necrotizing myositis

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Overview: A rare disease of muscle fiber necrosis without significant inflammation.

A rare disease characterized by necrosis of muscle fibers without a significant inflammatory response, often characterized by muscle weakness, atrophy, and pain in the neck, shoulders, and hips. The cause of the disease is complex, and is primarily related to autoimmune responses, but can also be associated with drugs, toxins, and viral infections. Treatment is based on immune-suppressing medications, and removal of the harmful substances that cause the disease.

Definition

Necrotizing myositis is a rare muscle disease characterized by necrosis of muscle fibers without a significant lymphocytic inflammatory infiltrate. It usually occurs in people with autoimmune diseases or exposure to certain drugs or toxins [1-2].

Broadly defined necrotizing myositis includes immune-mediated necrotizing myositis (IMNM) and non-immune-mediated necrotizing myositis (NIMNM). Since the former accounts for the vast majority of cases, necrotizing myositis in the narrower sense, i.e., immune-associated necrotizing myositis, also known as necrotizing autoimmune myopathy, is the focus of this content.

Patients primarily present with muscle weakness and atrophy in the proximal muscles of the body, including the buttocks, thighs, upper arms, shoulders, and neck, and elevated creatine kinase levels.

Muscle weakness is usually severe and may last for days, weeks or months. It makes it difficult for the patient to climb stairs, get up from a chair or the floor, turn over in bed, lift things, comb their hair, brush their teeth, or reach over their head for something on a shelf.

The onset of the disease may be associated with certain medications, especially statins, specific autoantibodies, tumors, viral infections, or other connective tissue diseases.

The disease is difficult to cure, and treatment is based on immunosuppressive drugs, in addition to removing harmful factors such as drugs and toxins associated with the development of the disease.

Classification

Two types of specific autoantibodies are often seen in patients with IMNM, one recognizing signal recognition particles (SRP) and the other targeting hydroxy 3-methylglutaryl coenzyme A reductase (HMGCR) [1-2].

Anti-HMGCR antibodies

Anti-HMGCR antibodies are pharmacologic targets of statins. In this type of patients, the lesions are usually limited to necrosis of skeletal muscle fibers, while muscle weakness is not evident.

Dysphagia, muscle pain and fatigue may also be present.

This antibody may be associated with malignancy and tumor screening is recommended in this patient population.

Anti-SRP Antibody

Anti-SRP antibodies were the first antibodies identified as being specifically associated with IMNM.

Muscle weakness in this type of patient is often very severe, with extremely elevated creatine kinase (CK) levels.

Patients also experience dysphagia, arrhythmias or conduction blocks and cardiac insufficiency, interstitial lung disease, muscle pain and extreme fatigue.

The prognosis for this type of patient is poor, with only half of the patients regaining normal strength after four years.

Antibody negative

Some patients do not have any of the above antibodies found in their blood, but a muscle biopsy shows similar results to the above type and very similar clinical symptoms, including elevated CK levels, muscle pain and extreme fatigue.

A muscle biopsy is required to make a correct diagnosis.

Morbidity

The incidence of IMNM is estimated to be less than 1 in 100,000 [1-2].

The average age of onset is between 40-60 years.

Both anti-SRP and anti-HMGCR myopathies can occur in children and adults. Patients with anti-SRP myopathy are usually younger compared to anti-HMGCR myopathy.

The incidence rate is essentially the same in men and women.

Etiology

The etiology of necrotizing myositis is complex, and the pathogenesis has not been clearly defined; it is mainly related to autoimmune reactions, but can also be associated with drugs, toxins, and viral infections.

Causes

The etiology of this disease is complex, mainly including autoimmune reactions, but also can be associated with drugs, toxins, viral infections, etc [3-4].

IMNM is an autoimmune disease and the exact cause is not known. However, scientists have found a strong association between some genetic changes and anti-HMGCR myopathy. In adults, the DRB111:01 allele is associated with the disease. And in children with anti-HMGCR antibodies, the prevalence of the DRB107:01 allele is even higher.

Predisposing Factors

Statins are one of the risk factors for anti-HMGCR myopathy.

Viral infections may also be a predisposing factor for IMNM.

