What Are the Treatments for Inflammation Pain?

There are two main categories, one is infectious myopathy with a clear etiology, such as viral myositis, parasitic myositis, and tropical myositis, and the other is the so-called idiopathic disease with unknown etiology but related to autoimmunity. Idiopathic inflammatory myopathies (IIMs) include polymyositis (PM), dermatomyositis (DM), and inclusion body myositis. This section mainly introduces IIMs.

Wang Min	(Attending physician)	Department of Neurology, Xuanwu Hospital, Capital Medical University
Wu Yuwei	(Chief physician)	Department of Neurology, Xuanwu Hospital, Capital Medical University

Inflammatory myopathy is a group of heterogeneous diseases with skeletal muscle inflammatory cell infiltration and muscle fiber necrosis as the main pathological features. Although belonging to the same disease spectrum, different types of inflammatory myopathy can affect different target organs such as skin, lung and muscle, so the clinical manifestations are more complicated.

Western Medicine Name: Inflammatory myopathy
English name: inflammatory myopathy

Affiliated Department: Internal Medicine-Neurology
Whether to enter health insurance: Yes

Classification of inflammatory myopathy diseases

Pathogenesis of inflammatory myopathy

The muscle pathology of patients with PM, DM, and IBM shows infiltration of activated lymphocytes in muscle tissue, peripheral blood lymphocytes are sensitive to muscle antigens, and have obvious cytotoxic effects on cultured muscle cells. These all indicate that inflammatory myopathy and itself Immune-related but different immunopathological mechanisms.

1. Toxicity of T cells is the main pathway of PM muscle fiber injury. The expression of major histocompatibility antigen complex- (MHC-) in muscle fibers of PM patients is significantly increased. MHC- molecules can present autoantigens to sensitized CD8 +. T lymphocyte receptors on the surface of T cells activate CD8 + T cells under the action of co-stimulatory factors on the surface of muscle cells. Activated CD8 + T cells release perforin and granzyme, leading to muscle fiber necrosis . The intercellular adhesion molecule and interleukin-1 are closely related to the infiltration of inflammatory cells.

2. The onset of DM is mainly related to humoral immune abnormalities. Microvessels in muscle tissues are directly affected. Antibodies against their own target antigens can directly affect capillary endothelial cells, activate C3 complement, and form C3b, C3bNEO, C4b fragments, and C5b-9 membrane lysis attacks. Complex (MAC), which causes swelling, vacuolar degeneration, necrosis, and perivascular inflammation of capillary endothelial cells.

3 The presence of muscle fibrosis and autoimmune abnormalities in the muscle tissue of IBM. IBM's pathogenesis is not only related to PM-like T cell-mediated cytotoxicity, but also to muscle fiber degeneration itself. The two interact. Proinflammatory cytokines are not only related to the infiltration of myositis cells, but also induce tau phosphorylation, amyloid accumulation, and lens protein formation. At the same time, they can stimulate muscle fibers to produce inflammatory mediators to form their own amplification mechanism, further promoting chronic inflammation and starch. Like substance formed.

Clinical manifestations of inflammatory myopathy

PM is more common in adults over 18 years of age, and rare in children. Subacute or chronic onset, mainly manifested by weakness of the proximal limbs, arms can not be raised flat, difficulty standing up after squatting. The disease progressed slowly, and the neck muscles were gradually involved, especially the cervical flexor muscle, which was manifested by laborious efforts of the patient to lie on his back. Swallowing difficulties are more common and are mainly caused by involvement of the larynx and low muscle strength in the upper 1/3 of the esophagus. Severe cases can involve the trunk muscles and respiratory muscles, causing the patient to be bedridden and have difficulty breathing. Muscle pain and tenderness are more characteristic clinical manifestations of PM, but only about 25% of patients have significant myalgia or tenderness. Other systemic symptoms include loss of appetite, weight loss, fever, Raynaud's phenomenon, joint pain, and interstitial pneumonia. Muscle atrophy is rare in the early stages of the disease, and tendon reflexes are usually normal. Significant muscle atrophy and reduced tendon reflexes may occur in the later stages.

