRACT FROM AUTHOR]

Objectives In SSc, angiogenesis impairment advances in parallel with the development of fibrosis orchestrated by myofibroblasts originating from different sources, including endothelial-to-mesenchymal transition (EndoMT). Soluble guanylate cyclase (sGC) stimulation has shown antifibrotic effects in SSc skin fibroblasts and mouse models. Here, we investigated the effects of pharmacological sGC stimulation on impaired angiogenesis and myofibroblast-like features of SSc dermal microvascular endothelial cells (SSc-MVECs). Methods To determine whether sGC stimulation affected cell viability/proliferation, SSc-MVECs and healthy dermal MVECs (H-MVECs) were challenged with the sGC stimulator (sGCS) MK-2947 and assayed by annexin V/propidium iodide flow cytometry and the water-soluble tetrazolium salt (WST-1) assay. To study angiogenesis and EndoMT, MK-2947-treated SSc-MVECs were subjected to wound healing and capillary morphogenesis assays and analysed for the expression of endothelial/myofibroblast markers and contractile ability. Results MK-2947 treatment did not affect H-MVEC viability/proliferation, while it significantly increased SSc-MVEC proliferation, wound healing capability and angiogenic performance. After MK-2947 treatment, SSc-MVECs exhibited significantly increased proangiogenic MMP9 and decreased antiangiogenic MMP12 and PTX3 gene expression. A significant increase in the expression of CD31 and vascular endothelial cadherin paralleled by a decrease in α-smooth muscle actin, S100A4, type I collagen and Snail1 mesenchymal markers was also found in MK-2947-treated SSc-MVECs. Furthermore, stimulation of sGC with MK-2947 significantly counteracted the intrinsic ability of SSc-MVECs to contract collagen gels and reduced phosphorylated-extracellular signal-regulated kinases 1 and 2 protein levels. Conclusion These findings demonstrate for the first time that pharmacological sGC stimulation effectively ameliorates the angiogenic performance and blunts the myofibroblast-like profibrotic phenotype of SSc-MVECs, thus providing new evidence for repurposing sGCSs for SSc. [ABSTRACT FROM AUTHOR]

Objectives It has recently become possible to assess lung vascular and parenchymal changes quantitatively in thoracic CT images using automated software tools. We investigated the vessel parameters of patients with SSc, quantified by CT imaging, and correlated them with interstitial lung disease (ILD) features. Methods SSc patients undergoing standard of care pulmonary function testing and CT evaluation were retrospectively evaluated. CT images were analysed for ILD patterns and total pulmonary vascular volume (PVV) extents with Imbio lung texture analysis. Vascular analysis (volumes, numbers and densities of vessels, separating arteries and veins) was performed with an in-house developed software. A threshold of 5% ILD extent was chosen to define the presence of ILD, and commonly used cut-offs of lung function were adopted. Results A total of 79 patients [52 women, 40 ILD, mean age 56.2 (s. d. 14.2) years, total ILD extent 9.5 (10.7)%, PVV/lung volume % 2.8%] were enrolled. Vascular parameters for total and separated PVV significantly correlated with functional parameters and ILD pattern extents. SSc-associated ILD (SSc-ILD) patients presented with an increased number and volume of arterial vessels, in particular those between 2 and 4 mm of diameter, and with a higher density of arteries and veins of <6 mm in diameter. Considering radiological and functional criteria concomitantly, as well as the descriptive trends from the longitudinal evaluations, the normalized PVVs, vessel numbers and densities increased progressively with the increase/worsening of ILD extent and functional impairment. Conclusion In SSc patients CT vessel parameters increase in parallel with ILD extent and functional impairment, and may represent a biomarker of SSc-ILD severity. [ABSTRACT FROM AUTHOR]

