Muscle inflammatory processes and their clinical manifestations in patients with polymyositis and dermatomyositis
Authors:
J. Tomasová Studýnková
Authors place of work:
Revmatologický ústav, Praha
Published in the journal:
Čes. Revmatol., 15, 2007, No. 1, p. 34-46.
Category:
Summaries of Doctoral Dissertations
Summary
Idiopathic inflammatory myopathies (IIM) include dermatomyositis (DM), polymyositis (PM) and inclusion body myositis (IBM), which are clinically characterized by symmetrical proximal muscle weakness. The etiology and pathogenesis are unknown although immunological mechanisms appear to be involved. The hallmark and the basic histopathological criterion is an infiltrate with inflammatory cells. This muscle inflammation is often focal and heterogeneous. Not all of the muscles are affected at the same time with the same patient. Cases with persistent muscle weakness exist while at the same time the inflammatory infiltrate is only minimal or can no longer be found. The cause of the weakness appears to be largely unknown. The aim of our project was to find out and describe mechanisms that lead to the infiltration of inflammatory cells in the muscle tissue, muscle edema and the tissue damage, and subsequently to the clinical symptoms in patients with PM and DM. There is not much known about the factors that contribute to the persistence of inflammatory cells in muscle tissues and for the formation of edema in the muscle tissue. We searched for the contribution of COX and LOX enzymes production in the muscle during the evolution of myositis to understand the role that COX, LOX and their products might play in the pathogenesis of this disease. We observed for the first time the expression of COX-1, COX-2 and 5-LOX mRNA in muscle tissues from IIM patients. This expression of mRNA for these enzymes was increased in affected tissues and this was seen not only in inflammatory or vascular cells but also in muscle cells. The fact that COX and LOX enzymes are induced in myositis suggests their contribution to pathologic processes during the disease. The expression of IP-10-CXCR3 system in the muscle tissue samples points towards significant participation in the disease pathogenesis. The fact that CCR5 is not present in the infiltrating cells shows small representation of Th1 cells and it attributes the reaction between IP-10 and CXCR3 the role rather in activation of the muscle cells. The reason for hyperexpression of HLA class I molecules can be constituted by frequent expression of IFN-β. Acute inflammation in IIM causes edema that can be visualized by magnetic resonance imaging (MRI). The inflammatory infiltrate in IIM is thought to be frequent in a focal distribution. We tried to better evaluate the relationship of MR image of thigh muscles to clinical and histological parameters in patients with IIM. Assessment of the global and muscle disease activity correlated best with the intensity of MR image. Biopsies guided by positive MRI findings detect significantly more inflammatory infiltrate than the biopsies taken from MRI non-affected sites. The intensity of MRI oedema decreased significantly after the treatment, however, the improvement in the histologically detected inflammation has not been seen. This suggests that MRI could be a preferable parameter to histology in evaluation of clinical status and treatment effect in PM and DM patients. In our clinical study we attempted to determine the effectiveness and tolerance of treatment with cyclosporine A (CyA) or methotrexate (MTX) added to corticosteroids in patients with severe, active PM and DM. Significant improvement in muscle endurance and functional test (MEFT), clinical assessment (CA), global patient’s assessment (GPA) and muscle MRI was found in both groups MTX and CyA. Patients treated with MTX showed insignificantly better response than patients with CyA. CK levels in MTX group decreased significantly after 1, 3 and 6 months, whereas significant reduction in CyA group was first observed after 6 months. IL-1Ra serum levels significantly dropped in CyA group after two weeks, whereas in MTX group the significant decrease was first seen after 3 months of treatment. Good correlation was found between each of the clinical parameters (MEFT, CA and GPA), none of them showed any correlation with CK or IL-1Ra levels. Administration of MTX or CyA added to corticosteroids was associated with clinical and laboratory improvement. Changes in CK and IL-1Ra levels were not associated with parameters of clinical disease severity measured in this study.
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Štítky
Dermatology & STDs Paediatric rheumatology RheumatologyČlánok vyšiel v časopise
Czech Rheumatology
2007 Číslo 1
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