Contributions to optimal care in systemic sclerosis
(2012)
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ThèseMVAVECRESTRICTIONS.pdf
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Details
- Authors
- Supervisors
- Houssiau, Frédéric
- Abstract
- (en) Systemic sclerosis (SSc) is a rare disease that preferentially affects females, with a reported female-to-male ratio of 4.6:1.0 and a typical onset between 45 and 64 years. The prevalence is difficult to evaluate and may well differ between countries and ethnicities. In France, the prevalence among adults is about 158/million. Thus, by extrapolation, the number of SSc cases in Belgium should be around 1,700. SSc is a multisystemic disease purportedly resulting from three types of injuries: fibrosis, immune dysregulation and vascular damage. The exact trigger and the precise relation between the three types of injuries are complex, remain incompletely understood and depend in part on extrinsic factors (such as environmental, viral or toxic factors) and genetic susceptibility. This disease is characterized by excessive production of extracellular matrix proteins by fibroblasts and the clinical picture mainly results from tissue fibrosis and vascular occlusions. Clinical manifestations are various but Raynaud’s phenomenon, digital ulcers, sclerodactyly, interstitial lung disease, oeso-gastro-intestinal hypotony, arthritis, myositis and pulmonary arterial hypertension are common symptoms. Mortality in some series of SSc is as high as 30% at 10 years. However, survival is variable due to disease heterogeneousness, impact of therapy, and difficulties in assessing the time of disease onset. There are only a few evidence-based drugs available in SSc. The lack of relevant animal models and the remaining uncertainties regarding pathophysiology largely explain this unmet need. Moreover, the rarity of the disease and the heterogeneous nature of the clinical manifestations limit the possibility to run randomized controlled trials. However, in 2009, recommendations for the treatment of SSc were published so that current treatment is based on expert opinions and on a patient-tailored multi-drug approach, according to the extent of skin/internal organ involvement. The Belgian Systemic Sclerosis Cohort (BSSC) is a nationwide initiative launched by Frédéric Houssiau in 2006. The aim of this long-term prospective observational study was to define the natural history of SSc, to identify prognostic factors, and, in parallel, to improve the quality of care. All prevalent and incident cases of SSc, fulfilling LeRoy and Medsger’s classification criteria followed in Belgian teaching hospitals were asked to participate. Data were collected in a prospective way, at baseline, 6 months and then yearly, within the regulatory frame required by good clinical practices. Since April 2006, 540 patients have been included. The first paper reports baseline and follow-up data on the first 438 patients included in the BSSC with a special emphasis on death rate and on correlations between disease severity scores, cutaneous subsets and autoantibody profile (paper 1). The BSSC is the backbone of this thesis; moreover, this large serie of well characterized cases gave us the opportunity to launch spin-off studies. First, we performed a study dealing with hand radiological damage in a large group of SSc patients, with a special emphasis on the distinction between osteoarthritic- and inflammation-driven damage. The originality of our work stems from the comparison with a gender- and age-matched control group and from the correlations we were able to test with the clinical and functional characteristics of SSc patients available through the BSSC (paper 2). Second, we developed and validated a questionnaire specifically aimed at testing manual ability of SSc patients. The latter was created using the Rasch model that estimates the item difficulty and the patient’s manual ability on a common linear scale from the answers given to each item, within a probablistic framework (paper 3). Third, in a small and retrospective study, we reported the safety, in terms of renal function and blood pressure, of monthly intravenous (IV) methylprednisolone (MP) pulses in early SSc patients suffering from interstitial lung disease (ILD), myositis, arthritis or rapidly progressing diffuse cutaneous involvement (paper 4). Finally, we suggested the efficacy and safety of mycophenolate mofetil combined to IV and oral glucocorticoids in a small one-year pilot study including 16 early SSc patients suffering from either interstitial lung disease or diffuse skin disease (paper 5).
- Affiliations
Citations
Vanthuyne, M. (2012). Contributions to optimal care in systemic sclerosis. https://hdl.handle.net/2078.5/46501