Pathogenesis

The cause of myofiber necrosis in proximal muscles of patients with this disease is unknown [1-2].

It has been found that a substance called membrane attack complex is present in the muscles of patients with IMNM, and this substance may be associated with muscle cell toxicity.

Anti-HMGCR and anti-SRP antibodies may have direct toxic effects on muscle cells, which can lead to muscle atrophy; these antibodies also increase the production of reactive oxygen species and levels of inflammatory factors, as well as decreasing the production of the regulatory immune systems IL-4 and IL-13, exacerbating muscle fiber damage.

Symptoms

Patients may experience weakness, atrophy, and muscle pain in the proximal muscles of the body, with wide variations between individuals.

Main Symptoms

Symmetric proximal muscle weakness of the extremities

Shoulder and neck muscle weakness is the first symptom.

When the proximal muscles of the upper limbs are involved, there may be difficulty in lifting the arms and inability to comb the hair and dress.

When the proximal muscles of the lower limbs are involved, it often manifests as difficulty in walking up and down stairs, squatting or standing up from a seat.

It gradually progresses to an inability to walk or stand.

Cervical flexor weakness

Difficulty in raising the head when lying down.

The head is often tilted back.

Pharyngeal muscle weakness

This is characterized by slurred speech, choking, and difficulty swallowing.

Muscle pain

Muscle pain, which may be aching or tingling, is not severe.

Other symptoms

Symptoms of lung involvement

Respiratory muscle involvement may be characterized by shallow breathing, dyspnea, and cyanosis.

Chest tightness, shortness of breath, and cough may be present in patients with combined interstitial pneumonia.

Symptoms of heart involvement

Palpitations, syncope, dyspnea, bilateral lower extremity edema, etc.

Seek medical attention

Once necrotizing myositis is suspected, it is necessary to consult a rheumatologist promptly.

The doctor will ask detailed questions about the symptoms, the onset of the disease, past medical history and related treatments.

Department of Rheumatology

Rheumatology and Immunology

Symptoms such as muscle weakness in the proximal muscles, muscle atrophy and muscle pain may occur in patients, and may vary greatly from one patient to another. Patients with symptoms should consult the Department of Rheumatology and Immunology in a timely manner.

For generalized symptoms and dysfunction, patients may also need to consult the Department of Cardiology, Department of Respiratory Medicine, and Department of Rehabilitation Medicine.

Preparation

Preparing for your visit: registering, preparing your documents, FAQs

Tips for medical treatment

Patients with mobility problems need to be accompanied during the consultation to avoid falls and injuries.

Preparation List

Symptom list

Pay particular attention to the time of onset of symptoms, special manifestations, etc.

  • Are the following symptoms present?
  • Whether muscle weakness is felt, whether there is difficulty in limb movement, site and degree of weakness.
  • Whether there are symptoms of muscle pain, the location, degree and nature of pain (e.g., tingling, aching, etc.), etc.
  • Whether respiratory symptoms such as dyspnea, lung infection, cough, etc. are present, and whether cardiac symptoms such as palpitations, chest tightness, edema, etc. are present.
  • Whether symptoms such as sore throat, throat cramps, difficulty in swallowing, dry mouth and bad breath are present.
  • Whether there are other related symptoms such as fever, malaise, weight loss, skin symptoms, etc. in order to make a thorough assessment of the condition.
  • When did these manifestations appear? Did the symptoms get progressively worse?
    • Medical History Checklist
  • Are any of the following etiologies present?
  • Has a statin drug ever been taken for cholesterol control?
  • Is there a history of disease associated with anti-HMGCR and anti-SRP autoantibodies?
  • Has there been a history of cancer or other connective tissue disease?
  • Is there a history of viral infections?
  • The doctor will also ask about the patient’s family medical history and any previous similar symptoms or illnesses.
  • Has there been any previous diagnosis or treatment? How was it treated?
    • Checklist

    Test results from the last six months, which can be brought to the doctor’s office

  • Laboratory tests: serum muscle enzyme test, creatine kinase (CK or CPK), erythrocyte sedimentation rate, autoantibody test.
  • Imaging tests: magnetic resonance imaging (MRI) of the limbs, X-ray or CT of the lungs, cardiac ultrasound.
  • Other tests: electromyography (EMG), pathology.
    • Medication list

    Medication used in the last 3 months, if available in a box or package, bring it with you to the doctor’s office

    Immunomodulatory drugs: prednisone, methylprednisolone, immunoglobulin.

