Necrotising Myositis

Necrotising myositis is a rare inflammatory muscle disease where the body’s immune system attacks its own muscle cells, causing them to die. This leads to severe muscle weakness, particularly in the muscles closest to the center of the body, such as the shoulders, hips, and thighs.

Table of contents

• What is Necrotising Myositis?
• Other Names for This Disease
• Signs and Symptoms
• What Causes This Disease?
• Who Gets Necrotising Myositis?
• Different Types of Necrotising Myositis
• How Is It Diagnosed?
• Treatment Options
• Can You Recover?

What is Necrotising Myositis?

Necrotising myositis, also known as immune-mediated necrotizing myopathy or necrotizing autoimmune myopathy, is an inflammatory muscle disease that involves necrosis, or cell death, in the muscles^[1]. The term “myopathy” generally means muscle weakness, while “necrotizing” means cell death and necrosis^[5].

This condition causes weakness that appears on both sides of the body in a symmetrical pattern^[1]. The disease primarily affects proximal muscles, which are the muscles closest to the center of the body, such as the shoulders, forearms, hips, thighs, neck, and back^[1].

Necrotising myositis is a distinct type of idiopathic inflammatory myopathy, or myositis. The term “idiopathic” refers to a disease for which the cause is not known. In this condition, patients have muscle biopsies that show significant necrosis of muscle cells, often with less inflammation than other types of myositis^[1][3].

This is a very rare form of muscle disease. Currently, the incidence rate of all idiopathic inflammatory myopathy is about 1.16 to 19 million cases per year, and necrotizing myopathy represents 10% of these cases^[5]. It is estimated that approximately 21 people per million are affected by this condition, which means roughly 6,300 people in the United States have it^[21].

Immune-mediated necrotizing myopathy (IMNM), Necrotizing autoimmune myopathy (NAM), Necrotizing myopathy (NM)

Other Names for This Disease

This disease is known by several different names. Doctors may refer to it as immune-mediated necrotizing myopathy (IMNM), necrotizing autoimmune myopathy (NAM), or simply necrotizing myopathy (NM)^[1][5]. These terms all describe the same condition and may be used interchangeably^[21].

Signs and Symptoms

The most noticeable symptom of necrotising myositis is muscle weakness. This weakness develops in the muscles closest to the center of the body and can make everyday activities challenging^[1].

People with necrotising myositis may experience the following symptoms:

• Weakness in the muscles of the shoulders, forearms, hips, thighs, neck, and back^[1]
• Difficulty climbing stairs and standing up from a chair^[1]
• Difficulty lifting arms over the head^[1]
• Falling and difficulty getting up from a fall^[1]
• A general feeling of tiredness^[5]

The weakness in necrotising myositis often develops relatively quickly, happening over days, weeks, or months^[1]. The onset is usually faster than in some other types of muscle diseases.

In some cases, other muscles may be affected as well, although this is far less common. These can include muscles of the neck, causing difficulty in head and neck movement, muscles of the throat, causing difficulty swallowing (a condition called dysphagia) or voice changes, chest muscles causing difficulty breathing or shortness of breath, and in rare cases, muscles of the heart^[1][5].

Most people with necrotising myositis experience only weakness, and other symptoms affecting the skin or lungs are uncommon^[3]. This helps doctors distinguish it from other types of inflammatory muscle diseases.

What Causes This Disease?

The exact cause of necrotising myositis is poorly understood, but it is thought to be an autoimmune disorder. In an autoimmune disorder, the body’s immune system, which normally protects us from infections, mistakenly turns against the body’s own tissues^[1][3].

In necrotising myositis, the immune system attacks muscle fibers, causing chronic inflammation and damage. This leads to the death of muscle cells, a process called necrosis^[5].

Certain triggers can lead to the development of necrotising myositis. These include:

• Statins: A group of drugs used to control cholesterol levels in the body. Some patients exposed to statin medications can develop this condition^[1][5]
• Cancer: Certain types of cancers are associated with necrotising myositis^[5][8]
• Connective tissue disease: This is a disease that affects the tissue that connects all the parts of the body together^[5]
• HIV: This virus can sometimes trigger the body to attack its own cells, including muscle cells^[5]

As with other types of myositis, there is no known single cause, and sometimes no environmental triggers are found to explain why the disease develops^[1].

Who Gets Necrotising Myositis?

Necrotising myositis usually occurs in adults between the ages of 40 and 60^[1]. However, the disease can also affect children, where it may look like a muscular dystrophy^[21].

The disease affects both women and men^[21]. While some types of inflammatory muscle disease are more common in women, necrotising myositis can occur in people of any gender.

Young age at the time the disease begins is considered a poor prognostic factor, meaning that younger patients may have more severe disease^[2][9].

Different Types of Necrotising Myositis

There are different categories of necrotising myositis. These categories are mainly identified based on autoantibodies measured in the patient’s blood. Autoantibodies are immune system proteins that attack the body’s own tissues^[1].

The three main types are:

Patients with Anti-SRP Autoantibodies

Anti-signal recognition particle (SRP) autoantibodies are found in some patients with necrotising myositis. People with these autoantibodies often have severe muscle weakness and difficulty swallowing. Inflammation of the lungs and heart can also be seen in this group^[1].

Patients with anti-SRP antibodies tend to have more severe muscle involvement and more common extra-muscular features. They may respond best to treatment plans that include a medication called rituximab^[2].

