Prognosis Of Systemic Sclerosis Research Articles

Autologous hematopoietic stem cell transplantation in the treatment of systemic sclerosis. Part 1. Clinical aspects

Diffuse cutaneous systemic sclerosis (SSc) characterized by an acute, rapidly progressive course and severe damage to the internal organs has an unfavorable prognosis, while the treatment of this often fatal type of the disease has not been sufficiently developed. This paper reviews an update on an autologous hematopoietic stem cell transplantation (auto-HSCT) procedure, transplantation stages, and conditioning modes in patients with SSc. It presents the characteristics of auto-HSCT studies conducted in 2005 to 2016. The inclusion and exclusion criteria used in these studies are described and their outcomes compared. The results of three randomized controlled trials concerning auto-HSCT are analyzed separately. These findings confirm that auto-HSCT is currently more effective than standard immunosuppressive therapy. Auto-HSCT produces better results that can provide a more favorable long-term prognosis of SSc; it can prevent worsening of organ damages and improve skin scores and lung function. Patients with early diffuse SSc, a rapidly progressive course, and poor prognostic factors in the first 4–5 years of the disease before the development of functional insufficiency of the vital organs can be considered most promising for auto-HSCT.

Prognostic role of right ventricular and atrial mechanics in systemic sclerosis

Abstract Background Left ventricular diastolic dysfunction implies a worse prognosis in systemic sclerosis (SSc). Little is known, however, about the prognostic value of right ventricular (RV) and right atrial (RA) mechanics in this disease. Thus we aimed to investigate the long term prognostic value of the traditional and modern echocardiographic parameters of the RV and RA function as well as N-terminal pro B-type natriuretic peptide (NT-proBNP) levels in SSc patients. Patients and methods Seventy SSc patients (age: 57±12 years) were enrolled into the study. They underwent echocardiography in the years 2014–15. Parameters of the RV systolic function (tricuspid annular plane systolic excursion /TAPSE/, RV fractional area change /RVFAC/), inferior vena cava, collapsibility index, RV wall thickness were measured. Doppler data were collected: tricuspid E and A, peak velocity of tricuspid regurgitation (TR), tricuspid annular myocardial systolic (S), early- (e') and late- (a') diastolic velocities, tricuspid E/e' ratio. Maximal RA volume index as well as RA reservoir (εR), conduit (εCD) and contractile (εCT) strain were measured with the speckle tracking method. RA stiffness was calculated as ratio of E/e' to εR. Survival was assessed after 5 years. Since in some cases the cause of death was unknown, all-cause mortality was chosen as outcome. Results During the follow-up period of 4.7±0.9 years, 6 patients (8.6%) died. In univariate Cox regression analysis TAPSE, peak velocity of TR, tricuspid annular a' and S, tricuspid E/e' ratio, maximal RA volume index, RA stiffness and lnNT-proBNP were significantly associated with outcome. In multivariate Cox regression analysis RA stiffness was proved to be the only independent predictor of mortality (p=0.013). Using ROC analysis, RA stiffness ≥0.156 was the strongest predictor of the mortality (sensitivity=83.3%, specificity =89.1%, AUC=0.859). Conclusion Our results suggest that RA stiffness is an independent predictor of all-cause mortality in SSc. Larger prospective validation studies are required to prove our findings. ROC and Kaplan-Meier survival curve Funding Acknowledgement Type of funding source: None

Metabolic Pattern of Systemic Sclerosis: Association of Changes in Plasma Concentrations of Amino Acid-Related Compounds With Disease Presentation.

ObjectiveAmino acids (AA) and their derivatives play an integral role in the synthesis of structural and regulatory elements in human organisms and therefore pathologies such as systemic sclerosis that may alter the blood pattern of these compounds. This study aimed to evaluate changes in plasma concentrations of amino acid-related metabolites in systemic sclerosis in a search for potential biomarkers and mechanisms of the disease.MethodsPlasma samples from 42 patients diagnosed with systemic sclerosis (SSc) according to the 2013 American College of Rheumatology and European League Against Rheumatism ACR/EULAR classification criteria were compared to 27 matched healthy controls. Liquid chromatography/mass spectrometry was applied for the analysis of 36 amino acid-related metabolites.ResultsThe analysis of plasma AA metabolite patterns revealed the number of changes including an increase (20%) in concentrations of NO synthase (NOS) inhibitor asymmetric dimethylarginine (ADMA) in SSc vs. healthy subjects. Furthermore, SSc patients had higher glutamine, proline, betaine, 1-methylhistidine, and methylnicotinamide levels, while the concentration of tryptophan was lower. The specific metabolic pattern was identified for several aspects of disease presentation. Most interestingly NOS inhibitor L-NAME was elevated in patients with diffuse systemic sclerosis or telangiectasia.ConclusionsThese results provide further evidence for the involvement of endothelium-dependent pathways in the mechanisms and presentation of SSc. Endothelial dysfunction biomarkers may be useful in the assessment of presentation and prognosis in SSc.

