European Scleroderma Trials And Research Group Research Articles

CD19 CAR T-Cell Therapy in Autoimmune Disease — A Case Series with Follow-up

BackgroundTreatment for autoimmune diseases such as systemic lupus erythematosus (SLE), idiopathic inflammatory myositis, and systemic sclerosis often involves long-term immune suppression. Resetting aberrant autoimmunity in these diseases through deep depletion of B cells is a potential strategy for achieving sustained drug-free remission.MethodsWe evaluated 15 patients with severe SLE (8 patients), idiopathic inflammatory myositis (3 patients), or systemic sclerosis (4 patients) who received a single infusion of CD19 chimeric antigen receptor (CAR) T cells after preconditioning with fludarabine and cyclophosphamide. Efficacy up to 2 years after CAR T-cell infusion was assessed by means of Definition of Remission in SLE (DORIS) remission criteria, American College of Rheumatology–European League against Rheumatism (ACR–EULAR) major clinical response, and the score on the European Scleroderma Trials and Research Group (EUSTAR) activity index (with higher scores indicating greater disease activity), among others. Safety variables, including cytokine release syndrome and infections, were recorded.ResultsThe median follow-up was 15 months (range, 4 to 29). The mean (±SD) duration of B-cell aplasia was 112±47 days. All the patients with SLE had DORIS remission, all the patients with idiopathic inflammatory myositis had an ACR–EULAR major clinical response, and all the patients with systemic sclerosis had a decrease in the score on the EUSTAR activity index. Immunosuppressive therapy was completely stopped in all the patients. Grade 1 cytokine release syndrome occurred in 10 patients. One patient each had grade 2 cytokine release syndrome, grade 1 immune effector cell–associated neurotoxicity syndrome, and pneumonia that resulted in hospitalization.ConclusionsIn this case series, CD19 CAR T-cell transfer appeared to be feasible, safe, and efficacious in three different autoimmune diseases, providing rationale for further controlled clinical trials. (Funded by Deutsche Forschungsgemeinschaft and others.)

Does the Impact of COVID-19 on Patients With Systemic Sclerosis Change Over Time?

The outcome of patients with COVID-19 improved over the pandemic, including patients with systemic rheumatic diseases. However, data on patients with systemic sclerosis (SSc) are lacking. This study aimed to assess the outcome of patients with both SSc and COVID-19 over several waves. Patients with both SSc and COVID-19 who were registered in the European Scleroderma Trials and Research group (EUSTAR) were collected between April 2020 and April 2021. Patients were assigned to waves 1, 2, or 3 depending on the date of their COVID-19 diagnosis. Primary endpoints were death, intensive care unit stay, or ventilatory support (severe outcome). Subgroup analyses of patients who were hospitalized or died were conducted. General and SSc-specific characteristics and treatment were compared over the waves. Descriptive statistics and multivariate logistic regression were applied. A total of 333 patients were included; 57 patients (17%) had a severe outcome, and 30 patients (9%) died. Compared to wave 1, significantly fewer patients with SSc suffered from severe COVID-19 in waves 2 and 3 (28.2% vs 9.8% and 12.7%; P < 0.001), fewer patients required hospitalization (46.7% vs 19.6% and 25.5%; P < 0.001) or ventilatory support (24.0% vs 8.7% and 10.9%; P = 0.001), and fewer patients died (15.7% vs 5.0% and 7.5%; P = 0.011). Patients were significantly younger, more often men, had less frequent arterial hypertension, and less SSc cardiac involvement over waves 1 to 3. Patients received significantly less medium to high doses of corticosteroids as they did SSc treatment. The outcome of patients with both SSc and COVID-19 improved significantly over time because of intrinsic and extrinsic factors.

Vision transformer assisting rheumatologists in screening for capillaroscopy changes in systemic sclerosis: an artificial intelligence model.

