What is the cause of myopathic necrosis (muscle tissue death)?

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Last updated: March 12, 2025View editorial policy

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From the Guidelines

Myopathic necrosis is primarily caused by muscle cell death resulting from various underlying conditions, including autoimmune inflammatory myopathies, toxic myopathies from medications, metabolic disorders, infectious processes, trauma, and ischemia from compromised blood flow, as reported in the most recent study 1. The main causes of myopathic necrosis include:

  • Autoimmune inflammatory myopathies (such as polymyositis and dermatomyositis)
  • Toxic myopathies from medications (particularly statins like atorvastatin and simvastatin)
  • Metabolic disorders (including mitochondrial myopathies and glycogen storage diseases)
  • Infectious processes
  • Trauma
  • Ischemia from compromised blood flow Statin-induced myopathy typically resolves with medication discontinuation, though it may require 2-3 months for complete recovery, as noted in 1. Autoimmune myopathies often need immunosuppressive therapy, commonly starting with prednisone at 1mg/kg/day with a gradual taper, sometimes adding steroid-sparing agents like methotrexate or azathioprine, as recommended in 1. The pathophysiology involves disruption of muscle cell membranes, leading to release of muscle enzymes like creatine kinase (CK) into the bloodstream, which serves as a diagnostic marker, as explained in 1. Muscle necrosis occurs when cellular repair mechanisms cannot keep pace with damage, resulting in irreversible cell death and potential permanent muscle weakness if not properly addressed, highlighting the importance of prompt diagnosis and treatment, as emphasized in 1. In the context of immune checkpoint inhibitor therapy, myositis is a rare but potentially severe complication, with a higher incidence associated with anti-PD-1/PD-L1 agents, as reported in 1. Therefore, it is essential to monitor patients receiving immune checkpoint inhibitors for signs of myositis and to promptly initiate treatment with high-dose corticosteroids and other immunosuppressive agents as needed, to prevent irreversible muscle damage and improve outcomes, as recommended in the most recent guideline update 1.

From the FDA Drug Label

An acute myopathy has been observed with the use of high doses of corticosteroids, most often occurring in patients with disorders of neuromuscular transmission (e.g., myasthenia gravis), or in patients receiving concomitant therapy with neuromuscular blocking drugs (e.g., pancuronium). The cause of myopathic necrosis (muscle tissue death) is associated with the use of high doses of corticosteroids, particularly in patients with disorders of neuromuscular transmission or those receiving concomitant therapy with neuromuscular blocking drugs 2.

  • Key factors include:
    • High doses of corticosteroids
    • Disorders of neuromuscular transmission (e.g., myasthenia gravis)
    • Concomitant therapy with neuromuscular blocking drugs (e.g., pancuronium)

From the Research

Causes of Myopathic Necrosis

The causes of myopathic necrosis, also known as necrotizing myopathy, can be divided into two main categories: immune-mediated and nonimmune-mediated.

  • Immune-mediated necrotizing myopathy (IMNM) has been associated with:
    • Anti-signal recognition particle antibodies 3
    • Connective tissue diseases 3
    • Cancer 3, 4
    • Post-statin exposure with 3-hydroxy-3-methylglutaryl-coenzyme A antibodies 3, 5, 6
    • Viral infections, including HIV and hepatitis C 3
  • Nonimmune-mediated necrotizing myopathy (NIMNM) is linked to:
    • Medications 3
    • Toxic exposures 3, 7

Other Associated Conditions

Other conditions that can cause myopathic necrosis include:

  • Muscular dystrophies 7
  • Infections, such as severe acute respiratory syndrome coronavirus 2 infection 4
  • Graft-versus-host disease 4
  • Hypothyroidism 4
  • Checkpoint inhibitors, a type of cancer treatment 4

Autoantibodies and Myopathic Necrosis

Certain autoantibodies have been associated with myopathic necrosis, including:

  • Anti-hydroxy-3-methylglutaryl-CoA reductase 6, 4
  • Anti-signal recognition particle 3, 6, 4
  • Anti-Mi2, associated with dermatomyositis 4
  • Antisynthetase syndrome 6, 4
  • Antimitochondrial antibodies, associated with myositis 4

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Necrotizing myopathies: an update.

Journal of clinical neuromuscular disease, 2015

Research

Differential diagnosis of necrotizing myopathy.

Current opinion in rheumatology, 2021

Research

Statin-associated Autoimmune Myopathies: A Pathophysiologic Spectrum.

The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques, 2014

Research

Necrotizing myopathies: beyond statins.

Current opinion in rheumatology, 2014

Research

[Necrotizing myopathies: From genetic to acquired forms].

La Revue de medecine interne, 2014

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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