CLINICAL AND SEROLOGICAL PARAMETERS OF PROGRESSION AND PROGNOSIS IN PATIENTS WITH SYSTEMIC SCLEROSIS – A STATE OF THE ART REVIEW

Systemic sclerosis (SSc) is a multi-organ connective tissue disease that leads to the dysfunction and the impaired morphology of blood vessels due to non-specific inflammation and progressive fibrosis. Due to the diversity of SSc and even though the factors predisposing to the severe course of SSc are known, it is not always possible to predict the disease progression and to determine the prognosis. Ideally, the group of patients with faster progression of organ lesions and a worse course of the disease should be identified and the early intensive treatment should be instituted. The aim of the article, is an attempt to identify the factors that worsen the prognosis in the course of SSc. The analysis of numerous studies demonstrated that patients with short-lasting SSc, with the presence of anti-RNA polymerase III antibodies, with a generalized type of SSc with quickly progressing skin lesions and males should be most strictly monitored. Moreover, vascular complications, tendon ruptures and fast capillaries loss observed in nailfold capillaroscopy are the factors deteriorating the prognosis in SSc. In conclusion, despite the known, the factors that worsen the prognosis, it is difficult to predict the course of systemic sclerosis. Due to its incompletely elucidated etiopathology as well as the diverse and unpredictable nature of the disease, reliable markers to determine the prognosis in SSc have not been found.

Systemic sclerosis: Recent insight in clinical management.

Systemic sclerosis (SSc) is a connective tissue disease characterized by diffuse microangiopathy and immune dysregulation which ultimately result in widespread fibrosis of skin and internal organs. Although the 2013 EULAR/ACR criteria have allowed to improve the sensitivity for SSc diagnosis, it has recently come to light that the traditional subclassification into limited and diffuse cutaneous forms does not appear to fully capture the different phenotypes of the scleroderma spectrum. In this regard, a recent large cluster analysis-based study and other ongoing projects are trying to achieve a better stratification of SSc patients, as the disease course remains largely unpredictable to date. Recent preclinical studies and randomized controlled trials have yielded encouraging results with new drugs targeting inflammatory/immunological and fibrotic pathways. One of the main unmet needs in SSc remains the early identification of patients at high mortality risk, for whom aggressiveness of therapies ought to be determined and weighed against disease prognosis. Furthermore, lung and cardiac transplantation may also be taken into account in some carefully selected patients. Though the prognosis of SSc remains poor, an optimized stratification of patients along with the recent and ongoing advances in therapies could greatly impact the natural course of the disease in the near future. Moreover, it is envisioned that there will be an increasing need in the future to further develop combination therapies to better fight against this complex disease. In this review we discussed new insights into organ involvements and therapeutic options.

Serum YKL-40 and IL-6 levels correlate with ultrasound findings of articular and periarticular involvement in patients with systemic sclerosis.

