Inflammatory myopathies

Inflammatory myopathies are a heterogeneous group of acquired muscle diseases characterized by their degeneration and inflammatory infiltration. The most common variants of inflammatory myopathy are dermatomyositis (DM), polymyositis (PM), and inclusion body myositis (MB).

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Epidemiology

Because dermatomyositis, polymyositis, and inclusion body myositis are characterized by inflammatory muscle lesions and their etiology is unknown, they have often been grouped together in clinical studies in the past, which has resulted in the loss of clinically significant information. However, these conditions should be considered separate diseases, since there is no evidence that they represent different manifestations of the same disease. The three diseases differ in age of onset, with dermatomyositis affecting both children and adults, polymyositis being rare in children and usually developing starting in the third decade of life, and inclusion body myositis most often occurring after 40 years of age. According to some data, inclusion body myositis is the most common myopathy in the elderly. The three diseases also differ in their relationships with malignant neoplasms. Dermatomyositis is most closely associated with cancer, especially in men over 40 years of age. In addition, these diseases may differ in clinical manifestations, the nature and localization of inflammatory infiltrates, and the response to immunosuppressive agents (including corticosteroids).

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Causes inflammatory myopathy

It is important to note that inflammatory myopathies may also be associated with parasitic infestations or viral infections, as well as with systemic diseases such as vasculitis, sarcoidosis, polymyalgia rheumatica, rheumatoid arthritis "overlap syndromes", mixed connective tissue disease, systemic lupus erythematosus, Sjogren's syndrome or scleroderma.

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Pathogenesis

The presence of inflammatory infiltrates in dermatomyositis, polymyositis, and inclusion body myositis primarily indicates the importance of autoimmune mechanisms in the pathogenesis of these diseases. Studies of HLA antigens have shown that patients with dermatomyositis and polymyositis more often have the HLA-DR3 antigen in linkage disequilibrium with HLA-B8. However, in none of these diseases has it been possible to identify an antigen that would be specific enough to meet the criteria for an autoimmune disease.

In dermatomyositis, severe angiopathy of the intramuscular vessels with pronounced infiltration by B-lymphocytes is detected, and in the wall of the perimysial vessels, deposits of immunoglobulins and the C3 component of complement are found. Components of the membrane attack complex (MAC) of complement C5b-9 can be detected immunohistochemically using light and electron microscopy. Macrophages and cytotoxic T-lymphocytes are also present, but to a lesser extent.

Inflammatory Myopathies - What's Happening?

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Symptoms inflammatory myopathy

In dermatomyositis, especially in children, the disease begins with systemic manifestations such as fever and malaise. A characteristic rash then appears, which accompanies or, more commonly, precedes the development of proximal muscle weakness. The cheeks become flushed; a purplish rash appears on the eyelids, especially the upper ones, often accompanied by edema and telangiectasias. An erythematous rash appears on exposed areas of the chest and neck. Discoloration and thickening of the skin is noted on the extensor surfaces of the knees and elbows. An erythematous rash is also found in the area of the interphalangeal joints of the hands. Discoloration of the nail beds is also observed, followed by telangiectasias and edema. Over time, muscle weakness progresses, accompanied by pain and stiffness. The proximal muscles of the upper and lower extremities are involved to a greater extent than the distal ones. Children with dermatomyositis may develop flexion contracture in the ankle joints.

Inflammatory myopathies - Symptoms

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Diagnostics inflammatory myopathy

ESR may be elevated in dermatomyositis and polymyositis (but not in inclusion body myositis). However, ESR remains normal in almost 50% of patients with dermatomyositis and polymyositis. In general, ESR does not correlate with the severity of muscle weakness and cannot be used as an indicator of treatment effectiveness. Creatine phosphokinase (CPK) levels are a sensitive indicator of muscle damage in dermatomyositis and polymyositis. Skeletal muscle (SM)-specific CPK is usually elevated. However, CNS-specific (CB) isoenzyme levels may also be elevated, which is associated with the ongoing muscle regeneration process. Other enzymes, such as aldolase and lactate dehydrogenase, are also elevated in dermatomyositis and polymyositis, but CPK is a more sensitive indicator of muscle degeneration and muscle membrane damage and is therefore a more reliable indicator of disease progression and the effectiveness of therapy. Serum myoglobin is also elevated in dermatomyositis and polymyositis and can serve as an indicator of disease progression and guide treatment.

Inflammatory myopathies - Diagnosis

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Treatment inflammatory myopathy

The use of drugs in inflammatory myopathies is empirical. Their effectiveness has not been confirmed in large-scale double-blind placebo-controlled trials. Moreover, many clinical trials have not identified subgroups of patients with dermatomyositis and polymyositis. Therefore, the course and true effectiveness of certain treatments for each of these different diseases remain unclear. Thus, current treatment regimens are often based on isolated case reports. Despite the lack of comprehensive information, most experts agree that immunosuppressive therapy is effective in many patients with inflammatory myopathies. This will create ethical difficulties in conducting large-scale controlled trials of these drugs in the future. However, such studies are of great importance to assess the efficacy of new, more specific approaches to the treatment of inflammatory myopathies that are directed against immunological “targets” that are not currently being addressed (e.g., the complement-mediated humoral “attack” on perimysial vessels in dermatomyositis or the oligoclonal cytotoxic T-lymphocyte attack on muscle fibers in polymyositis).

Inflammatory myopathies - Treatment