Immune-Mediated Necrotizing Myopathy (IMNM)
Immune-Mediated Necrotizing Myopathy (IMNM), also referred to as Necrotizing Autoimmune Myopathy (NAM), one of the Inflammatory Myopathies, is a rare, thought to be complement-mediated muscle disease. IMNM can present much like polymyositis and causes muscle cell death (necrosis) that leads to weakness of the skeletal muscles on both sides of the body (symmetrical), commonly those closest to the body’s core (proximal), such as the hips, thighs, upper arms, shoulders, and neck.
Muscle weakness, which is often severe, can develop over a period of days, weeks, or months. This weakness often leads to difficulty climbing stairs, rising from a chair or from the floor, turning in bed, lifting, combing hair, brushing teeth, or reaching over the head for something like an item on a shelf. There is no cure for IMNM, nor any FDA approved treatments.
Causes of IMNM can be associated with certain medications, especially statins used to manage cholesterol, anti-HMGCR and anti-SRP autoantibodies, cancer, viral infections, or other connective tissue diseases.
Autoimmune Necrotizing Myopathy (NAM) / Immune-Mediated Necrotizing Myopathy (IMNM) – These terms may be used interchangeably. IMNM may look the same as necrotizing myopathies, but they have other features that prove they are autoimmune. Also, IMNM often responds to steroid and immune suppression therapy.
Who is affected by IMNM?
Immune-Mediated Necrotizing Myopathy affects:
- women and men with an average age of onset between ages 40-60
- children, where it may mimic a muscular dystrophy
- an estimated 21 people per million
- an estimated 6,300 people in the U.S.
Immune-Mediated Necrotizing Myopathy is a rare disease. A rare disease in the U.S. is defined as a condition affecting fewer than 200,000 people.
Here is some additional information:
- IMNM has been recently reclassified (ENMC) according to myositis-specific autoantibodies including anti-HMCGR, anti-SRP, and antibody negative. Some prior classifications, including some still used today, would classify anti-SRP positive patients as having polymyositis.
- Age of onset ranges from 30 to 70 years of age in the reported cases.
Other organ involvement and IMNM
IMNM may affect other organ systems of the body, referred to as a systemic disease.
Extramuscular organ involvement
- Respiratory muscles may be involved.
- Interstitial lung disease (ILD) has been reported.
- Cardiac involvement has been reported.
Potential associations with IMNM
IMNM may be associated with:
- Myositis autoantibodies anti-SRP and anti-HMGCR
- Anti-mitochondrial antibodies, and on very rare occasions, anti-Jo-1
- With cancer
- With viral infections, or,
- With other connective tissue diseases like scleroderma
The anti-HMGCR autoantibody (3-hydroxy-3-methylglutaryl-coenzyme A reductase), the pharmacologic target of statins and one of the myositis-specific antibodies, is highly specific and is not usually found in healthy people or those with other autoimmune or inflammatory diseases. Patients with genetically proven muscular dystrophy do not have anti-HMGCR autoantibodies.
The presentation of each patient may vary, however, these patients can be grouped into a specific subtype of disease based on shared muscle biopsy features and the presence of anti-HMGCR autoantibodies.
This subtype does not typically have extramuscular involvement and is often limited to skeletal muscle fiber necrosis with little-to-no inflammation leading to muscle weakness. Other symptoms may include dysphagia (trouble swallowing), muscle pain (myalgia), and fatigue.
Some studies suggest there may be an association with malignancy, so cancer screenings are suggested.
Anti-SRP (signal recognition particle) autoantibodies were the first identified as being specifically associated with IMNM, although these findings were diagnosed as polymyositis in the past.
Muscle weakness tends to severely affect the lower limbs, and the creatine kinase (CK) levels are extremely elevated. The anti-SRP autoantibody is thought to correlate with CK levels and this may be a good indication of disease activity for some patients; a way to monitor if treatment is working.
Extramuscular features may include dysphagia (trouble swallowing) as well as a rare risk of cardiac involvement, including rhythm or conduction abnormalities and cardiac insufficiency. Interstitial lung disease (ILD) may also be present, but it is usually mild. Other associated symptoms often include muscle pain (myalgia) and extreme fatigue.