Systemic sclerosis (SSc) is a rare connective tissue disease characterized by vascular, immune and fibrotic abnormalities in the skin and in many internal organs. New biomarkers with predictive value associated with target organ involvement are needed. The up-regulation of IL-6 production is associated with the disease activity and in the development of cardiopulmonary manifestations in SSc patients. The protein YKL-40 is a promising and intensively investigated biomarker related to inflammatory and tumor diseases. The objective of the study was to investigate how serum levels of YKL-40 and IL-6 correlate with articular and periarticular involvement in patients with SSc assessed by high-frequency ultrasonography. 59 SSc patients (56 women, 3 men) and 23 age-matched healthy subjects (21 women and 2 men) were investigated for serum YKL-40 and IL-6 (by ELISA). All the patients and healthy controls underwent clinically and high-frequency ultrasound assessment of articular and periarticular structures. Joint involvement was scored according to the new US10SSc score. Clinical data about the SSc patients showed significantly higher mRSS in the dcSSc patients (p = 0.015). Clinical synovitis was diagnosed in 16.9% of all patients: 22.5% of the dcSSc group and 10.7% of the lcSSc group (p = 0.306). On the other hand, US synovitis was detected in a higher percentage: 44% of all SSc patients; 54.8% of the dcSSc group and 32% of the lcSSc patients (p = 0.116). Clinical tenosynovitis was established in 6.7% of all patients: 9.7% of the dcSSc group and 3.5% of the lcSSc group (p = 0.614). US tenosynovitis was detected at a higher rate: 27% of all patients; 32.25% of the dcSSc group and 21.4% of the lcSSc group (p = 0.393). Serum level of YKL-40 was significantly higher in SSc patients (115.62ng/ml ± 89.51, median 86.76) compared to the healthy controls (46.28ng/ml ± 18.91, median 44.02), p < 0.001. IL-6 level was also significantly higher in the patient group (27.60 ± 48.80pg/ml; median 8.32) vs. the healthy controls (5.79 ± 2.46pg/ml, median 5.52). In the patient subgroups, YKL-40 and IL-6 levels were significantly elevated in dcSSc compared to lcSSc patients: YKL-40 dcSSc (159.52ng/ml ± 102.81; median 136.20ng/ml) vs. lcSSc patients (89.31ng/ml ± 50.36; median 68.03ng/ml;), p < 0.001; IL-6 dcSSc patients (49.64pg/ml ± 46.37; median 16.36pg/ml) vs. lcSSc patients (13.22pg/ml ± 8.95; median 8.65pg/ml), p = 0.048. A statistically significant correlation of high magnitude (rs = 0.884, p < 0.001) was observed between YKL-40 and the ultrasound 10 Systemic sclerosis score (US10SSc) and between IL-6 and the US10SSc score (rs = 0.808, p < 0.001). Serum YKL-40 and IL-6 in combination with US may have a potential role in defining disease activity and stratification, predicting organ involvement, and in the prognosis of SSc.

Serum uric acid as a marker of disease risk, severity, and survival in systemic sclerosis-related pulmonary arterial hypertension.

The object of this paper is to assess associations between serum uric acid (UA) and pulmonary arterial hypertension (PAH) risk, disease severity, and mortality in a well-characterized cohort of systemic sclerosis (SSc) patients referred for evaluation of possible PAH. Consecutive SSc patients aged >18 years with serum UA drawn within two weeks of a diagnostic right heart catheterization (RHC) were included. Associations between baseline serum UA and PAH at RHC were examined using logistic regression and receiver operating characteristic curves. Relationships between UA levels and metrics of disease severity were assessed using Pearson and Spearman correlation. Associations between UA and survival were assessed using Kaplan–Meier analysis and Cox proportional hazard modeling. A total of 162 SSc patients were included; 82 received a diagnosis of PAH at RHC. Patients found to have PAH had significantly higher UA than those without PAH. Elevated baseline UA was associated with significantly increased odds of PAH diagnosis at RHC (odds ratio [OR] = 4.07, 95% confidence interval [CI] = 2.11–7.87, P < 0.001). Each mg/dL higher UA was associated with a 14% increase in mortality (hazard ratio [HR] = 1.14, 95% CI = 1.02–1.28, P < 0.05). In multivariable models adjusting for potential confounders of the relationship between UA and survival, UA > 6.3 mg/dL remained significantly associated with increased mortality (HR = 1.84, 95% CI = 1.02–3.32, P < 0.05). Among SSc patients with suspected PAH, elevated serum UA is associated with increased risk of SSc-PAH. Among individuals diagnosed with SSc-PAH by RHC, UA is associated with disease severity and survival. These results indicate UA is a useful predictor of PAH risk and prognosis in SSc.

Malnutrition is an independent risk factor for mortality in Mexican patients with systemic sclerosis: a cohort study.

