European Scleroderma Study Group Research Articles

Calcinosis in Rheumatic Disease Is Still an Unmet Need: A Retrospective Single-Center Study.

Patients with immune-mediated rheumatic disease-related calcinosis comprise a subgroup at risk of encountering a more severe clinical outcome. Early assessment is pivotal for preventing overall disease progression, as calcinosis is commonly overlooked until several years into the disease and is considered as a 'non-lethal' manifestation. This single-center retrospective study explored the prevalence, clinical associations, and impact on survival of subcutaneous calcinosis in 86 patients with immune-mediated rheumatic diseases (IMRD). Calcinosis predominantly appeared in individuals with longstanding disease, particularly systemic sclerosis (SSc), constituting 74% of cases. Smaller calcinosis lesions (≤1 cm) were associated with interstitial lung disease, musculoskeletal involvement, and digital ulcerations, while larger lesions (≥4 cm) were associated with malignancy, severe peripheral artery disease, and systemic arterial hypertension. The SSc calcinosis subgroup exhibited a higher mean adjusted European Scleroderma Study Group Activity Index score than those without. However, survival rates did not significantly differ between the two groups. Diltiazem was the most commonly used treatment, and while bisphosphonates reduced complications related to calcinosis, complete resolution was not achieved. The findings underscore current limitations in diagnosing, monitoring, and treating calcinosis, emphasizing the need for further research and improved therapeutic strategies to improve patient care and outcomes.

Efficacy of rituximab on disease activity, severity, and disease-related damage in patients with immunosuppressive-resistant systemic sclerosis.

B-cell depletion with rituximab (RTX) is widely used as a rescue therapy in patients with systemic sclerosis (SSc). The aim herein was to analyze the progress of disease-related outcomes after RTX therapy in severe SSc patients. Included in this study were 27 SSc patients who were followed-up between 2012 and 2020 and received at least 1 cycle of RTX for active disease, despite receiving standard immunosuppressives (ISs). In addition to the European Scleroderma Study Group and European Scleroderma Trials and Research Group activity scores, Medsger's severity, and the recently developed Scleroderma Clinical Trials Consortium Damage Index values were evaluated initially and at 1 year after the first infusion. The progress of individual organ damage was also assessed at the end of the follow-up period (at least 6 months after the last infusion) using the data extracted from the medical records. Disease activity and severity-improved and disease-related overall damage worsened after the first year of RTX therapy (p < 0.001, p = 0.008, and p = 0.005). Some of the disease-related organ damage had improved at the end of the follow-up period, indicating its reversibility. Overall damage scores ≥11 after the first year of RTX therapy were found to be associated with mortality (p = 0.035). RTX contributed to reducing the activity and severity in SSc patients with severe disease, nonetheless the efficacy related to the damage was limited. High damage scores in the first year were found to be associated with mortality. Spontaneous progress of manifestations requiring a longer period to improve and irregular consecutive RTX courses might lead to difficulties in differentiation between activity and damage.

The value of shear wave elastography in diagnosis and assessment of systemic sclerosis.

The aim was to determine the efficacy of shear wave elastography (SWE) in assessing skin stiffness and aiding in the diagnosis of patients with systemic sclerosis (SSc). A total of 66 patients with SSc, 100 healthy individuals and 27 patients with SSc-like disorders were included. SWE was performed at 17 modified Rodnan skin score (mRSS) measurement sites. The correlation between SWE and clinical profiles was assessed, and the diagnostic value of SSc was explored. The SWE values at all 17 mRSS sites were significantly higher in SSc than in the healthy group [54.95 (45.95, 66.55) vs 41.10 (39.18, 45.45) m/s, P < 0.001]. For clinically uninvolved sites (mRSS = 0) of patients with SSc, 11 of 17 sites showed significantly higher SWE values compared with healthy controls. SWE was positively correlated with total mRSS (r = 0.783, P < 0.001), the European Scleroderma Study Group disease activity index (r = 0.707, P < 0.001) and histological collagen deposition (r = 0.749, P = 0.013). SWE effectively distinguished patients with SSc from patients with SSc-like disorders (area under the curve, AUC = 0.819). Use of SWE-detected skin sclerosis showed a significantly higher sensitivity compared with 1980 ACR criteria [0.818 (95% CI 0.709, 0.893) vs 0.727 (95% CI 0.610, 0.820), P = 0.031]. SWE correlates well with disease activity and collagen deposition in the skin, provides greater reliability than mRSS and aids in the diagnosis of SSc. SWE could be considered as a convenient and reliable quantitative tool for assessing skin sclerosis and disease progression in SSc.