DM can occur in children and adults, and DM in children is more common in 4 to 14 years old. The characteristics of affected muscle distribution in patients with DM are consistent with PM. The difference between the two is that DM has obvious skin damage. Typical skin lesions include periocular edema erythema and Gottron's sign, the latter of which manifests as nodular desquamative erythema and flat papules on the extremities of the extremities, sometimes accompanied by redness of the skin around the nails and telangiectasia. Other skin lesions include butterfly-like erythema on the cheeks that resemble lupus erythematosus, and solar allergic erythema in a "V" pattern on the neck and back of the chest. Dermatomyositis can cause skin damage before muscle weakness occurs, or both. In some patients, the skin damage is transient and can return to normal within a short time. PM is often diagnosed due to lack of skin damage at the time of consultation.

When PM and DM coexist with other connective tissue diseases, it is called overlap syndrome. Common concomitant connective tissue diseases include rheumatoid arthritis, systemic lupus erythematosus, progressive systemic sclerosis, Sjogren's syndrome, Behcet's disease, mixed connective tissue disease and necrotizing vasculitis. The risk of tumors in patients with PM / DM may increase, and DM is higher than PM.

IBM is mainly seen in elderly people over 50 years of age, with hidden onset and slow progress. The first symptom of 70% of patients is weakness in the proximal lower extremity, and it can also occur in the distal, upper or extremities. Special muscle weakness and atrophy distribution, that is, proximal and distal involvement, especially biceps, triceps, forearm, lumbosacral, quadriceps, and tibialis anterior The medulla oblongata is involved; however, there are generally no facial, deltoid, pectoral, and interosseous muscles involved. The most characteristic are: weak flexor fingers; weak flexor wrist muscles weaker than extensor wrist muscles; quadriceps muscle strength is below grade . Muscle weakness can be symmetrical or asymmetrical. Tendon reflexes are often reduced, especially the knee and ankle reflexes. ^[1]

Auxiliary examination of inflammatory myopathy

Creatine creatine

Often significantly increased, reflecting the degree of muscle fiber necrosis.

Inflammatory myopathy

A few patients may have increased erythrocyte sedimentation, but it has nothing to do with the degree of muscle fiber necrosis.

Inflammatory myopathy myoglobin

Often increased, with the same significance as serum CK.

Inflammatory myopathy autoantibodies

Including myositis-specific autoantibodies (MSAs) and myositis-associated autoantibodies (MAAs). MSAs mainly include three types: anti-aminoacyl-tRNA synthetase (ARS) antibody, anti-signal recognition particle antibody and anti-Mi-2 antibody.

(1) Myositis-specific autoantibodies are highly selective and have unique clinical manifestations and genetic phenotypes. MSAs mainly target nuclear or cytoplasmic proteins involved in gene transcription, protein translation and antiviral. Aminoacyl tRNA synthetases are a group of specific cytosolic enzymes that are involved in protein synthesis. Patients who are positive for anti-aminoacyl tRNA synthetase antibodies have similar clinical symptoms, including myositis, interstitial pneumonia, polyarthralgia, fever, Raynaud's phenomenon, and manipulators, the so-called anti-synthetase antibody syndrome. Among them, Jo-1 antibody is the most common ARS antibody, and it is also the earliest specific antibody identified as idiopathic inflammatory dermatomyopathy. The signal recognition particle is a ribonucleoprotein complex located in the cytoplasm. Anti-SRP antibody-positive patients have unique clinical and histopathological characteristics. Patients often have acute onset of severe myositis with significantly increased muscle enzymes, resistance to conventional treatment, and higher mortality. However, the incidence of interstitial pneumonia in this antibody-positive patient is low, and early heart involvement is more common. The positive rate of Mi-2 antibody was 9% in PM and 20% in DM. This antibody is more common in DM and less common in PM. Mi-2 antibody-positive patients had typical DM skin lesions, including Gottron pimples, erythematous erythema, erythema of the neck V region, etc., while myositis was mild, and the incidence of interstitial pneumonia was reduced, which was more sensitive to treatment.

