Immune myopathy with necrosis causes symptoms and treatment

Immune-Mediated Necrotizing Myopathy (IMNM) is a rare type of inflammatory myopathy and an autoimmune disease in which the immune system mistakenly attacks the muscle tissue, leading to severe muscle weakness and muscle fiber damage. It can affect both adults and children and is considered a serious condition that requires accurate diagnosis and early medical intervention to prevent complications.In this comprehensive guide from Dalil Medical, we explore the causes of IMNM, its key symptoms, the most effective modern treatment options, and how to live with the condition to improve quality of life.

❓1. What is Immune-Mediated Necrotizing Myopathy (IMNM)?

It is a rare autoimmune disease in which the immune system attacks healthy muscle cells, leading to muscle fiber necrosis and severe muscle weakness, especially in the thighs and shoulders.

❓2. How is IMNM different from other types of inflammatory myopathies?

Unlike conditions such as dermatomyositis or polymyositis, IMNM is characterized by significant muscle fiber necrosis with minimal inflammatory cell infiltration. It also shows distinct findings in muscle biopsy and autoantibody profiles.

❓3. What are the causes of IMNM?

Potential causes include:

Autoimmune disorders
Use of certain medications (especially statins)
Hidden malignancies (in some cases)
Sometimes the cause remains unknown (idiopathic)

❌4. Is IMNM a genetic disease?

No, IMNM is not inherited. However, it is linked to immune system dysfunction, which may be influenced by environmental or drug-related factors.

✅5. Is IMNM a chronic disease?

Yes, it is generally chronic. However, it can be well-controlled with proper medical treatment, and many patients show significant improvement—especially when diagnosed early.

❓6. What are the main symptoms of IMNM?

Gradual muscle weakness, particularly in the hips and shoulders
Difficulty walking or lifting the arms
Muscle pain or general fatigue
In advanced cases: trouble swallowing (dysphagia) or breathing

❓7. How is IMNM diagnosed?

Diagnosis typically involves:

Blood tests: CK, Anti-SRP, Anti-HMGCR, ANA
Electromyography (EMG)
Muscle biopsy confirming necrosis
Ruling out other causes such as infections or drug side effects

❓8. What is the recovery or improvement rate for IMNM?

The outcome depends on how early the disease is diagnosed and treated.
Most patients respond well to treatment if started promptly, although some may require long-term therapy to maintain disease stability.

9. Can patients with Immune-Mediated Necrotizing Myopathy (IMNM) exercise?

✅ Yes, but only after the condition stabilizes and under the supervision of a doctor or physical therapist.
Recommended exercises include:

Light daily walking
Stretching and flexibility exercises
Swimming (very suitable for strengthening muscles without strain)

10. Can the disease relapse after improvement?

⚠️ Yes, relapse is possible, especially in cases of:

Sudden discontinuation of medications
Acute infections
Severe psychological or physical stress
Therefore, it is very important to adhere to treatment and regular follow-up.

11. Is there a special diet for patients with IMNM?

✅ Yes, it is recommended to follow an anti-inflammatory diet that supports muscle health and reduces immune activity, including:

Healthy proteins (fish, legumes, chicken)
Fresh vegetables and fruits
Healthy fats such as olive oil and omega-3
⚠️ While reducing sugars, hydrogenated fats, and preservatives.

12. Does IMNM affect pregnancy?

It may affect pregnancy, especially if symptoms are active or immunosuppressive medications are being used.
Pregnancy planning should be done with a specialist to adjust treatment and ensure the safety of both mother and fetus.

13. Can IMNM be completely cured?

✅ In some cases, yes, patients may reach long-term complete remission.
However, most patients require ongoing monitoring and maintenance therapy to prevent relapses.

Causes of Immune-Mediated Necrotizing Myopathy (IMNM)

IMNM is a rare and serious inflammatory muscle disease characterized by widespread muscle necrosis with relatively little inflammatory cell infiltration on biopsy, which distinguishes it from other inflammatory myopathies.