Application and performance of disease activity indices proposed for patients with systemic sclerosis in an international cohort of patients with juvenile systemic sclerosis.

Juvenile systemic sclerosis is a rare childhood disease. Three disease activity indices have been published for adult patients with systemic sclerosis: the European Scleroderma Study Group Index, a modified version of the European Scleroderma Study Group Index and the revised European Scleroderma Trials and Research index. The objective of this study was to determine the feasibility and performance of the three disease activity indices in a prospectively followed cohort of patients with juvenile systemic sclerosis. The analysis cohort was selected from the prospective international inception cohort enrolling juvenile systemic sclerosis patients. The correlation of the disease activity indices with the physicians' and the patients' global assessment of disease activity was determined. The disease activity indices were compared between patients with active and inactive disease. Sensitivity to change between 6- and 12-month follow-up was investigated by mixed models. Eighty percent of the 70 patients had a diffuse cutaneous subtype. The revised European Scleroderma Trials and Research index was highly correlated with the physician-reported global disease activity/parents-reported global disease activity (r = 0.74/0.64), followed by the European Scleroderma Study Group activity index (r = 0.61/0.55) and the modified version of the European Scleroderma Study Group activity index (r = 0.51/0.43). The disease activity indices significantly differed between active and inactive patients. The disease activity indices showed sensitivity to change between 6- and 12-month follow-up among patients who improved or worsened according to the physician-reported global disease activity and the parents-reported global disease activity. Overall, no disease activity score is superior to the other, and all three scores have limitations in the application in juvenile systemic sclerosis patients. Furthermore, research on the concept of disease activity and suitable scores to measure disease activity in patients with juvenile systemic sclerosis is necessary in future.

Increased QT dispersion and related factors in patients with systemic sclerosis

Introduction: Cardiac arrhythmias and sudden death may occur as a result of ventricular myocardial fibrosis or ischemia in patients with systemic sclerosis (SSc). QT prolongation and QT dispersion, which facilitate the development of ventricular fibrillation, are important cardiac problems associated with increased mortality. In this study, we aimed to investigate the prevalence of corrected QT dispersion (cQTD) and related factors in our patients with systemic sclerosis compared to healthy controls. Material and Method: The 12-lead electrocardiograms with a rate of 25 mm/s of patients with no previous history of cardiovascular disease and controls were analyzed. cQTD was defined as the difference between the maximum QT interval and the minimum QT interval. Nailfold capillaroscopy examination was performed. Disease activity was evaluated using revised European Scleroderma Study Group activity index. Results: Forty-nine SSc patients (45 females, mean age 53.26±10.63 years, and disease duration 8.0 (1-25) years) and 41 controls (37 females, mean age 49.29±8.02 years) were included. While the frequency of smoking was significantly higher in controls (p=0.025), erythrocyte sedimentation rate was higher in patients (p&amp;lt;0.001). cQTD was significantly higher in the patient group compared to the control group (65.14±17.57 ms and 42.73±10.03 ms, respectively, p&amp;lt;0.001). A significant positive correlation was found between erythrocyte sedimentation rate and cQTD in the patient group. We found no association between cQTD and disease activity, medications, anti-SSA/Ro positivity, capillaroscopy paterns, presence of interstitial lung disease and pulmonary arterial hypertension. Conclusion: In our study, cQTD, which indicates an increased risk for ventricular arrhythmia and cardiovascular mortality, was found to be significantly higher in the patients compared to the controls. Determining cardiac risks with an electrocardiogram, which is a non-invasive and easily available method, is important in the follow-up of SSc patients.

Proprotein convertase subtilisin/kexin 9 (PCSK9) in patients with diffuse systemic sclerosis: A marker of disease activity and severe disease manifestations with potential therapeutic implementations.