    Diagnosis

    The diagnosis of necrotizing myositis is based on history, clinical manifestations and ancillary tests. Abnormalities in blood creatine kinase and autoimmune antibodies are important diagnostic values, while muscle biopsy is required to confirm the diagnosis.

    Necrotizing myositis is often differentiated from polymyositis, dermatomyositis, and inclusion body myositis.

    Diagnosis is based on

    Medical history

    History of associated diseases, family history.

    Symptoms of infection prior to the onset of the disease.

    Suffering from autoimmune disease, tumor disease.

    Taking statins before the onset of the disease.

    Clinical manifestations

    Symptoms

    Patients may experience muscle weakness, muscle atrophy and muscle pain in the proximal part of the body, with a wide range of individual differences.

    Physical signs

    The doctor will perform the following physical examination according to the patient’s condition.

  • Muscle strength examination: Observe whether the patient can accomplish movements such as lifting hands, sitting up, standing, walking, etc., and whether he/she needs assistance.
  • Muscle tone check: To find out which parts of the muscle tone change by feeling the resistance when passively flexing and extending the patient’s joints with the hands.
  • Swallowing function test: Observe whether there is choking when drinking water to assess the swallowing function.

    • Laboratory Tests

    Laboratory tests
  • Common items: including serum muscle enzyme test, creatine kinase (CK or CPK), erythrocyte sedimentation rate, autoantibody test (including antinuclear antibody, HMGCR and SRP antibody, etc.).
  • Purpose of the test: to understand the general status, whether there is muscle damage, inflammatory reaction, autoimmune antibodies, etc.
  • Precautions: Avoid strenuous exercise before blood sampling.
    • Imaging Tests

    Common imaging tests include magnetic resonance imaging (MRI) of the limbs, X-ray or CT of the lungs, and cardiac ultrasound.

  • Magnetic resonance imaging (MRI): diffuse or focal edema is seen in the thighs and lower legs.
  • Lung X-ray or CT: examination reveals flaky shadows in the lungs.
  • Cardiac ultrasound: pericardial effusion and cardiac valvular lesions can be excluded.
    • Other tests
  • Electromyography: spontaneous fibrillatory potentials and positive sharp waves are seen, polyphasic waves are increased, the time limit of motor potentials is shortened and the wave amplitude is reduced, and other manifestations of myogenic damage are seen.
  • Muscle biopsy: degeneration and necrosis of muscle fibers can be seen. The manifestation of myofiber edema vacuolike degeneration and myofibrillar lysis phenomenon. There is a small amount of lymphocyte infiltration between muscle fibers, and there can be obvious muscle fiber hypertrophy, hyperplasia and splitting phenomenon. In severe cases, the number of muscle fibers is significantly reduced.

    • Differential diagnosis

    Necrotizing myositis is often differentiated from myositis diseases that can cause muscle weakness and muscle pain [4-6].

  • Polymyositis: there are often signs of pulmonary or joint involvement. Pathologic examination shows a high degree of lymphocytic inflammation of the muscle fibers, and specific autoantibodies may be present.
  • Dermatomyositis: there are cutaneous changes such as pteronyssinus erythematosus or Gottron’s nodules; pathologic examination shows the presence of a more extensive inflammatory infiltrate and atrophy of muscle bundles; specific autoantibodies may be present.
  • Inclusion body myositis: patients are usually older and present with distal muscle weakness; muscle biopsy shows vacuolar myopathy and ring vacuole association; poor response to immunosuppressive drugs.

    • Treatment

    Therapeutic goals: eliminate or reduce inflammation, restore muscle performance and strength, reduce morbidity, and improve patient quality of life.

    Principle of treatment: Treatment is based on immunosuppressive drugs, while removing harmful substances that cause the disease.