Factors for mortality in systemic sclerosis (SSc) vary in different cohorts around the world. Case-control study nested in a cohort. We included patients ≥16years of age with SSc (ACR/EULAR 2013), from 2005 to 2015. Demographic and clinical variables and causes of mortality were recorded. We calculated Crude Mortality Rate (CMR), Standardized Mortality Ratio (SMR), and Kaplan-Meier survival analysis was performed. A Cox proportional hazard (HR) regression analysis of the potential risk factors associated with mortality was also performed. A total of 220 patients with SSc were included. During follow-up, 28 deaths occurred. The sum of total time contributed by all subjects was 1074 years-person, the CMR was 12.72%, the overall SMR was 4.5, in women 3.7, and in men 4.7. The survival rate at 5 and 10years was 83 and 70%, respectively. The causes of death were definitively attributed to SSc in 21.4% of the cases, probably in 28.7%, unrelated in 35.6%, and unknown in 14.3%. The direct cause of death of the patients was infection in 25% of cases, cardiovascular disease in 14%, lung involvement in 14%, pulmonary embolism in 11%, and neoplasia in 11%. The Cox regression analysis showed that the factors associated with mortality were: male gender (HR 5.84, CI 95% 1.31-26, p=0.013), severe Medsger's score for general symptoms (HR 5.12, CI 95% 1.74-14.97, p=0.021) and severe malnutrition (HR 3.77, CI 95% 1.23-11.06, p=0.008). Infections, cardiovascular disease, and lung involvement were the leading cause of death. Male gender and severe general affection and malnutrition were associated with a poorer prognosis of SSc.

Early systemic sclerosis-opportunities for treatment.

Systemic sclerosis (SSc) is characterized by microvasculopathy (Raynaud's phenomenon and fibrointimal proliferation), presence of autoantibodies and collagen deposition in skin (scleroderma) and internal organs. Microvasculopathy, detected by nailfold capillaroscopy, and disease-specific autoantibodies (anti-topoisomerase I, anti-centromere, anti-RNA polymerase III antibodies) usually appear earlier, even years before scleroderma. At that stage of the disease, immune activation with T cells and B cells promote fibrosis. Diagnosis of SSc has been relied on scleroderma, and by this time, internal organs may have developed fibrosis, a lethal feature with no available treatment. The new EULAR/ACR 2013 criteria for the classification of SSc will help identify SSc patients before fibrosis of internal organs. The early diagnosis of SSc, before the development of fibrosis in internal organs, will allow the introduction of immunosuppressive medications in these patients in a controlled setting (randomized trials). It is anticipated that this approach will change the hitherto grim prognosis of SSc for the better.

Serological profile of patients with systemic sclerosis.

The systemic sclerosis-associated autoantibodies include anti-centromere, anti-topoisomerase I (anti-topo I), anti-RNA polymerase III, anti-fibrillarin, anti-Th/To, and anti-PDGFR. A specific serological profile is connected with clinical manifestations and prognosis in systemic sclerosis (SSc). The aim of the study was to assess the serological profile in limited cutaneous and diffuse cutaneous SSc (lcSSc and dcSSc). 87 (68 female and 19 male) consecutive SSc patients treated between 2006 and 2011 were assessed. Patients fulfilled the American College of Rheumatology classification criteria of SSc: 35 - dcSSc and 52 - lcSSc. The following marker antibodies were determined: anti-topo I, anti-centromere A and B (CENP A, CENP B), anti-RNA polymerase III (RP11, RP 155), anti-fibrillarin (U3RNP), anti- -NOR90, anti-Th/To, anti-PM-Scl-100, anti-PM-Scl-75, anti-Ku, anti-Ro-52, anti-PDGFR. The presence of antibodies was assessed using a test - EUROLINE Systemic Sclerosis Profile. 82 patients (94%) had positive antinuclear antibodies; anti-topo I - 29 patients; anti-CENP-A - 20 and anti-CENP-B - 20; anti-RP11 - 9 and anti-RP155 - 7; anti-U3RNP - 1; anti-NOR90 - 6; anti-Th/ To - 3; anti-PM-Scl-100 - 7; anti-PM-Scl-75 - 11; anti-Ku - 5; anti-Ro-52 - 23 patients. We found significant differences in prevalence of anti-topo I: 25/35 vs. 4/52 p=0.0000; anti-CENP A: 0/35 vs. 20/52 p=0.0001; anti-CENP B: 0/35 vs. 20/52 p=0.0001 between dcSSc and lcSSc. Some antibodies in SSc, e.g. anti-topo I and anti-centromere, are useful in defining the clinical subset of disease and provide prognostic information. There are no significant differences in the prevalence of other autoantibodies associated with SSc between dcSSc and lcSSc patients.

