Mortality In Systemic Sclerosis Research Articles

Exercise Pulmonary Resistances Predict Long-Term Survival in Systemic Sclerosis

Pulmonary hemodynamics during exercise may reveal early pulmonary vascular disease and may be of clinical and prognostic relevance in systemic sclerosis (SSc). We aimed to assess the prognostic relevance of exercise pulmonary resistances in patients with SSc with no or mildly increased mean pulmonary arterial pressure (mPAP). Are pulmonary resistances at peak exercise independent predictors of mortality in systemic sclerosis? All SSc patients with resting mPAP< 25mmHg and at least one year of follow-up data who underwent symptom-limited exercise right heart catheterization between April 2005 and December 2018 were analyzed retrospectively. Age-adjusted Cox regression analysis was used to evaluate the association between pulmonary resistances and all-cause mortality. The cohort consisted of 80 patients: 73 women and 7 men with a mean age of 57 years (interquartile range [IQR], 47-67 years) and a mean follow-up time of 10.4 years (IQR, 8.5-11.8 years). At baseline, resting mPAP of≤ 20mmHg and 21 to 24mmHg was found in 68 and 12 patients, respectively. Pulmonary vascular resistance (PVR) and total pulmonary resistance (TPR) at peak exercise were associated significantly with mortality (P= .006 [hazard ratio (HR), 2.20; 95%CI, 1.26-3.87] and P= .026 [HR, 1.56; 95%CI, 1.06-2.29]), whereas resting PVR and TPR were not (P= .087 [HR, 2.27; 95%CI, 0.89-5.83] and P= .079 [HR, 1.88; 95%CI, 0.93-3.80]). The mPAP per cardiac output (CO) and transpulmonary gradient (TPG) per CO slopes were associated significantly with mortality (P= .047 [HR, 1.14; 95%CI, 1.002-1.286] and P= .034 [HR, 1.34; 95%CI, 1.02-1.76]) as well. The area under the receiver operating characteristic curve for exercise PVR to predict 10-year mortality was 0.917 (95%CI, 0.797-1.000). PVR and TPR at peak exercise, mPAP/CO slope, and TPG/CO slope are predictors of age-adjusted long-term mortality in SSc patients with no or mildly increased pulmonary arterial pressure.

Systemic sclerosis is an independent risk factor for ischemic heart disease, especially in patients carrying certain antiphospholipid antibodies: A large cross-sectional study

BackgroundA higher prevalence of ischemic heart disease (IHD) in patients with systemic sclerosis (SSc) was reported. However, contrasting findings were published concerning the role of SSc-related autoantibodies in IHD risk which remains controversial. The current study explored the link between SSc and IHD, impact of putative links on SSc mortality and the role of SSc-related and antiphospholipid autoantibodies in disease associated IHD. MethodsA large cohort study utilising the Clalit-Health-Service (CHS) database was conducted on 2431 SSc patients and 12,710 age- and sex matched controls. The proportion of IHD was compared between patients diagnosed with SSc and age- and gender-matched controls. The role of SSc-linked and antiphospholipid autoantibodies in disease associated IHD was assessed. ResultsThe prevalence rate of IHD was significantly higher in SSc than controls (20.4% vs 15.0%, p <0.001). At the multivariate analysis, SSc was an independent predictor of IHD with an OR of 1.91 (95%CI 1.57–2.31, p < 0.0001). SSc patients with IHD had a higher mortality rate with an HR of 2.67 (95%CI 2.03–3.53, p < 0.0001) than those without IHD. In SSc patients positivity for anti-beta2GPI (IgM-isotype) or anti-cardiolipin (aCL) (IgA-isotype) represented a risk factor for IHD with an OR 1.89 (95% 1.04–3.45, p = 0.0369) and OR of 3.72 (95% 1.25–11.11, p = 0.0184), respectively. ConclusionsPatients with SSc are at higher risk for developing IHD with an additional risk for the latter in those positive for aCL or anti-beta2GPI. A high degree of suspicion is needed during routine patient follow-up and pre-emptive screening should be considered.

