Involvement In Systemic Sclerosis Patients Research Articles

Evaluating Skin Involvement in Systemic Sclerosis Using High-Frequency Ultrasound and Virtual Touch Tissue Imaging

ObjectiveThis study aimed to explore the diagnostic significance of high-frequency ultrasound combined with visual touch tissue imaging quantification (VTIQ) in the diagnosis and management of systemic sclerosis (SSc). MethodsPatients diagnosed with SSc and normal volunteers were recruited and divided into an experimental group and a control group, with 30 cases in each group, respectively. The skin thickness at six sites was assessed using high-frequency ultrasound, and the shear wave velocity (SWV) was determined using the VTIQ method. The differences in skin thickness and SWV between the experimental group and the control group were compared and a receiver operating characteristic (ROC) curve was plotted. The value of high-frequency ultrasound, VTIQ, and high-frequency ultrasound combined with VTIQ for evaluating skin involvement in SSc was determined. ResultsThe difference in SWV sum at six sites and the thickness sum was statistically significant (all p = 0.000 < 0.05) from that of the control group, and there was a strong association between the SWV sum, thickness sum, and Rodnan skin score at the six sites in the experimental group (p = 0.000, r = 0.726; p = 0.000, r = 0.679). Based on the ROC curve, the area under the curve (AUC) for high-frequency ultrasound examination was 0.789. The AUC for VTIQ examination was 0.893, while the AUC for high-frequency ultrasound combined with VTIQ examination was 0.923. The combined examination method showed the highest AUC, indicating the best diagnostic performance. ConclusionThe integration of high-frequency ultrasound and VTIQ provides a quantitative approach for assessing the extent of skin involvement in SSc patients, offering valuable insights for clinical diagnosis and treatment purposes.

The burden of face affected questionnaire in patients with systemic sclerosis: Translation, cross-cultural adaptation and psychometric properties in the Turkish version

Aim of the work: Facial skin involvement is one of the most important features in systemic sclerosis (SSc) patients with physical, emotional and social effects. A newly developed burden of face affected (BoFA) questionnaire is available to quantify the disability associated with facial involvement in SSc patients. This study aimed to translate the BoFA questionnaire into Turkish (BoFA-T) and investigate its psychometric properties. Patients and Methods: Forty-nine SSc patients were included in the study. The translation and cross-cultural adaptation of the BoFA-T were conducted. The BoFA-T, the scleroderma mouth handicap in SSc scale (MHISS), the Rosenberg self-esteem scale (RSS), and the perceived stress scale (PSS) were applied to construct validity. The patients were re-evaluated 7 days later to assess the test–retest reliability of the BoFA-T. Results:The mean age of the 49 patients was 48.5 ± 9.97 years, age at diagnosis 40.1 ± 11.5 years,48 females and 1 male. 24 had diffuse cutaneous and 25 limited cutaneous SSc. The mean BoFA-T was 16.81 ± 22.37, MHISS was 16.93 ± 12.19, RSS was 2.04 ± 1.92 and PSS was 24.89 ± 12.31. BoFA-T has excellent internal consistency (Cronbach’s α = 0.97) and test–retest reliability (ICC = 0.94, 95 %CI = 0.88–0.97). The correlation of BoFA-T with MHISS (r = 0.56, p < 0.001), RSS (r = 0.51, p < 0.001), and PSS (r = 0.57, p < 0.001) was moderate. The BoFA-T questionnaire consists of three-factor subgroups (''self-esteem'', ''future anxiety'', and ''sexuality''), and no floor or ceiling effects were observed in relation to BoFA-T. Conclusion: The BoFA-T demonstrates appropriate psychometric properties and may be effectively utilized to assess facial involvement and disability in Turkish SSc patients.

Pericardial effusions and cardiac tamponade in hospitalized systemic sclerosis patients: analysis of the national inpatient sample

IntroductionClinically significant pericardial effusions and cardiac tamponade in systemic sclerosis (SSc) patients is uncommon and the factors that contribute to progression of pericardial involvement in SSc patients have not been well established.MethodsA review of the national inpatient sample database was performed looking SSc related hospitalizations between 2002 and 2019. Data was collected on patients with pericardial effusions and cardiac tamponade and analyzed to identify and describe patient characteristics and comorbidities.ResultsOut of a total of 523,410 SSc hospitalizations, with an overall inpatient mortality rate of 4.7% (24,764 patients), pericardial effusion was identified in 3.1% of all hospitalizations (16,141 patients) out of which 0.2% (838 patients) had a diagnosis of cardiac tamponade. Patients with pericardial effusion were significantly more likely to have pulmonary circulatory disease (p = < 0.0001), congestive heart failure (p = < 0.0001) end stage renal disease (p = < 0.0001), diabetes (p = 0.015), and hypothyroidism (p = 0.025). Patients with cardiac tamponade were significantly more likely to have a history of coronary artery bypass graft surgery (p = 0.001) or atrial fibrillation (p = < 0.0001). Hospitalized patients with cardiac tamponade had a significantly increased mortality rate of 17.7% compared to 8.8% in patients with pericardial effusions without a tamponade physiology, with an odds ratio of 2.3 (1.97–2.86), p = < 0.0001.ConclusionPericardial effusion and tamponade are associated with increased morbidity and mortality in SSc patients. Further studies are required to explore the role of patient comorbidities and characteristics in development into pericardial effusions or tamponade.