(2) Myositis-associated autoantibodies are a class of autoimmune diseases that are associated with idiopathic myopathy and are more common in other autoimmune diseases associated with idiopathic inflammatory myopathy. Anti-Ku antibody is a rare anti-nuclear antibody, which is more common in systemic scleroderma and PM overlap syndrome. The distribution and positive rate in different types of connective tissue diseases are different. Common clinical manifestations associated with Ku antibodies are Raynaud's phenomenon, joint pain, esophageal reflux, and myalgia. Anti-PM-Scl antibodies: Highly related to the occurrence of interstitial pneumonia and esophageal involvement, often suggesting a poor prognosis. In addition, tumors can be combined with symptoms such as manipulators, Raynaud's phenomenon, and joint pain.

Pathological characteristics of inflammatory myopathy muscle biopsy

The common pathological features of PM, DM, and IBM are muscle fibrosis, necrosis, regeneration, and inflammatory cell infiltration. The muscle fiber atrophy and necrosis of PM are mostly scattered or segmental. The inflammatory cell infiltration is mostly located in the muscular underwear. Monocytes are surrounded and infiltrated into non-necrotic muscle fibers. The muscle fiber atrophy of DM is mainly distributed around the muscle bundle. For perianal atrophy, inflammatory cell infiltration is mainly located around the blood vessels and the myofascial membranes. Intermuscular small blood vessel membranes can show the deposition of attack complexes, reduce capillary density, thicken and swell vascular endothelial cells, and narrow or occlude vascular lumen. Ultrastructural observation can reveal the accumulation of microtubules in the endothelium of endothelial capillaries. In addition to muscle fiber necrosis and inflammatory cell infiltration in IBM muscle biopsy, its prominent pathological features are: mononuclear cells infiltrate non-necrotic muscle fibers; degenerate muscle fibers show rimmed vacuoles; inclusions exist in rimmed vacuoles That is, purple stained particles in HE staining or red staining in Gomori staining; the inclusions can be observed under the myometrium or in the nucleus under electron microscopy, which are mainly piles of tube-like structures with a diameter of 18 to 23 nm. Or myeloid.

Inflammatory myopathy EMG

Abnormal EMG changes include prolonged insertion potentials, a large number of fibrillation, positive sharp waves, and myotonic-like potentials, shortening the duration of motor units, decreasing amplitudes, increasing polyphase waves, and recruiting potentials presenting pathological disturbances. ^[2]

Diagnosis of inflammatory myopathy

IIMs are diagnosed based on subacute or chronic onset of weakness in the proximal limbs, weakness of the cervical flexor muscles, difficulty swallowing, and typical skin damage. Laboratory tests showed a significant increase in serum muscle enzymes, and EMG showed myogenic damage. The final diagnosis depends on muscle biopsy to find the above-mentioned typical pathological features.

Differential diagnosis of inflammatory myopathy

Because the clinical manifestations of most IIMs are not characteristic, almost all patients with proximal muscle weakness should be identified, such as progressive muscular dystrophy, mitochondrial myopathy, lipid deposition myopathy, and proximal Spinal muscular atrophy. Inflammatory cell infiltration is an important pathological basis for the diagnosis of inflammatory myopathy, but the finding of inflammatory cell infiltration on pathological examination of muscle biopsy does not exclude the disease. Conversely, it is not found that inflammatory cell infiltration is not always IIMs, and some have severe muscle fibers Necrotic Duchenne-type, limb-girdle-type, or facial-shoulder-brachial muscular dystrophy may be accompanied by an inflammatory response to the muscle, but the latter is secondary and is different from the mechanism of inflammatory infiltration of IIMs and does not respond to hormone therapy. same. In short, the diagnosis of inflammatory myopathy needs to be considered in combination with clinical and muscle biopsy pathology. Because most PM or DM respond well to corticosteroids, in some cases experimental treatment with steroids is used as an exclusion diagnosis. It is also necessary. ^[3]

Inflammatory myopathy treatment

Except that IBM has no effective treatment at present, most PM and DM have obvious effects on immunosuppressive agents.

Corticosteroids for inflammatory myopathy

It has been recognized as the drug of choice for the treatment of IIMs, but the selection of steroid hormones, the starting dose of treatment, the mode of administration, and the rate of reduction are mostly empirical, and evidence-based medicine is lacking. A commonly used steroid hormone is prednisone. Because dexamethasone is prone to cause steroid myopathy, it is generally avoided. In recent years, high-dose methylprednisolone shock therapy has also been used to treat severe IIMs.

