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Objective. To evaluate the serum levels of tumour-associated antigens (TAAs) in patients with SSc and interstitial lung disease (ILD) and to define whether their levels mirror the severity and the progression of lung damage. Methods. Data from 80 SSc patients with ILD were collected at baseline and after 2 years as well as from 40 SSc controls without ILD. The occurrence of any malignancy was recorded. Results. At baseline, an increase of at least one TAA was present in 35 SSc patients with ILD compared with 6 SSc patients without ILD (P< 0.0001); this was associated with lower forced vital capacity (FVC) and higher interstitial and alveolar scores. Levels of carbohydrate antigen 15-3 and carcinoembryonic antigen inversely correlated with FVC and directly correlated with alveolar and interstitial scores and their levels were higher in patients who presented a progression of lung damage after 2 years. During 4 years of follow-up, a malignancy was detected in seven patients who already had an increase of at least one TAA. Values of TAAs increased over time in patients who developed cancer, while their trend remained stable in the others. At multivariate analysis, to have three or more TAAs emerged as a strong independent predictor of the development of malignancies [relative risk 24.1 (95% CI 1.8, 315.0), P = 0.02]. Conclusion. TAAs can be elevated in the sera of SSc patients and correlate with the degree of lung damage, suggesting a role as severity biomarkers. Close follow-up is necessary in SSc patients because of the increased cancer risk overall in patients with increased TAAs. [ABSTRACT FROM AUTHOR]

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]

Objectives Survival and death prognostic factors of SSc patients varied during the past decades. We aimed to update the 5- and 10-year survival rates and identify prognostic factors in a multicentre cohort of Italian SSc patients diagnosed after 2009. Material and methods Patients who received a diagnosis of SSc after 1 January 2009 and were longitudinally followed up in four Italian rheumatologic centres were retrospectively assessed up to 31 December 2020. Overall survival of SSc patients was described using the Kaplan–Meier method. Predictors of mortality at 10-year follow-up were assessed by the Cox regression model. A comparison of our cohort with the Italian general population was performed by determining the standardized mortality ratio (SMR). Results A total of 912 patients (91.6% females, 20% dcSSc) were included. Overall survival rates at 5 and 10 years were 94.4% and 89.4%, respectively. The SMR was 0.96 (95% CI 0.81, 1.13), like that expected in the Italian general population. Pulmonary arterial hypertension (PAH) and interstitial lung disease (ILD) associated with pulmonary hypertension (PH) significantly reduced survival (P  < 0.0001). Main death predictors were male gender (HR = 2.76), diffuse cutaneous involvement (HR = 3.14), older age at diagnosis (HR = 1.08), PAH (HR = 3.21), ILD-associated PH (HR = 4.11), comorbidities (HR = 3.53) and glucocorticoid treatment (HR= 2.02). Conclusions In the past decade, SSc patients have reached similar mortality of that expected in the Italian general population. Male gender, diffuse cutaneous involvement, comorbidities and PAH with or without ILD represent the main poor prognostic factors. [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]

Objective. To evaluate the performance of a computerized-aided method (CaM) for quantification of interstitial lung disease (ILD) in patients with systemic sclerosis and to determine its correlation with the conventional visual reader-based score (CoVR) and the pulmonary function tests (PFTs). Methods. Seventy-nine patients were enrolled. All patients underwent chest high resolution computed tomography (HRCT) scored by two radiologists adopting the CoVR. All HRCT images were then analysed by a CaM using a DICOM software. The relationships among the lung segmentation analysis, the readers, and the PFTs results were calculated using linear regression analysis and Pearson’s correlation. Receiver operating curve analysis was performed for determination of CaM extent threshold. Results. A strong correlation between CaM and CoVR was observed (P<0.0001). The CaM showed a significant negative correlation with forced vital capacity (FVC) (P<0.0001) and the single breath carbon monoxide diffusing capacity of the lung (DLco) (P<0.0001). A CaM optimal extent threshold of 20% represented the best compromise between sensitivity (75.6%) and specificity (97.4%). Conclusions. CaM quantification of SSc-ILD can be useful in the assessment of extent of lung disease and may provide reliable tool in daily clinical practice and clinical trials. [ABSTRACT FROM AUTHOR]

Objective To outline the clinical, histological and prognostic features of systemic sclerosis (SSc) endomyocardial biopsy-proven myocarditis with respect to those of diverse endomyocardial biopsy-proven virus-negative myocarditis (VNM). Methods We retrospectively analysed data from three cohorts of endomyocardial biopsy-proven myocarditis: SSc-related VNM (SSc-VNM); isolated VNM (i-VNM); and VNM related to other systemic autoimmune diseases (a-VNM). The degree of myocardial fibrosis was expressed as relative percentage and fibrotic score (0–3). Clinical data, cardiac enzymes, echocardiogram, 24 h ECG Holter and cardiac magnetic resonance were obtained at baseline and during follow-up. Non-parametric tests were used. Results We enrolled 12 SSc-VNM [11 females, mean age 49.3 (14.2) years; seven diffuse-SSc, five early-SSc], 12 i-VNM [12 females, mean age 47.7 (10.8) years] and 10 a-VNM [four females, mean age 48.4 (16.3) years] patients. SSc patients had higher degrees of myocardial fibrosis as assessed by both percentage [SSc-VNM: 44.8 (18.8)%; a-VNM: 28.6 (16.5)%; i-VNM: 24.9 (10.3)%; P  = 0.019] and score [SSc-VNM: 2.3 (0.8); a-VNM: 1.4 (1.1); i-VNM: 1.2 (0.7); P  = 0.002]. Myocardial fibrosis directly correlated with skin score (r  = 0.625, P  = 0.03) and number of ventricular ectopic beats on 24 h ECG Holter in SSc patients (r  = 0.756, P  = 0.01). Dyspnoea class was higher at presentation in SSc-VNM patients (P  = 0.041) and we found heart failure only in SSc patients (25%) (P  = 0.05). At cardiac magnetic resonance, myocardial oedema was nearly undetectable in SSc-VNM patients compared with others (P  = 0.02). All patients received immunosuppressive treatment. The number of patients who died during follow-up due to cardiac complications was significantly higher in SSc-VNM patients (50%), as compared with a-VNM (0%) and i-VNM (8.3%) patients (P  = 0.006). Patients who died during follow-up had higher degrees of myocardial fibrosis [52.2 (11.6)% vs 27.5 (12.9)%, P  = 0.024; fibrotic score: 2.83 (0.41) vs 1.4 (0.9), P  < 0.001]. Conclusion SSc has unique clinical and histological features, as it tends to present more frequently with heart failure and a higher dyspnoea class and to show higher degrees of myocardial fibrosis. These specific features are paralleled by a worse cardiac prognosis. [ABSTRACT FROM AUTHOR]