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Inclusion body myositis


1 History inclusion body myositis (inclusion body myositis, IBM) is a chronic inflammatory myopathy. The main pathological features or muscle sarcoplasmic tubular filaments within the nuclear inclusion bodies. Yunis [1] IBM first proposed the name of the disease. Prior to Adams [2] reported 1 case of other intracellular inclusion body myopathy muscle, such inclusion bodies in the light microscope, and Yunis described the inclusion bodies are similar. Later Chou [3] in 1 case of chronic polymyositis patients found that inclusion bodies in muscle, when the virus-like structure called sticky. Until 1978, Carpenter [4] of 14 patients with clinical and pathological features of IBM are summarized, and IBM formally established as a separate disease. Since then IBM has a large number of clinical and pathological report, and in immune pathology, molecular biology, cell chemistry and conducted in-depth research. Recently, Griggs [5] and other published article, IBM presented the clinical and laboratory diagnostic criteria, and further established the IBM concept of clinical pathology. 2 clinical manifestations 2.1 incidence and age of onset [6 ~ 8] IBM clinic is not uncommon, accounting for 15% of inflammatory myopathy ~ 28%. Male predilection to female ratio was 3:1. After more than 50 years old to 20 years but can be early onset. Lotz reported mean age at onset was 56.1 years. Chou [9] and Eisen [10] reported 20 to 30 years old and 60 to 70 years of age is the age incidence of the two peaks. China currently has not been confirmed by electron microscope IBM case reports, this is not necessarily that of IBM rare, probably not popular with the electron microscope and observation method to poor. IBM and more distributed, but since 1988, Coll reported, after a family of IBM, there are a number of familial cases reported [11,12]. IBM is related to inheritance, is still not sure. 2.2 MG features [6 ~ 8] IBM occult onset, slow progress, about 70% of the first symptom of the proximal lower limb weakness, but also for distal lower extremity, upper extremity or limb weakness uniform onset. Weakness can be symmetrical or asymmetrical, with the progress of the disease, up to 50% distal muscle weakness, but only 35% of the extent of its inability to reach remote or more proximal weakness. Muscle is most likely affected biceps, triceps, iliopsoas, quadriceps and anterior tibial muscles, and deltoid, pectoralis major, interosseous muscle, neck flexors, gastrocnemius and toe flexion muscle affected less. 2.3 Other symptoms and signs [6 ~ 8] tendon reflexes are often reduced, especially in patellar reflex decreased the most common. A small number of patients may have sensory dysfunction. Dysphagia is more common, about 50% of patients during treatment has been found difficulty swallowing. The latter multi-ring from the upper esophageal and pharyngeal muscle dysfunction caused. 2.4 complications [6] IBM is often associated with other diseases, according to their order of occurrence rates of cardiovascular disease, peripheral neuropathy, diabetes, autoimmune diseases, including interstitial pneumonia, psoriasis disease, lupus erythematosus and dermatomyositis. Between these complications and whether the cause of IBM's contact is not yet certain. 3 laboratory 3.1 electromyography (EMG) [6 ~ 8] IBM's EMG characteristics and PM / DM is similar to the performance of abnormal spontaneous increased sexual activity, short duration motor unit potentials and multi-phase wave increased. The difference is that IBM long range and short duration motor unit potentials can be simultaneously in the same muscle, which is called the mixed potential (mixed potentials). Mixed potential common denervation, but Lotz that IBM's mixed potential and independent of neurogenic damage. 3.2 muscle enzymes [5,6] IBM's serum CK level may be normal or slightly increased, generally no more than the normal 10 to 12 times. 3.3 muscle biopsy [4 ~ 8] under the light microscope IBM muscle pathology are: (1) rimmed vacuoles (rimmed vacuoles) or lined cavity (lined vacuoles). The cavity is usually located under the sarcolemma or muscle fiber central, circular, polygonal or irregular shape, a diameter of 2 ~ 25 μm. HE staining showed granular basophilic material edge cavity deposition, trim or lining which is named after the bubble. (2) intramuscular meningitis monocyte cell infiltration or invasion of non-necrotic fibers. (3) groups of atrophic fibers, the average visible under low magnification 2 groups. (4), eosinophilic inclusion bodies, a circular inclusion, HE staining red, often located around the rimmed vacuoles, each section is generally not more than 3. Pathological changes of more than 4 frequencies were 100%, 96%, 92% and 58%, the first appearance of 3 was 88%, 4 while only 46% appeared. Other pathological changes include a single muscle fiber necrosis, muscle nuclear large and loose, under the sarcolemma sarcoplasmic accumulation within the basophilic granules, and Congo red staining, observed under fluorescence microscope can be found dyed orange amyloid. IBM characteristic electron microscope, pathological changes or muscle sarcoplasmic tubular filaments within the nuclear inclusion bodies (tubulofilament containing inclusions), that