In this thesis two main aims were addressed. It has long been established that early treatment of rheumatoid arthritis (RA) improves disease outcomes. In Part I of this thesis we therefore further... Show moreIn this thesis two main aims were addressed. It has long been established that early treatment of rheumatoid arthritis (RA) improves disease outcomes. In Part I of this thesis we therefore further investigated the early detection of at-risk individuals by studying a large cohort of patients with clinically suspect arthralgia (CSA). We explored the value of two easy clinical tests, their potential to detect underlying inflammatory processes and to predict disease progression. In addition we investigated the presence of subclinical synovitis on imaging as starting point for treatment with disease modifying anti-rheumatic drugs (DMARDs) and the value of magnetic resonance imaging (MRI) detected erosions as new predictor for RA-development. In Part II of this thesis we aimed to determine which disease processes are involved in the different phases of RA-development. Knowledge on disease pathogenesis and timing of influencing factors can help to better target treatment during RA-development. We therefore evaluated whether autoantibody-response maturation occurred during the phase of CSA, and investigated the timing of genetic risk factor human leukocyte antigen-shared epitope (HLA-SE) and environmental risk factor smoking during the development of autoantibody-positive disease. Show less
Ohrndorf, S.; Boer, A.C.; Boeters, D.M.; Brinck, R.M. ten; Burmester, G.R.; Kortekaas, M.C.; Helm-van Mil, A.H.M. van der 2019
The field of rheumatoid arthritis (RA) is moving into identification of patients as early as possible and the ultimate aim is to prevent RA becoming a chronic disease. To this end, we studied the... Show moreThe field of rheumatoid arthritis (RA) is moving into identification of patients as early as possible and the ultimate aim is to prevent RA becoming a chronic disease. To this end, we studied the phase of Clinically Suspect Arthralgia (CSA). Patients with arthralgia that were considered by the rheumatologist to have an increased risk to progress to RA (CSA) had indeed an increased risk of RA. In addition, subclinical MRI-inflammation preceded clinical arthritis with a few months. Future research will shed more light on processes underlying progression from CSA to RA and effectiveness of treatment initiation in the CSA phase. The severity of the course of RA is variable between patients and this cannot be yet accurately predicted. In this thesis, we performed studies that contributed to the understanding of these differences in severity. Three genetic risk factors for more severe joint damage progression (two non-HLA and one HLA variation) and one for arthritis persistence were identified. Further research on functional implications of the identified variants and whether they might be useful as biomarkers to guide treatment decisions is needed. Show less
The main aim of this thesis is to determine the role of magnetic resonance imaging (MRI) in early rheumatoid arthritis (RA). We set out to improve the MRI protocol and sequences used in arthritis... Show moreThe main aim of this thesis is to determine the role of magnetic resonance imaging (MRI) in early rheumatoid arthritis (RA). We set out to improve the MRI protocol and sequences used in arthritis patients, to detect subclinical inflammation in various patient groups and to describe the clinical implications of MRI. Chapter 1 provides a general introduction to this thesis, in chapter 2 the earliest disease stages of rheumatoid arthritis and the concept of pre-rheumatoid arthritis are further explored. In chapters 3-5 various ways are described to optimize the scanning protocol for arthritis patients. In chapters 6-8 we looked at the presence of inflammation on MRI when no inflammation can be detected at physical examination, i.e. subclinical inflammation. In chapters 9 and 10 we explore some of the clinical implications of the MRI findings. Chapter 11 provides a summary of the thesis and a discussion of the main findings. Show less
Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disease that principally affects synovial joints. RA is present in 0,5% to 1% of the global population. The incidence of RA is higher in... Show moreRheumatoid arthritis (RA) is a chronic, systemic autoimmune disease that principally affects synovial joints. RA is present in 0,5% to 1% of the global population. The incidence of RA is higher in women than in men and increases with age (1). RA can affect any joint but preferably small joints in hands and feet (2). The symptoms of RA include pain, swelling, stiffness, redness, warmth and can finally lead to loss of joint functions (2). The systemic symptoms of RA include fatigue, malaise, loss of appetite and muscle ache. Next to the joints RA can affect other organs such as skin, lungs, heart and blood vessels (3). RA can be classified using the 2010 American College of Rheumatology/European League Against Rheumatism classification criteria for rheumatoid arthritis (2010 ACR/EULAR criteria) (4). This is a quantitative system in which scores can be obtained from: joint involvement, serologic markers, inflammation markers and duration of symptoms (4). Show less
Have, M. van der; Brakenhoff, L.K.P.M.; Erp, S.J.H. van; Kaptein, A.A.; Leenders, M.; Scharloo, M.; ... ; Fidder, H.H. 2015
Het werk beschreven in dit proefschrift richt zich op het identificeren van voorspellende factoren voor het ontwikkelen van reumato_de artritis en het ziekte beloop van reumato_de artritis.... Show moreHet werk beschreven in dit proefschrift richt zich op het identificeren van voorspellende factoren voor het ontwikkelen van reumato_de artritis en het ziekte beloop van reumato_de artritis. Allereerst wordt er gekeken naar voorspellende factoren voor het krijgen van reumato_de artritis in vroege artritis pati_nten, patienten met ongeclassificeerde artritis en artralgie pati_nten (pati_nten met gewrichtspijn zonder gewrichtsontsteking). Daarna wordt er gekeken naar voorspellende factoren voor een ernstiger ziekte beloop van reumato_de artritis, op zowel; genetisch, serologisch als beeldvormend vlak. Concluderend draagt dit proefschrift bij aan het inzicht om vroeger te behandelen/monitoren en aan het inzicht dat __personalized medicine__ en MRI een belangrijke rol verdienen in de behandeling van reumato_de artritis. Show less