The first objective of this study was to implement and assess the performance and reliability of a vision transformer (ViT)-based deep-learning model, an 'off-the-shelf' artificial intelligence solution, for identifying distinct signs of microangiopathy in nailfold capilloroscopy (NFC) images of patients with SSc. The second objective was to compare the ViT's analysis performance with that of practising rheumatologists. NFC images of patients prospectively enrolled in our European Scleroderma Trials and Research group (EUSTAR) and Very Early Diagnosis of Systemic Sclerosis (VEDOSS) local registries were used. The primary outcome investigated was the ViT's classification performance for identifying disease-associated changes (enlarged capillaries, giant capillaries, capillary loss, microhaemorrhages) and the presence of the scleroderma pattern in these images using a cross-fold validation setting. The secondary outcome involved a comparison of the ViT's performance vs that of rheumatologists on a reliability set, consisting of a subset of 464 NFC images with majority vote-derived ground-truth labels. We analysed 17 126 NFC images derived from 234 EUSTAR and 55 VEDOSS patients. The ViT had good performance in identifying the various microangiopathic changes in capillaries by NFC [area under the curve (AUC) from 81.8% to 84.5%]. In the reliability set, the rheumatologists reached a higher average accuracy, as well as a better trade-off between sensitivity and specificity compared with the ViT. However, the annotators' performance was variable, and one out of four rheumatologists showed equal or lower classification measures compared with the ViT. The ViT is a modern, well-performing and readily available tool for assessing patterns of microangiopathy on NFC images, and it may assist rheumatologists in generating consistent and high-quality NFC reports; however, the final diagnosis of a scleroderma pattern in any individual case needs the judgement of an experienced observer.

25-hydroxyvitamin D3 Levels and Their Clinical Associations in a Polish Cohort of Systemic Sclerosis Patients: A Cross-Sectional Study

Vitamin D exhibits immunomodulatory effects in autoimmune diseases. We aimed to evaluate the associations of vitamin D levels with clinical and laboratory features of systemic sclerosis (SSc) in a Polish cohort. The study was prospective in design. SSc patients who met ACR-EULAR 2013 criteria underwent comprehensive clinical and laboratory investigations using the European Scleroderma Trials and Research group (EUSTAR) methodology. We assessed patients’ sera for 25(OH)D3 using a radioimmunoassay, and the cutoff value for vitamin D deficiency was set at 20 ng/mL. Statistical analyses were performed using the Mann–Whitney U test, the Fisher’s exact, and the Spearman’s rho, where appropriate, with a significance threshold set at 0.05. We recruited 68 SSc patients (85% female). The mean 25(OH)D3 level was 21.6 ± 10 ng/mL, and 50% of subjects (n = 34) presented vitamin D deficiency (mean 13.7 ± 3.9 ng/mL). Vitamin D-deficient SSc patients exhibited higher prevalence of arterial hypertension (p = 0.002), proteinuria (p = 0.002), and lung fibrosis (p = 0.032), as well as higher CRP (p = 0.035). The modified Rodnan skin score correlated negatively with 25(OH)D3 in diffuse cutaneous SSc (dcSSc). We found no correlation with the disease duration, age, joints, and the heart. Vitamin D deficiency was common in the studied population of Polish SSc patients and was associated with arterial hypertension, proteinuria, lung involvement, and increased CRP.

POS0877 THE EFFECT OF PLATELET INHIBITORS ON DIGITAL ULCERS IN SYSTEMIC SCLEROSIS - A DERIVATION AND VALIDATION EUSTAR STUDY