    Drug therapy

    Commonly used drugs

    Mainly immunomodulatory drugs [5-8].

    Table 1.Commonly used drugs in necrotizing myositis

    Commonly used drugs Instructions for use Adverse reactionsPrednisone, methylprednisolone acute or severe patients can be high-dose methylprednisolone shock treatment, after stabilization can be gradually reduced to stop the drug can cause infection, osteoporosis, hypokalemia and other adverse reactionsPrednisone, methylprednisoloneAcute or severe patients can be high-dose methylprednisolone shock treatment, after stabilization can be gradually reduced to stop the drugMay cause infection, osteoporosis, hypokalemia and other adverse reactions

    Azathioprine, methotrexate azathioprine need to closely monitor blood and liver function, methotrexate there is a risk of lung damage azathioprine: anemia, leukopenia, liver damage and other adverse reactions during the use of the drug; methotrexate: bone marrow suppression, liver damage and gastrointestinal symptoms during the use of the drug, and other adverse reactions

    Azathioprine, Methotrexate

    Azathioprine requires close monitoring of blood and liver function; methotrexate poses a risk of lung damage

    Azathioprine: anemia, leukopenia, liver damage and other adverse reactions during use; methotrexate: myelosuppression, liver damage and gastrointestinal symptoms and other adverse reactions during use

    Gammaglobulin can be used in combination with other therapeutic drugs nausea, vomiting, dizziness, but can be relieved on their own

    Immunoglobulin C

    May be used in combination with other therapeutic agents

    Nausea, vomiting, dizziness, mostly self-resolving

    Rituximab is usually used as an anti-SRP in patients who do not respond to the above drugs Patients may have allergic reactions, infections, fatigue, headache, nausea, vomiting, etc.

    Rituximab

    Rituximab is usually used in anti-SRP patients who do not respond to the above medications.

    May have allergic reactions, infection, fatigue, headache, nausea, vomiting, etc.

    Medication precautions

    Suspension of statins, such as atorvastatin and simvastatin, is usually required.

    During the medication period, you should strictly follow the doctor’s instructions, do not change the drug dosage without authorization or stop the medication suddenly to ensure that the treatment plan is implemented.

    Do not believe in unidentified treatments such as local remedies, secret prescriptions, or biased prescriptions.

    Prognosis

    The disease is difficult to cure, and the prognosis depends on a variety of factors such as severity and timing of treatment.

    Cure

    The disease is difficult to cure and muscle symptoms usually recover more poorly than in other types of myositis.

    Even with standardized drug therapy, muscle weakness symptoms persist in a significant proportion of patients.

    Half of these patients with anti-SRP antibodies and anti-HMGCR antibodies still have significant muscle weakness after 2 years of treatment.

    Prognostic Factors

    Age is the factor most associated with prognosis, and children are more difficult to treat than adults.

    Hazards

    Weakness of the limbs, muscle pain, difficulty in lifting the head, joint pain and other symptoms often occur, which can seriously affect normal work and life.

    If glucocorticoids are taken for a long period of time, they are prone to infections, osteoporosis, hypokalemia, hypertension, hyperglycemia, hyperlipidemia and other serious adverse effects, which further affect the health and quality of life.

    Those with esophageal, pharyngeal and respiratory muscle involvement or interstitial lung fibrosis have a poor prognosis.

    Daily

    As a rheumatic immune disease, patients with necrotizing myositis have special precautions in diet and life.

    Regular use of statins and antiviral drugs, avoidance of exposure to organophosphorus pesticides, and prompt treatment of the underlying disease can help reduce the risk of morbidity.

    Daily Management

    Dietary management

    It is advisable to choose a diet high in protein and vitamins and rich in potassium and calcium.

    For those with dysphagia, try to sit when eating and avoid hard, dry and rough food. When choking on drinking water occurs, medication and food should not be forced.

    Patients with severe dysphagia can be given a nasal fluid diet.

  • Lifestyle
  • Rest and avoid exertion should be paid attention to after the disease.
  • When the symptoms of muscle weakness are mild, appropriate activities should be carried out without feeling fatigue.
  • Avoid driving and cycling when there are obvious symptoms of limb weakness.