Overall mortality.

Systemic sclerosis is a highly morbid, complex autoimmune disease that is variable both in its phenotype and the attendant mortality driven by such manifestations. This review article synthesizes mortality data from the best available meta-analyses, subgroup analyses of single cohorts, and subjective comparisons of individual cohort studies, which in aggregate suggest that mortality in systemic sclerosis has been gradually improving over the past several decades. This review also summarizes the literature describing various risk factors for mortality in systemic sclerosis.

Polyporus Polysaccharide Ameliorates Bleomycin-Induced Pulmonary Fibrosis by Suppressing Myofibroblast Differentiation via TGF-β/Smad2/3 Pathway.

Pulmonary fibrosis is a major cause of morbidity and mortality in systemic sclerosis (SSc) with no effective medication. Polyporus polysaccharide (PPS), extracted from Chinese herbs, has immune regulation, anticancer, antioxidant and antiinflammatory activities. This study aims to investigate antifibrotic effects of PPS. We show that PPS markedly ameliorates bleomycin-induced lung fibrosis in mice. Myofibroblasts are the effector cells responsible for excessive deposition of extracellular matrix (ECM) proteins in fibrotic diseases. In vitro evidence reveals that PPS exerts potent antifibrotic effects by inhibiting fibroblast-to-myofibroblast transition, suppressing ECM deposition, and repressing lung fibroblast proliferation and migration. We also find that PPS inhibits TGF-β1-induced Smad2/3 activating. This study is the first to demonstrate an antifibrotic role of PPS in lungs, thus warranting further therapeutic evaluation.

Update on Morbidity and Mortality in Systemic Sclerosis-Related Interstitial Lung Disease.

Contemporary studies of systemic sclerosis (SSc) consistently demonstrate that interstitial lung (ILD) is a leading cause of disease-related death. This review summarizes morbidity and mortality outcomes in SSc-ILD patients from high-quality observational and interventional studies over the last 50 years. The data presented suggest a trend for improved morbidity and mortality outcomes among present day SSc-ILD patients. Specifically, SSc-ILD patients appear to be living longer from the time of the initial diagnosis. Despite improved survival, the number one cause of death for most SSc-ILD patients remains respiratory failure from ILD. This review describes the most important demographic, clinical, and biological factors, which affect mortality in SSc-ILD, and could be used to help stratify patients for closer monitoring and more aggressive initial treatment. The review concludes with an overview of future research needed to (1) understand how to personalize the care of SSc-ILD patients to improve morbidity and mortality outcomes; and (2) investigate whether novel therapeutic interventions (e.g., anti-fibrotics, hematopoetic stem-cell transplantation) offer any meaningful long-term survival advantage over the current standard of care.

Spanish scleroderma risk score (RESCLESCORE) to predict 15-year all-cause mortality in scleroderma patients at the time of diagnosis based on the RESCLE cohort: Derivation and internal validation.

A few scores predicting the short-term risk of mortality in Systemic sclerosis (SSc) have been reported to date. Our study aimed to create a predictive 15-year all-cause mortality score at the time of the diagnosis of SSc. The study was based on the Spanish Scleroderma Registry (RESCLE). The cohort was split up in derivation (DC) and validation cohort (VC). A multivariate analysis to detect variables related to all-cause mortality within the first 15years from SSc diagnosis was performed, assigning points to the rounded beta values to create the score (RESCLESCORE). 1935 SSc patients were included. The variables in the final model were as follows: age at diagnosis (+2 points>65years-old), male gender (+1 point), lcSSc subset (-1 point), mode of onset other than Raynaud's (+1 point), cancer (+1 point) and visceral involvement, such as ILD (+1 point), PAH (+1 point), heart (+1 point) and renal involvement (+2 points). Autoantibodies did not achieve statistical significance in the multivariate analysis. The 3 categories of risk to predict 15-year all-cause mortality at the time of diagnosis were as follows: low risk (5% vs. 7%, p=.189), intermediate risk (26.5% vs. 25.5%, p=.911) and high risk (47.8% vs. 59%, p=.316). The AUC was 0.799 (DC) vs. 0.778 (VC) (p=.530). In conclusion, the RESCLESCORE demonstrated an excellent ability to categorize SSc patients at the time of diagnosis in separate 15-year all-cause mortality risk strata at the time of diagnosis.