The disease is linked to several immune and drug-related factors, and sometimes the cause is unknown. Below are the main known causes:

1. Presence of Specific Autoantibodies

Autoantibodies are the main cause in most IMNM cases, especially:

Anti-SRP (Signal Recognition Particle)
▪️ Associated with severe and rapidly progressive forms of the disease
▪️ Causes acute muscle weakness that is difficult to treat
▪️ Sometimes linked to lung or heart complications
Anti-HMGCR (HMG-CoA Reductase Antibodies)
▪️ Commonly found in patients who used statins (e.g., Atorvastatin, Rosuvastatin)
▪️ May persist long after stopping statin therapy
▪️ Associated with very high CPK levels and progressive weakness of hip and shoulder muscles

2. Statin-Induced IMNM

Cholesterol-lowering drugs (statins) such as:

Atorvastatin
Simvastatin
Rosuvastatin

May trigger the immune system to produce antibodies against the HMGCR enzyme, leading to ongoing muscle inflammation that does not improve simply by stopping the drug but requires intensive immunotherapy (such as IVIG or Rituximab).

3. Paraneoplastic IMNM (Cancer-Associated)

In some cases, IMNM is associated with malignant tumors and appears as a paraneoplastic autoimmune syndrome.

The most common cancers linked to IMNM are:

Breast cancer
Lung cancer
Stomach or colon cancer

Comprehensive cancer screening is recommended especially in elderly patients or when suspicious clinical signs appear.

4. Other Autoimmune Diseases

IMNM can coexist with other autoimmune diseases such as:

Systemic Lupus Erythematosus (SLE)
Systemic Sclerosis
Mixed Autoantibody Syndromes
Immune-mediated vasculitis

In such cases, IMNM is part of a multi-system autoimmune disorder.

5. Idiopathic IMNM (Unknown Cause)

In some patients, no clear cause is found. This form is classified as idiopathic and is thought to result from internal immune dysregulation without an obvious environmental or drug trigger.

Diagnostic Features of IMNM

Very high CPK levels (often > 5000 U/L)
Symmetrical proximal muscle weakness (hips, shoulders)
Muscle biopsy showing fiber necrosis without extensive inflammation
Good response to immunotherapy such as corticosteroids, IVIG, or biologic drugs

Types of Immune-Mediated Necrotizing Myopathy (IMNM)

IMNM is classified into three main types based on the specific autoantibodies detected in the blood. This classification helps guide treatment plans and predict disease course.

Types of Immune-Mediated Necrotizing Myopathy (IMNM)

1. Anti-HMGCR Positive IMNM

Cause: The body produces autoantibodies against the HMG-CoA reductase enzyme.
Often associated with statin use (e.g., Atorvastatin) in people over 50.
Key features:
- Markedly elevated muscle enzyme levels (CPK).
- Gradual muscle weakness, especially in thighs and shoulders.
- ❗️Symptoms may appear long after stopping statins.
- Rare in children or young adults without statin exposure.

2. Anti-SRP Positive IMNM

Cause: Autoantibodies targeting the Signal Recognition Particle (SRP).
Clinical features:
- Sudden and rapidly progressive muscle weakness.
- Severe weakness may involve swallowing and breathing muscles.
- ⚠️ Poorer response to treatment compared to other types.
- Sometimes associated with systemic autoimmune symptoms.

3. Seronegative IMNM

Definition: No specific autoantibodies (Anti-HMGCR or Anti-SRP) detected.
Cause: Unknown; considered idiopathic.
⚠️ Always screen for underlying malignancy, especially:
- Breast cancer
- Lung cancer
- Stomach or colon cancer
Diagnosis is based on muscle biopsy + lab results + exclusion of other causes.
Requires intensive immunotherapy despite absence of detectable antibodies.

Key Notes:

All types cause symmetrical proximal muscle weakness and elevated CPK.
Muscle biopsy is essential for confirmation.
Identifying the autoantibody type helps tailor treatment and predict response.

✅ Symptoms of IMNM

IMNM is one of the most aggressive inflammatory myopathies. Symptoms can develop gradually or suddenly and vary in severity. Recognizing early warning signs can aid timely diagnosis and treatment.

