EULAR Scleroderma Trials And Research Research Articles

Gender differences in organ involvement and survival in systemic sclerosis – experience of a EUSTAR center

Introduction. The low overall prevalence of systemic sclerosis (SSc) and the low proportion of male patients have resulted in a scarcity of studies assessing sex differences in SSc patients, and contradictory results have often been observed. Material and method. We performed a retrospective observational study using data extract from the EULAR scleroderma trials and research (EUSTAR) cohort 096 . We looked at sex influence on disease characteristics at baseline and then focused on patients with at least 2 years of follow-up to estimate the effects of sex on disease progression and survival. Results. 173 patients with SSc were available for the baseline analyses. In the longitudinal analysis after a mean follow-up of 3.5(±0.65) years, male sex was associated with a higher risk of scleroderma renal crisis (OR:9.45 (1.49 to 59.69); p = 0.004), digital contractures (OR:8.2 (3.1 to 21.9); p < 0.001), arrhythmias (OR: 3.37 (1.36 to 8.34); p = 0.006), pulmonary fibrosis (OR: 3.56, (1.51 to 8.41); p = 0.003), pulmonary hypertension (OR: 3.01 (1.19 to 7.59); p = 0.016), severe vascular involvement (OR:2.86, (1.22 to 6.73); p = 0.013) and low ventricular ejection fraction (OR: 2.84, (1.2 to 6.73); p = 0.014). Males had significantly reduced survival time after diagnosis (p = 0.004). The most frequent causes of death were scleroderma renal crisis in males and pulmonary hypertension in females. Conclusions. Although more common in women, SSc appears as strikingly more severe in men. Our results demonstrate a higher risk of severe organ involvement and poor prognosis in men. These results raise the point of including sex in the management and the decision-making process.

CD34+CD133+CD309+ circulating angiogenic cell level is reduced but positively related to hydroxychloroquine use in SLE patients-a case-control study and meta-regression analysis.

To identify and quantify the level of CD34+CD133+CD309+ circulating angiogenic cells (CAC) and explore factors associated with the level of CAC in patients with SLE. The peripheral blood mononuclear cells of consecutive SLE patients and demographically matched healthy controls (HC) were extracted and identified, enumerated and compared for CAC levels by multi-colour flow cytometry based on the EULAR Scleroderma Trials and Research (EUSTAR) recommendation. Meta-analyses were performed by combining the current and previous case-control studies, aiming to increase the statistical power to discern the difference in CAC level between SLE patients and HC. Mixed-model meta-regression was conducted to explore potential demographic and clinical factors that were associated with CAC level. A lower level of CAC was found in 29 SLE patients compared with 24 HC [mean (s.d.) 10.76 (13.9) vs 24.58 (25.4) cells/ml, P = 0.015]. Random-effects meta-analyses of the current and six previously published case-control studies involving 401 SLE patients and 228 HC revealed a lower CAC level compared with HC (standardized mean difference = -2.439, P = 0.001). Meta-regression analysis demonstrated that HCQ use was associated with a more discrepant CAC level between both groups (P = 0.01115). SLE patients had a significantly lower CD34+CD133+CD309+ CAC level than HC, and HCQ use was associated with a more discrepant CAC level between SLE patients and HC. This study triggers further observational, interventional and mechanistic studies to address the beneficial impact of HCQ on the functionality of CAC in SLE patients.

Scleroderma Lung Study II—clarity or obfuscation?

Systemic sclerosis (scleroderma) is one of the most recalcitrant of the immune-mediated rheumatic diseases because of its clinical impact and the high mortality associated with the internal organ complications that it causes. 1 Tyndall AJ Bannert B Vonk M et al. Causes and risk factors for death in systemic sclerosis: a study from the EULAR Scleroderma Trials and Research (EUSTAR) database. Ann Rheum Dis. 2010; 69: 1809-1815 Crossref PubMed Scopus (857) Google Scholar Lung fibrosis has emerged as a major cause of scleroderma-related death, and with better treatments for pulmonary arterial hypertension, the other main lethal lung manifestation of scleroderma, this looks set to continue. 2 Galiè N Barberà JA Frost AE et al. Initial use of ambrisentan plus tadalafil in pulmonary arterial hypertension. N Engl J Med. 2015; 373: 834-844 Crossref PubMed Scopus (732) Google Scholar Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II): a randomised controlled, double-blind, parallel group trialTreatment of scleroderma-related interstitial lung disease with mycophenolate mofetil for 2 years or cyclophosphamide for 1 year both resulted in significant improvements in prespecified measures of lung function over the 2 year course of the study. Although mycophenolate mofetil was better tolerated and associated with less toxicity, the hypothesis that it would have greater efficacy at 24 months than cyclophosphamide was not confirmed. These findings support the potential clinical effectiveness of both cyclophosphamide and mycophenolate mofetil for progressive scleroderma-related interstitial lung disease, and the present preference for mycophenolate mofetil because of its better tolerability and toxicity profile. Full-Text PDF

