Inclusion body myositis and hereditary inclusion body myopathy

Introduction to inclusion body myositis and hereditary inclusion body myopathy Inclusion body myositis (IBM) is a chronic inflammatory myopathy. Its main pathological feature is the inclusion of tubular filament inclusions in the sarcoplasm or muscle nucleus. In 1971, Yunis first used this name. In 1978, Carpenter summarized the clinical and pathological features of 14 cases of IBM, and officially established IBM as an independent disease. In 1995, Griggs and others published a special article, which presented IBM clinical and experimental. The laboratory diagnostic criteria further define the clinical pathology concept of IBM. In 1993, Askanas et al. showed that the clinical pathological findings were very similar to those of inclusion body myositis, but the muscle vacuole pathology lacked inflammatory cell infiltration. A group of spheroidal vacuole myopathy was called hereditary inclusion body myopathy (h-IBM). Because inclusion body myositis is mostly sporadic, people are used to call sporadicin bodymyositis (s-IBM) in order to distinguish it from h-IBM. basic knowledge Sickness ratio: 15%-28% Susceptible people: no specific people Mode of infection: non-infectious Complications: difficulty swallowing acne

Inclusion body myositis and hereditary inclusion body myopathy

(1) Causes of the disease

The exact pathogenesis of s-IBM is still unknown. Chou suspected that the inclusion body was a mucovirus product, and later found that the inclusion body can bind to measles virus antibodies, but the relationship between s-IBM and viral infection has not been confirmed.

Arahata used immunoelectron microscopy to study the immune mechanism of s-IBM. It was found that s-IBM mononuclear cells invaded non-necrotic fibers and endothelium mononuclear cells infiltrated with more myositis (PM). Dermatomyositis (DM) and Duchenne muscular dystrophy (DMD) are more common, suggesting that s-IBM may be associated with autoimmune abnormalities.

(two) pathogenesis

Oidfors' analysis of s-IBM mitochondrial DNA (mtDNA) found that about 47% of s-IBM has multiple mtDNA deletions, and this change in mtDNA cannot be explained by factors such as age or secondary inflammation, DiMauro believes Multiple mtDNA deletions in s-IBM may be caused by a disruption in the link between nuclear DNA and mtDNA, and suggest that this change in mitochondria plays an important role in the etiology of muscle degeneration and weakness.

In the study of the pathogenesis of s-IBM, changes in the nucleus, especially nuclear matrix changes, have received more and more attention. Nonaka proposed s-IBM, DMRV, oropharyngeal muscle in myopathy with rimmed vacuoles. Malnutrition, SjÖgren syndrome, etc., often have significant changes in the nucleus, indicating that there is some relationship between the two in terms of pathophysiological mechanisms. Karpati has observed ultrastructural observation of tubular filament inclusions in the nucleus, nuclear disintegration and The characteristic pathological changes of s-IBM such as the rimmed vacuoles thus formed are related to the muscle nucleus.

Askanas et al. used gold immunolocalization to find a variety of abnormal proteins in the vacuole fibers similar to those found in Alzheimer's disease. These proteins include beta amyloid, beta amyloid precursor protein, and ubiquitin (u-biquitin). ), prion protein (PrP), Tau protein, -antichymotrypsin and apolipoprotein E (Apo E), PrP-mRNA and -APP-mRNA are also increased, and some mRNAs are overexpressed and The production of abnormal proteins suggests abnormalities in the muscle DNA.

In conclusion, once the nucleus changes, as the starting cause of s-IBM is confirmed, then s-IBM inflammatory changes may be a secondary response.

1. The main muscle pathological changes of s-IBM under light microscope

(1) rimmed vacuoles or 1 ined vacuoles, which are often located in the submucosa or in the center of the muscle fibers, and are round, polygonal or irregular, with a diameter of 2 to 25 m. HE or MGT staining shows the deposition of granular basophilic material at the edge of the vacuole, and the rim or lining vacuole is named after it.

(2) Infiltration of muscle membrane cells or invasion of non-necrotic fibers by monocytes.

(3) Groups of atrophic fibers with an average of 2 groups per low power field of view.

(4) eosinophilic inclusion body, which is a circular inclusion body, HE stained with red, often located around the rimmed vacuoles, generally no more than 3 slices per slice, the frequency of occurrence of the above four pathological changes is 100% 96%, 92%, and 58%, the first three were 88%, and the four were 46%. Other pathological changes included single muscle fiber necrosis, large and loose muscles, and submuscular sarcoplasmic alkaloids. The accumulation of granules and Congo red staining revealed an orange-yellow amyloid substance observed under a fluorescence microscope.

Electron microscopy showed that the rimmed vacuoles were filled with a large amount of myeloid material and granular filament structure. The characteristic ultrastructural pathological changes of s-IBM were tubular filament containing inclusions in the sarcoplasm or muscle nucleus. The inclusion body is composed of coiled double filaments, the outer diameter of the filament is 10-20 nm, the inner diameter is 6-8 nm, the length is 1-5 m, and sometimes the 5 nm wide transverse stripes are visible thereon, and the filaments may be parallel or centripetal to each other. Arrangement, can also be disordered, surrounded by glycogen granules, irregular myeloid structures, membrane fragments and other organelle decomposition products, and a 6 to 10 nm diameter amyloid fiber can be seen in the cytoplasm. It is not easy to find the inclusion bodies in the form of flocculent unstructured materials. It is not easy to find inclusion bodies under electron microscope. First, semi-thin sections should be positioned under the light microscope. At least 3 vacuolar fibers should be selected. After careful observation, the inclusion bodies can be found. The changes of mitochondria include the quantity. Increased and intraorbital crystal-like inclusion body formation, Arahata and Engel applied immunoelectron microscopy studies found that s-IBM mononuclear cells are common for non-necrotic fiber invasion, invasive non-necrotic fiber cytoplasm and myofibril Often squeezed is partially substituted, it can cause serious damage throughout the muscle fibers.