1. Main Muscle Symptoms

Symptom	Description
Progressive Muscle Weakness	Starts in proximal muscles (hips, thighs, shoulders). Affects:
✔️ Climbing stairs
✔️ Rising from a chair
✔️ Lifting arms
Muscle Pain or Stiffness	May occur but not always present
Dysphagia (Difficulty Swallowing)	Due to pharyngeal muscle weakness in advanced cases
Shortness of Breath	From respiratory muscle involvement, especially in Anti-SRP type
Rapid Functional Decline	May lead to wheelchair dependency within weeks if untreated

2. Biochemical (Lab) Markers

Test	Notes
CPK (Creatine Kinase)	Often very high (>1000, sometimes >10,000 U/L)
Muscle Enzymes (AST, ALT, LDH)	Elevated; not necessarily indicating liver disease
Autoantibodies	Anti-HMGCR and Anti-SRP are key diagnostic markers

????️ 3. General/Systemic Symptoms

Symptom	When it Appears
Mild Fever	Sometimes at disease onset, especially in Anti-SRP type
Severe Fatigue	Due to systemic inflammation
Weight Loss	Rare; seen in chronic or cancer-associated cases

⚠️ Emergency Red Flags

Sudden loss of mobility
Difficulty swallowing or breathing
Chest pain or palpitations
New or worsening symptoms during treatment (could indicate relapse or complications)

⚠️ Complications of IMNM

Without timely treatment, IMNM can lead to serious, life-altering complications:

1. Permanent Muscle Disability

Irreversible muscle atrophy
Inability to walk without assistance or wheelchair dependence

2. Swallowing & Breathing Problems

Dysphagia: Risk of aspiration and pneumonia
Respiratory muscle weakness: May lead to respiratory failure in advanced stages

3. ❤️ Cardiac Involvement (Rare but serious)

Especially with Anti-SRP type
May include myocarditis or arrhythmias

4. Chronic Disease Course

May become treatment-resistant
Requires long-term immunosuppressive therapy

5. Cancer Association

More common with Anti-HMGCR antibodies
Most frequently linked to:
- Breast cancer
- Stomach cancer
- Lung cancer
Regular cancer screening is highly recommended

6. Medication-Related Side Effects

Drug	Potential Complications
Corticosteroids (Prednisone)	Osteoporosis, diabetes, hypertension, weight gain
Azathioprine / Mycophenolate	Immunosuppression, frequent infections, anemia
Rituximab	Severe viral infections, immune suppression, allergic reactions

How to Prevent IMNM Complications

Early diagnosis, appropriate treatment, and regular follow-up are the keys to avoiding severe outcomes. Here’s how to reduce risk:

✅ Prevention Strategies:

Regular monitoring of muscle, lung, and heart function
Strict adherence to medication plans — do not stop treatment suddenly
Routine cancer screening (especially after age 40 or in Anti-HMGCR cases)
Physiotherapy and rehabilitation to restore muscle strength and mobility

⚠️ Top Risks Associated with IMNM

⚠️ Risk	Explanation
1. Permanent Motor Disability	Persistent weakness in thighs and arms may result in loss of independent mobility
2. Respiratory Failure	From weakened breathing muscles — may require ventilatory support
3. Swallowing Difficulties	Risk of aspiration, leading to lung infections
4. Cardiac Issues	Rare but includes myocarditis or arrhythmias, especially in Anti-SRP cases
5. Hidden Cancers	Often associated with Anti-HMGCR — emphasizes need for cancer screening
6. Treatment Resistance	Some patients need stronger or combination immunosuppressants
7. Frequent Relapses	Especially when stopping medications or during infections/stress
8. Drug Side Effects	Steroids and immunosuppressants can cause infections, diabetes, bone loss

Diagnosis of Immune-Mediated Necrotizing Myopathy (IMNM)

Diagnosing IMNM can be challenging and requires a combination of clinical assessment, laboratory tests, imaging, and muscle biopsy.

1. Basic Laboratory Tests

Test	Expected Result	Interpretation
CPK	Significantly elevated (>5000 IU/L)	Indicates active muscle damage
LDH – AST – ALT	Elevated	Reflects muscle injury (not just liver dysfunction)
Anti-SRP / Anti-HMGCR	Positive	Identifies IMNM subtype
ANA – ENA	Sometimes positive	Helps exclude overlapping autoimmune conditions
ESR – CRP	Elevated	Suggests systemic inflammation

2. Advanced Immunological Testing

Myositis Specific Antibodies (MSAs): Identify specific markers for inflammatory myopathies.
Myositis Associated Antibodies (MAAs): Assess potential overlap with other autoimmune diseases like lupus or systemic sclerosis.

