What are the initial steps and tests for a myopathy lab workup?

Initial Myopathy Laboratory Workup

The initial laboratory workup for myopathy should include measurement of muscle enzymes (creatine kinase, aldolase, AST/ALT, LDH), inflammatory markers (ESR, CRP), complete blood count, comprehensive metabolic panel, thyroid function tests, and autoantibody testing. 1, 2

Muscle Enzyme Testing

• Creatine kinase (CK) is the most sensitive marker for muscle injury and should be the first test ordered 1, 2
• Aldolase should be measured, as it may be elevated even when CK is normal in some myopathies 1, 3
• Transaminases (AST/ALT) and lactate dehydrogenase (LDH) should be included as they can be elevated in myopathies 1, 2
• Troponin should be checked to evaluate for potential myocardial involvement 1

Inflammatory and Immune Markers

• Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) should be measured to assess for systemic inflammation 1, 2
• Complete blood count with differential to evaluate for underlying infection or malignancy 1
• Autoantibody testing including:
  • Myositis-specific antibodies (e.g., anti-Jo-1, anti-TIF1γ, anti-NXP2) 1, 2
  • Myositis-associated antibodies 1
  • Anti-AChR antibodies to rule out myasthenia gravis when clinically indicated 1

Metabolic and Endocrine Testing

• Thyroid function tests (TSH, free T4) to rule out thyroid disorders 1
• Fasting glucose and HbA1c to assess for diabetes 1
• 25-OH vitamin D level to rule out vitamin D deficiency and osteomalacia 4
• Consider fasting transferrin saturation to screen for hemochromatosis in appropriate patients 1

Additional Testing Based on Clinical Suspicion

• Urinalysis to evaluate for myoglobinuria in cases of suspected rhabdomyolysis 1
• HIV testing in high-risk patients 1
• Consider genetic testing when hereditary myopathies are suspected 5

Imaging and Electrophysiologic Studies

• Electromyography (EMG) should be performed to:
  • Confirm a myopathic process 1
  • Differentiate myopathy from neuropathy 1
  • Target a muscle for potential biopsy 1
• MRI of affected muscles with T2-weighted/STIR sequences can help detect muscle inflammation and guide biopsy site selection 1, 2

Muscle Biopsy Considerations

• Muscle biopsy should be considered when:
  • The presentation is atypical 1
  • There is absence of rash in suspected inflammatory myopathy 1
  • Diagnosis remains uncertain after initial testing 1
  • Metabolic or mitochondrial myopathies are suspected 5
• Biopsy should be performed on a weak muscle, often guided by EMG or MRI findings 1

Special Considerations

• For suspected drug-induced myopathy, detailed medication history is essential (especially statins, fibrates, corticosteroids, hydroxychloroquine, colchicine) 1, 6
• For suspected immune checkpoint inhibitor-related myositis, check CK, aldolase, and troponin immediately due to potential rapid progression 1
• In children with suspected juvenile dermatomyositis, nailfold capillaroscopy should be included in the workup 1
• For suspected vasculitic myopathy, aldolase may be elevated even when CK is normal 7

Diagnostic Algorithm

1. First-line tests (order all simultaneously):

   • Muscle enzymes: CK, aldolase, AST/ALT, LDH
   • Inflammatory markers: ESR, CRP
   • Complete blood count and comprehensive metabolic panel
   • Thyroid function tests
   • 25-OH vitamin D level 1, 2

2. Second-line tests (based on clinical suspicion and first-line results):

   • Autoantibody testing
   • EMG/nerve conduction studies
   • Muscle MRI
   • Specific metabolic or genetic testing 1, 5

3. Third-line tests:

   • Muscle biopsy when diagnosis remains uncertain
   • Specialized testing based on suspected etiology 1

Common Pitfalls to Avoid

• Failing to distinguish true muscle weakness from pain-limited movement 1, 2
• Not considering drug-induced causes of myopathy 6
• Missing cardiac involvement, which can be fatal if not detected early 1
• Overlooking metabolic and endocrine causes of myopathy 1, 5
• Relying solely on CK levels, as some myopathies (particularly vasculitic) may present with normal CK but elevated aldolase 7, 3