What is the initial approach to a myopathy (muscle disease) workup?

Initial Myopathy Workup

Begin with a focused history and examination targeting muscle weakness pattern, followed by creatine kinase (CK) measurement, and proceed to EMG and/or MRI when diagnosis remains uncertain, with muscle biopsy reserved for cases where inflammatory versus non-inflammatory myopathy cannot be distinguished. 1

History and Physical Examination

Key Clinical Features to Assess

• Pattern of weakness: Proximal versus distal distribution, symmetric versus asymmetric involvement 1
• Distinguish weakness from pain: True muscle weakness (difficulty standing, lifting arms, climbing stairs) is more typical of myositis than myalgia alone 1
• Temporal course: Acute (days to weeks) versus subacute (weeks to months) versus chronic (months to years) onset 1
• Associated symptoms: Myoglobinuria, contractures, myotonia, dysphagia, respiratory difficulty 2
• Skin examination: Look for heliotrope rash, Gottron papules, periorbital edema, periungual telangiectasias, photosensitive rash suggesting dermatomyositis 1
• Cardiac symptoms: Palpitations, chest pain, dyspnea on exertion 1, 3
• Medication history: Statins, corticosteroids, immune checkpoint inhibitors 1, 4
• Systemic symptoms: Fever, weight loss, malignancy risk factors 1

Neurologic Examination Specifics

• Muscle strength testing: Formal validated measures of proximal muscle groups (shoulder abduction, hip flexion) 1
• Nailfold capillaroscopy: Assess for capillary abnormalities suggestive of inflammatory myopathy 1

Initial Laboratory Testing

First-Line Blood Tests

• Creatine kinase (CK): Primary marker of muscle injury; can be normal despite active disease in some myopathies 1, 4
• Aldolase: May be elevated when CK is normal in certain myopathies (dermatomyositis, glycogen storage diseases) 5
• Transaminases (AST, ALT): Can be elevated in muscle disease, not just liver disease 1
• Lactate dehydrogenase (LDH): Additional muscle enzyme marker 1
• Inflammatory markers: ESR and CRP 1

Cardiac Evaluation

• Troponin: Essential to evaluate myocardial involvement, which can be life-threatening 1
• Electrocardiogram (ECG): Screen for conduction abnormalities 1, 4
• Echocardiogram: Assess for cardiomyopathy, particularly in suspected inflammatory myopathy 1

Additional Initial Tests

• Thyroid function tests: Exclude thyroid-related myopathy 6
• 25-OH vitamin D level: Screen for osteomalacia-related weakness 6
• Myositis-specific autoantibodies: Anti-Jo-1, anti-Mi-2, anti-SRP, anti-TIF1-γ, anti-NXP2, anti-MDA5 when inflammatory myopathy suspected 1, 5

Important caveat: Autoantibodies are absent in 20-30% of inflammatory myopathy cases, so negative results do not exclude the diagnosis 4

Advanced Diagnostic Testing

When to Proceed Beyond Initial Labs

Advance to EMG, MRI, or biopsy when: 1, 6

• No toxic, metabolic, or endocrine cause identified on initial testing
• Clinical features suggest inflammatory or hereditary myopathy
• Diagnosis remains uncertain despite initial workup

Electromyography (EMG)

Indications: 1

• Confirm myopathic versus neuropathic process
• Target muscle for biopsy
• Differentiate from neuromuscular junction disorders (myasthenia gravis)

Expected myopathic findings: Polyphasic motor unit action potentials of short duration and low amplitude with increased insertional and spontaneous activity, fibrillation potentials, sharp waves, or repetitive discharges 1

Limitations: Normal EMG does not exclude myopathy; EMG does not reliably detect metabolic myopathies 1, 4

Magnetic Resonance Imaging (MRI)

Technique: T2-weighted and STIR (short tau inversion recovery) sequences with fat suppression to detect muscle edema and inflammation 1

Utility: 1, 4

• Confirm myositis diagnosis
• Identify optimal muscle for biopsy (choose affected muscle showing edema)
• Monitor treatment response
• May avoid need for invasive EMG or biopsy in children

Active inflammatory myositis shows: T2 hyperintensity and muscle edema 4

Muscle Biopsy

Gold standard for diagnosis: Differentiates inflammatory from non-inflammatory myopathy and provides subclassification 1

Indications: 1

• Diagnosis uncertain after non-invasive testing
• Atypical presentation, especially absence of rash when inflammatory myopathy suspected
• Distinguish inflammatory myopathy from muscular dystrophy or metabolic myopathy
• Overlap with neurologic syndromes

Technique: 1

• Biopsy weak muscle identified by EMG or MRI
• Use opposite side muscle from EMG-tested muscle to avoid sampling artifact
• Standardized scoring tools should be used for interpretation
• Expert histopathology review required

Expected findings by diagnosis: 1

• Inflammatory myopathy: Mononuclear cell infiltration of non-necrotic muscle fibers (polymyositis), perivascular inflammation (dermatomyositis)
• Muscular dystrophy: Reduction/absence of dystrophin, degenerating/regenerating fibers, fat/connective tissue replacement
• Mitochondrial myopathy: Ragged red fibers on Gomori trichrome stain, subsarcolemmal mitochondrial accumulation

Screening for Associated Conditions

Pulmonary Assessment

• Pulmonary function tests: Including CO diffusion capacity 1, 4
• Chest X-ray or high-resolution CT: If PFTs suggest interstitial lung disease 1
• Negative inspiratory force and vital capacity: When respiratory muscle involvement suspected 4

Malignancy Screening

• Indicated for: Adult patients with dermatomyositis, particularly those with anti-TIF1-γ or anti-NXP2 antibodies 1
• Not routinely indicated: In children with juvenile dermatomyositis unless suggestive examination findings (hepatosplenomegaly, extensive lymphadenopathy) 1

Additional Organ System Evaluation

• Swallow assessment: Speech and language therapy evaluation, video fluoroscopy/barium studies for dysphagia 1
• Abdominal ultrasound: When gastrointestinal involvement suspected 1

Algorithmic Approach Summary

1. History and examination → Identify weakness pattern, associated features, medication exposures 1
2. Initial labs → CK, aldolase, AST, ALT, LDH, ESR, CRP, troponin, TSH, vitamin D 1, 6
3. Cardiac screening → ECG and echocardiogram 1
4. If inflammatory myopathy suspected → Myositis-specific autoantibodies, nailfold capillaroscopy 1
5. If diagnosis uncertain → MRI of proximal muscles with STIR sequences 1, 4
6. If still uncertain or atypical → EMG to confirm myopathic process 1
7. If definitive diagnosis needed → Muscle biopsy of affected muscle 1

Critical pitfall: Do not delay cardiac evaluation, as myocardial involvement can be life-threatening and requires urgent treatment 1, 4