Update on Polymyositis (PM): Latest Insights into Causes, Diagnosis, and Autoimmune Markers

Overview: What is Polymyositis?

Polymyositis (PM) is a chronic inflammatory myopathy characterized by symmetric, progressive muscle weakness, primarily affecting the proximal muscles (such as those in the hips, shoulders, and thighs). It is an autoimmune disease, meaning the immune system inappropriately attacks healthy muscle tissue. Though not directly inherited, some individuals may carry genetic traits that increase susceptibility, especially in the presence of environmental triggers like viral infections.

Dr. Andrew Mammen and researchers at the Muscle Disease Unit (MDU) study myositis, a family of autoimmune diseases that affect skeletal muscle and, in many cases, other organs such as the skin, lungs, and joints. These diseases include dermatomyositis, polymyositis, immune-mediated necrotizing myopathy, and inclusion body myositis.

Dr. Andrew Mammen (transcript excerpt): "And finally, some of those patients that would have, you know, years ago been diagnosed with polymyositis actually have an inherited muscle disease. So those are the major six types. And when I hear that somebody has a diagnosis of polymyositis, which is not one of those six, my conclusion is that we don't really have a definitive diagnosis yet, and I still need to think hard about what the real diagnosis is in that patient."

Myositis starts when the immune system malfunctions, mistakenly attacking healthy muscle tissue, or through other causes like viral infections or drug exposure. The exact triggers are not fully understood but likely involve a combination of genetic factors and environmental triggers, such as viral infections (like the flu), certain medications (like statins), or other autoimmune conditions. This process leads to muscle inflammation, weakness, and other symptoms depending on the specific type of myositis, such as polymyositis, dermatomyositis, or inclusion body myositis.

Myositis can start at any age, with different types having different typical age ranges: juvenile myositis typically affects children 5-15 years old, while adult forms like dermatomyositis and polymyositis most often appear in adults 30-60 years old, and inclusion body myositis usually affects those over 50

Is Polymyositis Genetic?

Not directly inherited: PM is not caused by a specific gene mutation and is not passed down in a predictable pattern like muscular dystrophies.
Genetic predisposition: People with family histories of autoimmune diseases may have a higher risk, suggesting immune-regulatory genes may contribute to disease susceptibility.

Causes and Contributing Factors

Polymyositis likely results from a complex interplay of:

Autoimmune dysfunction: The immune system mistakenly targets muscle fibers.
Genetic susceptibility: Certain HLA types may increase risk.
Environmental triggers: Viral infections, certain medications, and other immune challenges may initiate disease onset.

Symptoms of Polymyositis

Gradual onset of muscle weakness, often without pain.
Difficulty with activities like climbing stairs, lifting arms, or rising from a chair.
In severe cases: trouble swallowing or respiratory muscle involvement.
Fatigue and occasional low-grade fever.

Diagnostic Workup for PM

Diagnosis involves a combination of clinical evaluation and specialized testing:

1. Blood Tests

Elevated muscle enzymes: CK (creatine kinase), aldolase.
Autoantibodies: Presence of myositis-specific autoantibodies (MSAs) and myositis-associated antibodies (MAAs).

2. Electromyography (EMG)

Measures muscle electrical activity; abnormalities support muscle inflammation.

3. Magnetic Resonance Imaging (MRI)

Detects areas of muscle inflammation and damage.

4. Muscle Biopsy

Confirms diagnosis by revealing inflammation, necrosis, and immune cell infiltration.

5. Physical Examination

Focus on muscle strength and distribution of weakness.

The Role of Myositis-Specific Autoantibodies (MSAs)

MSAs are increasingly recognized as essential tools in classifying inflammatory myopathies, predicting prognosis, and guiding treatment.

Why MSAs Matter

Prognosis: Certain antibodies are linked to severe disease, while others indicate a milder course.
Treatment guidance: Helps tailor immunosuppressive therapy.
Phenotypic classification: Distinguishes between clinical subtypes.