Early trajectories of skin thickening are associated with severity and mortality in systemic sclerosis

BackgroundSystemic sclerosis (SSc) is a severe and highly heterogeneous disease. The modified Rodnan skin score (mRSS) is a widely used tool for the assessment of the extent and degree of skin thickness. This study aimed to identify the classes of patients with early similar skin thickening trajectories without any a priori assumptions and study their associations with organ involvement and survival.MethodsFrom the French SSc national cohort, patients with a disease duration of less than 2 years at inclusion and with at least 2 mRSS available within the first 4 years of follow-up were enrolled. Classes of patients with similar mRSS trajectories were identified based on a latent class mixed model. The clinical characteristics and survival rate were compared between the obtained classes.ResultsA total of 198 patients fulfilled the inclusion criteria, with a total of 641 mRSS available. The median disease duration and follow-up were 0.8 (interquartile range 0.4; 1.2) and 6.3 (3.8; 8.9) years, respectively. Individual trajectories of mRSS were highly heterogeneous between patients. Models with 1–6 latent classes of trajectories were sequentially assessed, and the 5-class model represented the best fit to data. Each class was characterized by a unique global trajectory of mRSS. The median disease duration did not differ significantly between classes. Baseline organ involvement was more frequent in classes with significant change over time (classes 2–5) than in class 1 (low baseline mRSS without significant change over time). Using Cox regression, we observed a progressively increasing risk of death from classes 1 to 5.ConclusionsEarly identification of clinical phenotype based on skin thickening trajectories could predict morbi-mortality in SSc. This study suggested that mRSS trajectories characterization might be pivotal for clinical practice and future trial designs.

Assessment of interstitial lung disease in systemic sclerosis using the quantitative CT algorithm CALIPER.

Interstitial lung disease (ILD) remains a major cause of morbidity and mortality in systemic sclerosis (SSc). Study aim is to characterize and quantify SSc-ILD by using Computer-Aided Lung Informatics for Pathology Evaluation and Rating (CALIPER). Secondly, our objective is to evaluate which radiological pattern is predictive of lung function decline at 12months follow-up. In the prospective study (IRB 5435), 66 SSc patients underwent high-resolution computerized tomography (HRCT) at baseline. HRCT was performed according to standard protocol using a CT 64GE light speed VCT power scanner. CALIPER classified lung parenchyma on volume units. Every volume unit was classified into radiological parenchymal patterns (honeycombing, reticular and ground glass). Pulmonary function tests (PFTs) were performed at baseline and after 12months of follow-up. Cigarette smoking and other lung diseases unrelated to SSc are exclusion criteria. CALIPER analysis showed normal lung parenchyma 87.4± 9.8%, ground glass 2.8± 5.3%, reticular 4 ± 5.7%, and honeycombing 1 ± 1%. In multiple regression analysis, FEV1 (p < 0.0001), FVC (p = 0.001), and DLCO (p < 0.0001) measurements at baseline showed a negative correlation with the reticular pattern percentage. At follow-up, DLCO reduction showed a positive correlation (p < 0.001) with the percentage of ground glass pattern (r = 0.33, beta coefficient = 0.51). In the ROC curve analysis, ground glass score is a good predictor (0.75, p = 0.009; 95% CI 0.59-0.91) of DLCO worsening, defined as a decrease of more than 10% of DLCO. Using a cutoff ≥ 4.5 for ground glass score, the RR for DLCO worsening is 6.8 (p < 0.01; 95% CI 1.6-29.2). The results of this study show that CALIPER is useful not only for quantifying lung damage but also for assessing worsening PFTs, but larger studies are needed to confirm these preliminary data.Key Points• At baseline reticular pattern showed negative correlation with PFTs• At follow-up ground glass pattern predicts worsening of DLCO• CALIPER is a useful to quantify lung damage.

