Immune-Mediated Necrotizing Myopathy (IMNM)

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Also Known As: Necrotizing Autoimmune Myopathy (NAM)

Immune-mediated necrotizing myopathy (IMNM)—also called necrotizing autoimmune myopathy (NAM)—is a rare but severe inflammatory muscle disease. It is characterized by rapidly progressive proximal muscle weakness, markedly elevated muscle enzymes, and extensive muscle fiber necrosis with minimal inflammatory cell infiltration on biopsy.

Unlike inherited muscular dystrophies, IMNM is an acquired autoimmune condition in which the immune system mistakenly attacks muscle tissue.

What Is IMNM?

IMNM belongs to the group of idiopathic inflammatory myopathies, but it differs from other forms such as polymyositis or dermatomyositis because:

  • Muscle cell death (necrosis) is prominent

  • Inflammatory cells are sparse on biopsy

  • Specific autoantibodies are commonly present

  • The disease often progresses quickly

Without treatment, IMNM can lead to significant disability.

Is IMNM Genetic?

IMNM is not a directly inherited genetic disorder, but genetic susceptibility plays a major role.

Genetic Associations

Research shows strong links with certain immune system genes, particularly:

  • HLA-DRB1*11:01 allele(especially in anti-HMGCR cases)

  • Variations within the major histocompatibility complex (MHC)

These genetic factors influence:

  • Who develops the disease

  • Which autoantibodies are produced (anti-HMGCR or anti-SRP)

  • How the immune system responds to environmental triggers (such as statins)

In genetically susceptible individuals, exposure to triggers can initiate the autoimmune attack.

Causes and Subtypes

IMNM is classified based on specific autoantibodies.

1. Anti-HMGCR Myopathy

  • Often associated with statin exposure

  • Linked to antibodies against HMG-CoA reductase (HMGCR)

  • Can occur even without prior statin use

  • Generally responds well to IVIg therapy

2. Anti-SRP Myopathy

  • Associated with antibodies against the signal recognition particle (SRP)

  • Typically more severe

  • Rapid onset

  • May involve:

    • Swallowing muscles

    • Respiratory muscles

    • Heart (cardiac involvement)

3. Seronegative IMNM

  • No detectable antibodies

  • Sometimes associated with malignancy

  • Diagnosis depends heavily on biopsy findings

Symptoms

Core Feature: Severe Proximal Muscle Weakness

Weakness typically affects muscles closest to the trunk:

  • Hips and thighs

  • Shoulders and upper arms

  • Neck flexors

Common Functional Difficulties

Patients often report:

  • Difficulty rising from a chair

  • Trouble climbing stairs

  • Problems lifting arms overhead

  • Frequent falls

  • Difficulty combing hair or lifting objects

Additional Symptoms

  • Fatigue (very common and often severe)

  • Muscle pain or tenderness (in some patients)

  • Difficulty swallowing (dysphagia)

  • Shortness of breath (if respiratory muscles involved)

  • Cardiac issues (more common in anti-SRP subtype)

  • Interstitial lung disease (rare but possible)

  • Occasional fever or weight loss

Symptoms usually progress over weeks to months.

Laboratory Findings

A hallmark feature is markedly elevated creatine kinase (CK)—often many times above normal.

Other laboratory findings may include:

  • Positive anti-HMGCR antibodies

  • Positive anti-SRP antibodies

  • Elevated aldolase

  • Abnormal liver enzymes (secondary to muscle breakdown)

Diagnosis

Diagnosis is based on a combination of:

1. Clinical Features

  • Symmetrical proximal weakness

  • Rapid progression

2. Blood Tests

  • Very high CK levels

  • Autoantibody testing (anti-HMGCR, anti-SRP)

3. Muscle Biopsy (Key Test)

Shows:

  • Prominent muscle fiber necrosis

  • Regenerating fibers

  • Minimal inflammatory infiltrates

4. MRI of Muscles

  • Detects muscle edema

  • Identifies areas of active inflammation

Early diagnosis is crucial to prevent irreversible muscle damage.

Treatment

IMNM requires aggressive immunosuppressive therapy.