Association between esophageal motor disorders and pulmonary involvement in patients affected by systemic sclerosis: a retrospective study.

Systemic sclerosis (SSc) is a rare autoimmune disease of the connective tissue that can affect multiple organs. The esophagus is the most affected gastrointestinal tract, while interstitial lung disease (ILD) is a main feature associated with SSc. The aim of the present study was to evaluate the association and prognostic implication between motor esophageal disorders and pulmonary involvement in SSc patients. We retrospectively assessed patients with SSc who underwent both the HRM with the new Chicago Classification 4.0 and pulmonary evaluation comprehensive of function tests and high-resolution computer tomography (HrCT) with the use of Warrick score. A total score ≥ 7 was considered predictive of ILD, while a score ≥ 10 in a HrCT acquired prospectively from baseline evaluation was considered to establish significant interstitial involvement. Forty-two patients were included. We found a score ≥ 7 in 11 patients with aperistalsis, in 6 subjects with IEM and in 6 patients with a normal manometry. Otherwise, a score < 7 was observed in 3 patients with aperistalsis, and in 2 and 14 patients with IEM and with a normal contractility, respectively. Higher scores were observed in subjects with absent contractility or ineffective esophageal motility than subjects with normal motility, indeed DCI and HrCT score were inversely correlated in linear and logarithmic regression analysis. Prospectively, lower baseline LESP and greater HrCT scores at follow-up evaluation were significantly correlated. This study shows an association between motor esophageal disorder and pulmonary involvement in SSc patients: more severe is the esophageal involvement, more critical is the pulmonary disease.

Spatial frequency domain imaging for the assessment of scleroderma skin involvement.

Systemic sclerosis (SSc) is an autoimmune disease characterized by the widespread deposition of excess collagen in the skin and internal organs, as well as vascular dysfunction. The current standard of care technique used to quantify the extent of skin fibrosis in SSc patients is the modified Rodnan skin score (mRSS), which is an assessment of skin thickness based on clinical palpation. Despite being considered the gold standard, mRSS testing requires a trained physician and suffers from high inter-observer variability. In this study, we evaluated the use of spatial frequency domain imaging (SFDI) as a more quantitative and reliable method for assessing skin fibrosis in SSc patients. SFDI is a wide-field and non-contact imaging technique that utilizes spatially modulated light to generate a map of optical properties in biological tissue. The SFDI data were collected at six measurement sites (left and right forearms, hands, and fingers) of eight control subjects and ten SSc patients. mRSS were assessed by a physician, and skin biopsies were collected from subject's forearms and used to assess for markers of skin fibrosis. Our results indicate that SFDI is sensitive to skin changes even at an early stage, as we found a significant difference in the measured optical scattering () between healthy controls and SSc patients with a local mRSS score of zero (no appreciable skin fibrosis by gold standard). Furthermore, we found a strong correlation between the diffuse reflectance (Rd) at a spatial frequency of 0.2 mm-1 and the total mRSS between all subjects (Spearman correlation coefficient = -0.73, p-value < 0.0028), as well as high correlation with histology results. The healthy volunteer results show excellent inter- and intra-observer reliability (ICC > 0.8). Our results suggest that the measurement of tissue and Rd at specific spatial frequencies and wavelengths can provide an objective and quantitative assessment of skin involvement in SSc patients, which could greatly improve the accuracy and efficiency of monitoring disease progression and evaluating drug efficacy.

