Systemic sclerosis (SSc) is a serious multiorgan disease, characterized by progressive fibrosis, vasculopathy and distinct serum auto antibodies (1, 2). Patients with SSc have an increased mortality risk and reduced quality of life (3-5). Interstitial lung disease (ILD) is a common manifestation in SSc and the leading cause of morbidity and mortality in the SSc population (3, 6). Classification of SSc was done with the 1980 American College of Rheumatology (ACR) classification criteria until 2013, when EULAR and ACR launched unified new classification criteria for SSc (7, 8).
The aim of the study was to estimate the prevalence of SSc in Norway, investigate survival and causes of deaths and to study fibrosis progression and lung function by serial assessments of high resolution computed tomography (HRCT) and concurrent pulmonary function tests (PFT). Additionally, we wanted to confirm the true value of the 2013 ACR/EULAR classification criteria for SSc.
We found a prevalence of SSc in Norway of 9.9/100 000, a value comparable to other Northern European countries, supporting the notion of a north-south gradient of SSc in Europe with the lowest prevalence in Northern Europe. Our data show that mortality in SSc is still increased compared to the background population and the major causes of death are pulmonary hypertension (PH) and ILD. When studying lung fibrosis and lung function in serial assessments, we demonstrate that a normal baseline HRCT was highly predictive against later fibrosis development, and that HRCT findings at baseline predicted fibrosis progression rates and the deterioration rates of pulmonary function. Male gender, SSc subtype, antibodies, baseline fibrosis and baseline lung function were main risk factors for fibrosis development and progression. The 2013 ACR/EULAR SSc criteria performed remarkably well in our cohort and the sensitivity was significantly better than the ACR1980 criteria using the combination of the ACR 1980 criteria and/or the Leroy & Medsger criteria as the “gold standard” for SSc.
Our results reinforce the view that SSc is a rare but serious disease with increased morbidity and mortality and that pulmonary disease is a devastating complication. Our data support the notion that the 2013 ACR/EULAR criteria are a major step forward and that their application should improve the quality of clinical and epidemiological SSc research in the years to come.
List of papers. The papers are removed from the thesis due to publisher restrictions.
Paper I Prevalence of systemic sclerosis in southeast Norway in the period 1999-2009 Hoffmann-Vold AM, Midtvedt O, Molberg O, Garen T, Gran JT. Rheumatology (Oxford) 2012 Sep;51(9):1600-5. doi:10.1093/rheumatology/kes076
Paper II Survival and causes of death in an unselected and complete cohort of Norwegian patients with systemic sclerosis. Hoffmann-Vold AM, Molberg Ø, Midtvedt Ø, Garen T, Gran JT. J Rheum 2013 Jul; 40(7):1127-33. doi:10.3899/jrheum.121390
Paper III Performance of the 2013 ACR/EULAR classification criteria for systemic sclerosis (SSc) in large, well-defined cohorts of SSc and mixed connective tissue disease. Hoffmann-Vold AM, Gunnarsson R, Garen T, Midtvedt O, Molberg O. J Rheum E PUB ahead of print, Oct 2014 doi:10.3899/jrheum.140047
Paper IV Predictive value of serial HRCT analyses and concurrent lung function tests in systemic sclerosis Hoffmann-Vold AM, Aaløkken TM , Lund MB, Garen T, Midtvedt O, Brunborg C, Gran JT, Molberg O. Submitted