What are the diagnostic criteria and treatment options for polymyositis?

Polymyositis Diagnosis

Diagnostic Criteria

Polymyositis diagnosis requires a combination of clinical weakness (primarily proximal), elevated muscle enzymes, characteristic electromyography findings, and inflammatory changes on muscle biopsy, with muscle biopsy serving as the gold standard for definitive diagnosis. 1, 2, 3

Clinical Presentation

• Proximal muscle weakness is the hallmark symptom, affecting shoulders and hips more than distal muscles, with patients experiencing difficulty standing up, lifting arms, and moving around 4, 1, 2
• Weakness, not pain, is the primary feature distinguishing true myositis from polymyalgia-like syndromes 4
• Subacute onset over weeks to months is typical, though presentation varies 1
• Neck flexor and extensor weakness may be prominent, particularly in cervicobrachial variants 5
• Myalgia occurs in severe cases but is not the dominant feature 4

Laboratory Evaluation

Creatine kinase (CK) elevation is present in approximately 64% of cases and serves as the primary screening test 6, 1:

• Median CK levels around 1,275-2,650 IU/L in active disease 6, 5
• Normal CK does not exclude polymyositis but makes the diagnosis less likely 6

Additional muscle enzymes to assess 4:

• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT)
• Lactate dehydrogenase (LDH)
• Aldolase

Inflammatory markers (ESR and CRP) are elevated in approximately 55% of cases 4, 6

Autoantibody testing should include 4:

• Antinuclear antibody (ANA)
• Rheumatoid factor (RF)
• Anti-citrullinated protein antibody (anti-CCP)
• Myositis-specific antibodies (anti-Jo-1, anti-synthetase panel)
• Anti-acetylcholine receptor antibodies if myasthenia gravis is suspected 4

Electromyography (EMG)

EMG shows characteristic findings in 45-93% of cases 6, 5, 3:

• Active irritative myopathy with fibrillation potentials (most common finding) 3
• Motor unit action potential changes in configuration, duration, and amplitude 3
• Fibrillation potentials reflect active disease and diminish with successful treatment 3
• Normal EMG occurs in only 11% of cases but does not exclude diagnosis 6

Muscle Biopsy

Muscle biopsy remains the gold standard for definitive diagnosis 1, 2:

• Inflammatory infiltration with endomysial inflammation is virtually diagnostic 6
• 65% show changes with inflammatory infiltration diagnostic of polymyositis 6
• 17% may have normal biopsy despite clinical disease 6
• Biopsy should be performed when diagnosis is uncertain or to differentiate from other myopathies 4

Imaging

MRI of affected muscles provides noninvasive diagnostic support 4:

• T2 hyperintensities indicate muscle inflammation 5
• Contrast enhancement in affected muscles 5
• Useful for guiding biopsy site selection 5
• Can monitor treatment response 7

Critical Differential Diagnoses and Red Flags

Life-Threatening Complications to Rule Out

Myocarditis must be systematically excluded in every polymyositis patient 8:

• Check troponin I (more specific than troponin T when skeletal muscle disease is present) 8
• Obtain electrocardiogram looking for QTc prolongation, conduction abnormalities, or ST-T wave changes 8
• Measure BNP (levels >500 pg/ml indicate significant concern) 8
• Cardiac MRI if any clinical suspicion, elevated troponin, or ECG abnormalities 8
• Myocarditis increases mortality from <10% to approximately 20% 8

Myasthenia gravis co-occurs in 12.5% of immune checkpoint inhibitor-related myositis cases 8:

• Test anti-acetylcholine receptor antibodies 4
• Look for ptosis, diplopia, bulbar symptoms (dysphagia, dysarthria, dysphonia) 8
• Concomitant myasthenia gravis and myocarditis carries ominous prognosis with high mortality 4

Other Important Differentials

• Statin-induced myopathy: Check medication history 4
• Polymyalgia rheumatica: Pain without true weakness, normal CK, no EMG evidence of myopathy 4
• Inclusion body myositis: Chronic progressive course, often refractory to treatment 1
• Necrotizing myopathy: May be immune-mediated or statin-associated 1
• Dermatomyositis: Distinguished by characteristic rash 4, 1

Diagnostic Algorithm

1. Initial clinical assessment: Document pattern and severity of weakness, focusing on proximal muscles 4

2. Laboratory screening 4, 7:

   • CK, AST, ALT, LDH, aldolase
   • ESR and CRP
   • Troponin I and ECG (mandatory cardiac screening)
   • Autoantibody panel (ANA, RF, anti-CCP, myositis-specific antibodies)

3. Cardiac evaluation if any concern 8:

   • BNP measurement
   • Echocardiogram
   • Cardiac MRI if indicated

4. EMG of affected muscles to demonstrate active myopathy 4, 3

5. MRI of affected muscle groups to identify inflammation and guide biopsy 4, 5

6. Muscle biopsy for definitive diagnosis when diagnosis uncertain or to exclude mimics 4, 1

Common Diagnostic Pitfalls

• Failure to screen for malignancy in adult patients, especially with dermatomyositis—this is a critical oversight 7
• Relying solely on CK levels: Normal CK occurs in up to 36% of cases 6
• Missing cardiac involvement: Always obtain troponin and ECG regardless of symptoms 8
• Confusing polymyalgia rheumatica with polymyositis: PMR has pain without weakness and normal CK 4
• Delaying biopsy: When clinical picture is atypical, biopsy should not be delayed 1, 2
• Overlooking immune checkpoint inhibitor history: Myositis can occur weeks to months after ICI initiation 4

Treatment Considerations

High-dose corticosteroids (prednisone 0.5-1 mg/kg/day, typically 60-80 mg daily) should be initiated concurrently with a steroid-sparing immunosuppressive agent such as methotrexate, azathioprine, or mycophenolate mofetil 7, 9, 2:

• Methotrexate works faster and is more effective than azathioprine but should be avoided in patients with anti-Jo-1 antibodies or existing pulmonary disease 2
• Azathioprine is preferred when interstitial lung disease is present 7, 2
• Mycophenolate mofetil is another suitable steroid-sparing option 7

For severe disease with significant weakness limiting mobility, respiratory compromise, or dysphagia 4:

• Consider methylprednisolone 1-2 mg/kg IV or higher-dose pulse therapy
• IVIG therapy (used in up to 20% of severe cases) 8, 2
• Plasmapheresis (used in approximately 10% of cases) 8

If myocarditis is confirmed or suspected, permanently discontinue immune checkpoint inhibitors and initiate emergent high-dose corticosteroids (1 mg/kg methylprednisolone IV) 8

Maximum clinical improvement typically occurs within the first three years of treatment, with 66% of survivors achieving essentially no functional disability 6