728 GALECTINE-3 AND SST2 IN SYSTEMIC SCLEROSIS: AN EARLY DETECTION OF PULMONARY VASCULAR INVOLVEMENT IS REALLY POSSIBLE?

Abstract Introduction Pulmonary arterial hypertension (PAH) is a rare form of pulmonary hypertension (PH) that may also be associated with connective tissue diseases (CTD). In particular, PAH may affect from 5 to 19% of patients with systemic sclerosis (SSc), leading to a significant prognostic worsening. The current challenge is an early detection of PAH in such patients, in order to provide an early referral to PH centers to supply specific therapies as soon as possible. In the latest ESC guidelines for PH, cardiopulmonary exercise testing (CPET) has been included in the diagnostic algorithm for patients with unexplained exertional dyspnoea and/or suspected PH. Patients with PAH show a typical pattern, with a low end-tidal partial pressure of carbon dioxide (PETCO2), high ventilatory equivalent for carbon dioxide (VE/VCO2), low oxygen pulse (VO2/ HR) and low peak oxygen uptake (VO2). CPET may identify patients with SSc at low risk of PAH, to avoid unnecessary right heart catheterization (RHC). However, CPET is not available in all centers. So, we designed a preliminary study to identify new biomarkers that correlate with CPET's parameters. Material and Methods We enrolled 62 SSc patients [53 females, median age 52 years] with no other comorbidities and asymptomatic for dyspnea or other symptoms. 56% and 44% of them presented limited cutaneous SSc (lcSSc) and diffuse cutaneous SSc (dcSSc), respectively. For all patients we performed serum analysis for sST2, Galectine-3, pro-ANP, BNP and IL6, diagnostic imaging with echocardiography and cardiac MRI, CPET and pulmonary functionality test (PFT). Results All patients presented normal echocardiographic and RMI imaging findings. Galectin-3, sST2, pro-ANP, BNP and IL6 presented respectively the following median value: 13.45 ng/mL [11.78; 18.70], 23.25 ng/mL [13.04; 43.35], 1897 fmol/ml [1487; 2445], 12.18 pg/mL [9.34; 15.01]. Both Galectin-3 and sST2 showed a linear correlation with VE/VCO2 slope with R 0.339 (P-value 0.018) and 0.355 (P-value 0.013) respectively. After linear regression analysis, Galectin-3 and sST2 were overall statistically significant with R2 of 0.115 and 0.126, F of 5.97 and 6.62 and P-value of 0.018 and 0.013, respectively. It was found that Galectin-3 and SST2 significantly predicted VE/VCO2 slope with β = 0.364 [0,064; 0,665] for Galectin-3 and 0.137 [0,030; 0,244] for SST2. All other CPET parameters did not show correlation with the biomarkers. Conclusion Our preliminary results suggest that Galectine-3 and sST2 may be useful biomarkers for predicting increasing VE/VCO2 slope. Future analysis may confirm the role of these new biomarkers for early detection of pulmonary vascular involvement in SSc patients to allow an early referral and treatment and, conversely, to avoid unnecessary RHC.

Role of kinurenic acid in the systemic sclerosis renal involvement.

Systemic sclerosis (SSc) subclinical renal vasculopathy is characterized by progressive increase of intrarenal stiffness and reduction of parenchymal thickness due to post ischemic fibrosis secondary to the renal Raynaud phenomenon. Aims of this study were to evaluate kinurenic acid (KYNA) serum level in SSc patients and healthy controls (HC) and to assess the role of KYNA in SSc subclinical nephropathy. Serum level of KYNA was evaluated in 52 SSc patients and 20 HC, matched for sex and age. Renal function was calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation to estimate glomerular filtration rate (eGFR) and renal doppler ultrasound was performed to evaluate kidneys' morphology and indices of intrarenal stiffness. The parameters registered were renal longitudinal length, atrophy index (AI), renal sinus, parenchymal thickness, renal resistive index (RRI), pulsatile index (PI) and systolic/diastolic ratio (S/D). SSc patients had lower median value of KYNA than HC [54.43ng/ml (IQR 44.44-63.64) vs 61.94ng/ml (IQR 55.23-88.75), p < 0.001]. SSc patients with AI ≥ 0.70 had lower KYNA than SSc patients with AI < 0.70 [47.85ng/ml (IQR 41.16-59.91) vs 55.5ng/ml (IQR 49.99-67.33), p < 0.05] and a slightly significant negative linear correlation was found between KYNA and AI (r = - 0.249, p < 0.05). SSc patient with RRI ≥ 0.70 had higher KYNA than SSc patients with RRI < 0.70 [58.25ng/ml (IQR 50.49-69.68) vs 50.07ng/ml (IQR 42.70-56.31), p < 0.05] and a significant positive correlation was found between KYNA and RRI (r = 0.318, p < 0.05). KYNA may be used as a marker to evaluate the renal involvement in SSc patients.

