Abstract: Polymyosit (PM), dermatomyositis (DM) and sporadic inclusion body myositis (sIBM) are chronic inflammatory myopathies which are characterized by muscle weakness, fatigue and extra-muscular involvement. Mononuclear inflammatory cells are typically found in muscle tissue. Treatment is based on glucocorticoids together with other immunosuppressive agents. Despite favorable response most patients with PM and DM develop sustained muscle weakness and some patients do not respond at all, including sIBM. The explanation for this is unknown. Aims: The overall aim was to achieve increased understanding of disease mechanisms in myositis by evaluating therapeutic effects on muscle performance and variables in muscle tissue of pharmacological (high dose IVIg treatment and TNF-blockade, infliximab) and of non-pharmacological treatment, endurance and resistance training. Patients and methods: Clinical outcome measures (disease activity and muscle performance), laboratory tests and muscle biopsies were performed before and after the interventions. Muscle biopsies were investigated for signs of inflammation, fibrosis and muscle fiber characteristics. Patients with chronic, refractory myositis were treated with high dose IVIg for 12 weeks (study I, n= 13) or with infliximab for 16 weeks (study II, n= 12). In studies III and IV patients with chronic, stable and low active inflammatory DM or PM were applied to endurance training for 12 weeks (study III, n = 8) or resistance training for 7 weeks (study IV, n= 8). Results: After high dose IVIg treatment muscle performance improved in 3 of 13 patients. In two patients there were signs of decreased inflammation in muscle biopsies, but there was no correlation between improved muscle performance and changes of inflammatory markers in muscle tissue. There was still a pronounced expression of inflammatory markers in muscle tissue after treatment. After infliximab treatment 3 patients had decreased, 2 had increased and 5 had unchanged disease activity. Four stopped prematurely due to ...
Relation: I. Helmers SB, Dastmalchi M, Alexanderson H, Nennesmo I, Esbjörnsson M, Lindvall B, Lundberg IE (2007). "Limited effects of high-dose intravenous immunoglobulin (IVIG) treatment on molecular expression in muscle tissue of patients with inflammatory myopathies." Ann Rheum Dis 66(10): 1276-83. Epub 2007 Feb 2 ::pmid::17277004; II. Dastmalchi M, Grundtman C, Alexanderson H, Einarsdottir H, Barbasso Helmers S, Elvin K, Nennesmo I, Lundberg IE (2007). "A high incidence of disease flares in an open study of infliximab in patients with refractory inflammatory myopathies." (Submitted); III. Dastmalchi M, Alexanderson H, Loell I, Ståhlberg M, Borg K, Lundberg IE, Esbjörnsson M (2007). "Effect of physical training on the proportion of slow-twitch type I muscle fibers, a novel nonimmune-mediated mechanism for muscle impairment in polymyositis or dermatomyositis." Arthritis Rheum 57(7): 1303-1310 [Epub ahead of print] ::pmid::17907213; IV. Nader G, Dastmalchi M, Alexanderson H, Grundtman C, Esbjörnsson M, Rönnelid J, Hoffman E, Nagaraju K, Lundberg IE (2007). "Resistance exercise reduces the expression of inflammation and fibrosis associated genes in autoimmune myositis patients." (Submitted); 20071102dast; http://hdl.handle.net/10616/38736
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