Muscle weakness associated with anti-SRP myopathy is often severe and disabling, and it makes anti-SRP myopathy considered as one of the most severely disabling autoimmune diseases. Even with treatment, recovery for many patients is poor.
In his research, Allenbach notes that “the outcome of anti-SRP myopathy is poor since only half of the patients recover normal strength after four years.”
Ab (antibody) negative immune-mediated necrotizing myopathy is a subtype where no known associated autoantibody is found circulating in the blood. Muscle biopsies show similar findings to those with antibody-positive anti-HMGCR and anti-SRP myopathy, and they share many of the same symptoms including highly-elevated CK levels, myalgia (muscle pain), and extreme fatigue.
The Ab negative subtype will most likely require a muscle biopsy for a proper diagnosis. Myositis autoantibody research is ongoing.
Pain and IMNM
Myalgia (muscle pain) is a reality for many patients with immune-mediated necrotizing myopathy. Some describe the pain as sharp and stabbing, while others say it feels crushing and achy. Finding effective pain management is often a challenge. Talk openly and honestly about your pain with your doctors, and explain how it impacts your life.
Physicians: Looking to order the autoantibody labs?
For healthcare providers wanting to order lab testing for patients to include the anti-HMGCR and anti-SRP antibodies, the information is below. (MSU does not endorse any particular lab or facility. This information is posted for educational/informational convenience.)
(anti-HMGCR is not included in the full myositis panel)
Anti-SRP: http://www.rdlinc.com/test_menu/srp/ or order the full myositis panel.
Polymyositis: The evolution of this diagnosis in light of recent research
by Dr. Lisa Christopher-Stine
While this session is about polymyositis, Dr. Lisa Christopher-Stine goes into a lot of detail about IMNM as well. This is a great resource to understand IMNM.
Signs & Symptoms of IMNM
- Symmetric, proximal muscle weakness, like found with polymyositis (weakness is often severe)
- Weakness in other muscles, including breathing and swallowing muscles, and distal muscles (furthest from the body’s core)
- Muscle pain (myalgia)
- Inability or difficulty climbing stairs, getting into a car and rising from a seated position
- Difficulty washing, combing or brushing one’s hair, or raising arms to lift an item such as putting a plate in a cabinet
- Dysphagia (trouble swallowing)
- Fatigue, which can be severe and debilitating
- Weight loss
Diagnosing Immune-Mediated Necrotizing Myopathy (IMNM)
Which doctors do I see?
Due to the rarity of immune-mediated necrotizing myopathy (IMNM), diagnosis and treatment are usually managed by a specialty center with experience in diagnosing and treating inflammatory myopathies and may include rheumatologists, neurologists, and neuromuscular specialists. This may be in coordination with a primary care physician (PCP). Consultation with other specialists may be required depending on your symptoms, other coexisting illnesses, and other organ involvement and may include: cardiologist, pulmonologist, oncologist, endocrinologist, and pain management.
Exercise is important for myositis patients. Therefore, you may also see a physical therapist, occupational therapist, and, if you have trouble swallowing (dysphagia), you may also see a speech-language pathologist.
Clinical and Physical Exam
A complete medical and family history is important in helping to diagnosis a rare and complex disease such as IMNM. We suggest writing a detailed medical and family history that you can share with your medical team and that can be used for all future appointments.
The physical exam and complete medication history are also very important.
Your doctor will likely order various blood tests when suspecting IMNM in order to measure autoimmune and inflammatory markers and to check for myositis-specific and myositis-associated antibodies, cancer markers, and other antibodies. Some of these tests may include:
- Creatine Kinase (CK or CPK) (muscle enzymes)
- ALT and AST
- LD (Lactate dehydrogenase)
- Sed Rate (also called ESR or Erythrocyte sedimentation rate)
- ANA (Antinuclear Antibodies panel)
- HMGCR and SRP antibody testing (found in roughly two-thirds of patients)
EMG and Nerve Conduction Study (NCS)
An EMG (Electromyography) is a test that checks the health of the muscles and the nerves that control the muscles. With IMNM, the EMG may show an irritable myopathy pattern as with other inflammatory myopathies. EMG testing can help distinguish between weakness due to muscle disease from weakness due to nerve problems. Nerve conduction study is usually done during the same visit and is a test to see how fast electrical signals move through a nerve.