Incidence and predictors of cardiac arrhythmias in patients with systemic sclerosis

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Heart involvement in systemic sclerosis patients is frequent and represents a negative prognostic factor with around 25% of SSc patients dying from cardiovascular related causes. Cardiac arrhythmias represent 6% of the overall causes of death in SSc patients. Not only a plethora of conditions typical of the disease seem to favour the presence of an arrhythmic substrate such as microvascular disease or fibrosis but autoimmunity itself has been recognized as a pathogenic mechanism for cardiac arrhythmias. Purpose The aim of our study was to investigate the incidence of arrhythmias in patients with systemic sclerosis and identify potential predictors. Methods Prospective longitudinal study enrolling all consecutive patients with a diagnosis of SSc and no overt cardiac disease nor pulmonary hypertension. Echocardiographic parameters and GLS were obtained at baseline and at each follow up as well as 12 lead ECG. Presence of atrial fibrillation (AF), atrial tachycardia (AT), ventricular ectopic beats &amp;gt;1000/24 h (VEB), supraventricular ectopic beats (SVEB), bundle branch block (BBB) and atrioventricular block (AVB) was registered. Results 160 patients (144 females, 90%, mean age 59±14 years) were enrolled from June 2016 to December 2021. At enrolment, 11.3% of patients with SSc presented a previous history of supraventricular arrhythmia (5.6% supraventricular ectopic beats, 3.1% atrial fibrillation, 2.5% atrial flutter) and 5.6% a history of ventricular arrhythmia (5.0% ventricular ectopic beats, 0.6% ventricular tachycardia). After a median follow-up of 3.1 years (95% CI 1.4-4.8 years), five patients (3.1%) died of cardiovascular causes, of which three (1.8%) experienced a sudden cardiac death. During the same period, 16 patients (10%) presented a new diagnosis of supraventricular arrythmia (8.7% atrial fibrillation, 1.3% atrial flutter) and two patients (1.2%) a new diagnosis of ventricular tachycardia. PR interval significantly increased during the 3.1-year follow-up (154±27 vs. 178±32 ms; p=0.013), as well as corrected QT interval (420±23 vs. 436±19 ms; p=0.001). New diagnosis of complete right and left bundle branch block was made in 18 (11.2%) and two (1.2%) of all SSc patients. Diagnosis of pulmonary arterial hypertension was associated with a 4-fold and a 10-fold increased risk of supraventricular and ventricular arrhythmias, respectively (Figure 1). A diffuse SSc variant (p=0.049), indexed right (p=0.020) and left atrial volumes (p=0.035), and E/E’ ratios (p=0.016) were all associated with an increased risk of supraventricular arrhythmias. TAPSE (p=0.040), as well as right (p=0.030) global longitudinal strain were associated with an increased risk of ventricular arrhythmias. Conclusions Ssc patients are often by an arrhythmic profile with an increased risk of supraventricular and ventricular events as well as sudden cardiac death. A comprehensive cardiological work up may help in lowering the risk of arrhythmic complications.

A Machine Learning Application to Predict Early Lung Involvement in Scleroderma: A Feasibility Evaluation.

Introduction: Systemic sclerosis (SSc) is a systemic immune-mediated disease, featuring fibrosis of the skin and organs, and has the greatest mortality among rheumatic diseases. The nervous system involvement has recently been demonstrated, although actual lung involvement is considered the leading cause of death in SSc and, therefore, should be diagnosed early. Pulmonary function tests are not sensitive enough to be used for screening purposes, thus they should be flanked by other clinical examinations; however, this would lead to a risk of overtesting, with considerable costs for the health system and an unnecessary burden for the patients. To this extent, Machine Learning (ML) algorithms could represent a useful add-on to the current clinical practice for diagnostic purposes and could help retrieve the most useful exams to be carried out for diagnostic purposes. Method: Here, we retrospectively collected high resolution computed tomography, pulmonary function tests, esophageal pH impedance tests, esophageal manometry and reflux disease questionnaires of 38 patients with SSc, applying, with R, different supervised ML algorithms, including lasso, ridge, elastic net, classification and regression trees (CART) and random forest to estimate the most important predictors for pulmonary involvement from such data. Results: In terms of performance, the random forest algorithm outperformed the other classifiers, with an estimated root-mean-square error (RMSE) of 0.810. However, this algorithm was seen to be computationally intensive, leaving room for the usefulness of other classifiers when a shorter response time is needed. Conclusions: Despite the notably small sample size, that could have prevented obtaining fully reliable data, the powerful tools available for ML can be useful for predicting early lung involvement in SSc patients. The use of predictors coming from spirometry and pH impedentiometry together might perform optimally for predicting early lung involvement in SSc.