SAT0221 Can Changes in NT-PROBNP Predict Early Response to Therapy And Prognosis in Systemic Sclerosis Associated Pre-Capillary Pulmonary Hypertension?

BackgroundPulmonary hypertension (PH) is a severe complication of systemic sclerosis (SSc), affecting 5-12% of patients. Despite recent progress in treatment, prognosis remains poor. Early therapeutic management and goal-oriented approach can...

OP0305 Assessment of Skin Involvement by Acoustic Radiation Force Impulse (ARFI) Imaging in Patients with Systemic Sclerosis

BackgroundMeasurement of skin involvement is essential for diagnosis and assessment of prognosis in systemic sclerosis (SSc). The modified Rodnan Skin Score (mRSS) is the gold standard outcome measure for assessment...

Low Socioeconomic Status (Measured by Education) and Outcomes in Systemic Sclerosis: Data from the Canadian Scleroderma Research Group

In systemic lupus erythematosus, socioeconomic status (SES) affects outcomes. SES can modify outcomes by altering timing of access to care and adherence. It is unknown whether SES affects systemic sclerosis (SSc) outcomes. Disease can affect income and cause work disability, thus education (completed long before SSc onset) may be a proxy for SES. The Canadian Scleroderma Research Group collects annual data on patients with SSc. Baseline data were used from a prevalent cohort. Education was stratified by whether participants completed high school. Regression models assessed effects of education on organ complications and survival. In our study, 1145 patients with SSc had 11.0 ± 9.5 years' disease duration; 86% were women, with a mean age of 55.4 ± 12.1 years. About one-quarter did not complete high school; this was more common in older patients (p < 0.0001), men (p = 0.017), those with lower income (p < 0.0001), the unemployed (p < 0.054), smokers (p < 0.001), where DLCO was < 70% predicted (p = 0.009), in those with arthritis (p = 0.047), higher Health Assessment Questionnaire-Disability Index (p = 0.017), elevated erythrocyte sedimentation rate (p = 0.019), median C-reactive protein (p = 0.002), proteinuria (p = 0.016), steroid use ever (p = 0.039), and those more likely to have died in followup (12.7% vs 8.0%; p = 0.024). However, adjusting for confounders, there was no effect of education on mortality; whereas mortality was related to age, diffuse cutaneous SSc (dcSSc) subset, elevated pulmonary arterial (PA) pressure on echocardiography, low forced vital capacity expressed as percentage of predicted, and proteinuria (similar in the dcSSc subset and in limited cutaneous SSc), mortality was increased in older patients, those with elevated PA pressure, and those with low DLCO. Completing less education than high school was not associated with a worse prognosis in SSc after adjustment for confounding characteristics.

Periungual Capillaroscopy Findings in a Series of Patients with Granulomatosis with Polyangiitis (Wegener): An Observational Study

Introduction: Periungual capillaroscopy studies skin microcirculation. Its main indication is in the differential diagnosis of Raynaud’s phenomenon as well as diagnosis and prognosis of systemic sclerosis (SS). Many rheumatic diseases present characteristic capillaroscopic alterations, but little is known at present about the alterations in skin microcirculation of systemic vasculitis. Objective: Our main objective was to study the alterations in skin microcirculation by capillaroscopy in patients with granulomatosis with polyangiitis (GPA). The secondary objective was to evaluate the association of capillaroscopic alterations with systemic alteration. Material and Methods: We studied patients in our unit with GPA, and we collected demographic and clinical variables. Periungual capillaroscopy was performed on all patients, and always by the same investigator. Results: We reviewed 10 patients with a mean age of 55.7. They were predominantly women. We found capillaroscopic alterations in 8 of the 10 patients. Morphological alteration was the most common finding (62.5%), followed by bleeding (50%). We found no mega-capillaries or neovessels. These findings were not related to any specific organ system involvement. Discussion: The tortuous pattern with bleeding was predominant in our series, with lower capillary density, findings which were unrelated to any specific organ system involvement. A single study describes capillaroscopic alterations in GPA, detecting a high percentage (92%) of avascular areas, in contrast with the predominance of a twisting pattern and bleeding found in our study. Further studies are warranted to confirm these results.