Step 1: Remove Triggers

  • Discontinue statins (if applicable)

Step 2: Immunotherapy

Corticosteroids

  • Prednisone is usually started at high doses

  • Rapid control of inflammation

Steroid-Sparing Agents

Often added early to reduce long-term steroid exposure:

  • Methotrexate

  • Azathioprine

  • Mycophenolate mofetil

Intravenous Immunoglobulin (IVIg)

  • Particularly effective in anti-HMGCR subtype

  • Often used in severe cases

Other Options (Refractory Cases)

  • Rituximab

  • Cyclophosphamide

Long-term treatment is often required, and relapses can occur.

Prognosis

Prognosis varies by subtype:

  • Anti-HMGCR: Often responds well, especially with IVIg

  • Anti-SRP: May be more severe and resistant to therapy

  • Seronegative: Variable outcomes

Early treatment improves outcomes significantly.

Some patients achieve remission, while others may have:

  • Persistent weakness

  • Muscle atrophy

  • Long-term need for immunosuppression

Key Takeaways

  • IMNM (NAM) is a rare autoimmune muscle disease

  • Causes rapid, severe proximal muscle weakness

  • Marked by high CK and muscle fiber necrosis with minimal inflammation

  • Strongly associated with anti-HMGCR or anti-SRP antibodies

  • Genetic susceptibility (HLA-DRB1*11:01) plays a role

  • Requires early, aggressive immunosuppressive therapy

  • Prognosis improves with prompt treatment

Inflammatory myopathies are a group of autoimmune muscle diseases that share proximal muscle weakness but differ in pathology, antibody associations, and systemic features. 

Immune-mediated necrotizing myopathy (IMNM) is characterized by prominent muscle fiber necrosis with minimal inflammation and is strongly associated with anti-HMGCR or anti-SRP antibodies. Polymyositis (PM) primarily involves T-cell–mediated muscle inflammation without skin involvement, while Dermatomyositis (DM) features both muscle inflammation and characteristic skin rashes with complement-mediated microvascular injury. The table below summarizes their key distinguishing features:

Feature

Immune-Mediated Necrotizing Myopathy (IMNM)

Polymyositis (PM)

Dermatomyositis (DM)

Primary Pathology

Muscle fiber necrosis with minimal inflammation

Endomysial inflammation with CD8+ T cells

Perifascicular atrophy, perivascular inflammation

Autoantibodies

Anti-HMGCR, Anti-SRP

Anti-Jo-1 (sometimes)

Anti-Mi-2, Anti-MDA5, Anti-TIF1-γ

CK Levels

Very high (often markedly elevated)

Elevated

Elevated

Skin Involvement

No

No

Yes (heliotrope rash, Gottron’s papules)

Onset

Rapid, severe

Subacute

Subacute

Association with Statins

Common (anti-HMGCR subtype)

No

No

Malignancy Risk

Possible (seronegative cases)

Mild

Increased risk in adults

Treatment

Aggressive immunosuppression, IVIg often required

Steroids + immunosuppressants

Steroids + immunosuppressants

While there is no known cure, prompt treatment can lead to significant improvement, according to this YouTube video. https://www.youtube.com/watch?v=Y4TGSPO8jZQ&t=130s

References:

The Genetics of Autoimmune Myositis
https://pmc.ncbi.nlm.nih.gov/articles/PMC9178267/

Immune Mediated Necrotizing Myopathy
https://www.myositis.org/about-myositis/types-of-myositis/necrotizing-myopathy/

Statin-Induced Necrotizing Autoimmune Myopathy: https://pmc.ncbi.nlm.nih.gov/articles/PMC8311592/#:~:text=Statin%2Dinduced%20necrotizing%20autoimmune%20myopathy%20(SINAM)%20is%20an,statin%20therapy%20that%20can%20occur%20at%20any%E2%80%A6

Diagnosing immune-mediated necrotizing myopathy https://www.myositis.org/about-myositis/diagnosis/diagnostic-criteria/diagnostic-criteria-for-necrotizing-myopathy/

© 2000-2030 Sieglinde W. Alexander. All writings by Sieglinde W. Alexander have a fife year copy right. Library of Congress Card Number: LCN 00-192742 ISBN: 0-9703195-0-9 

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