Cardiovascular Magnetic Resonance Identifies High-Risk Systemic Sclerosis Patients with Normal Echocardiograms and Provides Incremental Prognostic Value.

Background: Acute cardiac events are a significant contributor to mortality in systemic sclerosis (SSc). However, echocardiographic evaluation may be deceptively normal during an acute presentation. We hypothesized that in diffuse SSc patients presenting with acute cardiac events and a normal echocardiogram, cardiovascular magnetic resonance (CMR) would have incremental diagnostic/prognostic value. Methods. 50 consecutive diffuse SSc patients with normal echocardiograms were evaluated using a 1.5T system. A total of 27 (63%) had experienced an acute cardiac event three to tendays before CMR evaluation (rhythm disturbances, angina pectoris, shortness of breath). Left/right ventricular (LV/RV) volumes and ejection fractions (EF), as well as LV mass, the T2-signal ratio, early/late gadolinium enhancement (EGE/LGE), native/post-contrast T1-mapping, T2-mapping and extracellular volume fraction (ECV) were compared between the event and no-event groups. Results: No differences were identified in LV/RV volumes/EF/mass. In logistic regression analyses, independent predictors of belonging to the event group were EGE (odds ratio (95% CI): 1.55 (1.06–2.26), p = 0.024), LGE (1.81 (1.23–2.67), p = 0.003), T2 mapping (1.20 (1.06–1.36), p = 0.004) and native/post-contrast T1 mapping (1.17 (1.04–1.32), p = 0.007 and 0.86 (0.75–0.98), p = 0.025). At a median follow-up of ~1.2 years, 42% vs. 11% of the event/no-event group respectively reached a combined endpoint of event occurrence/recurrence or cardiovascular mortality. Of the independent predictors resulting from logistic regression analyses, only LGE (hazard ratio (95% CI): 1.20 (1.11–1.30), p < 0.001), T2-mapping (1.07 (1.01–1.14), p = 0.025) and native T1-mapping (1.08 (1.01–1.15), p = 0.017) independently predicted the combined endpoint. Conclusions: A normal echocardiogram does not preclude myocardial lesions in diffuse SSc patients, which can be detected by CMR especially in symptomatic patients.

The relationship between serum level of matrix metalloproteinase-7 and interstitial lung disease in patients with systemic sclerosis

BackgroundInterstitial lung disease (ILD) remains a leading cause of mortality in systemic sclerosis (SSc). Matrix metalloproteinases (MMPs) play an important role in inflammation, autoimmune diseases and aberrant fibrotic tissue remodeling.AimThe aim of this work was to evaluate the relation between serum level of MMP-7 and ILD in SSc patients.Patients and methodsThe study was conducted on 30 SSc patients. Pulmonary function tests and chest high-resolution computed tomography were assessed. Degree of fibrosis was assessed according to Warrick severity and extent scores. Serum level of MMP-7 was measured.ResultsThe 30 patients had a mean age of 41.60±11.11 years and disease duration of 3.50 ±1.81 years; 23 with diffuse and seven with limited subtype. ILD was present in 20 patients. Serum MMP-7 was significantly higher in those with ILD (412.5±52.4 ng/ml) compared with those without (disease control group) (351.4±56.4 ng/ml) (P=0.007). In patients with ILD, MMP-7 was significantly higher in those with ground-glass opacities, honeycombing and reticular infiltration on high-resolution computed tomography; yet, it was comparable among the different grades of pulmonary restriction by pulmonary function test. There was a significant negative correlation between serum MMP-7 level and forced vital capacity and forced expiratory volume in one second (r=−0.46, P< 0.05 and r=−0.65, P< 0.0001, respectively). Correlations between MMP-7 and Warrick severity and extent were significant (P=0.002 and 0.007, respectively). MMP-7 at a cutoff value of 367.4 ng/ml was 85% sensitive and 80% specific for detection of ILD.ConclusionThere is a strong association between serum MMP-7 and the presence, severity and extent of ILD in scleroderma patients. It might be a useful marker for ILD in SSc.