A comparison between nailfold capillaroscopy patterns in adulthood in juvenile and adult-onset systemic sclerosis: A EUSTAR exploratory study

ObjectiveQualitative capillaroscopy patterns in juvenile- and adult-onset systemic sclerosis (SSc) were studied in adulthood using data from the EULAR Scleroderma Trials and Research (EUSTAR) database. MethodsData collected between June 2004 and April 2013 were examined with focus on capillaroscopy. In this retrospective exploratory study, series of patients with juvenile-onset SSc were matched with series of adult-onset SSc having the same gender and autoantibody profile. Results30 of 123 patients with juvenile-onset and 2108 of 7133 with adult-onset SSc had data on capillaroscopy. Juvenile-onset SSc showed scleroderma pattern more frequently than adult-onset SSc (93.3% and 88%). The OR was 2.44 and 95% CI 0.57–10.41. An active scleroderma pattern was present in 58% of juvenile- and 61% of adult-onset SSc. The OR was 0.91 and 95% CI 0.28–2.93. The late scleroderma pattern was present in 61% of juvenile- and 55.5% of adult-onset SSc. The OR was 1.06 and 95% CI 0.34–3.56. ConclusionThis is the first exploratory study on the comparison of capillaroscopy between juvenile- and adult-onset SSc in adulthood. Juvenile-onset SSc had an increase prevalence of scleroderma pattern, but a similar distribution of the three patterns was suggested. Further studies are needed to define this issue.

Digital ulcers predict a worse disease course in patients with systemic sclerosis

ObjectiveSystemic sclerosis (SSc) is a systemic autoimmune disease with high morbidity and significant mortality. There is a great need of predictors that would allow risk stratification of patients with SSc...

A gender gap in primary and secondary heart dysfunctions in systemic sclerosis: a EUSTAR prospective study

ObjectivesIn agreement with other autoimmune diseases, systemic sclerosis (SSc) is associated with a strong sex bias. However, unlike lupus, the effects of sex on disease phenotype and prognosis are poorly...

Nailfold capillaroscopy in systemic sclerosis: Data from the EULAR scleroderma trials and research (EUSTAR) database

ObjectiveThe aims of this study were to obtain cross-sectional data on capillaroscopy in an international multi-center cohort of Systemic Sclerosis (SSc) and to investigate the frequency of the capillaroscopic patterns and their disease-phenotype associations. MethodsData collected between June 2004 and October 2011 in the EULAR Scleroderma Trials and Research (EUSTAR) registry were examined. Patients' profiles based on clinical and laboratory data were obtained by cluster analysis and the association between profiles and capillaroscopy was investigated by multinomial logistic regression. Results62 of the 110 EUSTAR centers entered data on capillaroscopy in the EUSTAR database. 376 of the 2754 patients (13.65%) were classified as scleroderma pattern absent, but non-specific capillary abnormalities were noted in 55.48% of the cases. Four major patients' profiles were identified characterized by a progressive severity for skin involvement, as well as an increased number of systemic manifestations. The “early” and “active” scleroderma patterns were generally observed in patients with mild/moderate skin involvement and a low number of disease manifestations, while the “late” scleroderma pattern was found more frequently in the more severe forms of the disease. ConclusionThese data indicate the importance of capillaroscopy in SSc management and that capillaroscopic patterns are directly related to the extent of organ involvement.

FRI0499 Nailfold capillaroscopy in systemic sclerosis: data from the eular scleroderma trials and research (EUSTAR) registry

BackgroundMicrovascular findings in Systemic Sclerosis (SSc) document a significant loss of the peripheral vascular network, with loss of capillaries, deficient vascular repair and the absence of new vessel growth, and...

FRI0371 Prediction of worsening of skin fibrosis in patients with diffuse cutaneous systemic sclerosis using the eular scleroderma trials and research (EUSTAR) registry

BackgroundSpontaneous stabilization and regression of skin fibrosis in patients with diffuse cutaneous SSc (dSSc) is a major limitation in clinical trials, and enrichment strategies for patients with progressive skin fibrosis...

SAT0406 Quantification of interstitial pulmonary fibrosis in systemic sclerosis using an open-source dicom viewer software (OSIRIX)

BackgroundInterstitial pulmonary fibrosis (IPF) is a frequent manifestation in patients with systemic sclerosis (SSc). The severity of lung involvement may vary considerably depending on the underlying disease and it can...

Outcomes of patients with systemic sclerosis-associated polyarthritis and myopathy treated with tocilizumab or abatacept: a EUSTAR observational study

ObjectiveTo evaluate the safety and effectiveness of tocilizumab and abatacept in systemic sclerosis (SSc)-polyarthritis or SSc-myopathy.Methods20 patients with SSc with refractory polyarthritis and seven with refractory myopathy from the EUSTAR...