Manifestations abdominales révélant des affections systémiques

Systemic sclerosis (SSc) is a connective tissue disease characterized by diffuse microangiopathy and immune dysregulation which ultimately result in widespread fibrosis of skin and internal organs. Although the 2013 EULAR/ACR criteria have allowed to improve the sensitivity for SSc diagnosis, it has recently come to light that the traditional subclassification into limited and diffuse cutaneous forms does not appear to fully capture the different phenotypes of the scleroderma spectrum. In this regard, a recent large cluster analysis-based study and other ongoing projects are trying to achieve a better stratification of SSc patients, as the disease course remains largely unpredictable to date. Recent preclinical studies and randomized controlled trials have yielded encouraging results with new drugs targeting inflammatory/immunological and fibrotic pathways. One of the main unmet needs in SSc remains the early identification of patients at high mortality risk, for whom aggressiveness of therapies ought to be determined and weighed against disease prognosis. Furthermore, lung and cardiac transplantation may also be taken into account in some carefully selected patients. Though the prognosis of SSc remains poor, an optimized stratification of patients along with the recent and ongoing advances in therapies could greatly impact the natural course of the disease in the near future. Moreover, it is envisioned that there will be an increasing need in the future to further develop combination therapies to better fight against this complex disease. In this review we discussed new insights into organ involvements and therapeutic options.

Tc-99m diethylenetriamine pentaacetic acid (DTPA) renal function reserve estimation: is it a reliable predictive tool for assessment of preclinical renal involvement in scleroderma patients?

Prognosis of systemic sclerosis (SSc) depends on internal organ involvement. We assessed the value of renal function reserve (RFR) for the detection of preclinical nephropathy in scleroderma. Thirty SSc patients with normal serum creatinine and 30 healthy controls were included. Medsger disease severity score, glomerular filtration rate (GFR), and microalbuminuria were measured. Tc-99m DTPA was utilized for GFR measurement at baseline and after oral protein overload (stimulated GFR). RFR was calculated as the percentile increase of stimulated GFR. SSc patients had lower means of baseline GFR (P=0.001), stimulated GFR (P=0.004), RFR (P=0.046), and higher microalbuminuria (P=0.009) than controls. According to baseline GFR, SSc patients showed three categories-normal baseline GFR (n=12), hyperfiltration GFR (n=3), and reduced baseline GFR (n=15). In the former category, RFR was normal in 6/12 patients and abnormal in the remainders (50%). Hyperfiltration patients and those with reduced baseline GFR showed abnormal RFR. A statistically significant negative association was found between microalbuminuria versus stimulated GFR and RFR (r= -0.5, P=0.007 and r= -0.45, P=0.013, respectively). The majority of SSc patients with abnormal RFR had disease duration of ≥48 months (60% vs. 20%, P=0.008). All SSc patients with pulmonary hypertension had abnormal RFR, while reduced baseline GFR was noted in only 60%. A significant negative correlation was found between reduced baseline GFR and cumulative dose of corticosteroids in SSc patients (r= -0.4, P=0.022). RFR estimation could be a useful predictive marker for preclinical renal involvement in SSc patients so that early prophylactic measures and therapy modifications could be considered.

A new immunoprecipitation-real time quantitative PCR assay for anti-Th/To and anti-U3RNP antibody detection in systemic sclerosis

IntroductionClassic anti-nucleolar antibodies anti-Th/To and U3 ribonucleoprotein (-U3RNP) can help in the diagnosis, prediction of organ involvement and prognosis in systemic sclerosis (SSc); however, no validated commercial assay is available. We aimed at establishing a novel quantitative real time PCR (qPCR) method to detect these antibodies.MethodsStandard immunoprecipitation (IP) was performed using K562 cell extract and RNA components were extracted. cDNA was reverse transcribed from RNA components and Th RNA and U3 RNA were detected by qPCR using custom primers. Cycle threshold (Ct) values were compared in a titration experiment to determine the assay efficacy. The new assay was evaluated by testing 22 anti-Th/To and 12 anti-U3RNP positive samples in addition to 88 controls, and the results were compared with IP as a gold standard.ResultsBy testing serial 1:8 dilutions of cell lysate as the substrate in the IP step, RNA extracted after IP, and its derived cDNA, linear dose response curves were noted for both anti-Th/To and -U3RNP. With every dilution, Ct values changed approximately three as expected, reflecting the eight-fold difference of cDNA. The Ct difference between positive and negative samples was 8 to 13, which was similar throughout the dilutions. In the specificity analysis, the Ct values of positive samples were clearly different from the negative groups and the results by qPCR had a near perfect correlation with IP.ConclusionsOur new method readily detects these two clinically important antibodies in SSc. Making tests for anti-Th/To and -U3RNP antibodies widely available to clinicians should be helpful in the diagnosis and follow-up of SSc patients.