Systemic sclerosis

Systemic sclerosis (SSc) is arare fibrosing rheumatic multi-systemic disease involving many medical specialties. The mortality of SSc is determined by lung fibrosis, pulmonary arterial hypertension and cardiac involvement. With early and intensive treatment, the disease can be stabilized and symptoms relieved. This review summarizes insights into pathophysiology, disease classification, clinical manifestations and successful therapies, as well as recent studies on new immunosuppressant, biological and vasoactive therapies.

Mortality and hospitalization outcomes of interstitial lung disease and pulmonary hypertension in the Singapore systemic sclerosis cohort

ObjectivesWe compared mortality and hospitalization rates in four groups of patients with systemic sclerosis (SSc) [isolated pulmonary arterial hypertension (PAH) or interstitial lung disease (ILD), concomitant ILD-pulmonary hypertension (PH), and no/mild pulmonary involvement]. MethodsIn the Systemic Sclerosis Cohort Singapore (SCORE), ILD was diagnosed by HRCT and significant ILD was defined by forced vital capacity <70% predicted. Patients were classified as PAH if echocardiographic systolic pulmonary artery pressure (sPAP) ≥50 mmHg or right heart catheterization (RHC) mean PAP ≥25 mmHg. Multivariable regression analyses were performed to determine factors associated with mortality and hospital admissions per year. Cox proportional hazard model was used to analyze survival. ResultsOf 490 SSc patients, 50 patients had PAH, 92 patients had ILD and 43 patients had ILD-PH. Of 93 patients with PAH or ILD-PH, 56 were based on echocardiography and 37 on RHC. Patients with ILD-PH (HR 3.77, 95% CI: 2.05–6.93) had the highest risk of death, followed by PAH (HR 3.03, 95% CI: 1.60–5.76) and ILD (HR 1.84, 95% CI: 1.04–3.28). After adjustment for confounders, PAH (HR 2.39, 95% CI: 1.13–5.07) remained independently associated with mortality, but not ILD-PH or ILD. Other factors associated with mortality were male gender, age at SSc diagnosis, malabsorption and digital ulcer/ gangrene. Increased hospitalization rate was associated with renal crisis, right heart failure and PAH medications, but not SSc groups. ConclusionPAH is an independent risk factor of mortality in SSc. Increased hospitalization rate was not associated with SSc groups. Other factors associated with increased mortality and hospital admissions were identified.

Geographic disparity in systemic sclerosis mortality in the United States: 1999-2017.

Previous studies reported a progressive decrease in the systemic sclerosis mortality rates in the United States from 1959 to 2002. Identification of areas with clusters of higher mortality rates is important to implement targeted interventions. In this study, we aimed to estimate the mortality rates of scleroderma and to analyze its geographic variability at the state level in the United States. Mortality rates of scleroderma from 1999 to 2017 were obtained from the CDC Wonder Underlying Cause of Death database and its query system, using International Classification of Diseases, Tenth Revision codes. Age-adjusted rates were calculated by state and demographics. A linear regression model was applied to evaluate trends over time. Over the period studied, a total of 24,525 deaths had scleroderma as the underlying cause of death. The age-adjusted mortality rate was 3.962 per million (95% CI: 3.912-4.012), decreasing progressively from 4.679 (95%CI: 4.423-4.934) in 1999 to 2.993 (95% CI: 2.817-3.170) per million in 2017. The age-adjusted mortality rate was 5.885 (95% CI: 5.802-5.967) and 1.651 (95% CI: 1.604-1.698) per million in females and males, respectively. Per races, the highest age-adjusted mortality rate was in Blacks or African Americans, at 5.703 per million (95% CI: 5.521-5.885), followed by American Indians or Alaska Native at 5.047 per million (95% CI: 4.428-5.667). Clusters of states with higher and lower mortality rates were identified. South Dakota had the highest whereas Hawaii had the lowest mortality rate. We found a trend to a progressive decrease in mortality rates of scleroderma during the years of our study. In addition, we found relevant state-by-state variation in mortality with several geographical clusters with higher mortality rates. Further analyses are warranted in order to better understand the factors associated with the observed geographic disparities.

