Inflammatory myopathies

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

[1], [2]

Epidemiology

Since dermatomyositis, polymyositis and myositis with inclusions are characterized by inflammatory muscle damage, and their etiology is unknown, they were often combined together in clinical studies in the past, which led to the loss of clinically relevant information. Meanwhile, these conditions should be considered as separate diseases, since there is no evidence that they represent different manifestations of the same disease. These three diseases differ in the age of onset, with dermatomyositis affecting both children and adults, polymyositis is rarely seen in children and usually develops from the third decade of life, myositis with inclusions usually occurs after 40 years. According to some reports, myositis with inclusions is the most frequent myopathy of the elderly. These three diseases also differ in the relationship with malignant neoplasms. The most closely related to oncological diseases is dermatomyositis, especially in men older than 40 years. In addition, these diseases can differ in the clinical manifestations, nature and localization of inflammatory infiltrates, the response to immunosuppressive agents (including corticosteroids).

[3], [4], [5], [6], [7], [8]

Causes of the inflammatory myopathy

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

[9], [10]

Pathogenesis

The presence of inflammatory infiltrates with dermatomyositis, polymyositis and myositis with inclusions, first of all, demonstrates the importance of autoimmune mechanisms in the pathogenesis of these diseases. Studies of HLA antigens have shown that in patients with dermatomyositis and polymyositis, HLA-DR3 antigen is more common in disequilibrium with HLA-B8. However, none of these diseases has been able to identify an antigen that is sufficiently specific to meet the criteria for an autoimmune disease.

With dermatomyositis, severe angiopathy of intramuscular vessels with severe infiltration of B-lymphocytes is detected, and in the wall of the vessels, perimisation is the deposition of immunoglobulins and the SZ component of complement. Components of the membrane-  coagulation complex (MAK) of complement C5b-9 can be detected immunohistochemically by light and electron microscopy. There are also macrophages and cytotoxic T-lymphocytes, but to a lesser extent.

Inflammatory myopathies - What's going on?

[11], [12], [13], [14], [15]

Symptoms of the inflammatory myopathy

With dermatomyositis, especially in children, the disease begins with general manifestations, such as fever and malaise. Then there is a characteristic rash that accompanies or, more often, precedes the development of weakness of the proximal muscles. There is hyperemia of the cheeks; on the eyelids, especially the upper ones, there is a rash with a purple hue, often accompanied by edema and telangiectasias. In open areas of the skin of the chest and neck, there is an erythematous rash. The extensor surface of the knee and elbow joints is marked by discoloration and thickening of the skin. Erythematous rash is also evident in the area of interphalangeal joints on the hands. Discoloration of the nail beds is also observed, followed by the development of telangiectasia and edema. Over time, muscle weakness progresses, accompanied by pain and stiffness. The proximal muscles on the upper and lower extremities are involved to a greater extent than the distal muscles. Children with dermatomyositis may develop flexion contracture in the ankle joints.

Inflammatory myopathies - Symptoms

[16]

Diagnostics of the inflammatory myopathy

With dermatomyositis and polymyositis (but not with myositis with inclusions), an increase in ESR is possible. However, in almost 50% of patients with dermatomyositis and polymyositis, ESR remains normal. In general, the level of ESR does not correlate with the severity of muscle weakness and can not serve as an indicator of the effectiveness of treatment. The level of creatine phosphokinase (CK) is a sensitive indicator of muscle damage in dermatomyositis and polymyositis. Usually there is an increase in the isoenzyme of CKK, specific for skeletal muscle (MM). However, the level of the isoenzyme specific for the central nervous system (VV) can also be increased, which is associated with the current process of regeneration. The activity of other enzymes such as aldolase and lactate dehydrogenase is also increased in dermatomyositis and polymyositis, but the level of CK is a more sensitive indicator of muscle degeneration and damage to the muscle membrane and, therefore, a more reliable indicator of the progression of the disease and the effectiveness of therapy. The serum content of myoglobin in dermatomyositis and polymyositis is also increased and may serve as an indicator of the progression of the disease and a guide for the treatment.

Inflammatory myopathies - Diagnosis

[17], [18], [19], [20]

Treatment of the inflammatory myopathy

The use of drugs in inflammatory myopathies has an empirical character. Their efficacy has not been confirmed in large-scale, double-blind, placebo-controlled trials. Moreover, in many clinical studies, subgroups of patients with dermatomyositis and polymyositis were not isolated. In this regard, the course and the true effectiveness of various treatments for each of these differing diseases remain unclear. Thus, modern treatment regimens are often based only on individual casuistic observations. Despite the lack of comprehensive information, most specialists agree that immunosuppressive therapy is effective in many patients with inflammatory myopathies. This will create ethical difficulties in the conduct of large-scale controlled trials of these funds in the future. Nevertheless, such studies are extremely important for evaluating the effectiveness of new, more specific approaches to the treatment of inflammatory myopathies directed against those immunological "targets" that are not currently being exposed (for example, to the complement-mediated humoral "attack" on the vessels of perimisation Dermatomyositis or attack of oligoclonal cytotoxic T-lymphocytes on muscle fibers in polymyositis).

Inflammatory myopathies - Treatment