This study aims to investigate proprotein convertase subtilisin/kexin 9 (PCSK9) in patients with diffuse systemic sclerosis (d-SSc) and its relation to disease activity, severity and subclinical atherosclerosis in such group of patients. Between December 2019 and July 2021, a total of 41 patients with d-SSc (17 males, 24 females; mean age: 36.1±1.9 years; range, 19 to 58 years) and 41- age and sex-matched healthy controls (17 males, 24 females; mean age: 40.1±1.7 years; range, 20 to 60 years) were included. Disease activity and skin thickness of the patients were evaluated using the European Scleroderma Study Group (EScSG) score and modified Rodnan skin score (mRSS), respectively. Serum PCSK9 and carotid intima-media thickness (CIMT) were measured using enzyme-linked immunosorbent assay (ELISA) and Duplex ultrasound, respectively. Serum PCSK9 was higher in patients compared to controls (p=0.003), particularly in those with digital ulcer (DU) and interstitial lung disease (ILD) (p<0.001). The PCSK9 positively correlated with the mean pulmonary artery pressure, EScSG, mRSS, C-reactive protein (p<0.001), erythrocyte sedimentation rate (p<0.05), lipid profile, and mean CIMT (p<0.01). In the multivariate analysis, EScSG, mRSS, lipid profile, and waist circumference were significantly correlated with PCSK9. Serum PCSK9 levels of (182.6 ng/mL) had 77.7% sensitivity and 81.2% specificity for diagnosing DU versus (172.8 ng/mL) 90.1% and 73.5% for ILD (p<0.001). Serum PCSK9 is upregulated in d-SSc with higher levels in severe disease manifestations such as DU and ILD. It is correlated well with disease activity, more severe disease manifestations, and CIMT. The PCSK9 inhibitors may be a target of therapy in diseases with premature atherosclerosis such as d-SSc regardless of its anti-cholesterol effect, at least in more severe manifestations.

Current Advanced Therapies Based on Human Mesenchymal Stem Cells for Skin Diseases.

Skin disease may be related with immunological disorders, external aggressions, or genetic conditions. Injuries or cutaneous diseases such as wounds, burns, psoriasis, and scleroderma among others are common pathologies in dermatology, and in some cases, conventional treatments are ineffective. In recent years, advanced therapies using human mesenchymal stem cells (hMSCs) from different sources has emerged as a promising strategy for the treatment of many pathologies. Due to their properties; regenerative, immunomodulatory and differentiation capacities, they could be applied for the treatment of cutaneous diseases. In this review, a total of thirteen types of hMSCs used as advanced therapy have been analyzed, considering the last 5 years (2015–2020). The most investigated types were those isolated from umbilical cord blood (hUCB-MSCs), adipose tissue (hAT-MSCs) and bone marrow (hBM-MSCs). The most studied diseases were wounds and ulcers, burns and psoriasis. At preclinical level, in vivo studies with mice and rats were the main animal models used, and a wide range of types of hMSCs were used. Clinical studies analyzed revealed that cell therapy by intravenous administration was the advanced therapy preferred except in the case of wounds and burns where tissue engineering was also reported. Although in most of the clinical trials reviewed results have not been posted yet, safety was high and only local slight adverse events (mild nausea or abdominal pain) were reported. In terms of effectiveness, it was difficult to compare the results due to the different doses administered and variables measured, but in general, percentage of wound’s size reduction was higher than 80% in wounds, Psoriasis Area and Severity Index and Severity Scoring for Atopic Dermatitis were significantly reduced, for scleroderma, parameters such as Modified Rodnan skin score (MRSC) or European Scleroderma Study Group activity index reported an improvement of the disease and for hypertrophic scars, Vancouver Scar Scale (VSS) score was decreased after applying these therapies. On balance, hMSCs used for the treatment of cutaneous diseases is a promising strategy, however, the different experimental designs and endpoints stablished in each study, makes necessary more research to find the best way to treat each patient and disease.

Capillary loss reflects disease activity and prognosis in patients with systemic sclerosis.