Patients with Anti-HMGCR Autoantibodies

HMGCR stands for 3-hydroxy-3-methylglutaryl-coenzyme A reductase, which is a key enzyme in the production of cholesterol in the body. Some patients exposed to HMGCR inhibitors for cholesterol treatment (that is, statins) or through dietary sources (for example, red yeast rice and oyster mushrooms) can develop anti-HMGCR autoantibodies^[1].

However, sometimes no environmental triggers are found to explain their presence^[1]. Anti-HMGCR positive necrotising myositis usually presents with mainly severe muscle symptoms^[1].

This type is often associated with statin exposure, although the link is not always clear^[8]. Treatment with intravenous immunoglobulin (IVIG) may be effective, even as the only treatment in some cases^[2].

Patients with No Autoantibodies

Patients with necrotising myositis without anti-SRP or anti-HMGCR autoantibodies in their blood are considered by some experts to be included in a separate, third grouping called seronegative^[1]. In some cases, this form can be related to underlying cancers^[8].

How Is It Diagnosed?

If you are experiencing muscle symptoms involving weakness or fatigue, it is important to talk to your doctor to begin the diagnosis process^[1].

Since necrotising myositis is a rare disease, many doctors may not be familiar with its signs and symptoms. If you are struggling to find an accurate diagnosis, visiting a specialist can help^[1].

The diagnosis process typically includes several tests:

Blood Tests

Blood tests can show autoimmune markers and elevated levels of creatine kinase (CK), an enzyme that leaks from damaged muscles. Highly elevated creatine kinase levels are characteristic of this disease^[2][9].

Blood tests are also used to detect the presence of autoantibodies such as anti-SRP and anti-HMGCR. These autoantibodies help doctors determine which type of necrotising myositis a person has^[1][3].

Muscle Biopsy

A muscle biopsy is essential for diagnosis. This involves taking a small sample of muscle tissue and examining it under a microscope. The biopsy shows necrosis or death of muscle cells as a prominent feature, with often less inflammation than in other types of myositis^[1][8].

Electromyography

Electromyography (EMG) is an electric testing of the muscles to check their strength. These tests usually show signs of muscle weakness but are not particularly helpful in identifying the cause or type of muscle disease^[5].

Treatment Options

As with other types of myositis, there is no cure for necrotising myositis. However, treatments are available that can successfully manage symptoms^[1].

Early and intensive treatment with drugs that suppress the immune system (immunosuppressive drugs) can sometimes help manage the disease and avoid long-term disability^[12]. Prompt initiation of aggressive treatment is often indicated, as the disease can cause debilitating weakness, and muscle atrophy and irreversible fatty replacement of muscle can happen early in the disease course^[2][9].

Removal of the Cause

If a trigger for the disease is identified, such as statin medications, stopping that medication is an important first step^[5].

Corticosteroids Therapy

Glucocorticoids, particularly prednisone, are often the first-line treatment. These medications help to reduce inflammation and swelling and suppress damaging autoimmune responses^[12].

However, long-term use of high-dose glucocorticoid therapy may produce unwanted side effects, such as steroid myopathy (weakness from high dose steroids), decreased bone density, increased tissue swelling, and weight gain^[12].

Immunosuppressive Therapy

Therapy with other immunosuppressive drugs may be beneficial. These include medications such as azathioprine, methotrexate, mycophenolate mofetil, tacrolimus, or cyclosporine^[12].

Patients with necrotising myositis frequently require combination therapy to achieve disease control. They have a high rate of relapse when tapering immunosuppression, meaning the disease can come back when medications are reduced^[9].

Immunoglobulin Therapy

Additional treatment options used alone or in combination may include intravenous immunoglobulin (IVIG). This treatment may be particularly effective for patients with anti-HMGCR autoantibodies, and in some cases can work well even as the only treatment^[2][12].

Rituximab

The monoclonal antibody rituximab is another treatment option. For patients with anti-SRP antibodies, early rituximab is commonly favored^[2][9][12].

Physical Therapy and Exercise

Physical therapy may be recommended to help improve muscle strength and avoid development of contractures, which is muscle shortening or tightening^[12]. Exercise is considered medicine for myositis, and staying as physically active as possible is beneficial^[14].

After drug treatment takes effect, a program of regular stretching exercises prescribed by your doctor can help maintain range of motion in weakened arms and legs^[16].

Rest and Energy Conservation

Getting enough rest is an important component of managing the disease. Taking frequent breaks during the day and limiting activity can help conserve energy^[16].

Individualized Treatment Plans

Treatment plans are typically individualized to meet the needs of each person, and ongoing monitoring is required to adjust the treatment as needed^[12]. The treatment strategy should be informed by the severity of presenting features and autoantibody status^[9].

Can You Recover?

The ability to recover from necrotising myositis varies from person to person. Some people may experience mild symptoms that have little impact on their quality of life, while others may experience more serious symptoms that require ongoing medical treatment^[5].

With proper treatment, many people can achieve good disease control and maintain their strength. The disease can be severely disabling and often requires aggressive immunosuppression^[9].

Both anti-SRP and anti-HMGCR myopathy can cause severe weakness. Patients may experience fatty replacement of muscle soon after disease onset, which suggests that intense and early treatment may provide the best chance to avoid long-term disability^[2].

Young age of onset is a poor prognostic factor, meaning that younger patients, including children, may face more challenges^[2][9]. However, in children, the dystrophy-like features may be potentially reversible with immunosuppressant treatment^[2].

Many people with necrotising myositis are living successfully for many years after diagnosis. With more research, we now know that more and more people are living well with the disease^[14].

The first year after diagnosis is often the hardest, but with patience, support, and proper treatment, many people learn to manage their symptoms and adapt to life with the disease^[18].