Evaluation of microalbuminuria in patients with systemic sclerosis as an indicator of early renal damage and increased morbidity

IntroductionRenal involvement and systemic vascular damage have been shown to be significantly affecting prognosis in systemic sclerosis. Aim of workMicroalbuminuria detection in SSc patients as an indicator of early renal involvement and its correlation with various SSc clinical, laboratory parameters and severity of organ systems’ damage assessed by Scleroderma Assessment Questionnaire. Patients and methodsForty SSc patients (33 females and 7 males) with mean age of 27.48±12.56years and mean disease duration of 6.2±4.14years were included. Twenty-four (60%) had lSSc; 13 (32.5%) had dSSc and 3 (7.5%) patients had SSc sine scleroderma. ResultsEight (20%) had microalbuminuria and 9 (22.5%) patients had decreased creatinine clearance. Albumin/creatinine ratio was significantly higher among dSSc patients compared to those with lSSc and SSc sine scleroderma (X2=9.077; p=0.01). Albumin/creatinine ratio showed significant positive correlations with telangiectasia (r=0.322; p=0.04) and mRodnan’s skin score (r=0.352; p=0.026) and negative correlations with inter-incisor distance (r=−0.525; p=0.001) and pleurisy (r=−0.446; p=0.004). Albumin/creatinine ratio correlated significantly and positively with IMSS and IDS indices of SAQ (r=0.378, 0.32; p=0.016, 0.044, respectively). SSc patients with microalbuminuria showed significantly higher mean IDS than those without (1.058 vs. 0.631, p=0.04). No statistically significant correlations were found between creatinine clearance and the different demographic, clinical features and the indices of SAQ. ConclusionMicroalbuminuria compared to creatinine clearance may be a more sensitive indicator of early renal affection and predictor of increased morbidity.

Implantable Cardioverter Defibrillator Prevents Sudden Cardiac Death in Systemic Sclerosis

Cardiac involvement means a poor prognosis in systemic sclerosis (SSc). Conduction defects and arrhythmias are frequent in patients with SSc, and may result in sudden cardiac death. We tested whether electrophysiologic studies and implantation of cardioverter defibrillators are recommended when ventricular arrhythmias are present. A cardioverter defibrillator was implanted in 10 patients with SSc who had heart involvement. After 36 months, analysis of the device showed several episodes of ventricular tachycardia in 3 patients, which were promptly reverted by electrical shock delivery. In patients with SSc who are affected by ventricular arrhythmias, the implantation of a cardioverter defibrillator may prevent sudden cardiac death.

Therapeutic options for systemic sclerosis related interstitial lung diseases

Interstitial lung disease (ILD) is a common manifestation of systemic sclerosis (SSc) mainly encountered in patients with diffuse disease. Unlike idiopathic interstitial pneumonias (IIP), SSc associated ILD corresponds to non-specific interstitial pneumonia (NSIP) in most cases, whereas usual interstitial pneumonia (UIP) is encountered less frequently. This explains the better prognosis of SSc associated ILD compared to IIP. However, severe restrictive lung disease represents one of the two main causes of disease-related death in SSc patients. The treatment of SSc associated ILD is not very well established. Anti-fibrosing treatments have failed to demonstrate any benefit and cyclophosphamide, which has been used in the treatment of this condition for about 15 years, has recently been evaluated in two prospective randomised studies which showed a significant but modest effect on respiratory function. Since none of the patients included in retrospective or prospective studies were selected on the basis of progression of ILD, and since only a minority of SSc patients develop severe ILD, further studies should focus on the subgroup of SSc patients with worsening ILD. A subgroup of patients with rapidly progressive ILD might benefit from pulsed intravenous cyclophosphamide combined with prednisone 15 mg daily but this remains to be confirmed.