Capillary density on nailfold capillaroscopy (NFC) is considered a promising instrument for assessing disease characteristics in patients with systemic sclerosis (SSc), however, there is no agreement yet over how to analyze and interpret the results. The objective of this study was to investigate the possible associations of the mean number of capillaries with disease characteristics, disease activity [measured by the European Scleroderma Study Group (EScSG) disease activity score] and survival in a single-center cohort of patients with SSc. Sixty-eight patients were included; 54 had follow-up at 6 months. Thirty-two images per patient were assessed independently by two raters, scoring the mean number of capillaries in all fingers (N), in the 3rd finger of the dominant hand (dN3) and in the 4th finger of the non-dominant hand (ndN4) for each patient. NFC 'early', 'active' and 'late' patterns were also assessed. Two thousand and seventy-six images were scored at baseline, 1,728 at follow-up. Baseline N was median (IQR) 5.1 (2.7) for rater 1, and 4.9 (1.7) for rater 2, respectively. N was significantly lower in patients with a history of digital ulcers (DUs), vs. those who never had DUs 4.8 (1.4) vs. 6.4 (3.1), P=0.016. A lower N was associated with higher disease activity at baseline and follow-up (linear regression adjusted for age, sex and history of DUs). A lower ndN4 was associated with increased mortality (logistic regression adjusted for age and sex). In conclusion, in patients with SSc, a lower mean number of capillaries assessed by NFC was associated with higher disease activity after 6 months of follow-up and with shorter survival.

AB0164 ACTIVITIES OF THE OXIDATIVE-RELATED ENZYMES IN SYSTEMIC SCLEROSIS

Background:The oxidative-related enzymes are involved in the pathogenesis of various stages of systemic sclerosis (SSc). SSc is a chronic autoimmune disorder that is intimately associated with vascular damage and therefore with chronic perfusion/reperfusion and oxidative organ injury. Mesenchymal cell activation in SSc is now also considered to be mediated primarily through oxidative burst. Regulation of oxidative stress by specific enzymes including several purine metabolism enzymes is likely to play an important role in SSc progression.Objectives:to characterize interrelationships among circulating xanthine oxidase (XO), xanthine dehydrogenase (XDH), superoxide dismutase (SOD) activities and SSc activity.Methods:The study was performed according to bioethical standards. 51 patients with verified SSc and 30 healthy controls were included in the study. The diagnosis was verified according to ACR/EULAR 2013 criteria. We assessed SSc activity in compliance with the original activity scale that is commonly used in Russia [Guseva N.G., 1993] and by the 2001 European Scleroderma Study Group Activity Index. XO (EC 1.17.3.2), XDH (EC 1.17.1.4), and SOD (EC 1.15.1.1) plasma activities were measured using spectrophotometric techniques as previously described [Dubinina E.E., 1986; Karpova O.V., 2006]. Results are expressed as mean±SD. The Mann-Whitney U test and Spearman’s correlation coefficient were used for statistical analysis.Results:Mean age of patients was 42.8±1.3 years, mean SSc duration was 7.9±0.7 years. Mean enzymatic activities in normal controls were 3.43±0.56 nmol/ml min (for XO), 5.19±0.71 nmol/ml min (for XDH), and 5.40±1.03 units (for SOD). The respective enzymatic activities in SSc group were 3.91±0.62 nmol/ml min, 7.10±0.71 nmol/ml min, and 7.10±2.19 units. All these mean activities were significantly higher in SSc patients comparing to healthy individuals (p&lt;0.001). XO and XDH activities positively correlated with SSc activity (r=0.499, p&lt;0.001, and r=0.741, p&lt;0.001, respectively). The opposite but weaker trend was observed for SOD activity and SSc disease activity (r=-0.190, p=0.188).Conclusion:SSc is characterized by an increase in the intensity of oxidative and antioxidant processes, more pronounced in high disease activity. A close relationship between function of prooxidant/antioxidant enzymes and some of the key SSc pathogenetic mechanisms, especially vascular disease and fibroblast activation, is widely considered. Overall increase of oxidative stress in patients with higher disease activity, as well as depletion of antioxidant capacity can be also linked with disturbance of purine metabolism through XO and XDH modulation. Pathogenetic influence of this imbalance can also be mediated through initial phase of neutrophil extracellular traps (NETs) formation, an eventual source of nucleoprotein containing autoepitopes.Disclosure of Interests:None declared

Quantification of Ground Glass Opacities Can Be Useful to Describe Disease Activity in Systemic Sclerosis.