Clinical Outcomes of Asymptomatic Cardiac Involvement in Systemic Sclerosis Patients After a 2-Year Follow-Up (Extended Study)

Asymptomatic cardiac involvement in systemic sclerosis (SSc) has been reported. Long-term follow-up might elucidate the clinical implications of these abnormalities. The aim was to identify the clinical outcomes of asymptomatic cardiac involvement in SSc patients after 2 years of follow-up. A cohort study was done at Khon Kaen University, Thailand, on adult patients with SSc who completed the preliminary study. Repeated investigations included electrocardiography, chest radiography, echocardiography, and blood tests for creatine kinase-MB, high sensitivity cardiac troponin-T, and N-terminal prohormone of brain natriuretic peptide. Seventy-four of the 103 patients from the previous study were enrolled. The mean duration of follow-up was 3.1±0.9 years. Five patients developed symptomatic cardiac involvement-all of whom had pulmonary arterial hypertension (PAH). The incidence of symptomatic cardiac involvement for the combined 315 person-years was 1.6 per 100-person-years (95%CI 0.7-3.4). Fourteen patients died resulting in a mortality incidence of 4.4 per 100-person-years (95%CI 4.3-5.4). Persistent cardiac involvement was found in 35 patients for an incidence of 11.1 per 100-person-years (95%CI 8.0-15.5). Two of the patients who had persistent elevated cardiac enzyme developed PAH at a respective 3.7 and 39.4 months after the initial evaluation. None of the clinical parameters were predictive of symptomatic and persistent cardiac involvement. Only male sex was associated with mortality (hazard ratio 3.70; 95%CI 1.22-11.11). Cardiac involvement in SSc can progress slowly or even be reversed. Based on a previous test, the incidence of symptomatic cardiac involvement after 2 years was low despite its being a persistent involvement. If symptomatic cardiac involvement develops, PAH is the most prevalent symptom.

S100A6, Calumenin and Cytohesin 2 as Biomarkers for Cutaneous Involvement in Systemic Sclerosis Patients: A Case Control Study.

Background: Systemic sclerosis (Ssc) is an autoimmune disease with incomplete known physiopathology. There is a high number of candidate proteomic biomarkers for Ssc that have not yet been confirmed on independent Ssc cohorts. The aim of the study was to confirm circulating S100A6, calumenin, and cytohesin 2 as biomarkers for Ssc. Methods: 53 Ssc patients and 26 age- and gender-matched controls were included. Serum S100A6, calumenin, and cytohesin 2 were evaluated with commercial ELISA kits. Associations between serum expression and clinical Ssc characteristics were evaluated. Results: Serum calumenin, S100A6, and cytohesin 2 were higher in Ssc patients compared to controls. Calumenin associated with extensive cutaneous fibrosis, frequency of Raynaud phenomenon, and low complement level, and had a tendency to be higher in Ssc patients with pulmonary fibrosis. S100A6 correlated with the number of active digital ulcers. Serum cytohesin 2 levels were higher in patients with teleangiectasia and associated with pulmonary artery pressure. Conclusions: Serum calumenin, S100A6, and cytohesin 2 were confirmed as biomarkers on an independent group of Ssc patients. Calumenin had the best predictive capacity for cutaneous Ssc manifestations. Future studies are needed to evaluate the prognostic value of these biomarkers and evaluate them as possible therapeutic targets.

The Relationship between Pulmonary Damage and Peripheral Vascular Manifestations in Systemic Sclerosis Patients.

Systemic sclerosis (SSc) is an autoimmune disease, characterized by the presence of generalized vasculopathy and tissue fibrosis. Collagen vascular disorder in SSc is due to fibroblast and endothelial cell dysfunctions. This leads to collagen overproduction, vascular impairment and immune system abnormalities and, in the last stage, multi-organ damage. Thus, to avoid organ damage, which has a poor prognosis, all patients should be carefully evaluated and followed. This is particularly important in the initial disease phase, so as to facilitate early identification of any organ involvement and to allow for appropriate therapy. Pulmonary disease in SSc mainly involves interstitial lung disease (ILD) and pulmonary arterial hypertension (PAH). High-resolution computed tomography (HRCT) and pulmonary function tests (PFT) have been proposed to monitor parenchymal damage. Although transthoracic echocardiography is the most commonly used screening tool for PAH in SSc patients, definitive diagnosis necessitates confirmation by right heart catheterization (RHC). Moreover, some studies have demonstrated that nailfold videocapillaroscopy (NVC) provides an accurate evaluation of the microvascular damage in SSc and is able to predict internal organ involvement, such as lung impairment. This review provides an overview of the correlation between lung damage and microvascular involvement in SSc patients.

Efficacy and safety of rituximab therapy in patients with systemic sclerosis disease (SSc): systematic review and meta-analysis.

