Inflammatory myopathies - Diagnosis

Diagnosis of inflammatory myopathies

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 marker of muscle degeneration and muscle membrane damage and is therefore a more reliable indicator of disease progression and treatment response. Serum myoglobin is also elevated in dermatomyositis and polymyositis and can be used to measure disease progression and guide treatment. When serum enzyme levels do not correlate with clinical status, particularly after immunosuppressive therapy and plasmapheresis, clinical features such as muscle strength are more reliable indicators of disease progression and treatment response. In inclusion body myositis, serum CPK is usually within normal limits and is therefore not a good indicator of treatment response. In 20% of patients with polymyositis, antibodies to ctRNA synthetase, primarily to histidyl-tRNA synthetase (Jo-1 antibodies), are detected in the serum. They are especially often detected in combination with polymyositis and inflammatory arthritis and, to a lesser extent, with Raynaud's phenomenon. Other antibodies, such as Mi2 antibodies (to nuclear helicase) or SRP (signal recognition particle - antibodies directed against one of the components of the cytoplasm), can correlate with the rate of disease progression, but their pathogenetic significance remains unclear.

EMG findings in inflammatory myopathies are important but not always specific. In polymyositis and dermatomyositis, motor unit potentials are reduced in amplitude and duration, and short-term polyphasic motor unit potentials are usually present, especially in the proximal muscles. Moreover, these diseases may exhibit increased needle insertion response, fibrillation potentials, and positive sharp waves. Similar changes in the form of short-term polyphasic motor unit potentials, fibrillation potentials, positive sharp waves, and increased electrical excitability are also observed in inclusion body myositis in both proximal and distal muscles, and these signs are often asymmetric. A mixed pattern of changes, characterized by a combination of short-term low-amplitude motor unit potentials characteristic of myopathy and prolonged high-amplitude motor unit potentials characteristic of neurogenic disease, is characteristic of inclusion body myositis. In some muscles, EMG may reveal signs characteristic of myopathy, while in others, signs characteristic of neurogenic damage. However, EMG changes by themselves do not allow reliable differentiation of inclusion body myositis from polymyositis and dermatomyositis.

Muscle biopsy is of great diagnostic importance and allows to clarify the nature and extent of the inflammatory process. In all three diseases, such signs characteristic of myopathy as variations in the diameter of muscle fibers, the presence of necrotic and regenerating fibers, and proliferation of connective tissue are revealed. In dermatomyositis, perivascular inflammation with diffusely scattered inflammatory cells in the perimysium is especially pronounced, while inflammatory changes in the endomysium are less pronounced. The concentration of inflammatory lymphocytes (B- and CD4+-lymphocytes) is highest in the perivascular zones and minimal in the endomysium. One of the characteristic features of dermatomyositis is that signs of degeneration and regeneration are revealed in the endothelial cells of intramuscular vessels, and characteristic microtubular inclusions are revealed during ultrastructural examination. In dermatomyositis, but not in polymyositis and inclusion body myositis, perifascicular atrophy of type 1 and 2 fibers is often detected.

In polymyositis, inflammatory cells are also localized perivascularly, in the perimysium and endomysium, but the endomysium is more significantly involved. Macrophages and CD8+ lymphocytes predominate in the infiltrate, and there are only a small number of B lymphocytes surrounding the non-necrotic muscle fibers. Thus, in polymyositis, there are fewer B lymphocytes and T helpers in the perimysium and endomysium than in dermatomyositis, and there are no pronounced signs of vasculopathy, endothelial cell damage, or perifascicular atrophy. In polymyositis, patients often do not respond to immunosuppressive therapy, and repeated muscle biopsy often reveals histological signs of myositis with inclusions.

Inclusion body myositis may show angular fibers and variations in muscle fiber diameter, and the extent of inflammatory changes may also be variable. Infiltrates in the endomysium resemble those seen in polymyositis with activated CD8+ lymphocytes and macrophages, but without B lymphocytes. However, changes in muscle fibers in inclusion body myositis are different from those seen in polymyositis. Inclusion body myositis shows cytoplasmic vacuoles surrounded by basophilic material in the fibers. An intriguing feature of muscle pathology in inclusion body myositis is its striking similarity to changes in the brain in Alzheimer's disease. Eosinophilic inclusions are often found near the vacuoles. These are congophilic inclusions that react with antibodies to beta-amyloid, beta-amyloid precursor protein, and ubiquitin and apolipoprotein E. Paired convoluted filaments that react with antibodies to hyperphosphorylated tau protein, as in the brain in Alzheimer's disease, are also found. Muscle biopsies from patients with hereditary inclusion body myositis also typically show rimmed vacuoles and congophilia, although hereditary inclusion body myositis differs from sporadic cases in immunoreactivity to phosphorylated tau protein.

It is important to note that the muscle involvement in inclusion body myositis is not specific. Chronic dystrophies such as oculopharyngeal dystrophy also show cytoplasmic inclusions that stain for amyloid and ubiquitin, and rimmed vacuoles are found in Welander's distal muscular dystrophy. The presence of rimmed vacuoles, inflammatory changes, and typical cytoplasmic and nuclear filamentous inclusions may also be seen in patients with inclusion body myositis who have atypical clinical manifestations. Four patients have been described, one with scapuloperoneal syndrome, one with postpoliomyelitis-like syndrome, and two with concomitant immune-mediated diseases. Two of them responded to high-dose corticosteroids. These reports indicate that much remains to be learned about the clinical spectrum of inclusion body myositis.

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