Interstitial lung disease (ILD) is the main cause of death in systemic sclerosis (SSc) patients. Usually, patients have lung involvement characterized by ground glass opacities (GGOs), but honeycombing (HC) is also possible. The Wells score is a semi-quantitative index, which is able to assess ILD by distinguishing its main components. The aim of this work is to evaluate the Wells score in relation to the disease activity (DA) index. We enrolled 40 consecutive SSc-ILD patients (26 diffuse cutaneous form, dcSSc, and 14 limited form, lcSSc). All patients were evaluated by the European Scleroderma Study Group (ESSG) index, high-resolution computed tomography, transthoracic echocardiogram, pulmonary function tests (PTSs), and nailfold videocapillaroscopy for the number of microhemorrhages (NEMO) score. In our study, the total extent of ILD (TE-ILD), fibrosis and GGOs correlated with dyspnea (p = 0.03, 0.01 and 0.01 respectively), but not with the ESSG index. Considering only the dcSSc patients, TE-ILD and GGOs correlated with the ESSG index (r = 0.5 p = 0.009), while fibrosis grade correlated with disease duration and systolic pulmonary artery pressure. In conclusion, our data suggest that GGO correlates with DA, while fibrosis may be a sign of disease damage. The quantification of pulmonary involvement using the Wells score can be a useful tool for assessing the appropriate treatment in SSc patients.

NEMO score in nailfold videocapillaroscopy is a good tool to assess both steady state levels and overtime changes of disease activity in patients with systemic sclerosis: a comparison with the proposed composite indices for this disease status entity

BackgroundIn previous studies, we demonstrated that the NEMO score, i.e. the cumulative number of microhaemorrhages (MHEs) and microthromboses (MTs), observed in nailfold videocapillaroscopy was a good indicator of the steady state level of disease activity (DA) in patients with systemic sclerosis (SSc) when the European Scleroderma Study Group (EScSG) index was considered the gold standard.Aim of the studyTo verify whether the NEMO score could be (i) a valid tool to assess DA, even when the modified European Scleroderma Trials and Research (EUSTAR) index was considered to be the comparator, and (ii) a sensitive method to capture the DA overtime changes.Patients and methodsThe NEMO score and the EScSG and EUSTAR indices were contemporarily assessed at baseline (T0) and after a follow-up of 4–56 months (T1) in 98 patients with SSc. The differences (Δ) between the T1 and T0 values of the NEMO score and the EScSG and EUSTAR indices were calculated and compared to each other.ResultsNEMO score values were very closely correlated with the corresponding values of the EScSG and EUSTAR indices both at T0 and T1 observations (p < 0.0001 in all cases with the exception of the correlation with EScSG values at T1 (p < 0.03)). The values of the two composite DA indices were also strictly related to each other in both T0 and T1 observations (p < 0.0001).Receiver operating characteristic (ROC) curve analysis showed the NEMO score had a good sensitivity and specificity in classifying patients with a predefined level of DA (scores ≥ 3.0 and ≥ 2.5 for the EScSG and EUSTAR indices, respectively, p < 0.0001 in both cases).Δ values of the NEMO score were significantly correlated with the corresponding values of both the EScSG and EUSTAR indices. Weighted Cohen’s k level of agreement between Δ values of the NEMO score and those of the EScSG and EUSTAR indices was moderate (0.55 and 0.59, respectively).ConclusionsNEMO score proves to be a feasible, non-invasive, and valid tool to assess steady state levels and changes over time of DA in patients with SSc. Thus, it can represent an alternative or complementary method to measure this disease status entity in this disorder.

Revised European Scleroderma Trials and Research Group Activity Index is the best predictor of short-term severity accrual

BackgroundThe European Scleroderma Trials and Research Group (EUSTAR) recently developed a preliminarily revised activity index (AI) that performed better than the European Scleroderma Study Group Activity Index (EScSG-AI) in systemic...

Less severe disease in patients with early systemic sclerosis?

