Inflammatory myopathies: diagnosis

Diagnosis of inflammatory myopathies

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. When the level of serum enzymes does not correlate with clinical status, especially after immunosuppressive therapy and plasmapheresis, clinical signs, such as muscle strength, are more reliable indicators of disease progression and treatment effectiveness. In case of myositis with inclusions, serum CK level usually remains within the norm and, therefore, can not serve as an indicator of the effectiveness of treatment. In 20% of patients with polymyositis in the serum, antibodies to ctRNA synthetase are detected, primarily to histidyl-tRNA synthetase (Jo-1 antibodies). Especially often, they are detected with a combination of polymyositis with inflammatory arthritis and, to a lesser extent, with the phenomenon of Raynaud. Other antibodies, for example, 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, however their pathogenetic value remains unclear.

EMG data for inflammatory myopathies are important, but not always specific. With polymyositis and dermatomyositis, the potentials of the motor units are reduced in amplitude and duration, usually short-term polyphase potentials of the motor units are present, especially in the proximal muscles. Moreover, with these diseases, the reaction to needle administration, potentials of fibrillation and positive acute waves are possible. Similar changes in the form of short-term polyphasic potentials of motor units, fibrillation potentials, positive acute waves and increased electrical excitability are also observed in myositis with inclusions in both proximal and distal muscles, and these signs are often asymmetric. A mixed type of change characterized by a combination of short-term low-amplitude potentials of motor units characteristic of myopathy and long high-amplitude potentials of motor units characteristic of a neurogenic disease is characteristic of myositis with inclusions. In some muscles, EMG can detect signs characteristic of myopathy, and in others - characteristic for neurogenic lesions. However, changes in EMG alone do not reliably differentiate myositis with inclusions from polymyositis and dermatomyositis.

A muscle biopsy has an important diagnostic value and allows us to clarify the nature and prevalence of the inflammatory process. In all three diseases, such characteristic for myopathy symptoms as a variation in the diameter of muscle fibers, the presence of necrotic and regenerating fibers, the proliferation of connective tissue are revealed. With dermatomyositis, perivascular inflammation with diffusely diffused inflammatory cells in perimisia is especially pronounced, whereas inflammatory changes in endomysia are less pronounced. The concentration of inflammatory lymphocytic cells (B- and CD4 + lymphocytes) is highest in the perivascular zones and is minimal in endomysia. One of the characteristic features of dermatomyositis is that in the endothelial cells of intramuscular vessels signs of degeneration and regeneration are revealed, and in the case of ultrastructural research, characteristic microtubular inclusions. With dermatomyositis, but not with polymyositis and myositis with inclusions, peri-fascicular atrophy of fibers of the 1st and 2nd types is often detected.

In polymyositis, inflammatory cells are also localized perivascularly, in perimisia and endomisis, but endomysia is involved more significantly. The infiltrate is dominated by macrophages and CD8 + lymphocytes and there is only a small number of B-lymphocytes surrounding non-necrosis muscle fibers. Thus, with polymyositis, there are less B-lymphocytes and T-helpers in perimisation and endomisis than with dermatomyositis, there are no significant signs of vasculopathy, lesions of endothelial cells, or perifascicular atrophy. With polymyositis, patients often do not respond to immunosuppressive therapy, and repeated muscular biopsy often reveals histological signs of myositis with inclusions.

In myositis with inclusions, angular fibers and variations in the diameter of muscle fibers can be detected, and the incidence of inflammatory changes is variable. Infiltrates in endomysia resemble infiltrates in polymyositis with activated CD8 + lymphocytes and macrophages, but without B-lymphocytes. However, changes in the muscle fibers with myositis with inclusions are different than in the case of pylmiosis. In myositis with inclusions in the fibers, cytoplasmic vacuoles surrounded by basophilic material are detected. The intriguing feature of muscle pathology in myositis with inclusions is a surprising resemblance to changes in the brain in Alzheimer's disease. Near the vacuoles, eosinophilic inclusions are often detected. These are congophilic inclusions reacting with antibodies to beta-amyloid, beta-amyloid precursor protein and ubiquitin and apolipoprotein E. Coupled crimped filaments that react with antibodies to hyperphosphorylated tau protein, as well as in the brain in Alzheimer's disease, have also been identified. When muscle biopsies in patients with a hereditary form of myositis with inclusions, vacuoles with a rim and congophilia are also usually detected, although the hereditary cases of myositis with inclusions are different from sporadic by immunoreactivity on the phosphorylated tau protein.

It is important to note that muscle damage in myositis with inclusions is not specific. In chronic dystrophies, for example, oculopharyngeal dystrophy, cytoplasmic inclusions that perceive coloration on amyloid and ubiquitin are also detected, and surrounded by vacuoles with rim are found in distal muscular dystrophy of Welander. The presence of vacuoles with a rim, inflammatory changes, typical cytoplasmic and nuclear filamentous inclusions, can be noted in patients with myositis with inclusions with atypical clinical manifestations. Four patients are described, one with scapulo-peroneal syndrome, the other with post-poliomyelitis-like syndrome, two with concomitant immune-mediated diseases. Two of them have a positive effect from a high dose of corticosteroids. These reports show that we still have much to learn about the clinical spectrum of myositis with inclusions.

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