MRI (Magnetic Resonance Imaging)
MRI is being used more frequently and can show changes suggesting muscle inflammation. Physicians may also use MRI to choose the best muscle for biopsy.
The muscle biopsy is important for a diagnosis of IMNM, especially when the antibodies (HMGCR and SRP) are negative. A doctor will remove a small piece of muscle tissue, either via a needle biopsy or an open surgical biopsy, and send it to a lab for testing. An open muscle biopsy is typically done as an outpatient procedure, however the exact plan will be determined by you and your doctors.
Your doctor will choose the weakest muscle, careful to avoid the site of any recent EMG, for biopsy. An MRI can be helpful in locating the best muscle to biopsy.
The above tests are not an exhaustive list your physician may use. Other testing will depend upon your symptoms and coexisting illnesses.
Since cancer is potentially associated with some cases of IMNM, your doctor may perform cancer screenings above the suggested for your age and race.
If you are experiencing difficulty swallowing (dysphagia)
Barium Swallow Test
A barium swallow is a test that may be used to determine the cause of painful swallowing, difficulty with swallowing, abdominal pain, bloodstained vomit, or unexplained weight loss. Barium sulfate is a metallic compound that shows up on X-rays and is used to help see abnormalities in the esophagus and stomach.
If there is lung involvement
CT Scan (computed tomography) and Chest X-ray
A chest X-ray and CT scan of the lungs can help identify lung disease associated with myositis such as Interstitial Lung Disease (ILD).
Pulmonary Function Tests (PFT’s)
When the lungs are involved, your physician may order PFTs, a group of tests that measure how well your lungs work. This includes how well you’re able to breathe and how effective your lungs are able to bring oxygen to the rest of your body.
Challenges of diagnosing IMNM
Differentiating IMNM from muscular dystrophies, toxic and other types of necrotizing myopathies may be difficult, especially for those who do not have an IMNM-associated antibody (Ab negative).
It is important that doctors rule out other, more common, causes of your symptoms as well as different forms of necrotizing myopathies.
Treating Immune-Mediated Necrotizing Myopathy (IMNM)
Such as with statins, it was once thought that discontinuing the offending drug would eliminate symptoms of IMNM within weeks or months. However, in recent years it has become recognized that some patients who discontinue the drug do not get better or improve because in these patients there is an autoimmune process involved.
There are no FDA approved therapies for IMNM or any of the inflammatory myopathies.
Patients use off-label medications with very little science behind them. These are a few standard medications used to treat many other autoimmune diseases with the most common being immunosuppressive medications.
Patients may start to see improvement after several weeks of high-dose corticosteroids. The physician will likely conduct a follow up with both a physical exam to determine if muscle strength has improved as well as another CK/CPK blood test to check to see if the levels have decreased.
The goals of treatment for IMNM are to eliminate or reduce inflammation, restore muscle performance and strength, reduce morbidity, and improve a patient’s quality of life.
There are no FDA approved therapies for IMNM, aside from steroids, which is a standard treatment for inflammatory myopathies, and which are not recommended for long-term use.
Finding a combination of medications is often needed for successful treatment.
Discontinue statin medication
If you are taking a statin medication your doctor will likely discontinue it.
The initial treatment is typically corticosteroids such as prednisone or prednisolone and may be dosed by the patient’s weight at 1 mg per kg. Corticosteroids address inflammation and simultaneously help suppress the overactive immune system.
Intravenous (IV) steroids, such as methylprednisolone, may also be used.
Steroids have many side effects including weight gain and redistribution of body fat to the face, neck, and abdomen; elevated blood sugars, mood swings, thinning of the skin, cataracts, and osteoporosis.
Additional drugs to suppress the immune system may be added to the steroids, sometimes at the beginning of treatment and other times once the determination has been made that steroids have shown to be effective.
Since steroids, especially in high doses and over prolonged periods, are known to have many adverse side effects and may cause many other health issues, the introduction of steroid-sparing medications should be considered when appropriate.
Note: Corticosteroids should NOT be confused with anabolic steroids, used by some weightlifters and athletes, to enhance performance.
Steroid-sparing agents, such as immunosuppressive drugs, have an added benefit as they often reduce or eliminate the need for steroids while also suppressing the overactive immune system. However, these medications are not without their own risks.