Objectives: To evaluate the disease severity and activity in patients with a diagnosis of systemic sclerosis (SSc) after the 2013 American College of Rheumatology and the European League Against Rheumatism (ACR/EULAR) classification criteria development compared to patients diagnosed before 2013.Methods: One hundred and fifty-four subjects were included and assigned to the following groups: 120 SSc patients meeting the 1980 ACR criteria and with a diagnosis before 2013 (historical group), and 34 patients diagnosed after 2013, fulfilling the new ACR/EULAR criteria (early SSc group). Disease activity was assessed by the 2001 European Scleroderma Study Group Activity Index (EScSG-AI) and by the revised European Scleroderma Trials and Research group (EUSTAR) activity index. Disease severity was assessed using the Medsger Disease Severity Scale (DSS) and the summed DSS score.Results: The time between the first non-Raynaud’s symptom and the diagnosis was shorter in early SSc than in the historical group (p = .001). The EScSG-AI and the EUSTAR activity index were similar between groups. The summed DSS score and the general, skin and gastrointestinal tract DSS scores were significantly lower in early SSc than in the historical group.Conclusion: SSc patients with a diagnosis after the new ACR/EULAR criteria development were diagnosed earlier and had a less severe disease than historical patients.

Correlation Between Serum C-Reactive Protein (CRP) and Soluble Cd40 Ligand (sCD40L) with Disease Activity by Modified Rodnan Skin Score (mRSS) in Systemic Sclerosis Patients in Indonesia

Introduction: Systemic Sclerosis (SSc) is a chronic autoimmune disease which presents immunological, endothelial dysfunction, skin and organs fibrosis. The inflammatory process is an important pathophysiology of systemic sclerosis. Disease activity assessment using clinical parameters of Modified Rodnan Skin Score (mRSS) changes and inflammatory laboratory parameters of C-Reactive Protein (CRP), Erytrocyte Sedimentation Rate (ESR) and soluble CD40 ligand. The European Scleroderma Study Group (EscSG) Activity Index uses CRP. CRP is higher sensitivity and specificity than ESR (80% and 91.2%). The study aims to evaluate the correlation between CRP and sCD40L with disease activity by mRSS.Methods: This research was a cross-sectional study, and data of mRSS and sCD40L were obtained from the study, "Blind Clinical Trials Extract Ciplukan Herbs on Clinical Improvement of Skin Disorders, Inflammatory Process, Immunology and Fibrosis in Scleroderma Patients”. CRP examination was done by using the rest samples of the study, conducted in December 2017. Data analysis with Rank-Spearman and Pearson Correlation..Result: There were fifty-eight subjects with mean age 38 ± 11 years old. Most of subjects were female (94.8%) and with a late disease duration &gt; 2 years (74.1 %). Subjects consisted of 35 (60.3%) diffuse SSc and 23 (39.7 %) limited SSc. CRP was measured by Turbidimetric Immunoassay. Median (range) CRP serum was 2.89 (0.16–17.29) mg/L, while the median of sCD40L was 6457 (1018–17976) pg/mL, and the median of mRSS was 17 (4–36). There was no correlation between CRP and sCD40L with mRSS (r = -0.134, p = 0.167; and r = 0.023, p = 0.433).Conclusion: There was no correlation between CRP and sCD40L serum with mRSS in systemic sclerosis patients.

Factors associated with the 6-minute walk distance in patients with systemic sclerosis

BackgroundThere is an ongoing debate regarding the relevance of the 6-minute walking distance (6MWD) in systemic sclerosis (SSc) assessment, widely used as a usual test in these patients as well as an outcome measure in clinical trials. In this work, we aimed to assess the associations between the 6MWD and various disease parameters in patients with SSc.MethodsConsecutive patients followed in our SSc National Reference Centre were included in this cross-sectional study if they fulfilled the 2013 American College of Rheumatology/European League Against Rheumatism criteria for SSc. Data were systematically collected during a comprehensive standardized evaluation that included a 6-minute walk test, clinical assessment, biological results, pulmonary function tests, transthoracic echocardiography, composite scores (European Scleroderma Study Group Activity Index, Medsger severity score, Health Assessment Questionnaire–Disability Index (HAQ-DI)) and treatments.Associations of the 6MWD with various disease parameters were assessed by linear regression in univariate and multivariate analyses.ResultsThe study population comprised 298 patients (females 81%; mean age 58.2 ± 13.3 years; limited cutaneous SSc 82%; interstitial lung disease (ILD) 42%; pulmonary arterial hypertension (PAH) 6%). The 6MWD was significantly and independently associated with gender, age, body mass index, baseline heart rate (HR), HR variation during the test, PAH, history of arterial thrombosis and C-reactive protein levels, as well as with the HAQ-DI score in a sensitivity analysis. Muscle involvement, joint involvement and ILD were not independently associated with the 6MWD.ConclusionsDuring SSc, the 6MWD is independently associated with initial HR and HR variation; with PAH but not ILD, suggesting that pulmonary vasculopathy may have a greater impact than parenchymal involvement on functional limitation; and with global markers of disease activity and patient disability. These results give clinicians further insight into how to interpret the 6MWD in the context of SSc.