inclusion bodies formed by the coiled tubular filaments, fine wire diameter of 10 ~ 20 nm, inner diameter of 3.6 ~ 8 nm, length of 1 ~ 5 μm. Sometimes it can be seen on the 5 nm wide stripes, high-resolution electron microscope, filaments from the 3 ~ 4.5 nm wide subunit from close succession. Sarcoplasmic inclusion bodies within the nucleus may come from muscle, filaments were parallel to each other or can be concentric arrangement can also be disorderly. Often surrounded the surrounding glycogen granules, irregular myelin, membrane fragments and cytoplasm of the decomposition products. Can also be seen in the cytoplasm of a diameter of 6 ~ 10 nm fiber and flocculent amyloid aggregation of unstructured material. Inclusion bodies under the electron microscope is not easy to find should do first semi-thin sections under light microscope positioning, at least choose three vacuolar fibers, inclusion bodies can be found by careful observation. IBM in the electron microscope, nuclear disintegration, and its contents released into the cytoplasm, some scholars believe that rimmed vacuoles is the result of decomposition of the nucleus. The changes include increasing the number of mitochondria and crystal-like inclusion bodies formed within the ridge. Capillary endothelial cells become apparent, the phenomenon brewing active. Arahata and Engel [13,14] found that immuno electron microscopy, IBM monocyte invasion of non-necrotic fibers common phenomenon, the non-necrotic fibers were invaded muscle fiber cytoplasm and are often partially replaced by crushed and seriously may cause the entire muscle fiber damage. 4 diagnostic criteria Carpenter [4], Ringel [15] and Lotz [6] had a history of clinical and pathological proposed diagnostic criteria for IBM, but has been is not universally accepted. Recently, Mendel et al [5] on the recent research results are summarized, presented a more detailed diagnostic criteria. 4.1 characteristic performance (1) clinical characteristics: 1) duration> 6 months; 2) age of onset> 30 years of age; 3) MG: involving the upper and lower limbs must be near local and remote, the performance of patients with at least one of the following: ① flexor weakness; ② wrist flexion was unable to afford more wrist; ③ quadriceps weakness (equal to or less than 4). (2) laboratory features: 1) serum CK less than 12 times the normal value; 2) Muscle biopsy: ① inflammatory myopathy with mononuclear cell invasion of non-necrotic fibers; ② cavity fiber; ③ the following two one of: (a) intracellular amyloid deposits (Congo red staining required observed under fluorescence microscope); (b) electron microscope found that 15 ~ 18 nm tubular filaments of inclusion bodies; (c) EMG consistent with inflammatory muscle disease characteristics (but common long-time potential). (3) family history: a small number of patients have family history. 4.2 IBM-related diseases can occur simultaneously with other diseases, particularly autoimmune diseases. 4.3 IBM's diagnostic criteria (1) diagnosis of IBM: All patients showed pathological features of muscle biopsy. IBM muscle biopsy confirmed upon any clinical manifestations and other laboratory tests are not able to its negation. (2) suspected IBM: IBM if the patient only has a pathological inflammatory changes in diagnostic criteria, that is non-mononuclear cells on the invasion of necrotic fibers, combined with clinical compliance (1) 1), 2), 3), laboratory Check the match (2) 1), 3) was suspected IBM. 5 pathogenesis IBM precise mechanism is still unknown. Chou [3,9] have been suspected of virus inclusion bodies is a sticky product, and later discovered that the measles virus antibody combined with IBM's inclusion, but the IBM and the relationship between viral infection has not been affirmed. Arahata [13,14] by immune electron microscopy of IBM's research found that the immune system,[link widoczny dla zalogowanych], IBM monocyte invasion of non-necrotic fibers and endomysial infiltration of mononuclear cells compared with PM, DM and DMD common. But the exact mechanism for this phenomenon is not clear. Oldfors [10] on IBM mitochondrial DNA (mtDNA) analysis of the study found that about 47% of IBM has multiple mtDNA deletion. This change in mtDNA can not use age or secondary to inflammation and other factors to explain. DiMauro [5] that IBM may appear multiple mtDNA deletion and mtDNA from nuclear DNA link between the disruption caused, and that this change in mitochondrial degeneration and weakness in the muscles play an important role in the etiology. in the pathogenesis of IBM, the muscle changes, especially the nuclear changes in nuclear matrix more and more attention. Ultrastructure within the tubular filament inclusion bodies of nuclear, nuclear disintegration and the resulting characteristics of IBM, rimmed vacuoles and other pathological changes were associated with muscle nuclear-related. Immuno-gold methods used in the vacuole is similar to fiber found in many brain of Alzheimer patients appear abnormal proteins. These include the β amyloid protein, β amyloid precursor protein, pan-protein (ubiquitin), prion protein (prion), Tau protein and apolipoprotein E (ApoE) [16,17]. These also suggest that abnormal protein production abnormal muscle expression of the nuclear DNA. In short, once the muscle nuclear changes