Objective. To investigate if there is a molecular correlate in muscle tissue to the persisting decreased muscle function in patients with chronic, inactive polymyositis (PM) and dermatomyositis (DM). Methods. Muscle function was assessed using a muscle function index of myositis.

To assess disease activity both histopathological investigation of muscle biopsies and magnetic resonance imaging (MRI) scans of the thigh muscles were performed. Inactive chronic disease was defined as persisting muscle weakness and absence of inflammatory infiltrates in muscle biopsy and absence of signs of inflammation on MRI. Expression of interleukin 1a (IL-1a), IL-1b, adhesion molecules, and MHC class I molecules in muscle tissue was investigated with immunohistochemistry.

Results. Muscle weakness was confirmed by a reduction of muscle function score. No signs of inflammation typical for myositis were observed. The most striking finding in our study was the strong expression of IL-1a and MHC class I molecules in muscle tissue from patients with inactive chronic PM and DM. Increased IL-1a expression was evident in capillaries and increased MHC class I expression was detected in muscle fiber membranes.

Conclusion. IL-1a and MHC class I molecules may have an importance in the pathogenesis of the chronic muscle weakness and fatigue in patients with PM and DM. (J Rheumatol 2000;27:940–8)

Myositis Therapy

Corticosteroids are still the initial therapy of choice for polymyositis (PM) and dermatomyositis (DM), but many patients are refractory to or do not tolerate the doses of steroids required to control the disease. Furthermore, these patients are often difficult to taper off their steroids. Often, drugs such as methotrexate, azathioprine, intravenous immunoglobulin, and cyclosporin A are used to help control the disease and decrease the steroid doses. Recent studies in several centers have shown that etanercept or infliximab can help to taper the patient off steroids.

The calcinosis associated with PM and DM is extremely difficult to treat and often appears to progress even when the other markers of muscle inflammation may be quiescent. Treatment of the active myositis remains the best plan for prevention of subsequent dystrophic calcification. However, after the calcifications are present, treatment with additional disease-modifying antirheumatic drugs, warfarin (usually Coumadin), or calcium channel blockers did not reliably reverse the calcifications.

Pathogenesis

Juvenile DM is a systemic vasculopathy characterized by capillary occlusion. Although this condition is rare, it provides an important model for vascular thrombosis. Increased tendencies toward blood clotting are present in these children and may contribute to the increased frequency of vascular thrombosis and endothelial cell hyperplasia. Also, impaired generation of ATP and low levels of ATP-bound magnesium in the mitochondrial cytochromes in these patients may contribute to muscle fatigue.

In adult DM and PM, CD8+ T cells infiltrating the muscle exhibit clonal expansion as manifested by the use of a particular V beta gene segment, although such clonal expansions were less frequent in the peripheral blood. However, different patients used different V betas. Apoptosis of muscle cells involves both Fas- and Trail-mediated pathways. Also, a decrease in an anti-apoptotic protein was noted in the PM muscle biopsies that could further contribute to myositis. There are increasing reports of a myofascitis in patients who have received vaccines. This most frequently occurs after hepatitis A, hepatitis B, and tetanus toxoid vaccine and may be due to formation of crystals of aluminum oxide that engender an inflammatory response.

Summary

Despite the lack of major breakthroughs, the emergence of new therapeutic opportunities based on the genetic map and new pathogenetic pathways has occurred. It is increasingly clear that diseases previously clumped under generic titles such as SLE, SS, APS, and myositis are really a series of different diseases. In the absence of knowledge of the underlying genetic or environment causes (ie, both necessary and sufficient for pathogenesis), better methods are needed to identify subsets of patients for rational therapy and prognosis.