Background:Digital ulcers (DUs) affect half of the patients with systemic sclerosis (SSc) and can be complicated by gangrene and amputation. The direct involvement of platelets in the development of DUs has been suggested by in vitro studies, which encouraged physicians to consider platelet inhibitors as a therapeutic option in the management of DUs. However, until now, there is no clinical study to assess the efficacy of platelet inhibitors for DUs in SSc patients.Objectives:To demonstrate a possible relationship between treatment with platelet inhibitors and the occurrence of DUs at the next follow-up visit in patients with SSc.Methods:This study used prospectively collected data from the European Scleroderma Trials and Research group (EUSTAR) registry. Patients fulfilling the 2013 ACR/EULAR SSc classification criteria with complete longitudinal data on the presence of DUs and platelet inhibitors were included in the analysis. Multiple imputation using a random forest algorithm was implemented to handle missing values.The dataset was split into a derivation and validation cohort. To investigate the response for the binary dependent variable of DUs, a generalized linear mixed model (GLMM) was developed in the derivation cohort and validated using ROC analysis and Brier scores to address discrimination and calibration, respectively.Results:Of 3,463 patients (2,961 in the derivation cohort, 722 in the validation cohort), 453 had current DUs at the baseline and 245 were exposed to platelet inhibitors (table 1).Our GLMM revealed that the exposure to platelet inhibitors is associated with a reduced risk of DUs at the next follow up visit (OR = 0.33, 95% CI = [0.13 to 0.82]). Further factors associated with absence or presence of DUs at the next follow-up visit are shown in figure 1. This confirmed the previously identified risk factors for the presence of DUs, supporting the overall robustness and the validity of our model.The performance was evaluated by ROC curve analysis and showed an AUC = 97.97% (95% CI = [96.93% to 97.67%]) for the derivation cohort and AUC = 77.3% (95% CI = [74.01% to 81.39%]) for the validation cohort, respectively, showing an acceptable discrimination. The Brier score was 0.05 in the derivation cohort and 0.07 in the validation cohort, suggesting a good calibration of the model.Conclusion:Our model, with acceptable discrimination and good calibration, suggests a positive treatment effect of platelet inhibitors on DUs in clinical practice.Table 1.Baseline characteristics of patients before imputationCharacteristicsOverallDerivation setValidation setn3,4632,691772Age (median [IQR])56.00 [47.00, 66.00]56.00 [47.00, 65.00] 57.00 [48.00, 67.00]Disease duration (median [IQR]) 9.00 [4.00, 16.00] 9.00 [4.00, 16.00] 8.00 [4.00, 15.00]Disease subset = Limited cutaneous SSc (%) 1562 (65.2) 1164 (64.6) 398 (66.9)DUs (%): Current 453 (13.1) 378 (14.0) 75 (9.7)DUs (%): Never 1783 (51.5) 1326 (49.3) 457 (59.2)DUs (%): Previously 1227 (35.4) 987 (36.7) 240 (31.1)mRSS (median [IQR]) 5.00 [2.00, 11.00] 6.00 [2.00, 12.00] 4.00 [1.00, 11.00]Joint Contractures = Yes (%) 881 (26.8) 770 (29.4) 111 (16.5)LVEF (median [IQR])62.00 [60.00, 65.00]60.00 [60.00, 65.00] 65.00 [60.00, 67.00]Dyspnea NYHA III and IV (%)300 (9.5)214 (8.6)86 (12.7)Pulmonary hypertension = Yes (%) 244 (10.7) 200 (11.3) 44 (8.4)Lung fibrosis on HRCT = Yes (%) 685 (46.6) 600 (47.7) 85 (39.7)FVC % predicted (median [IQR])97.00 [82.00, 111.00]95.00 [81.00, 110.00]101.00 [85.00, 115.00]Serum creatinine mg/dl (median [IQR]) 0.70 [0.60, 0.90] 0.70 [0.60, 0.90] 0.70 [0.70, 0.90]Anti-Scl-70 positive = Yes (%) 1147 (33.1) 958 (35.6) 189 (24.5)CRP elevation = Yes (%) 639 (21.1) 490 (20.8) 149 (22.1)Platelet inhibitors therapy = Yes (%) 245 (7.1) 206 (7.7) 39 (5.1)Oral anti-coagulants therapy = Yes (%) 53 (1.5) 50 (1.9) 3 (0.4)Disclosure of Interests:None declared

Estimated glomerular filtration rate is a marker of mortality in the European Scleroderma Trials and Research Group (EUSTAR) database.

The study aim was to evaluate the estimated glomerular filtration rate (eGFR), its association with clinical disease and its predictive ability with respect to mortality in SSc patients from the European Scleroderma Trials and Research Group (EUSTAR) database. SSc patients from the EUSTAR database who had items required for the calculation of eGFR at a baseline visit and a second follow-up visit available were included. A cut-off eGFR value of 60 ml/min was chosen for all SSc patients, and 30 ml/min for those with scleroderma renal crisis (SRC). Cox regression and competing risk analysis were performed to evaluate the use of eGFR as a predictive factor of mortality. A total of 3650 SSc patients were included in this study. The median serum level of creatinine and the mean of eGFR were 0.8 mg/dl (interquartile range = 0.6-0.9) and 86.6 ± 23.7 ml/min, respectively. The eGFR was significantly lower in patients with pulmonary hypertension. Overall survival (OS) was significantly reduced in SSc patients with eGFR < 60 ml/min compared with patients with eGFR ≥ 60 ml/min [OS at 5 years 0.763 (95% CI: 0.700, 0.814) vs 0.903 (95% CI: 0.883, 0.919; P < 0.001)]. In multivariable analysis, OS was associated with male gender (P < 0.01), systolic pulmonary arterial pressure (sPAP) (P < 0.001) and eGFR (P < 0.001). The cumulative incidence of deaths due to SSc was associated with increased sPAP (P < 0.001) and reduced eGFR (P < 0.05). The OS at 5 years of 53 SRC patients was not significantly different between SSc patients with eGFR > 30 ml/min and those with eGFR <30 ml/min. eGFR represents a predictive risk factor for overall survival in SSc. The eGFR, however, does not represent a risk factor for death in SRC.