The clinical benefits of rituximab in systemic sclerosis (SSc) are still contentious. The present meta-analysis aimed to systematically assess rituximab's safety and efficacy profile in SSc patients. A systematic online query was performed in PubMed, Scopus, Web of Science, and Embase. The studies on the application of rituximab for patients with SSc were reviewed comprehensively for over two years. In terms of efficacy profile, mRSS, MS, LVEF, sPAP, FVC, DLCO, TLC, FEV, DAS, severity activity, HAQ-DI and SF36 were assessed for organ involvement and quality of life. The level of biological and immunological markers was also evaluated in SSc patients treated with RTX. In total, 24 studies met the criteria. Although they did not have a high quality, they were free from heterogeneity and publication bias. The pooled results revealed a long-term improvement in mRSS and MS. HAQ-DI was improved to 0.78 after 12 months, and DAS was significantly reduced to 0.33, 0.23, and 0.24 following 6, 12, and 24 months of treatment, respectively (p = 0.00 for both parameters). The rest of the parameters remained stable over time in patients with SSc. The pooled analysis of these patients demonstrated that the induction of death, cancer, infection, and infusion were 9, 5, 18 and 10%, respectively. Based on the pooled results of this meta-analysis, rituximab improves skin score and disease indices and stabilizes organ involvement in SSc patients. Rituximab seems to possess reasonable safety, similar to previous data from other autoimmune diseases.

Subclinical progression of systemic sclerosis-related cardiomyopathy.

Cardiac involvement in patients with systemic sclerosis (SSc) is frequent and represents a negative prognostic factor. Recent studies have described subclinical heart involvement of both the right ventricle (RV) and left ventricle (LV) via speckle-tracking-derived global longitudinal strain (GLS). It is currently unknown if SSc-related cardiomyopathy progresses through time. Our aim was to assess the progression of subclinical cardiac involvement in patients with SSc via speckle-tracking-derived GLS. This was a prospective longitudinal study enrolling 72 consecutive patients with a diagnosis of SSc and no structural heart disease nor pulmonary hypertension. A standard echocardiographic exam and GLS calculations were performed at baseline and at follow-up. Traditional echocardiographic parameters did not differ from baseline to 20-month follow-up. LV GLS, despite being already impaired at baseline, worsened significantly during follow-up (from -19.8 ± 3.5% to -18.7 ± 3.5%, p = .034). RV GLS impairment progressed through the follow-up period (from -20.9 ± 6.1% to -18.7 ± 5.4%, p = .013). The impairment was more pronounced for the endocardial layers of both LV (from -22.5 ± 3.9% to -21.4 ± 3.9%, p = .041) and RV (-24.2 ± 6.2% to -20.6 ± 5.9%, p = .001). A 1% worsening in RV GLS was associated with an 18% increased risk of all-cause death or major cardiovascular event (p = .03) and with a 55% increased risk of pulmonary hypertension (p = .043). SSC-related cardiomyopathy progresses over time and can be detected by speckle-tracking GLS. The highest progression towards reduced deformation was registered for the endocardial layers, which supports the hypothesis that microvascular dysfunction is the main determinant of heart involvement in SSc patients and starts well before overt pulmonary hypertension.

Automatic Quantification of Interstitial Lung Disease From Chest Computed Tomography in Systemic Sclerosis.

Background: Interstitial lung disease (ILD) is a common complication in patients with systemic sclerosis (SSc), and its diagnosis contributes to early treatment decisions.Purposes: To quantify ILD associated with SSc (SSc-ILD) from chest CT images using an automatic quantification method based on the computation of the weight of interstitial lung opacities.Methods: Ninety-four patients with SSc underwent CT, forced vital capacity (FVC), and carbon monoxide diffusion capacity (DLCO) tests. Seventy-three healthy individuals without radiological evidence of lung disease served as controls. After lung and airway segmentation, the ratio between the weight of interstitial opacities [densities between −500 and +50 Hounsfield units (HU)] and the total lung weight (densities between −1,000 and +50 HU) was used as an ILD indicator (ILD[%] = 100 × [LW(−500 to +50HU)/LW(−1, 000 to +50HU)]). The cutoff of normality between controls and SSc was determined with a receiver operator characteristic curve. The severity of pulmonary involvement in SSc patients was also assessed by calculating Z scores of ILD relative to the average interstitial opacities in controls. Accordingly, SSc-ILD was classified as SSc Limited-ILD (Z score < 3) and SSc Extensive-ILD (Z score ≥ 3 or FVC < 70%).Results: Seventy-eight (83%) SSc patients were classified as presenting SSc-ILD (optimal ILD threshold of 23.4%, 0.83 sensitivity, 0.92 specificity, and 0.94 area under the receiver operator characteristic curve, 95% CI from 0.89 to 0.96, 0.93 positive predictive value, and 0.81 negative predictive value, p < 0.001) and exhibited radiological attenuations compatible with interstitial pneumonia dispersed in the lung parenchyma. Thirty-six (38%) patients were classified as SSc Extensive-ILD (ILD threshold ≥ 29.6% equivalent to a Z score ≥ 3) and 42 (45%) as SSc Limited-ILD. Eighteen (50%) patients with SSc Extensive-ILD presented FVC < 70%, being only five patients classified exclusively based on FVC. SSc Extensive-ILD also presented lower DLCO (57.9 ± 17.9% vs. 73.7 ± 19.8%; p < 0.001) and total lung volume (2,916 ± 674 vs. 4,286 ± 1,136, p < 0.001) compared with SSc Limited-ILD.Conclusion: The proposed method seems to provide an alternative to identify and quantify the extension of ILD in patients with SSc, mitigating the subjectivity of semiquantitative analyzes based on visual scores.