Since Askanas proposed the name of hereditary inclusion body myopathy (h-IBM) in 1993, the relationship between h-IBM, s-IBM and distal myopathy has caused widespread interest due to these three types of myopathy. The common pathological feature is the formation of vesicle vacuoles in the muscle fibers, so there has been much debate in the concept of disease and clinical pathology.

2.h-IBM's meaning The 1997 Mediterranean Muscules Association hosted the h-IBM Symposium. The results of the meeting agreed that h-IBM should include three one-sided meanings.

(1) The pathology of muscle biopsy revealed the formation of edging vacuoles and inclusion bodies in the nucleus, similar to s-IBM.

(2) Muscle biopsy pathology without inflammatory cell infiltration, this point can be identified with s-IBM.

(3) There are family genetic characteristics, which are autosomal dominant or recessive inheritance.

The rimmed vacuole myopathy, which occurs in Persian (Iranian) Jews, is a classic h-IBM. According to this definition, h-IBM should also include some distal myopathy, as reported by Japan. Distal myopathy with rimmed vacuole (DMRV), Welander type distal myopathy reported in Sweden and Finnish type distal myopathy or tibialis dystrophy (ahterior tibial muscular dystrophy).

Muscle pathological changes in s-IBM and h-IBM, in addition to the latter without inflammatory cell infiltration, also differ in the cytochemical properties of inclusion bodies. Askanas et al. found SMI-31 monoclonal that specifically binds to phosphorylated neurofilaments. The antibody can simultaneously label s-IBM and h-IBM inclusion body filaments (PHF), while the other monoclonal antibody SMI-31 can only bind to s-IBM inclusion body filaments, and almost no with h-IBM Combine.

In addition, s-IBM muscle biopsy specimens were stained with Congo red, and observed by fluorescence microscopy, orange-yellow amyloid was found, while in h-IBM, Congo red-positive amyloid was rarely found. Different chemical characteristics can be used to identify s-IBM and h-IBM.

Inclusion body myositis and hereditary inclusion body myopathy prevention

There is no effective prevention method, symptomatic treatment, and strengthening clinical medical care, which is an important part of improving the quality of life of patients.

Inclusion body myositis and hereditary inclusion body myopathy complications Complications, dysphagia, acne

No special records, limb weakness, long-term bed rest and difficulty swallowing, can lead to hemorrhoids and lung infections.

Inclusion body myositis and hereditary inclusion body myopathy symptoms Common symptoms Reflex disappeared knee, tendon reflex decreased dysphagia

Inclusion body myositis (s-IBM) is insidious and slowly progressing. The first symptom of 70% of patients is proximal weakness of the lower extremity. It can also be the distal end of the lower extremity, the upper limb or the extremities are evenly unable to start, and the muscle weakness can be symmetrical or asymmetrical. As the disease progresses, the distal muscle weakness can reach 50%, but only 35% of the distal weakness is at or above the proximal weakness, and some patients' muscle weakness and muscle atrophy can be limited to certain muscle groups, such as the chest. Locking mastoid muscle, upper limb muscles, lower quadriceps, etc. The most susceptible muscles are biceps, triceps, iliopsoas, quadriceps and tibia muscles, fingers, wrist extensors Early involvement is easy, and deltoid, pectoralis major, interosseous muscle, cervical flexor, gastrocnemius and flexor digitorum are less involved, about 20% of patients with neck muscles are involved, and 1/3 of patients may have facial muscle involvement In the orbicularis oculi muscle, dysphagia is more common, about 30% of patients have dysphagia at the time of treatment, the latter mostly caused by upper esophageal and pharyngeal muscle dysfunction.

The tendon reflex is often reduced, especially knee and sacral reflexes are the most common. When combined with peripheral neuropathy, there may be sensory disturbances. 20% of patients have muscle pain. If there is difficulty in swallowing, it is difficult to distinguish between clinical and polymyositis.

Inclusion body myositis and hereditary inclusion body myopathy

Serum muscle enzyme test s-IBM serum CK levels can be normal or slightly increased, generally not more than 10 to 12 times the normal value.

Electromyography s-IBM's EMG characteristics are similar to those of PM-DM, showing increased spontaneous activity, short-term exercise unit potential and multiphase waves, the difference is s-IBM long-term and short-term The motor unit can appear simultaneously on the same muscle, which is called mixed electric potentials.

Diagnosis and differentiation of inclusion body myositis and hereditary inclusion body myopathy

s-IBM should be differentiated from chronic polymyositis, amyotrophic lateral sclerosis (ALS), progressive spinal muscular atrophy, chronic GBS, and some late-onset distal myopathy.

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