Abstract

The idiopathic inflammatory myopathies (IIM) or briefly myositis is a heterogenous group of disorders where muscle weakness and inflammation in skeletal muscle tissue are predominating features but other organ involvement is common, such as skin, joints, lungs, gastrointestinal tract and heart. Treatment is based on a combination of pharmacological treatment in combination with physical exercise. However, treatment effect varies and may often be disappointing with persisting muscle weakness, muscle fatigue and low health related quality of life. Thus there is a high unmet need for new therapies and for this we need a better understanding on the molecular pathogenesis and this is likely to be different in different subsets.

Based on differences in clinical and histopathological features IIM has since long been subdivided into polymyositis, dermatomyositis and inclusion body myositis. This subclassification has several limitations as treatment response and prognosis varies within these subgroups. Furthermore, the varying treatment response suggests that there may be different pathogenic mechanisms in these different subgroups. During recent years several new myositis specific autoantibodies have been identified and they are associated with distinct clinical phenotypes and thus may be associated with differences in molecular pathways. Autoantibody profile is important in the clinic to alert for organ involvement such as interstitial lung disease (ILD) and malignancy. Autoantibodies may also predict treatment response.

Pharmacological treatment is based on high doses of glucocorticoids in combination with another immunosuppressive agent to improve the immunosuppressive effect and reduce the need of glucocorticoids. Most experts recommend methotrexate or azathioprine as first line treatment together with glucocorticoids, but other agents are also used with varying effect. New biologics such as anti-TNF therapies have had limited effect and even worsened inflammation in some cases. Treatment with the B- cell blocking agent rituximab has been more successful, but still with varying results. Presence of anti-Jo-1 or anti-Mi-2 antibodies seems to predict response. Interstitial lung disease (ILD) is a major risk factor for morbidity and mortality. Careful monitoring of pulmonary function is required in these patients As first line treatment for myositis associated ILD most experts recommend high doses of glucocorticoids in combination with pulse cyclophosphamide but controlled trials are lacking. Beneficial effect of rituximab on pulmonary function has been reported in case series but needs to be evaluated under controlled conditions.

Physical exercise in combination with immunosuppressive treatment is safe and has beneficial effects on muscle performance and health related quality of life. In addition, exercise has beneficial effects on muscle metabolism and may restore a disturbed mitochondrial function and may even have anti-inflammatory effects.

To learn more about which treatment should be preferred for a specific patient we need more knowledge on predictive markers. To achieve this an international collaboration where we collect validated clinical outcome data in a standardized way on a large number of patients will be important. This will be essential to analyze treatment effects in large enough homogenous subgroups. One such initiative is the Euromyositis register, www.euromyositis.eu. In addition, we need to perform controlled clinical trials in well-defined patient subgroups in large multi-center trials and we need to learn more about the pathogenesis of these diseases to develop new therapies.