Diagnosis of Myalgia: A Systematic Approach
The diagnosis of myalgia requires a structured evaluation that includes specific history elements, physical examination findings, and targeted laboratory testing to identify the underlying cause.
Initial Assessment
Key History Elements
- Pain characteristics: location, intensity, timing (constant vs. intermittent), exacerbating factors (exercise, rest)
- Associated symptoms: weakness, fatigue, fever, rash, joint pain
- Medication history: statins, corticosteroids, immunotherapy agents
- Recent infections or viral illnesses
- Family history of muscle disorders
- Occupational and recreational activities
Physical Examination
- Muscle strength assessment in all major muscle groups
- Evaluation for muscle tenderness, swelling, or atrophy
- Joint examination for evidence of arthritis
- Skin examination for rashes (especially in dermatomyositis)
- Neurological examination including deep tendon reflexes
Laboratory Investigations
First-line Tests
- Creatine kinase (CK) - most useful screening test 1
- Erythrocyte sedimentation rate (ESR) 1
- Complete blood count
- Comprehensive metabolic panel
- Thyroid function tests
- Vitamin D level
Second-line Tests (Based on Clinical Suspicion)
- Autoimmune markers (ANA, RF, anti-CCP)
- Myositis-specific antibodies
- Inflammatory markers (CRP)
- Lactate dehydrogenase (LDH)
Diagnostic Categories
Based on the ESMO guidelines, patients with myalgia can be classified into three main categories 2:
Non-specific myalgia
- Normal laboratory findings
- No evidence of muscle weakness
- Often related to overuse, stress, or fibromyalgia
Inflammatory myalgia
- Elevated inflammatory markers
- May have elevated CK
- Associated with autoimmune conditions or immune checkpoint inhibitor therapy
Metabolic/endocrine myalgia
- May have normal or elevated CK
- Associated with thyroid disorders, vitamin D deficiency, or metabolic myopathies
Advanced Diagnostic Testing
Advanced testing should be pursued when initial evaluation suggests specific muscle pathology 1:
Electromyography (EMG) - indicated when:
- Persistent myalgia with elevated CK
- Muscle weakness is present
- Suspected neurogenic component
Muscle biopsy - indicated when:
- Exertional myalgia with one or more of:
- Myoglobinuria
- Second wind phenomenon
- Muscle weakness
- Muscle hypertrophy/atrophy
- CK >2-3× normal
- Myopathic EMG findings
- Exertional myalgia with one or more of:
Muscle imaging (MRI) - helpful for:
- Localizing affected muscles
- Guiding biopsy site selection
- Assessing inflammation or edema
Special Considerations
Immune Checkpoint Inhibitor-Related Myalgia
For patients on immunotherapy, evaluate for 2:
- Myositis with elevated CK
- Bulbar symptoms (dysphagia, dysarthria)
- Potential myocardial involvement
- Associated myasthenia gravis
Fibromyalgia
Consider when 3:
- Chronic widespread pain (>3 months)
- Fatigue and unrefreshing sleep
- Cognitive issues
- Tender points on examination
- Normal laboratory findings
Myofascial Pain Syndrome
Evaluate for 4:
- Localized muscle pain
- Presence of trigger points
- Pain reproduction with pressure on trigger points
- Normal laboratory findings
Common Pitfalls to Avoid
Overlooking non-muscular causes of myalgia
- Referred pain from joints or bones
- Neurological conditions
- Systemic infections
Missing serious underlying conditions
- Inflammatory myopathies requiring immunosuppression
- Metabolic myopathies requiring specific management
- Endocrine disorders requiring hormone replacement
Premature attribution to psychogenic causes
- Up to two-thirds of patients with myalgia may have no identifiable specific muscle abnormalities on testing, but this doesn't necessarily mean the pain is psychogenic 5
Failure to consider medication-induced myalgia
- Particularly statins, which can cause myalgia with or without CK elevation
By following this systematic approach, clinicians can effectively diagnose the cause of myalgia and develop appropriate treatment strategies based on the underlying etiology.