Introduction: Vascular involvement plays a decisive role in systemic sclerosis (SSc) pathogenesis; it is responsible for some important clinical manifestations of the disease such as Raynaud's phenomenon and digital ulcers (DU). Bosentan, a dual receptor endothelin antagonist, and iloprost, often in combination therapy, seems to be able to interfere with the scleroderma microangiopathy. Objectives: Aim of the study was to evaluate the effect of bosentan and iloprost on scleroderma microangiopathy, analyzed by means of capillaroscopic skin ulcer risk index (CSURI), in SSc patients treated for the prevention of DU. Methods: Nailfold videocapillaroscopy (NVC) was performed in 95 SSc patients, treated with iloprost alone (group 1) or combination therapy with iloprost and bosentan (group 2), at baseline and after one year. In all patients CSURI was calculated according to the formula "diameter x number of megacapillaries/(total number of capillaries)2": in addition, total number of capillaries, giant capillaries, micro-hemorrhages, disorganization of the vascular array, and ramified capillaries were evaluated by means of a semiquantitative score. Results: After 12 months, we observed a reduction of the number of giant capillaries in both groups, while an increase of ramified capillaries was recorded only in group 2. CSURI improved slightly in group 2 without statistical significance; on the contrary, in group 1 a significant worsening was recorded (p ≤ 0.001). Conclusions: Our study confirms the effectiveness of bosentan, in combination with iloprost, in SSc microangiopathy observed to NVC. Moreover, the observed findings further support the role of CSURI in the evaluation and monitoring of SSc microangiopathy. [ABSTRACT FROM AUTHOR]

Objectives. Patients with SSc have an increased risk of malignancy compared with the general population. Before now, no study has evaluated the risk of thyroid cancer (TC) in SSc patients. The aim of the study was to evaluate the prevalence of TC in SSc patients. Methods. We studied the prevalence of TC in 327 unselected SSc patients in comparison with two population-based, gender- and age-matched control groups (654 subjects from an iodine-deficient area and 654 subjects from an iodine-sufficient area). Thyroid status was assessed by measurement of circulating thyroid hormones and autoantibodies, thyroid ultrasonography and fine-needle aspiration cytology (when necessary). Results. Circulating thyroid-stimulating hormone, anti-thyroglobulin and anti-thyroperoxidase antibody levels, and the prevalence of hypothyroidism were significantly higher in SSc patients (P<0.01, for all). Six patients with papillary TC (PTC) were detected among SSc patients, whereas only one case was observed in each of controls 1 and 2 (P = 0.007, for both). In SSc all patients with TC had evidence of thyroid autoimmunity vs 40% of the other SSc patients (P = 0.001). Conclusion. These data suggest a high prevalence of papillary TC in SSc patients, in particular in the presence of thyroid autoimmunity; careful thyroid monitoring would be opportune during the follow-up of these patients. [ABSTRACT FROM AUTHOR]

To demonstrate the efficacy and safety of long-term therapy with oxycodone in severe pain of scleroderma skin ulcers. Open study. Twenty-nine consecutive patients, referred to our Rheumatology Unit during 2006, affected by systemic sclerosis complicated by painful long-standing skin ulcers entered in the study. In all cases, pain was classified as severe according to World Health Organization guidelines, and oxycodone chloridrate (Oxycontin®; Mundipharma Pharmaceuticals, Milan, Italy) was administrated at the dosage of 10-20 mg twice daily for a mean period of 7.9 ± 3.2 standard deviation months. To evaluate the efficacy and safety of opioid therapy, the following parameters were recorded at standard time intervals: visual analog scale (VAS) pain, Pittsburgh sleep quality index (PSQI), hours of sleep per night, Health Assessment Questionnaire-Disability index, analgesics use (rescue therapy), side effects, vital signs, routine laboratory assessment. After 1 month of therapy, all patients experienced relief of pain (VAS decreased from 93.8 ± 8.72 to 56.7 ± 10.4, P < 0.0001), and better quality of sleep (total hours of sleep increased from 3.68 ± 1.28 to 5.27 ± 0.75, P < 0.0001; PSQI decreased from 9.72 ± 3.95 to 3.37 ± 1.04, P < 0.0001). These parameters further improved after 3 months of therapy and remained stable during the follow-up; moreover, an increase of daily dosage of oxycodone was never required. The observed side effects were always transient and mild; only constipation, when present, was persistent. Oxycodone showed to be effective and safe in the treatment of pain due to severe scleroderma skin ulcers; contemporarily, it markedly improved the patient's compliance to local wound care procedures. [ABSTRACT FROM AUTHOR]