(1) Starting dose and usage: The starting dose of prednisone treatment is generally 1 mg / (kg · d), and 60-100 mg / d for adults. It can be taken in 3 times or once. The dosage for children is usually 2mg / (kg · d). Some severely ill patients can be treated with high-dose methylprednisolone shock. Adults receive an intravenous infusion of 500-1000mg daily for 3 consecutive days, followed by prednisone 60mg / d.

(2) Judgment of hormone reduction and efficacy: The starting dose generally lasts 1 to 3 months, most of which are 4 to 6 weeks. If there is no significant decrease in CK, it can be extended to 2 to 3 months. If CK and clinical symptoms There is still no improvement, which usually indicates that steroid treatment is ineffective or the diagnosis of myositis should be reconsidered. The principle to be followed when reducing the dose is that the speed of the decrease will decrease as the dose decreases. Began to reduce 5mg for 1 week; take another 5mg for 2 weeks; take another 5mg for 3 weeks; and so on. When 30mg / d, take 2.5mg each time until the maintenance amount of 10 ~ 15mg / d. If the initial dose is 60 mg / d, the total reduction time is 55 weeks (about 1 year). According to the curative effect and the side effects of steroids, the reduction rate can be adjusted appropriately to achieve the best curative effect with the smallest dose in the shortest time. The efficacy of steroid therapy should be determined by combining serum CK levels with clinical muscle strength tests. If steroid treatment is effective, the decline in CK is generally 4-6 weeks earlier than the improvement in muscle strength. Therefore, early assessment of efficacy depends on monitoring serum CK levels rather than clinical muscle strength tests. If the symptoms recur during the reduction, the reduction should be suspended or re-increased to the initial dose.

(3) Side effects: Common side effects include Cushing's syndrome, peptic ulcer, hypertension, diabetes, osteoporosis, ischemic femoral head necrosis and opportunistic infection. When applying steroids, anti-gastric acid preparations, potassium and calcium supplements should be added. It is recommended that patients have a low-sugar, low-fat, high-protein diet.

IIMs Treatment of refractory IIMs in inflammatory myopathy

The vast majority of PM / DM patients can obtain satisfactory results after reasonable steroid treatment, but about 20% of patients are ineffective or intolerable to steroid treatment, which is called refractory IIMs. Mainly include the following: the application of prednisone 60-100mg / d, no decrease in serum CK or improvement of muscle strength within 1 to 2 months, the so-called "steroid resistance" phenomenon; hormone-dependent, steroids The treatment is effective, but it will recur after the reduction, which necessitates long-term application of large-dose prednisone maintenance treatment. If it exceeds 3 to 6 months, it is easy to have adverse reactions and be forced to discontinue treatment. In addition, for patients with steroid resistance, the diagnosis of IIMs should be reconsidered, and the possibility of secondary inflammation and infiltration of muscular dystrophy should be ruled out. The patient cannot tolerate hormonal side effects such as severe essential hypertension, diabetes, gastrointestinal bleeding, etc., or have contraindications. For the treatment of refractory IIMs, the following methods can be used in order:

(1) Azathioprine (AZA): The commonly used dose is 2 to 3 mg / (kg · d), and the average adult dose is 100 to 200 mg / d. Half of the patients were effective. The treatment began to be effective at 2 months, and the effect was significant at 6 to 9 months. The reduction rate was 25 mg per month. After the condition was relieved, the maintenance amount was 50 mg / d. In order to reduce the amount of prednisone, sometimes AZA and prednisone combined treatment is used at the beginning. After the clinical symptoms improve, the prednisone is reduced to 15 mg / d. The magnitude of side effects of AZA is dose-dependent, and the side effects of 2 mg / (kg · d) are very small. Nausea, vomiting, bone marrow suppression, opportunistic infections, and malignant lesions are common.