The cumulative number of micro-haemorrhages and micro-thromboses in nailfold videocapillaroscopy is a good indicator of disease activity in systemic sclerosis: a validation study of the NEMO score

BackgroundSome abnormalities in nailfold videocapillaroscopy (NVC), such as the presence of micro-haemorrhages (MHEs), micro-thromboses (MTs), giant capillaries (GCs) and reduction in the number of capillaries (nCs), suggest a disease activity (DA) phase in systemic sclerosis (SSc). In a previous paper, we showed that the number of micro-haemorrhages and micro-thromboses (the so-called NEMO score) was the NVC feature more closely associated with DA. The present study was aimed at validating the NEMO score as a measure of DA in patients with SSc.MethodsTwo cohorts of 122 and 97 patients with SSc who were referred to two different rheumatology units, one in Milan and one in Naples, respectively, constituted the validation cohorts. The NEMO score, the total number of GCs and the mean nCs per digit were the parameters defined in each patient by eight-finger NVC. An expert operator analysed the NVCs in each of the participating units. The European Scleroderma Study Group (ESSG) index was used to define the DA level in each patient at the time of NVC examination.ResultsThe NEMO score was the NVC parameter more strictly correlated with the ESSG score in both the Milan and Naples cohorts (p < 0.0001), and it was the only one among the NVC variables that gave a significant contribution in a logistic model where the ESSG score represented the dependent variable. ROC curve analysis confirmed that the NEMO score had the best performance in measuring DA. The AUC of the NEMO score was significantly greater than the AUCs obtained by plotting the sensitivity and specificity of the number of GCs and the mean nCs (p < 0.0001 in all cases). The NEMO score values that showed the best sensitivity-specificity balance in capturing patients with a relevant DA level were slightly higher in the Naples cohort than in the Milan cohort.ConclusionsThis study confirms that the presence of a certain number of MHEs and MTs in NVC may be considered a strong warning signal of a current phase of DA in patients with SSc.

The association of low complement with disease activity in systemic sclerosis: a prospective cohort study.

BackgroundIn some rheumatic diseases such as systemic lupus erythematosus (SLE), low serum complement (‘hypocomplementaemia’) is a feature of active disease. However, the role of hypocomplementaemia in systemic sclerosis (SSc) is unknown. We sought to determine the frequency, clinical associations and relationship to disease activity of hypocomplementaemia in SSc.MethodsThe study included 1140 patients fulfilling the 2013 American College of Rheumatology criteria for SSc. Demographic, serological and clinical data, obtained prospectively through annual review, were analysed using univariable methods. Linear and logistic regression, together with generalised estimating equations, were used to determine the independent correlates of hypocomplementaemia ever, and at each visit, respectively.ResultsAt least one episode of hypocomplementaemia (low C3 and/or low C4) occurred in 24.1 % of patients over 1893 visits; these patients were more likely to be seropositive for anti-ribonucleoprotein (OR = 3.8, p = 0.002), anti-Ro (OR = 2.2, p = 0.002), anti-Smith (OR = 6.3, p = 0.035) and anti-phospholipid antibodies (OR = 1.4, p = 0.021) and were more likely to display features of overlap connective tissue disease, in particular polymyositis (OR = 16.0, p = 0.012). However, no association was found between hypocomplementaemia and either the European Scleroderma Study Group disease activity score or any of its component variables (including erythrocyte sedimentation rate) in univariate analysis. Among patients with SSc overlap disease features, those who were hypocomplementaemic were more likely to have digital ulcers (OR = 1.6, p = 0.034), tendon friction rubs (OR = 2.4, p = 0.037), forced vital capacity <80 % predicted (OR = 2.9, p = 0.008) and lower body mass index (BMI) (OR for BMI = 0.9, p < 0.0005) at that visit, all of which are features associated with SSc disease activity and/or severity.ConclusionsWhile hypocomplementaemia is not associated with disease activity in patients with non-overlap SSc, it is associated with some features of increased SSc disease activity in patients with overlap disease features.