Systemic sclerosis without antinuclear antibodies or Raynaud's phenomenon: a multicentre study in the prospective EULAR Scleroderma Trials and Research (EUSTAR) database

To assess patients with SSc who present without circulating ANAs or RP. Five thousand three hundred and ninety patients who fulfilled the ACR criteria for SSc and were enrolled in the EULAR Scleroderma Trials and Research (EUSTAR) database were screened for the absence of both RP and circulating ANA. To differentiate SSc from its mimics, additional information was gathered using a standardized questionnaire. Five thousand three hundred and seventy-eight (99.8%) of the 5390 SSc patients in the EUSTAR database had either detectable ANA or a history of RP. Twelve (0.2%) patients lacked both circulating ANA and RP. Details of the medical history could be obtained for seven patients. Three cases were compatible with ANA-negative and RP-negative SSc and were not typical of any known SSc mimic. Four patients had a malignancy: two had breast cancer, one had multiple myeloma with possible scleromyxoedema and one had bladder carcinoma. There was no temporal relationship between the onset of skin fibrosis and that of the tumour. Although no patient with confirmed nephrogenic systemic fibrosis was identified among the cases of ANA-negative and RP-negative SSc, the presentation of one patient could be compatible with that of nephrogenic systemic fibrosis other than for the absence of chronic kidney disease or of known prior gadolinium exposure. We have identified a very small subgroup of SSc patients who lack both circulating ANA and RP, none of whom fulfils the diagnostic criteria for any known SSc mimic. Prospective studies are needed to elucidate the clinical presentation, evolution and outcome of such patients.

Juvenile and young adult-onset systemic sclerosis share the same organ involvement in adulthood: data from the EUSTAR database

The aim of the present study was to explore the long-term outcome and clinical characteristics of adult patients with juvenile onset in the EULAR Scleroderma Trials and Research (EUSTAR) cohort and compare them with adult patients with onset between 20 and 40 years of age. From the EUSTAR SSc cohort two patient groups were analysed: patients with juvenile SSc (jSSc) who are adults at present, and patients diagnosed between the age of 20 and 40 years (aSSc). Demographic data of the patients, organ involvement and outcome of the disease were examined using the Minimal Essential Data Set database system. From 5000 patients in the EUSTAR cohort, 60 patients (1.2%) with jSSc and 910 patients (18%) with aSSc were selected according the inclusion criteria. In the jSSc group, the mean age of disease onset was 12.4 years (range 2-15.9 years), and in the aSSc group, the mean age was 32 years (range 20-40 years). Disease subsets were similar. The antibody profile was also comparable except for ACAs, which were positive in 5% of the jSSc group and 26.9% of the aSSc group (P<0.005). Organ involvement (lung, kidney, joint, muscle and heart) was similar in the two groups of patients at the time of the last follow-up. The subset distribution in the jSSc and aSSc cohorts was found to be similar. Only the frequency of ACAs was significantly lower in the jSSc, which supports the hypothesis that the SSc patients with paediatric onset in the adult cohort may represent a distinct subgroup of the complete cohort of paediatric patients.

Late-onset systemic sclerosis--a systematic survey of the EULAR scleroderma trials and research group database

The clinical course of SSc depends on subtype, organ involvement and age. Few data are reported on patients suffering from late-onset SSc. We analysed data from 8554 patients prospectively followed in the EULAR Scleroderma Trials and Research (EUSTAR) group database. Late-onset SSc was defined as onset of non-RP disease features at or beyond 75 years of age. Disease characteristics, clinical features, disease course and mortality were evaluated. A total of 123 patients with SSc onset at or beyond 75 years of age were identified. Compared with patients<75 years they had more frequently limited than diffuse SSc and a higher prevalence of anti-centromere autoantibodies. Fewer old patients had digital ulcers. The modified Rodnan's skin score, the prevalence of lung fibrosis and renal crisis did not differ significantly between groups. Pulmonary hypertension (PH) measured by echocardiography was more prevalent in the late-onset group, as well as arterial hypertension and diastolic dysfunction. Late-onset SSc remained a positive predictor for PH in multivariate analyses. No significant difference of the two groups in skin score or diffusion capacity was observed during follow-up. Mortality due to SSc was higher in the late-onset group, but the survival time from diagnosis was longer compared with the younger patients. Late-onset SSc shows a distinct clinical presentation and outcome. Patients with late-onset SSc suffer more frequently from the limited subtype and PH, but fewer patients have digital ulcers. PH may in part be determined by underlying cardiovascular disease.

Causes and risk factors for death in systemic sclerosis: a study from the EULAR Scleroderma Trials and Research (EUSTAR) database

ObjectivesTo determine the causes and predictors of mortality in systemic sclerosis (SSc).MethodsPatients with SSc (n=5860) fulfilling the American College of Rheumatology criteria and prospectively followed in the EULAR Scleroderma Trials...

Geographical variation of disease manifestations in systemic sclerosis: a report from the EULAR Scleroderma Trials and Research (EUSTAR) group database

Background:Systemic sclerosis (SSc) is a vasculopathy with increased tissue deposition of collagen. The aetiology is unknown. Genetic and environmental susceptibility factors have been implicated. It is unknown whether disease presentation...