Impact of the revised haemodynamic definition on the diagnosis of pulmonary hypertension in patients with systemic sclerosis.

Pulmonary arterial hypertension (PAH) is one of the leading causes of mortality in systemic sclerosis (SSc). We explored the impact of the updated haemodynamic definition of pulmonary hypertension (PH), as proposed by the 6th World Symposium on Pulmonary Hypertension. In this single-centre retrospective analysis, patients with SSc who had right heart catheterisation (RHC) were included. We compared the prior PH definition to the updated PH definition. The prior definition classified PH as mean pulmonary arterial pressure (mPAP) ≥25 mmHg and further divided into pre-capillary PH (PAH and PH due to lung disease and/or hypoxia), post-capillary PH, and combined pre- and post-capillary PH groups. For the updated definition, PH was classified as mPAP >20 mmHg and further divided into the different groups. We validated our findings in the DETECT cohort. Between 2005 and March 2019, 268 RHCs were performed in this single-centre cohort. Using the prior definition, 137 (51%) were diagnosed with PH, with 89 classified as pre-capillary PH (56 with PAH and 33 with PH due to lung diseaseand/or hypoxia), 29 as post-capillary PH, and 19 as combined pre- and post-capillary PH. When the updated definition was applied to the cohort, seven out of 131 (5%) with no PH were reclassified to pre-capillary PH (PAH (n=1), PH due to lung disease (n=3) and post-capillary PH (n=3)). In those with mPAP 21-24 mmHg, with no left heart or significantlung disease, one out of 28 (4%) in our cohort and four out of 36 (11%) in the DETECT cohort were reclassified as PAH. The updated PH definition does not appear to have a significant impact on the diagnosis of PH in two different screening cohorts.

Systolic Dysfunction in Systemic Sclerosis: Prevalence and Prognostic Implications.

ObjectivePrimary cardiac involvement is presumed to account for a substantial part of disease‐related mortality in systemic sclerosis (SSc). Still, there are knowledge gaps on the evolution and total burden of systolic dysfunction in SSc. Here we evaluated prospective left ventricular (LV) and right ventricular (RV) systolic function in an unselected SSc cohort and assessed the burden of systolic dysfunction on mortality.MethodsFrom the Oslo University Hospital cohort, 277 SSc patients were included from 2003‐2016 and compared with healthy controls. Serial echocardiographies were reevaluated in order to detect change in systolic function. Right heart catheterization was performed on patients suspected of pulmonary hypertension. Descriptive and regression analyses were conducted.ResultsAt baseline, LV systolic dysfunction by ejection fraction less than 50%, or a global longitudinal strain greater than −17.0%, was found in 12% and 24%, respectively. RV systolic dysfunction measured by tricuspid annular plane systolic excursion (TAPSE) less than 17 mm was evident in 10%. Follow‐up echocardiography was performed after a median of 3.3 years (interquartile range [IQR] 1.5‐5.6). At follow‐up, LV systolic function remained stable, whereas RV function evaluated by TAPSE deteriorated (mean 23.1 to 21.7 mm, P = 0.005) equaling a 15% prevalence of RV systolic dysfunction. RV systolic function predicted mortality in multivariable models (hazard ratio 0.41, 95% confidence interval [CI] 0.19‐0.90, P value 0.027), whereas LV systolic function lost predictive significance when adjusted for TAPSE.ConclusionIn this unselected and prospective study, systolic dysfunction of the LV and RV was a frequent complication of SSc. LV systolic function remained stable across the observation period, whereas RV function deteriorated and predicted mortality.

Increased Risk of Ischemic Stroke in Systemic Sclerosis: A National Cohort Study of US Veterans.