Some immunosuppressive drugs used with NAM include mycophenolate mofetil (Cellcept), azathioprine (Imuran), and methotrexate.
Immunoglobulin Therapy (IVIg, SubQ Ig)
Immunoglobulin comes from antibodies extracted from the plasma from thousands of blood donors. IVIg is the intravenous (IV) method. SubQ Ig is also available, and can be approved for some, and is infused quicker under the skin and eliminates the need for continuous home nursing.
Observational studies show that statin-exposed anti-HMGCR-positive patients often improve dramatically with intravenous immunoglobulin, whereas statin-naive anti-HMGCR patients may be refractory to any immunosuppressive therapy.
Rituximab belongs to a class of drugs called monoclonal antibodies. It is given intravenously (IV).
Observational studies show that patients anti-SRP patients usually respond well to treatment with rituximab.
Managing Immune-Mediated Necrotizing Myopathy (IMNM)
Day-to-day management of IMNM can take many forms. Adapting to a “new normal” can be challenging and require many lifestyle changes.
It was once thought exercise caused damage to myositis patients. This has now been proven false through research.
We now know there are massive benefits in having an approved exercise program. This may start with a doctor referring you to physical therapy or rehabilitation center. Exercise plans that are supervised by your medical and healthcare team are most effective so you do not injure yourself.
Before starting any type of exercise plan, talk to your doctor first.
Diet and Nutrition
Eating a well-balanced diet high in protein may be beneficial for those with IMNM, and is for your overall health.
Corticosteroids have many side effects including weight gain and redistribution of body fat to the face, neck, and abdomen, elevated blood sugars, and osteoporosis, so you may need to make adjustments in your diet for these conditions.
Ask your doctor about nutrition and a referral to a dietician or nutritionist.
When living with Immune-Mediated Necrotizing Myopathy (IMNM), having a good support system in place is important.
IMNM is chronic illness and some people in your life may not understand the challenging aspects of the symptoms, treatments, and stress involved in managing this complex, sometimes even invisible illness. It can feel lonely. Depression and anxiety can also be difficult aspects of this disease which may be exacerbated by the use of steroids.
We offer several online support options for patients, family members, caregivers, and friends of those living with IMNM. Having an emotional outlet is helpful, and our groups are also educational, resourceful, and we even try to add some fun group activities to help members connect.
MSU provides a free, monthly online video support session just for myositis patients. This is a chance to meet others face-to-face, discuss challenges, share tips, and just talk to others who completely understand. View our Events page for upcoming support sessions.
NEW: Monthly Video Support Session just for patients with immune-mediated necrotizing myopathy (IMNM) on the last Saturday of each month at 3 PM Eastern Time. See our events calendar for the dates and times to join us.
Have you been diagnosed with IMNM?
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Immune-Mediated Necrotizing Myopathy In Focus
What does IMNM look like?
IMNM patients may require the use of assistive devices for mobility such as a cane, walker, or wheelchair, either for short periods like during flares or for long-term muscle weakness and damage.
If the lungs are involved, some may wear oxygen.
Some people living with IMNM may look perfectly healthy on the outside, but on the inside, they are very sick and struggling on many levels.
The prognosis of IMNM depends on many varying factors including response to available treatments, none of which are FDA-approved for IMNM, the severity of disease and its manifestations, the presence of pulmonary or cardiac involvement, and associated autoantibodies or malignancy.
Some IMNM patients respond very well to treatment, while others may not. Finding the right treatment, or a combination of treatments can take a very long time. Some of the medications used require months to start working.
Long-term steroid use may be a major source of morbidity.
Research and Clinical Trials
Research helps us better understand diseases and can lead to advances in diagnosis and treatment. As there are currently no approved treatments for IMNM, research is important, as are patients participating in clinical trials.
We have partnered with Antidote to help make your clinical trial match easier.
Below find some of the important research articles, some of which were used for this page.
“Simply Put” is a service of Myositis Support and Understanding, to provide overviews of Myositis-related medical and scientific information in understandable language.
MSU volunteers, who have no medical background, read and analyze often-complicated medical information and present it in more simplified terms so that readers have a starting point for further investigation and consultation with healthcare providers. The information provided is not meant to be medical advice of any type.