Drugs that May Trigger or Worsen Myositis:

Statins (e.g., atorvastatin, simvastatin): May induce autoimmune myopathy; associated with anti-HMGCR antibodies.
Colchicine: Known to cause drug-induced myopathy.
Hydroxychloroquine: Can cause myopathy, especially in certain myositis subtypes.
Vincristine and other chemotherapy agents: Linked to muscle toxicity.
Cardiovascular drugs (e.g., amiodarone, clofibrate): May contribute to muscle inflammation.
Interferon alpha: Can induce myositis in some cases.

Steroids: Use with Monitoring

High-dose corticosteroids are first-line but long-term use can cause steroid-induced myopathy.
Gradual tapering and combination with steroid-sparing agents like methotrexate or azathioprine are often necessary.

Management Strategies

Individualized treatment plans based on antibody status, clinical severity, and organ involvement.
Immunosuppressive therapy: Steroids, methotrexate, azathioprine, mycophenolate mofetil, or IVIG.
Monitoring for ILD and other systemic involvement, particularly in anti-synthetase and anti-MDA5 positive patients.
Physical therapy and rehabilitation for muscle strength and function.

Medications to Use with Caution in PM

While treatment often involves corticosteroids and immunosuppressants, certain medications can worsen muscle inflammation or mimic PM symptoms.

Medications to Avoid or Monitor Closely:

Statins (e.g., atorvastatin, simvastatin)
Linked to muscle toxicity and can trigger or mimic polymyositis.
Colchicine & Hydroxychloroquine
Known to cause drug-induced myopathy. Hydroxychloroquine is especially controversial—it may worsen PM but is sometimes used in dermatomyositis.
High-dose Corticosteroids
Although they reduce inflammation, prolonged use can lead to steroid-induced myopathy. Dose tapering and monitoring are essential.
Chemotherapy Drugs
Agents like vincristine, hydroxyurea, and some interferons have been associated with myositis.
Cardiovascular Agents
Drugs like amiodarone and clofibrate can cause muscle inflammation.

Key Principle:

Treatment should be individualized. Risk-benefit analysis is crucial when selecting medications, especially in patients with co-existing conditions or a history of drug sensitivity.

Management Strategies

Individualized treatment plans based on antibody status, clinical severity, and organ involvement.
Immunosuppressive therapy: Steroids, methotrexate, azathioprine, mycophenolate mofetil, or IVIG.
Monitoring for ILD and other systemic involvement, particularly in anti-synthetase and anti-MDA5 positive patients.
Physical therapy and rehabilitation for muscle strength and function.

Conclusion

Polymyositis is a complex autoimmune muscle disease with a variable presentation and prognosis. The growing understanding of myositis-specific autoantibodies (MSAs) has revolutionized how clinicians diagnose, classify, and treat this condition.

By identifying specific antibodies like anti-Jo-1, anti-SRP, or anti-MDA5, healthcare providers can predict disease behavior, tailor treatments, and anticipate complications such as interstitial lung disease or malignancy.

Ongoing research continues to refine our understanding of PM and related myopathies, with the ultimate goal of personalized and more effective care for patients.

References:
Polymyositis (PM) https://www.musculardystrophyuk.org/conditions/a-z/polymyositis-pm/

Polymyositis https://my.clevelandclinic.org/health/diseases/12053-polymyositis

Polymyositis (PM) https://www.mda.org/disease/polymyositis/causes-inheritance

Updates on All Things Myositis – Part 1 https://www.youtube.com/watch?v=WNRy_llTiRI

Is Myositis related to TLR3 and ATG 13
https://swaresearch.blogspot.com/2023/11/is-myositis-related-to-tlr3-and-atg-13.html

Disclaimer: By accessing and reading this blog, you acknowledge that the information provided is for general informational purposes only and does not constitute medical advice, diagnosis, or treatment. The content is intended to address commonly asked questions and is derived from reputable scientific literature. Always consult a qualified healthcare professional for medical concerns or conditions.

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