Previously thought to involve primarily the microvasculature, systemic sclerosis (SSc) has been increasingly linked to macrovascular disease. Cardiovascular (CV) and cerebrovascular disease are responsible for 20-30% of mortality in SSc, but few studies have shown an independent association between SSc and stroke. We assessed whether SSc was an independent risk factor for ischemic stroke. We conducted a retrospective cohort study using the national Veterans Affairs (VA) administrative database containing records from 1999 to 2014. We obtained data for all patients with a diagnosis of SSc as well as 2 controls per SSc patient matched on sex, race, smoking status, and VA site. All patients were followed until development of ischemic stroke, death, or last encounter. We used a Cox proportional hazard regression model to estimate risk of ischemic stroke, with adjustments for CV comorbidities (hypertension, diabetes, atrial fibrillation, non-cerebrovascular atherosclerotic disease, hyperlipidemia), baseline medication use (aspirin, nonsteroidal antiinflammatory drugs), and Medicare enrollment. Among 4545 individuals with SSc (83% male, mean age 60.9 yrs), the incidence rate of ischemic stroke was 15.3 per 1000 person-years (vs 12.2 in the control cohort), with an unadjusted HR 1.28 (95% CI 1.11-1.47). The adjusted HR was 1.21 (95% CI 1.05-1.40) after adjusting for baseline CV risk factors, medications, and Medicare enrollment. SSc is independently associated with a higher risk of ischemic stroke among US veterans. Patients with SSc represent a population likely to benefit from targeted stroke screening or prevention therapies.

Progression of Left Ventricular Myocardial Dysfunction in Systemic Sclerosis: A Speckle-tracking Strain Echocardiography Study.

Cardiac involvement is a main cause of mortality in systemic sclerosis (SSc). Its detection remains challenging using conventional echocardiography and little is known about its potential progression. This study assessed changes in cardiac performance over time in a prospective cohort of patients with SSc, including echocardiographic speckle-tracking strain analysis. The study included 234 patients with SSc [196 women, age 52 ± 14 yrs, 165 limited SSc, time since diagnosis 5.2 yrs, interquartile range (IQR) 2.9-11.3]. Clinical variables, laboratory tests, pulmonary function tests, and echocardiographic measures were recorded at baseline and followup (median 2.3 yrs, IQR 1.3-3.9). Additionally, left ventricular (LV) systolic function was assessed with global longitudinal strain (GLS) by echocardiographic speckle-tracking analysis. At followup, GLS had significantly worsened (-21% ± 2 vs -19% ± 2, p < 0.001) while LV ejection fraction had not changed (62% ± 7 vs 61% ± 8, p = 0.124). In particular, 39 patients showed a significant deterioration of GLS as defined by a ≥ 15% decrease, which was accompanied by a concomitant worsening of proximal muscle weakness, lung fibrosis, renal function, LV diastolic function, and right ventricular systolic function. Baseline variables associated with ≥ 15% deterioration in GLS were proximal muscle weakness (OR 3.437, 95% CI 1.13-10.43, p = 0.020), decreased DLCO (OR 3.621, 95% CI 1.25-10.51, p = 0.049), and LV diastolic dysfunction (OR 2.378, 95% CI 1.07-5.27, p = 0.033). In patients with SSc, progression of LV systolic dysfunction was demonstrated by GLS but not by LV ejection fraction. Proximal muscle weakness, DLCO, and LV diastolic dysfunction may identify patients at risk for progressive LV systolic dysfunction and in need of closer cardiac monitoring.

Prevalence and associated factors of small intestinal bacterial overgrowth among systemic sclerosis patients.

Small intestinal bacterial overgrowth (SIBO) results in nutrient malabsorption and malnutrition, thereby increasing the morbidity and mortality in systemic sclerosis (SSc) patients. To evaluate the prevalence and associated factors of SIBO in SSc patients. A cross-sectional study was conducted between July 2015 and January 2016 in SSc patients over 18, using the glucose H2 /CH4 breath test to evaluate SIBO. Eighty-nine SSc patients (30 male and 59 female) underwent the glucose H2 /CH4 breath test. The mean age was 54.4. Twelve participants were positive for the glucose H2 /CH4 breath test, yielding a SIBO prevalence of 13.5% (95% CI 7.2-22.4) among SSc patients. A multivariate analysis revealed that duration of disease >5years was significantly associated with SIBO (adjusted odds ratio 9.38; 95% CI 1.09-80.47). The prevalence of SIBO, using the glucose H2 /CH4 breath test, is not common among Thai SSc patients. However, a positive result was associated with longer duration of disease.