(2) Methotrexate (MTX): Adult oral dose is 7.5mg 10mg / week, once administration, can also be divided into 3 times, 2.5mg each time, every 12 hours interval, increase weekly thereafter 2.5mg, until 20 to 25mg per week. It takes at least 4 to 6 weeks to take effect. Sometimes it takes 4 months. It can better control muscle inflammation and improve skin symptoms of DM. It is easier to tolerate than azathioprine. In patients who have failed steroid treatment, about 60 ~ 75% is effective for MTX. Because it is faster than AZA, it is also advocated as the drug of choice for non-steroid treatment. The method of reduction is to reduce or extend the weekly dose. Generally, the dosage interval is decreased or prolonged by 25% of the total amount, and the administration is started once every 2 weeks, and then changed to once a month. If used in combination with steroids, steroids should be reduced first, and MTX should be reduced later. The main side effects of MTX are bone marrow suppression, gastritis, diarrhea, rash, infection, hepatitis, and malignant tumors. It is dangerous for obesity, diabetes, kidney disease, elderly and alcoholics, and should be used with caution. In addition, MTX-related allergic pneumonia or pulmonary fibrosis may occur during MTX treatment, which is difficult to distinguish clinically from interstitial pneumonia caused by PM / DM, especially for rapidly progressive cases. Azathioprine and MTX can also be given a combination treatment when the treatment alone is not effective, and the effect is better than the treatment alone. These two drugs are also the main non-hormonal immunosuppressants for PM / DM.

(3) Cyclophosphamide (CTX): The oral dose is 50 200mg / d. It has been reported that high-dose shock therapy can increase efficacy and reduce side effects. Methods 1000mg CTX was added to 500 1000ml physiological saline, intravenous drip, once a week, blood routine check before use, discontinued when the white blood cell count was less than 3.0 × 109 / L, recheck after a week, continue to apply after recovery, total 8 10g. The side effects of CTX are hemorrhagic cystitis, bone marrow suppression, potential carcinogenesis, and opportunistic infections. The efficacy of CTX is uncertain, and the side effects are large. Most scholars recommend that it be limited to the treatment of patients with PM / DM with interstitial lung disease and / or severe disease.

(4) intravenous immunoglobulin: used in combination with prednisone for the first treatment of refractory myositis or severe patients. The usage is 400 mg / (kg · d) for 5 days. Once a month, it usually works after 2 infusions, with an average course of 4 months. The main side effects were aseptic meningitis, transient nausea, headache and vomiting. ^[4]

Prognosis of inflammatory myopathy

The majority of patients with IBM have a poor prognosis, and their condition is slowly progressive. The prognosis of patients with PM and DM is mainly related to the duration and age of the disease. The longer the course, the older the age, the worse the prognosis. Elderly patients with tumors, especially those with obvious lung, heart, and gastrointestinal involvement, have a poor prognosis. In general, the treatment response of DM is better than PM. After reasonable treatment, the muscle weakness symptoms of most patients with PM and DM can be improved, but almost all need maintenance treatment. About 30% of patients will have varying degrees of muscle weakness. Foreign data show that the 5-year survival rate of patients with PM and DM can reach 80%.

Prevention of inflammatory myopathy

Inflammatory myopathy should be diagnosed as early as possible and treated in time to obtain better results. Some PM / DM patients are accompanied by malignant tumors, so early detection is essential. In addition, many factors in daily life should be noted. Such as dermatomyositis patients should try to avoid sunlight, wear hats, gloves or wear long-sleeved clothes when going out. Do not eat or eat less celery, daylily, shiitake and other foods that enhance light sensitivity, as well as foods that are prone to allergies such as sea fish, shrimp, and crab. Avoid tobacco and alcohol. No lipstick, makeup, hair dye, etc. Avoid contact with pesticides and certain chemicals. According to the condition and diagnosis and treatment, regular follow-up inspections are needed to keep abreast of changes in the condition and adjust the medication according to the doctor's order.

Inflammatory Myopathy Care

The main point of nursing is to assist the patient's life care and prevent complications. Patients who cannot take care of themselves should strengthen life care, and assist and encourage patients to carry out appropriate activities and rehabilitation training to maintain muscle function and avoid contractures. For patients with swallowing disorders, a nasal feeding diet can be used to ensure sufficient energy supply and avoid lung infections caused by cough. If swallowing function is restored, semi-liquid and soft food can be given gradually, and patients should not be fed too fast. Patients with chest tightness, belching and dyspnea should pay attention to cardiopulmonary function and seek medical treatment in time to avoid delaying the timing of rescue treatment.