Incidence, predictors, and survival of pulmonary hypertension determined by echocardiography in Thai patients with early systemic sclerosis (SSc): inception cohort study.

We investigated the incidence, predictors, and survival of pulmonary hypertension (PH) determined by Doppler echocardiography in Thai patients with early SSc (systemic sclerosis), in which the majority were diffuse cutaneous SSc (DcSSc) with anti-topoisomerase I-positive. We used an inception cohort study of patients with early SSc seen at the Rheumatology Clinic, Maharaj Nakorn Chiang Mai Hospital. All patients were assessed for clinical data and underwent Doppler echocardiography at the study entry and then annually. A total of 133 patients (81 female, 106 DcSSc, 103 anti-topoisomerase I-positive) with a mean disease duration of 11.9months were recruited. During the mean observational period of 4.2years, 14 patients developed PH concurrent with ILD and 6 with left heart disease. The incidence rate for the development of PH was 3.95 per 100 person years. The multivariate Cox regression analysis indicated higher NYHA class (HR 6.90, 95% CI 2.28-20.94, p = 0.001), telangiectasia (HR 4.18, 95% CI 1.25-13.92, p = 0.020), and enlarged LA diameter (HR 1.16, 95% CI 1.05-1.28, p = 0.005) as predictors of PH. Raynaud's phenomenon (HR 0.22, 95% CI 0.06-0.84, p = 0.026) and high oxygen saturation (HR 0.80, 95% CI 0.65-0.99, p = 0.047) were protective factors. The survival rate after PH diagnosis at 1, 3, and 5years were 88.9%, 82.3%, and 48.0%, respectively. In this study cohort, the majority had early DcSSc, the incidence of PH was modest, and all cases developed concomitantly with ILD or left heart disease, resulting in poor survival. The presence of higher NYHA class, telangiectasia, and enlarged LA diameter was predictors of secondary PH. Further study regarding the treatment strategies for PH associated with ILD and left heart disease in SSc is needed. Key Points • In this cohort of early SSc in which the main subtype was DcSSc, the incidence of PH was modest and all PH was secondary PH associated with ILD and left heart disease, resulting in poor survival. • The presence of higher NYHA functional class, telangiectasia, and enlarged LA diameter was baseline predictors of developing secondary PH. • Effective treatment strategies for secondary PH due to ILD and cardiac involvement in SSc patients are urgently needed.

Vitamin D and Cytokine Profiles in Patients With Systemic Sclerosis.

Hypovitaminosis D has been frequently described in systemic sclerosis (SSc). Cytokines are important mediators of tissue damage and clinical dysfunction in SSc and may be influenced by vitamin D levels. To evaluate the serum levels of vitamin D and its correlation with the clinical features and cytokine profiles in SSc patients. Case-control study, including 50 SSc patients and 35 healthy non matched controls. Serum levels of 25(OH) vitamin D were measured by chemiluminescence assay, and serum concentrations of interleukin 2 (IL-2), IL-4, IL-6, IL-10, tumor necrosis factor, and interferon γ were determined by flow cytometry. Fourteen patients (28%) had diffuse cutaneous SSc, 94% were female, 80% European derived, with a mean age of 57.2 ± 12.8 years. The serum vitamin D levels in SSc patients were 23.9 ± 8.5 ng/mL and 30.2 ± 6.2 ng/mL in the control group (standardized mean difference -6.19; 95% confidence interval, -9.9 to -2.3; p = 0.002), despite the more frequent supplementation of vitamin D in SSc patients (p = 0.014). No significant associations were found among vitamin D concentrations and cytokine levels. Serum levels of IL-6 were significantly elevated in SSc patients (p = 0.024) and were positively correlated with the modified Rodnan skin score (rs = 0.291, p =0.041). Despite lower vitamin D levels in SSc patients, there was no clear association with any cytokine. Serum levels of IL-6 were significantly elevated and positively correlated with the extent of skin involvement in SSc patients.