Interstitial lung disease in Systemic sclerosis: insights into pathogenesis and evolving therapies.

Interstitial lung disease (ILD) is a leading cause of mortality in systemic sclerosis (SSc). However, mortality is improving as pathogenesis is being better understood and new therapies emerge. The roles of the inflammasome and NETosis in fibrosis are being elucidated. Epigenetic targets like DNA methylation and microRNA show promise as new targets for anti-fibrotic agents. The IL17-23 pathway has been shown to be active in SSc-ILD. Newer biomarkers are being described like CCL18 and the anti-eIF2B antibody. Hypothesis-free approaches are identifying newer genes like the ALOX5AP and XRCC4 genes. Computer-aided interpretations of CT scans, screening with ultrasonography and magnetic resonance imaging (MRI) are gradually emerging into practice. Imaging can also predict prognosis. A plethora of studies has shown the benefit of immunosuppression in halting ILD progression. Extent of lung involvement and PFT parameters are used to initiate therapy. The best evidence is for cyclophosphamide and mycophenolate. Besides these, corticosteroids and rituximab are being used in cases refractory to the first line drugs. Stem cell transplant is also backed by evidence in SSc. Longer studies on maintenance therapy are awaited. The inflammation in SSc is mostly subclinical and there is great interest in developing anti-fibrotic drugs for SSc-ILD. Perfinidone and nintedanib are under trial. The last resort is lung transplantation.

Correlation of sCD40L Level with Force Vital Capacity Value in Restrictive Lung Disease of Systemic Sclerosis Patients

Background: Interstitial Lung Disease (ILD) is one of the major cause of morbidity and mortality in Systemic Sclerosis (SSc). The gold standard to diagnose ILD is using High Resolution Computed Tomography (HRCT) scan. HRCT scan need a lot of cost and not always available, so another diagnosing test is needed as an alternative modality to diagnose ILD. ILD is a restrictive lung disease caused by lung fibrosis which is proved by the decrease of Forced Vital Capacity (FVC) in spirometry, and followed by the increase of soluble CD40L (sCD40L) level in plasma. This sCD40L may become a potential biomarker to evaluate lung fibrosis in SSc patients. The aim of this study is to analyze the correlation of sCD40L levels with FVC score in SSc patients with restrictive lung disease.Method:This cross sectional study was enrolled by the SSc patient who has restrictive lung disease based on spirometry test, at Rheumatology outpatient clinic dr. Hasan Sadikin Hospital from May 2015 to May 2016. All subject took underwent history, physical examination, spirometry and blood test for sCD40L. Data were analyzed using Pearson correlation.Result:There were 38 subjects involved in this study, dominated bywoman (92.1%) with mean age 41(±11) years. Subjects consist of 22(57,9%) with limited SSc, 16(42,1%) with diffuse SSc patients and 33 subjects treated with DMARD. Mean sCD40L serum in this study was 6.690,3(±2.377,3) pg/mL, with no statistical difference between limited and diffuse type (p=0.154). Mean FVC score in this study was 58.2(±10,8). There was no significant correlation between sCD40L serum with FVC (r=0.058; p=0.366). There was weak correlation on DMARD naïve subject between sCD40L serum and FVC (r=0.058; p=0.366) but statistically insignificant. There was no significant correlation between sCD40L serum with mRSS (r=0,066; p=0,346).Conclusion: This study founds no correlation between sCD40L with FVC in SSc at dr. Hasan Sadikin Hospital. Keyword : sCD40L, Forced Vital Capacity, Restrictive Lung Disease, Systemic Sclerosis