Abstract

Myositis or Idiopathic inflammatory myopathies (IIMs) are acquired, heterogeneous autoimmune disorders characterized by immune-mediated skeletal muscle inflammation leading to muscle weakness and to damage to muscle tissue. Traditionally IIMs include dermatomyositis, polymyositis, cancer associated dermatomyositis, juvenile dermatomyositis and myositis as part of the overlap syndromes. Immune mediated necrotizing myopathy (IMNM) is newly recognized myositis subgroup with a majority of patients having anti-SRP or anti-HMGCR antibody in their serum. The data shows that anti-HMGCR+ IMNM is associated with previous use of statins that presumably induce autoimmune reaction towards the 3-hydroxy-3-methyl glutaryl-coenzyme A reductase (HMGCR). The incidence of this form of IMNM is increasing, probably due to the growing use of statins in the population. Patients with anti-HMGCR+ IMNM tend to respond to immunosuppressive treatments and if resistant to this, then usually favourably react to intravenous immunoglobulins, even without concomitant glucocorticoids. Anti-SRP+ patients, on the other hand, are notoriously difficult to treat. Recent studies showed that some of these patients may respond to rituximab.

Inclusion body myositis (IBM) is a late onset myositis leading to progressive muscle wasting. It is still debated whether IBM is a primary autoimmune disease or a degenerative myopathy. Recent discovery of antibodies to cytosolic 5'-nucleotidase 1A (anti-cN1A) that are present in a certain proportion of IBM patients points to immune pathogenesis. This is supported by the fact that anti-cN1A may be seen also in some other autoimmune diseases. IBM is usually resistant to immunosuppressive treatment. Several new directions in the treatment are being explored in the early phases of clinical trials, e.g. with ariclomol (increases expression of cytoprotective heat shock proteins in muscle), bimagrumab (monoclonal antibody that blocks the activin IIA and IIB receptors that bind myostatin) or follistatin (gene therapy inhibiting myostatin expression).

Patients with IIMs may have several myositis specific autoantibodies (MSA) which are associated with particular clinical manifestations. The most recent addition to this rule is the antibody to muscle-specific protein FHL1. Presence of anti-FHL1 is predictive for muscle atrophy, dysphagia, pronounced muscle fibre damage, and vasculitis. Interestingly, mutations of the gene encoding four-and-a-half LIM domain 1 (FHL1) are the causative factor of several X-linked hereditary myopathies, suggesting that antibodies to this protein may have pathogenic properties.

Most of the recent treatment studies performed in patients with IIMs did not meet primary endpoints, with the exception of the trial in juvenile DM, in which combination of prednisone with either cyclosporine or methotrexate was more effective than prednisone alone. The safety profile and steroid-sparing effect favoured the combination of prednisone plus methotrexate.

Newly developed criteria for clinical response quantitatively assess the improvement on the 0–100 scale and use thresholds for minimal, moderate, and major improvement. They provide a sensitive and specific tool for longitudinal patient follow-up and hopefully will perform better in proving efficacy of new treatments in the future.