3. Imaging Studies

Test	Purpose
Muscle MRI	Detects edema, inflammation, or necrosis; guides biopsy site
EMG (Electromyography)	Shows a myopathic pattern; helps differentiate from neuropathies

4. Muscle Biopsy (Gold Standard)

Typical findings:

Widespread muscle fiber necrosis
Minimal or absent inflammatory infiltrate
Less immune cell infiltration compared to other myositis types
Possible immune deposits on muscle membranes

5. Cancer Screening

Essential in cases with Anti-HMGCR antibodies or in older patients.
Recommended tests include:

CT scan of chest, abdomen, pelvis
Mammogram (for women)
Colonoscopy (for men >50 years)

6. EULAR/ACR Diagnostic Criteria

Criterion	Note
Symmetric proximal muscle weakness	Key clinical sign
Elevated CPK (often >5000 IU/L)	Major biochemical marker
Muscle biopsy with necrosis & minimal inflammation	Confirmatory
Presence of anti-SRP or anti-HMGCR antibodies	Supports diagnosis & subtype classification

Treatment of IMNM: A Comprehensive Approach

IMNM treatment depends on disease severity and antibody subtype (e.g., Anti-SRP or Anti-HMGCR). The goals are to suppress the immune response, restore muscle strength, and prevent long-term complications.

1. First-Line Immunosuppressive Therapies

Medication	Use	Notes
Corticosteroids (Prednisone)	Initial mainstay therapy	Started at high doses, then tapered gradually
Mycophenolate Mofetil (MMF)	Adjunct or alternative to steroids	Effective in chronic cases
Azathioprine	Long-term management	Takes weeks to show efficacy
Methotrexate	Used in select cases	Caution with liver or kidney disease
Rituximab	For severe or refractory cases	Especially effective in Anti-SRP positive IMNM
IVIG (Intravenous Immunoglobulins)	For severe cases or steroid intolerance	Relatively safe, especially in pregnancy and children
Plasmapheresis	For rapidly progressive disease	Removes harmful antibodies from the bloodstream

2. Treatment by Antibody Type

Antibody Type	Suggested Protocol
Anti-HMGCR	Steroids + IVIG ± MMF
Anti-SRP	High-dose steroids + Rituximab or plasmapheresis

3. Rehabilitation and Supportive Care

Recovery requires a holistic plan:

Domain	Details
Physical Therapy	Gentle exercises and resistance training to rebuild strength
Nutrition	Anti-inflammatory, high-protein diet rich in vegetables
Managing Side Effects	Vitamin D, calcium, glucose and blood pressure monitoring, infection control

⚠️ Critical Treatment Notes

Start treatment early to reduce risk of permanent muscle damage.
Regular CPK monitoring is essential for tracking response.
Improvement may take weeks to months.
Some patients require long-term maintenance therapy.
Monitor closely for infections and medication side effects.

Recommended Exercises for IMNM Patients

Exercise is a key part of recovery, but must be done cautiously and under supervision.

Type of Exercise	Benefit	Notes
Light aerobic (walking, stationary cycling)	Improves circulation and endurance	Start with 10 min/day and increase gradually
Daily stretching	Reduces stiffness and improves flexibility	Gentle movements only
Light resistance training	Builds muscle strength	Only under supervision of a physical therapist
Hydrotherapy	Reduces joint stress	Ideal for those with severe muscle pain
Yoga & breathing	Enhances balance and mental wellbeing	Helps with stress and coordination

Exercises to Avoid

Exercise	Why to Avoid
High-intensity or heavy resistance workouts	Can damage already weakened muscles
Cold environment training	Increases stiffness and slows recovery
Unsupervised routines	Risk of injury or exacerbation

Preventing Relapse or Disease Worsening

✅ Recommendation	???? Explanation
Medication adherence	Never stop immunosuppressants without medical advice
Avoid overexertion	Muscle fatigue can worsen weakness
Infection prevention	Hand hygiene, avoid crowds, update vaccines as advised
No smoking/alcohol	Weakens immune system and impairs healing
Monitor liver and muscle function	Track ALT, AST, and CPK levels regularly

IMNM-Friendly Diet

✅ Recommended & Beneficial Foods

Category	Examples	Benefits
Lean Protein	Chicken, fish, lentils, beans, egg whites	Muscle building and repair
Leafy Greens	Spinach, arugula, broccoli	High in vitamins & antioxidants
Anti-inflammatory Fruits	Berries, pomegranate, kiwi, oranges	Reduce inflammation & support immunity
Healthy Fats	Olive oil, nuts, avocado	Supports nerve function and reduces inflammation
Whole Grains	Oats, brown rice, quinoa	Energy and digestive health
Hydration	Water, herbal teas, natural juices	Supports kidney function and detoxification