Search

Systemic sclerosis (SSc) is a complex, heterogeneous, multi-organ disease, the etiology of which is not yet fully understood. Although fibrosis of the skin and major organs is a well-known, characteristic sign of this condition, the primary dysfunctions contributing to the disease phenotype appear to be vascular and immune in nature. The mechanisms leading to vasculopathy in SSc include dysregulation of vascular tone and endothelial dysfunction, followed by vascular remodeling, as well as abnormal angiogenesis and vasculogenesis. In addition, coagulopathy also plays a role in the disease process. Together, these factors produce a form of vasculopathy specific to SSc, characterized by vascular intimal proliferation in the macro- and micro-circulation, as well as qualitative and quantitative capillary changes. [ABSTRACT FROM AUTHOR]

Background. Systemic sclerosis (SSc) is a complex chronic autoimmune disease, with an unpredictable evolution and high morbidity and mortality rates. Objective. Evaluation of long-term survival and identification of prognostic factors in patients with systemic sclerosis. Methods. All patients with SSc of the EUSTAR100 center, having at least one visit between 2004 and 2016, were included. Data were analyzed for survival, cause of death, as well as for the following events defining disease worsening: increase in modified Rodnan score (mRSS) with at least 25% and 5 points (compared to baseline visit), decrease with at least 10% (compared to baseline) of predicted forced vital capacity (FVC) and predicted diffusing capacity of the lungs for carbon monoxide (DLCO), and presence of new digital ulcers (DUs). Logistic regression (LR), Cox proportional hazards regression and Kaplan-Meier survival curves were used in univariate and multivariate analysis to study survival and identify prognostic factors. Results. 137 patients were included in the study (89.1% females, mean age ± SD 56.7 ± 12.6 years, disease duration 9.7 ± 7.1 years), with a follow-up duration of up to 19 years. 96 patients had at least one follow-up visit and 66 (not including patients who died earlier than 2 years after the first presentation) had follow-up data at 2 years (± 6 months) after the first visit in the clinic. There were 19 reported deaths (13.9%), 11 attributed to SSc (of whom 8 were due to lung involvement). Risk factors for death were diffuse cutaneous subset and mRSS>14 at baseline (identified by LR adjusted for age and sex), male sex and proteinuria (Cox analysis). While in over half of the patients FVC and mRSS were stable or improved (86% and 96% respectively), and no new DUs occurred (64%), 52% of the patients presented significant worsening of DLCO during the entire followup. Risk factors for DLCO worsening at 2 years, by LR adjusted for sex and age, were male sex and diffuse cutaneous subset, while Cox analysis identified only male sex. The only risk factor identified for appearance of new DUs was the history of DUs at the first presentation. Conclusions. SSc often presents an unfavorable disease course, particularly due to lung involvement. Risk factors for disease worsening were male sex, diffuse cutaneous subset, and mRSS>14 at baseline. SSc-related deaths were mainly due to lung involvement, thus underlining the necessity of identifying predictive factors for lung function deterioration at the first presentation. [ABSTRACT FROM AUTHOR]

Background. Semi-quantitative nailfold capillaroscopy (NFC) scoring represents a promising tool for assessing disease activity, severity and change in systemic sclerosis (SSc), however there is no consensus yet over which capillaroscopy abnormalities should be analyzed and how. Objective. Investigation of the reliability of the qualitative and semi-quantitative scoring of NFC assessment between two raters and test-retest for each rater in a SSc cohort. Methods. This is a single-center pilot study where 2 raters assessed the NFC images of 48 consecutive patients with SSc. Data were analyzed in 3 ways: 1. qualitatively by “normal/abnormal” category; 2. qualitatively by the following categories: “early'', “active", “late” SSc patterns, “normal”, and unclassifiable in any pattern, and step; 3. Semi-quantitatively by calculating the mean score for capillary loss, disorganization of the microvasculat array, giant capillaries, microhaemorrhages and capillary ramifications, and combinations of giant capillaries and microhaemorrhages (as a surrogate for vascular activity) and disorganization and ramifications (surrogate for vascular damage) were also assessed. Variables for all steps were calculated for all fingers and for each finger. Inter-rater/ intra-rater agreement was assessed by Cohen's kappa coefficients for qualitative variables and by intraclass correlation coefficients (ICC) for mean score values of abnormalities. Results. Inter-rater reliability ranged from good to excellent agreement for mean score values of abnormalities in all fingers (ICC coefficients 0.745 to 0.897) and was excellent for activity (ICC coefficient of 0.923) and damage combinations (ICC coefficient of 0.918). Assessment of abnormalities in a qualitative manner (normal/abnormal or with capillaroscopy patterns) showed weaker inter-rater agreement than the semi-quantitative assessment (k coefficient <0.7). Intra-rater variability was good to excellent for mean score values of abnormalities and activity and damage combinations in all fingers and separate fingers for both raters: for qualitative assessment, only one of the raters had good test-retest reliability. Conclusion. Reliability of NFC assessment is essential in SSc trials/clinical practice to ensure quality of data. This pilot study demonstrates very good reliability between raters of the semi-quantitative NFC assessment in a SSc cohort. Combinations of NFC abnormalities had very good reliability and might be preferred because they are less time consuming. [ABSTRACT FROM AUTHOR]

Background. Lung involvement is the main disease related death cause in patients with systemic sclerosis (SSc). The most frequent lung manifestations in SSc are interstitial lung disease (ILD) and pulmonary arterial hypertension (PAH). Objectives. Evaluation of lung involvement in patients with SSc and identification of predictive factors for severe lung involvement. Patients and methods. All patients with SSc of the EUSTAR100 center, having at least two visits between 2004 and 2016, were included. Survival status, cause of death, dyspnea, ILD on thorax radiography or high resonance thorax computer tomography (HRCT) and lung function tests were recorded during the entire follow-up. Severe lung involvement was defined as severe or end-stage lung involvement on the Medsger severity scale at any time during follow-up, or death. Cox proportional hazards regression was used in univariate and multivariate analysis to identify prognostic factors. Results. 89 patients were included (12.4% males, mean age±SD 49.2±12.2 years, disease duration 4.1±7.5 years), with a follow-up duration up to 13 years. 14 deaths were reported, half due to lung involvement (4 deaths due to ILD, 3 deaths due to PAH). Pulmonary involvement was identified in a large proportion: at first visit 28/55 present ILD on thorax radiography, 7/12 on HRCT scans; at the most recent visit 41/71 present ILD on X-ray, 18/24 on HRCT scans. At least 10% decrease of pulmonary diffusion capacity for carbon monoxyde (DLCO) and of forced vital capacity (FVC) was observed in 18/32 and 8/35 respectively; 24/48 developed severe or end-stage pulmonary involvement on the Medsger scale or have died. Risk factors for severe lung involvement were age>60 years, disease duration<3 years and diffuse cutaneous subset. Conclusion. SSc often presents unfavourable disease course, mostly due to pulmonary involvement. While half of the deaths reported were due to lung involvement, only about half of the patients presenting ILD-typical findings on Rx develop end-stage lung involvement or death. It is of great importance to screen at baseline for ILD and PAH, following up annually, even while patients are asymptomatic. [ABSTRACT FROM AUTHOR]