Mixed Connective Tissue Disease. Results from a Nationwide Norwegian Cohort

I sin avhandling «Mixed Connective Tissue Disease – Results from a Nationwide Norwegian Cohort» har lege og forsker Silje Reiseter og medarbeidere studert en gruppe pasienter med bindevevssykdommen Mixed Connective Tissue Disease (MCTD) i Norge. Prosjektet har fokusert på tre hovedområder; mikrovaskulær skade, lungeskade og sykdomsforløp. De har vist at proteinet Endostatin kan være forbundet med nivået av mikrovaskulær skade i pasienter med MCTD og bindevevssykdommen Systemisk sklerose. Dette kan bety at måling av Endostatin kan brukes til å skille ut pasienter med mer alvorlige sykdomsmanifestasjoner. Videre fant de at omtrent 40 % av pasientene med MCTD hadde lungeforandringer og at halvparten av dem hadde økende lungeforandringer over tid. Forandringene i lungene var generelt moderate, men viste seg å være knyttet til høyere dødelighet i denne pasient gruppen. Risiko faktorer for økende lungeforandringer ble identifisert og kan bistå leger i klinikken til å identifisere MCTD pasienter som har behov for tettere oppfølging. Resultatet av forskningen til Silje Reiseter og medarbeidere viser at MCTD pasienter har et varierende sykdomsbilde, der sykdomsaktiviteten minsker over tid og lunge funksjonen ser ut til å være forbundet med sykdomsaktivitet. Dette betyr at det er en utfordring å følge opp pasienter med MCTD ettersom flere organsystemer må undersøkes og at spesielt lungefunksjon bør undersøkes jevnlig i denne pasientgruppen

Disease evolution in mixed connective tissue disease: results from a long-term nationwide prospective cohort study

Background The phenotypic stability of mixed connective tissue disease (MCTD) is not clear, and knowledge about disease activity and remission is scarce. We aimed to establish the occurrence of evolution from MCTD to another defined rheumatic condition, and the prevalence and durability of remission after long-term observation. Methods In this large population-based prospective observational MCTD cohort study (N = 118), disease conversion was defined by the development of new auto-antibodies and clinical features compliant with another well-defined rheumatic condition. Remission was defined by a combination of systemic lupus erythematosus disease activity index 2000 (SLEDAI-2 K) of 0 and European League Against Rheumatism scleroderma trials and research (EUSTAR) activity index <2.5. Predictors of phenotypic stability and disease remission were assessed by logistic regression. Results Among 118 patients, 14 (12%) developed another well-defined rheumatic condition other than MCTD after mean disease duration of 17 (SD 9) years. Puffy hands predicted a stable MCTD phenotype in univariable regression analysis (OR 7, CI 2–27, P = .010). Disease activity defined by SLEDAI-2 K, decreased gradually across the observation period and > 90% of patients had EUSTAR activity index <2.5. There were 13% patients in remission throughout the whole mean observation period of 7 (SD 2) years. The strongest predictor of remission was percentage of predicted higher forced vital capacity. Conclusions Our results strengthen the view of MCTD as a relatively stable disease entity. Long-term remission in MCTD is not frequent; however, the low SLEDAI-2 K and EUSTAR scores during the observation period suggests that the disease runs a milder course than systemic lupus erythematosus and systemic sclerosis

Pulmonary manifestations and progression of lung disease in juvenile-onset mixed connective tissue disease

Objective - To assess the occurrence and extent of interstitial lung disease (ILD) in patients with juvenile mixed connective tissue disease (JMCTD), compare pulmonary function in patients and matched controls, study associations between ILD and disease-related variables, and examine progression of pulmonary manifestations over time. Methods - A cohort of 52 patients with JMCTD were examined in a cross-sectional study after a mean 16.2 (SD 10.3) years of disease duration with high-resolution computed tomography (HRCT) and pulmonary function tests (PFT) comprising spirometry, DLCO, and total lung capacity (TLC). Matched controls were examined with PFT. Previous HRCT and PFT were available in 37 and 38 patients (mean 8.8 and 10.3 yrs before study inclusion), respectively. Results - Compared to controls, patients with JMCTD had lower forced vital capacity (FVC), DLCO, and TLC (p Conclusion - Compared to controls, patients with JMCTD had impaired pulmonary function. ILD was present in 27% of patients after a mean 16 years of disease duration, mostly as mild disease, and did not progress. ILD seems to be less common in juvenile-onset than in adult-onset MCTD, and ILD in JMCTD seems mostly mild and stable over time

Additional file 2: of Disease evolution in mixed connective tissue disease: results from a long-term nationwide prospective cohort study

Auto-antibodies at time point 2 in 118 patients with MCTD. (PDF 154 kb

Additional file 1: of Associations between circulating endostatin levels and vascular organ damage in systemic sclerosis and mixed connective tissue disease: an observational study

Previous studies of endostatin and/or vascular endothelial growth factor in SSc and MCTD. Listing of previous studies of endostatin and/or vascular endothelial growth factor levels in SSc and/or MCTD including methods and main results. (PDF 241 kb

Additional file 3: of Associations between circulating endostatin levels and vascular organ damage in systemic sclerosis and mixed connective tissue disease: an observational study

Results of logistic regression analyses. Known risk factors and endostatin in predicting pulmonary arterial hypertension and scleroderma renal crisis. (PDF 282 kb

The phenotype of mixed connective tissue disease patients having associated interstitial lung disease

International audienceObjectiveWe aimed to compare two matched populations of patients with MTCD with and without associated ILD and to identify predictive factors for ILD progression and severity.MethodsThis international multicenter retrospective study (14 tertiary hospitals), included MCTD patients who fulfilled at least one historical MCTD classification criteria. ILD was defined by the presence of typical chest high-resolution computed tomography (HRCT) abnormalities. Factors associated with ILD were assessed at baseline. Long-term progressive ILD was assessed in MCTD-ILD patients with multiple forced vital capacity (FVC) measurements.Results300 patients with MCTD were included. Mean age at diagnosis was 39.7 ± 15.4 years and 191 (63.7%) were women. Mean follow-up was 7.8 ± 5.5 years. At baseline, we identified several factors associated with ILD presence: older age (p = 0.01), skin thickening (p = 0.03), upper gastro-intestinal (GI) symptoms (p10%. During follow-up mortality was higher in the MTCD-ILD group (p<0.001).ConclusionIn this large international cohort of patients with MTCD, we identified different factors associated with ILD. Our findings also provide evidence that MCTD-ILD patients have increased mortality and that DU are associated with progressive lung disease