The European Scleroderma Trials and Research group (EUSTAR) task force for the development of revised activity criteria for systemic sclerosis: derivation and validation of a preliminarily revised EUSTAR activity index

BackgroundValidity of European Scleroderma Study Group (EScSG) activity indexes currently used to assess disease activity in systemic sclerosis (SSc) has been criticised.MethodsThree investigators assigned an activity score on a 0–10...

Validation of disease activity indices using the 28 joint counts in systemic sclerosis.

To validate the Disease Activity Score 28 using ESR (DAS28-ESR) and CRP (DAS28-CRP), the Simplified Disease Activity Index and the Clinical Disease Activity Index used in RA for SSc patients. Seventy-seven SSc patients, 40 RA patients, 20 patients with primary RP (PRP) and 28 healthy volunteers were assessed. Besides the disease activity composite indices, the European Scleroderma Study Group Activity Index (EScSG-AI), the HAQ-DI, the Cochin Hand Function Scale and the Short Form Health Survey (SF36) were evaluated. The validation procedure included the assessment for truth, discrimination and feasibility. DAS28-ESR, DAS28-CRP, Simplified Disease Activity Index and Clinical Disease Activity Index showed significant correlation with EScSG-AI, HAQ-DI, Cochin Hand Function Scale and the physical component of SF36 (P < 0.001). All four indices discriminated patients with SSc from RA, PRS and healthy controls, respectively (P < 0.01). With the exception of DAS28-CRP, the other three indices also discriminated between subgroups of SSc based on value of EScSG-AI (⩽3 and >3) (P < 0.05). All four disease activity composite indices showed a good inter- and intraobserver reliability based on repeated measures of two independent investigators (P < 0.001). All four disease activity composite indices were found to be valid measures for assessing arthritis in SSc. DAS28-ESR showed the best performance regarding reliability and construct validity.

A Cross Sectional Study of Cardiopulmonary Complications and Severity of Pulmonary Hypertension and Lung Fibrosis in Patients With Systemic Sclerosis

Objectives: This study aims to identify the characteristics of scleroderma patients in terms of sociodemographic and clinical characteristics and severity of lung fibrosis and pulmonary hypertension and to show the association between European Scleroderma Study Group (EScSG) scoring and severity of pulmonary hypertension and lung fibrosis. Patients and methods: This two center cross-sectional study included 43 scleroderma patients (4 males, 39 females; mean age 52 years; range 42 to 59 years) under clinical follow-up. Patients’ sociodemographic data were recorded. Median duration of illness was 10.0 years. All patients underwent blood tests, echocardiogram, full lung function test, six-minute walking test, and high resolution computed tomography of the thorax. Pulmonary hypertension was defined by echocardiogram as systolic pulmonary pressure >36 mmHg. Results: Limited systemic sclerosis was the predominant type (74.7%). Majority of high resolution computed tomography findings showed lung fibrosis with ground glass opacities (74.4%). Pulmonary hypertension was predominantly mild (31.7%), lung function test showed 36.1% restrictive lung disease, and a reduced diffusing capacity of the lungs for carbon monoxide (median 13.85) with reduced six-minute walking test distance (median 300.0 meters). Health Assessment Questionnaire scoring was predominantly in the mild to moderate disability group (median score of 0.5). Five patients (13.9%) had active disease based on the EScSG scoring. There were no significant associations between EScSG scoring and other clinical parameters. Conclusion: In our study, we found that scleroderma was predominant among females and the major type was limited systemic sclerosis. The lung function test revealed a sub-normal diffusing carbon monoxide with a reduced six-minute walking distance.