Diminished production of TWEAK by the peripheral blood mononuclear cells is associated with vascular involvement in patients with systemic sclerosis.

Widespread vasculopathy and profound fibrosis are key features of the pathogenesis of systemic sclerosis (SSc). We hypothesized that the TNF-like weak inducer of apoptosis (TWEAK), a recently recognized multifunctional cytokine which regulates angiogenesis and tissue remodeling, may play a role in the development of SSc. The production of TWEAK by the peripheral blood mononuclear cells (PBMC) was investigated, by means of ELISA, in 24 SSc patients and 14 healthy subjects. Moreover, production of TWEAK was correlated with clinical features of SSc. PBMC were isolated using density gradient centrifugation on Histopaque and were cultured in FCS supplemented RPMI medium at 37 degrees C under 5% CO2. Production of TWEAK by PBMC was significantly diminished in patients with more severe microvascular damage, as indicated by the presence of "active" capillaroscopic pattern, compared with SSc patients with less pronounced microangiopathy ("slow" pattern), and healthy subjects. Moreover production of TWEAK correlated inversely with duration of Raynaud's phenomenon. PBMC from patients with scleroderma-related interstitial lung disease tended to produce lower amounts of TWEAK compared with SSc patients without lung involvement but the difference was not significant. The results of our study suggest that diminished production of TWEAK might play a role in the pathogenesis of vascular injury in SSc patients. Whether TWEAK may represent a new therapeutic target in SSc requires further studies

Comparison of hyaluronic acid in patients with rheumatoid arthritis, systemic sclerosis and systemic lupus erythematosus

The aim of the present study was to determine and compare the concentration of hyaluronic acid (HA) in rheumatoid arthritis (RA), systemic sclerosis (SSc) and systemic lupus erythematosus (SLE), and its correlation with parameters of disease activity and duration. The hypothesis was that HA should be increased in rheumatic diseases. We also expected that HA could be a marker of disease activity and inflammation in some of these diseases. The study group comprised 149 patients with RA, SSc and SLE hospitalized in the Department of Rheumatology and Internal Diseases, Medical University of Bialystok (Bialystok, Poland) and 30 healthy controls. The concentrations of HA, C-reactive protein (CRP) and rheumatoid factor (RF) were measured using Architect ci8200; haemoglobin, platelets on Sysmex XS-800i; and erythrocyte sedimentation rate (ESR) on Sediplus S 2000 analysers. Statistical analysis was performed using Statistica 13.3 PL. Hyaluronic acid was increased in RA, SLE and SSc when compared to controls (P < 0.001, P = 0.011, and P = 0.015, respectively). There were no differences in HA between rheumatic diseases (P = 0.840). Hyaluronic acid positively correlated with SLE activity (P = 0.025). In RA, HA positively correlated with ESR (P = 0.028) and CRP (P = 0.009). However, HA was not found to correlate with the duration of rheumatic diseases. Hyaluronic acid concentration undergoes changes in rheumatic diseases with no difference between RA, SLE and SSc. In RA, HA concentration can be a marker of inflammation, while in SLE patients an indicator of disease activity

Impairment of microcirculation in juvenile idiopathic arthritis - studies by nailfold videocapillaroscopy and correlation with serum levels of sICAM and VEGF.

Impairment of vascular endothelium plays a key role in the pathogenesis of inflammatory diseases including juvenile idiopathic arthritis (JIA) and atherosclerosis. We hypothesized that structural abnormalities of the smallest blood vessels (capillaries) might exist and reflect endothelial dysfunction in children with JIA. Microcirculation was studied, by means of nailfold videocapillaroscopy with computer-associated image analysis, in 43 patients with JIA and compared with 20 healthy children. Moreover, capillaroscopic findings were correlated with the activity of the disease and the levels of serum biomarkers of endothelial injury, namely soluble intercellular adhesion molecule (sICAM) and vascular endothelial growth factor (VEGF). We found that in JIA patients capillaries were significantly wider and longer than in healthy controls. Moreover, irregular capillaries and dilated subpapillary venous plexus were found significantly more frequently in JIA in comparison with the control group. Serum levels of sICAM and VEGF were significantly higher in JIA patients with capillary abnormalities than in JIA patients with normal capillaroscopy. Our study indicates that there are structural changes in the microcirculation of patients with JIA and that these changes might reflect endothelial injury. Whether capillaroscopy might have a role in early identification of JIA patients being at higher risk of atherosclerosis requires further studies

Lymphatic microangiopathy of the skin in systemic sclerosis

METHODS: The cutaneous capillary lymphatic system in patients with systemic sclerosis was investigated using fluorescence microlymphography. The distal upper limbs of 16 healthy controls (mean age 62.3+/-13.1 yr) and 16 patients with systemic sclerosis (mean age 58.9+/-13.6 yr) were examined and the following parameters were evaluated: (a) single lymphatic capillaries; (b) lymphatic capillary network and cutaneous backflow; (c) extension of the stained lymphatics; (d) diameter of single lymphatic capillaries. RESULTS: At the finger level, lymphatic capillaries were lacking in five patients, while they were present in all controls (P < 0.05). Extension of the stained lymphatics was increased in 11 patients (8.1+/-6.0 mm) compared to the 16 healthy controls (2.0+/-1.2 mm) (P < 0.0001). Cutaneous backflow was observed in three patients (P < 0.05). At the hand level, lymphatic network extension was significantly different between patients (3.8+/-2.4 mm) and controls (1.2+/-0.8 mm) (P < 0.01); however, no significant differences were found at the forearm level. CONCLUSION: Lesional skin in patients with systemic sclerosis exhibits evidence of lymphatic microangiopath

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

Objective. 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. Methods. 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. Results. 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. Conclusion. 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 patient

Prediction of improvement in skin fibrosis in diffuse cutaneous systemic sclerosis: a EUSTAR analysis

OBJECTIVES Improvement of skin fibrosis is part of the natural course of diffuse cutaneous systemic sclerosis (dcSSc). Recognising those patients most likely to improve could help tailoring clinical management and cohort enrichment for clinical trials. In this study, we aimed to identify predictors for improvement of skin fibrosis in patients with dcSSc. METHODS We performed a longitudinal analysis of the European Scleroderma Trials And Research (EUSTAR) registry including patients with dcSSc, fulfilling American College of Rheumatology criteria, baseline modified Rodnan skin score (mRSS) ≥7 and follow-up mRSS at 12±2 months. The primary outcome was skin improvement (decrease in mRSS of >5 points and ≥25%) at 1 year follow-up. A respective increase in mRSS was considered progression. Candidate predictors for skin improvement were selected by expert opinion and logistic regression with bootstrap validation was applied. RESULTS From the 919 patients included, 218 (24%) improved and 95 (10%) progressed. Eleven candidate predictors for skin improvement were analysed. The final model identified high baseline mRSS and absence of tendon friction rubs as independent predictors of skin improvement. The baseline mRSS was the strongest predictor of skin improvement, independent of disease duration. An upper threshold between 18 and 25 performed best in enriching for progressors over regressors. CONCLUSIONS Patients with advanced skin fibrosis at baseline and absence of tendon friction rubs are more likely to regress in the next year than patients with milder skin fibrosis. These evidence-based data can be implemented in clinical trial design to minimise the inclusion of patients who would regress under standard of care