T1 mapping cardiac magnetic resonance imaging frequently detects subclinical diffuse myocardial fibrosis in systemic sclerosis patients

Objectivescardiac involvement is the second most frequent systemic sclerosis (SSc) related cause of death. It remains mostly asymptomatic in the early stage and is underdiagnosed with routine screening. Cardiac magnetic resonance imaging (CMR) could improve cardiac assessment of patients and noteworthily, new sequences allow the detection of diffuse myocardial fibrosis (DMF) by native T1 mapping. The aim of this study was to determine the prevalence of cardiac involvement by CMR native T1 mapping and its correlation with echocardiography data and non-cardiac manifestations in SSc patients. Methodspatients fulfilling the ACR/EULAR classification criteria for SSc were prospectively included between 2014 and 2016. They underwent CMR at 1.5T, including native T1 and T2 mapping, and Late Gadolinium Enhancement (LGE) as a part of routine follow up. Routine biological tests (mainly BNP and CRP) were centralized in the hospital laboratory. Resultsseventy-two unselected patients were included. Thirty six patients (50%) had elevated T1 (ET1) (mean T1 1097±14 ms). CMR cardiac functional parameters were similar in ET1 and normal T1 (NT1). Echocardiography was normal in 18 (50%) of ET1. ET1 and NT1 groups were similar for cardiovascular risk factors and ischemic heart disease. ET1 was not correlated with any clinical or echocardiographic parameter or antibody profile. Thirty-six percent of patients with ET1 had no cardiac symptoms, normal echocardiography and CMR LVEF, and no LGE. Conclusionnative T1 mapping detects left ventricular ET1 (potential DMF) in 50% of patients with SSc and a third of them had a normal conventional screening including standard CMR. In the future, further studies are needed to confirm the benefit of use of native T1 mapping as a part of routine follow up to detect earlier pejorative cardiac involvement in SSc patients.

Correlations between nailfold microvascular damage and skin involvement in systemic sclerosis patients

ObjectiveThe aim of this study was to identify any correlations between microvascular damage, assessed by nailfold videocapillaroscopy and skin impairment, evaluated by three different methods, the modified Rodnan skin score (mRSS), skin high-frequency ultrasound (US) and the plicometer skin test (PST) in systemic sclerosis (SSc) patients. MethodsSixty-three SSc patients and 63 healthy subjects were enrolled. Nailfold videocapillaroscopy (NVC) was used to assess the nailfold capillaroscopy pattern (“Early”, “Active” or “Late”), according to the Cutolo classification. All subjects were assessed by mRSS, US and PST to evaluate their dermal thickness (DT) in the seventeen skin areas of the body usually evaluated by mRSS (zygoma, fingers, hands, dorsum of hands, forearms, arms, chest, abdomen, thighs, legs, feet). Statistical evaluation was performed by nonparametric tests. ResultsAll the three methods demonstrated progressively higher values of skin impairment in patients with “Early”, “Active” or “Late” pattern of nailfold microangiopathy (for mRSS p < 0.01, US p < 0.02 and PST p < 0.02). A positive correlation was also observed in SSc patients between the three methods used to evaluate skin involvement (mRSS vs US, mRSS vs PST, PST vs US, p < 0.0001 respectively). ConclusionsThis study demonstrates that there is a correlation between two of the most important aspects to classify and monitor the SSc patients, i.e. microvascular damage progression (evaluated by NVC) and skin damage (assessed by mRss, US and PST).

Effect of rituximab on heart involvement in systemic sclerosis

As of now, there has been a great body of data on the use of rituximab (RTM) in systemic sclerosis (SS), mainly on its positive effect on skin fibrosis and lung injury. However, information is still scarce about the effect of RTM on other organs and systems, namely the heart affected by SS.Objective: to assess the time course of changes in the signs of heart involvement in SS patients one year after initiation of RTM therapy.Subjects and methods. The paper gives data on changes in cardiac disorders in 71 patients with SS one year after the prescription of RTM.Results and discussion. The rate of cardiac rhythm and conduction disorders and diastolic dysfunction was unchanged. At the same time, a significant increase in left ventricular ejection fraction (EF) and a reduction in the severity of dyspnea was achieved, which correlated with improved lung function (a significant rise in forced vital capacity). The results of treatment in three patients with predominant heart involvement associated with SS (coronary heart disease and hypertension were ruled out) were considered in detail. These patients displayed pronounced positive changes as increased EF, less severe cardiac arrhythmias, reduced chronic heart failure, better quality of life, as well as the synchronicity of lower disease activity, less skin induction, improved lung function, and stabilized pulmonary artery systolic pressure.Conclusion. RTM in combination with traditional therapy can be considered as a potentially effective drug for the treatment of heart involvement in SS.