Performance of the 2017 EUSTAR activity index in an scleroderma cohort

Assessment of disease activity in systemic sclerosis (SSc) is limited by the absence of a fully validated, multisystem measure of disease activity. The European Scleroderma Trials and Research Group (EUSTAR) SSc activity index (EScSG-AI) was recently revised, and a validation study within the EUSTAR cohort was performed. In this study, we evaluated the performance of the revised EScSG-AI in an external Australian cohort. The association between the EScSG-AI and the physician global assessment of disease activity (PhGA), both collected prospectively at each annual visit over up to 12years follow-up, was evaluated using Pearson's correlation coefficient and Cohen's kappa coefficient. Generalized linear modelling and time-dependent Cox regression analysis were performed to determine the association of disease activity measured by the EScSG-AI and the summed Medsger Severity Scale (MSS) and death, respectively. There was a moderate correlation between EScSG-AI and PhGA scores (r 0.42, p < 0.001) and moderate association between rising EScSG-AI and summed MSS (r 0.60, p < 0.001). High disease activity, measured by the EScSG-AI at any time during follow-up, was associated with a hazard ratio of 2.07 (95% CI 1.51-2.79) for mortality. The EScSG-AI has a moderate correlation with physician-assessed SSc disease activity. This suggests that the criterion and construct validity of the EScSG-AI are yet to be demonstrated in an external cohort of SSc patients. Key Points •There remains no gold standard measure of SSc disease activity. •The revised 2017 EUSTAR SSc disease activity index shows moderate correlation with physician-rated global disease activity. •Significant work remains to develop a validated multisystem measure of disease activity in SSc.

Fast track algorithm: How to differentiate a "scleroderma pattern" from a "non-scleroderma pattern".

This study was designed to propose a simple "Fast Track algorithm" for capillaroscopists of any level of experience to differentiate "scleroderma patterns" from "non-scleroderma patterns" on capillaroscopy and to assess its inter-rater reliability. Based on existing definitions to categorise capillaroscopic images as "scleroderma patterns" and taking into account the real life variability of capillaroscopic images described standardly according to the European League Against Rheumatism (EULAR) Study Group on Microcirculation in Rheumatic Diseases, a fast track decision tree, the "Fast Track algorithm" was created by the principal expert (VS) to facilitate swift categorisation of an image as "non-scleroderma pattern (category 1)" or "scleroderma pattern (category 2)". Mean inter-rater reliability between all raters (experts/attendees) of the 8th EULAR course on capillaroscopy in Rheumatic Diseases (Genoa, 2018) and, as external validation, of the 8th European Scleroderma Trials and Research group (EUSTAR) course on systemic sclerosis (SSc) (Nijmegen, 2019) versus the principal expert, as well as reliability between the rater pairs themselves was assessed by mean Cohen's and Light's kappa coefficients. Mean Cohen's kappa was 1/0.96 (95% CI 0.95-0.98) for the 6 experts/135 attendees of the 8th EULAR capillaroscopy course and 1/0.94 (95% CI 0.92-0.96) for the 3 experts/85 attendees of the 8th EUSTAR SSc course. Light's kappa was 1/0.92 at the 8th EULAR capillaroscopy course, and 1/0.87 at the 8th EUSTAR SSc course. For the first time, a clinical expert based fast track decision algorithm has been developed to differentiate a "non-scleroderma" from a "scleroderma pattern" on capillaroscopic images, demonstrating excellent reliability when applied by capillaroscopists with varying levels of expertise versus the principal expert and corroborated with external validation.

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...

Association of simple hematological parameters with disease manifestations, activity, and severity in patients with systemic sclerosis.

Neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), mean platelet volume (MPV), and red cell distribution width (RDW) may potentially reflect inflammatory status in systemic autoimmune diseases. The aim of this study is to investigate the association between these proposed markers and disease manifestations, activity, and severity in systemic sclerosis (SSc). We conducted a cross-sectional study of 69 systemic sclerosis (SSc) patients and 50 healthy volunteers in a single center. Adult patients with SSc and healthy controls were compared in terms of NLR, MLR, MPV, RDW, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP). Venous blood samples were drawn after at least 8h of fasting in the morning. Extension of skin fibrosis was evaluated by using modified Rodnan skin score (mRSS). Disease severity and activity were assessed by Medsger disease severity and European Scleroderma Trials and Research Group (EUSTAR) disease activity scores, respectively. Associations of disease manifestations, clinical, laboratory, and capillaroscopic findings, mRSS, and the disease activity and severity scores with the proposed hematological markers were evaluated. Multiple regression models were generated for significant associations. The neutrophil number was higher (p = 0.004) and lymphocyte number was lower (p < 0.001) in SSc group compared to controls. SSc group also had higher NLR, MLR, and RDW. In multiple logistic regression, only the NLR (regression coefficient = 3.49, p = 0.031) and CRP (regression coefficient = 0.17, p = 0.037) remained significantly different between SSc and healthy control groups (Cox and Snell R2 = 0.243, Nagelkerke R2 = 0.337, p < 0.001). NLR and MLR positively correlated with mRSS, EUSTAR score, and CRP. MLR also positively correlated with Medsger score. Higher monocyte counts independently predicted higher EUSTAR and Medsger scores in multiple linear regressions. Patients with digital ulcers had higher NLR and MLR. We did not find any difference in MPV values between SSc and healthy control groups. Globally available and inexpensive hematological tests, particularly the NLR and MLR, may be associated with vascular and cutaneous manifestations as well as disease activity and severity in SSc.Key Points• Monocyte count itself independently predicted higher activity and severity scores in SSc.• Globally available and inexpensive hematological markers, particularly the NLR and MLR, may have an association with vascular and cutaneous manifestations as well as disease activity and severity in patients with SSc.

Worldwide Expert Agreement on Updated Recommendations for the Treatment of Systemic Sclerosis

To evaluate agreement of the updated European League Against Rheumatism and European Scleroderma Trials and Research group (EUSTAR) recommendations for treatment of systemic sclerosis (SSc) among international experts. In addition, to determine factors that might influence agreement. Level of agreement (10-point scale: 0 = not at all, 10 = completely agree) and local drug availability (yes/no) were assessed using an online survey. The Web link to the survey was shared with 481 unique e-mail addresses and SSc networks (Scleroderma Clinical Trials Consortium, Australian Scleroderma Interest Group, International Systemic Sclerosis Inception Cohort). Level of agreement was compared between subgroups stratified for participant characteristics. In total, 263 experts participated, of whom n = 209 (79%) completed each single item. The majority were rheumatologists (n = 200, 76%) working in Europe (n = 185; 71%); 59% (n = 156) were EUSTAR members; and 57% (n = 151) had > 10 years of clinical experience. Overall level of agreement was high (mean 8.0, SD 2.5). The 3 highest mean agreements included (1) angiotensin-converting enzyme inhibitors for scleroderma renal crisis (9.2, SD 2.1); (2) blood pressure control in SSc-patients treated with corticosteroids (9.0, SD 2.2); (3) proton pump inhibitors to prevent reflux complications (9.0, SD 2.2). The 3 lowest mean agreements included (1) fluoxetine for Raynaud phenomenon (RP; 4.6, SD 2.8); (2) hematopoietic stem cell transplantation (HSCT) for severe SSc (7.1, SD 2.9); (3) phosphodiesterase inhibitors 5 for RP (7.3, SD 2.7). Agreement differed between Europe and non-Europe for the use of iloprost, bosentan, methotrexate, HSCT, and cyclophosphamide. Treatment availability could partially explain differential agreement for iloprost, bosentan, and HSCT. In general, worldwide expert agreement on updated recommendations for treatment of SSc is high, supporting their value. Differences in agreement are partially explained by geographical area and treatment availability.

Classification, categorization and essential items for digital ulcer evaluation in systemic sclerosis: a DeSScipher/European Scleroderma Trials and Research group (EUSTAR) survey

