Mixed connective tissue disease: Results from a nation-wide multicenter survey of Norwegian patients.
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AbstractThe Norwegian mixed connective tissue disease (MCTD) cohort study was the first nationwide study of this rare autoimmune, systemic connective tissue disease (CTD), which was first defined only four decades ago (3).
This nation-wide, multicenter study involved the Departments of Rheumatology in Norway. The inclusion criteria were: age = 18 years; a clinical diagnosis of MCTD; documented high titer serum anti-ribonucleoprotein antibody test; fulfillment of at least one of the three most used disease criteria for MCTD (4-6); and exclusion of other CTDs.
The study protocol included standardized questions about symptoms, clinical examinations, blood tests, high resolution computed tomography (HRCT), pulmonary function tests (PFT), echocardiography and in selected cases right heart catheterization (RHC).
The main results are presented in three papers. Paper I (1) showed a point prevalence of adult MCTD in Norway of 3.8 per 100,000 adults and the retrospective incidence estimate of adultonset MCTD of 2.1 per million per year. Paper II (2) showed that pulmonary disease was frequent in the cohort, with as much as 52% of the patients having an abnormal HRCT. Lung fibrosis was identified in 35% of the patients, classified as minor (7%), moderate (9%) and severe (19%), with a clear preference for the lower parts of the lungs. After a mean of four years of observation, the presence of lung fibrosis was associated with increased mortality (p< 0.05). Preliminary analysis supported an association between lung fibrosis and esophageal dilatation evaluated by HRCT. Paper III showed that the overall prevalence of pulmonary hypertension (PH) in the cohort was 3.4%, a rate far lower than previously found in small scale studies (7-9). The mean follow-up was 5.6 years, from inclusion to the 1st of January 2012 when a total of 12 (8.2%) patients had died. Three of the five patients identified with PH died, two of whom had PH associated with severe ILD. The causes of death in the nine other deceased patients were ILD (n=2), coronary heart disease (n=2), cancer (n=4) and unknown (n=1).
List of papers. The papers are removed due to publisher restrictions.
Paper I: The prevalence and incidence of mixed connective tissue disease: A national multicentre survey of Norwegian patients. Ragnar Gunnarsson, Øyvind Molberg, Inge-Margrethe Gilboe, Jan Tore Gran. PAHNOR1 study group: Åse Stavland Lexberg, Kari Time, Alvilde Sofie Strand Dhainaut, Liv-Turid Bertelsen, Øyvind Palm, Karen Irgens, Andrea Becker-Merok, Jan Leidulf Nordeide, Villy Johnsen, Sonja Pedersen, Anne Prøven, Sven Gøran Sidenvall and Lamya Samir Noori Garabet. Annals of the Rheumatic Diseases 2011;70(6): 1047-1051. (1) doi:10.1136/ard.2010.143792
Paper II: Prevalence and severity of interstitial lung disease in mixed connective tissue disease: A nationwide, cross-sectional study. Ragnar Gunnarsson, Trond Mogens Aaløkken, Øyvind Molberg, May Brit Lund, Georg Mynarek, Åse Stavland Lexberg, Kari Time, Alvilde Sofie Strand Dhainaut, Liv-Turid Bertelsen, Øyvind Palm, Karen Irgens, Andrea Becker-Merok, Jan Leidulf Nordeide, Villy Johnsen, Sonja Pedersen, Anne Prøven, Lamya Samir Noori Garabet, Jan Tore Gran. Annals of the Rheumatic Diseases 2012;71(12): 1966-72. (2) doi:10.1136/annrheumdis-2011-201253
Paper III: Prevalence of pulmonary hypertension in an unselected mixed connective tissue disease cohort: Results of a nationwide, Norwegian cross-sectional multicenter study and review of current literature. Ragnar Gunnarsson, Arne K Andreassen, Øyvind Molberg, Åse Stavland Lexberg, Kari Time, Alvilde Sofie Strand Dhainaut, Liv-Turid Bertelsen, Øyvind Palm, Karen Irgens, Andrea Becker-Merok, Jan Leidulf Nordeide, Villy Johnsen, Sonja Pedersen, Anne Prøven, Lamya Samir Noori Garabet, Torhild Garen, Trond Mogens Aaløkken, Inge-Margrethe Gilboe, Jan Tore Gran. Accepted version, published in: Rheumatology 2013;52(7): 1208-1213. doi:10.1093/rheumatology/kes430