BackgroundA consensus on digital ulcer (DU) definition in systemic sclerosis (SSc) has been recently reached (Suliman et al., J Scleroderma Relat Disord 2:115-20, 2017), while for their evaluation, classification and categorisation, it is still missing. The aims of this study were to identify a set of essential items for digital ulcer (DU) evaluation, to assess if the existing DU classification was useful and feasible in clinical practice and to investigate if the new categorisation was preferred to the simple distinction of DU in recurrent and not recurrent, in patients with systemic sclerosis (SSc).MethodsDeSScipher is the largest European multicentre study on SSc. It consists of five observational trials (OTs), and one of them, OT1, is focused on DU management. The DeSScipher OT1 items on DU that reached ≥ 60% of completion rate were administered to EUSTAR (European Scleroderma Trials and Research group) centres via online survey. Questions about feasibility and usefulness of the existing DU classification (DU due to digital pitting scars, to loss of tissue, derived from calcinosis and gangrene) and newly proposed categorisation (episodic, recurrent and chronic) were also asked.ResultsA total of 84/148 (56.8%) EUSTAR centres completed the questionnaire. DeSScipher items scored by ≥ 70% of the participants as essential and feasible for DU evaluation were the number of DU defined as a loss of tissue (level of agreement 92%), recurrent DU (84%) and number of new DU (74%). For 65% of the centres, the proposed classification of DU was considered useful and feasible in clinical practice. Moreover, 80% of the centres preferred the categorisation of DU in episodic, recurrent and chronic to simple distinction in recurrent/not recurrent DU.ConclusionsFor clinical practice, EUSTAR centres identified only three essential items for DU evaluation and considered the proposed classification and categorisation as useful and feasible. The set of items needs to be validated while further implementation of DU classification and categorisation is warranted.Trial registrationObservational trial on DU (OT1) is one of the five trials of the DeSScipher project (ClinicalTrials.gov; OT1 Identifier: NCT01836263, posted on April 19, 2013).

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.

Analysis of serum macrophage migration inhibitory factor and D‐dopachrome tautomerase in systemic sclerosis

ObjectivesMacrophage migration inhibitory factor (MIF) and D‐dopachrome tautomerase (DDT), members of the same cytokine superfamily, are linked to the pathogenesis of a number of inflammatory diseases. The aim of this study was to investigate their clinical relevance in systemic sclerosis (SSc).MethodsSerum MIF and DDT were quantified in 105 SSc patients by ELISA and levels compared to healthy controls (HC) (47) and patients with systemic lupus erythematosus (SLE) (184). Clinical parameters included organ involvement, serum laboratory markers and results of pulmonary function tests, and overall disease activity assessed using the European Scleroderma Trials and Research group (EUSTAR) activity index.ResultsThere was no significant difference in serum DDT concentrations between patients with SSc and HC. However, serum MIF was significantly increased in SSc compared to both HC and SLE cohorts. Serum MIF was increased in SSc patients with low forced vital capacity (FVC) and was also associated with the use of angiotensin II receptor blockers and beta blockers in SSc, confirmed after adjusting for the presence of systemic hypertension and low FVC. Serum DDT was significantly higher in SSc patients with low FEV1 and negatively correlated with EUSTAR score, particularly in patients with limited disease.ConclusionAlthough not significantly linked to specific clinical parameters, serum MIF was significantly higher in SSc patients than in HC and SLE patients, suggesting a fundamental role for MIF in SSc. DDT, while closely related to MIF, did not show a similar expression profile, suggesting functional differences between these molecules.

An international SUrvey on non-iNvaSive tecHniques to assess the mIcrocirculation in patients with RayNaud's phEnomenon (SUNSHINE survey).

To canvas opinion concerning the role of non-invasive techniques in the assessment of patients with Raynaud's phenomenon (Rp) in clinical and research settings: four nailfold capillaroscopy methods [videocapillaroscopy (NVC), dermoscopy, stereomicroscopy, digital USB microscopy], four laser Doppler methods (laser Doppler flowmetry, imaging, anemometry/velocimetry, laser speckle contrast analysis), thermographic imaging, and upper limb arterial Doppler ultrasound. Emails with a link to the survey were sent to physicians from the European Scleroderma Trials and Research group (EUSTAR), the EULAR Study Group on Microcirculation in Rheumatic Diseases (SG_MC/RD) and members of the pediatric rheumatology Email board. The main descriptive analysis related to physicians looking after adult patients, with some analysis also of opinions from paediatric rheumatologists. 106 'adult physicians' responded (a response rate of 25.8%), of whom 68.9% were European, and 81.1% practising for more than 10years. Nineteen paediatricians responded. The most widely available technique was NVC (72.7%). Nailfold capillaroscopy was most frequently performed by the physician him/herself, using different types of equipment relating to availability. Most rheumatologists reported high levels of appropriateness for NVC in both clinical and research settings for global assessment and differential diagnosis of Rp. Other techniques were less used. Of all the different techniques, nailfold capillaroscopy was the one most used in both clinical and research settings by adult physicians, the majority of whom use NVC in their everyday practice. The low proportion of clinicians using other techniques suggests that these are currently mainly research tools, available only in specialist centres.

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...