How to diagnose myopathy in a patient, considering their age, medical history, and potential causes?

How to Check for Myopathy

Begin with a focused history targeting the pattern of muscle weakness (proximal versus distal, symmetric versus asymmetric), temporal course (acute, subacute, or chronic), and associated symptoms, followed immediately by creatine kinase (CK) measurement as the primary screening test. 1

Initial Clinical Assessment

History Taking

• Document the specific pattern of weakness: Proximal weakness (difficulty rising from chairs, climbing stairs, lifting arms overhead) versus distal weakness (foot drop, hand weakness), and whether symmetric or asymmetric 1, 2
• Distinguish true weakness from pain or fatigue: Myalgia alone is less typical of myositis than objective weakness 1
• Identify the temporal course: Acute onset (days to weeks), subacute (weeks to months), or chronic/insidious onset (months to years) 1, 2
• Screen for medication exposures: Specifically ask about statins, corticosteroids (prolonged use), opioids, cyclizine, and anticholinergics 2, 3
• Assess for systemic features: Ask about skin rashes (heliotrope rash, Gottron papules), dysphagia, respiratory symptoms, cardiac symptoms, joint pain, Raynaud phenomenon, and weight loss 2
• Obtain family history: To detect congenital or hereditary myopathies 2
• Document travel history: Particularly for Chagas' disease 2

Physical Examination

• Perform a complete neuromuscular examination: Test proximal muscle strength in shoulder abductors, hip flexors, and neck flexors; test distal strength in finger flexors, wrist extensors/flexors, and ankle dorsiflexors 2
• Examine the skin thoroughly: Look for heliotrope rash (violaceous periorbital edema), Gottron papules (erythematous papules over knuckles), periungual telangiectasias, photosensitive rash, and mechanic's hands 1, 2
• Test for joint hypermobility: Assess for connective tissue disease features 2
• Assess for muscle atrophy: Particularly forearm flexors, finger flexors, and quadriceps (classic for inclusion body myositis) 2
• Evaluate for autonomic dysfunction: Check orthostatic pulse rate change (lying to standing), pupillary responses, and sweating patterns 2
• Perform nutritional assessment: Measure height, weight, BMI, and calculate percentage weight loss 2

Initial Laboratory Testing

First-Line Blood Tests

• Measure creatine kinase (CK) as the primary marker: This is the most important initial test, though it can be normal in some active myopathies 1, 4
• Measure aldolase: This may be elevated when CK is normal in certain myopathies, particularly dermatomyositis and metabolic myopathies 1, 4
• Check transaminases (AST, ALT): These can be elevated in muscle disease, not just liver disease 1
• Measure lactate dehydrogenase (LDH): As an additional muscle enzyme marker 1
• Obtain inflammatory markers: ESR and CRP 1

Screening for Secondary Causes

• Screen for hypothyroidism: TSH and free T4 2
• Test for diabetes: Fasting glucose or HbA1c 2
• Check for coeliac disease: Anti-tissue transglutaminase antibodies 2
• Assess electrolytes: Potassium, magnesium, calcium, and phosphate 2
• Evaluate renal and hepatic function: Creatinine, BUN, and liver function tests 2

Nutritional and Additional Markers (if malnourished or steatorrhea present)

• Fat-soluble vitamins: Vitamins A, E, D, and INR (for vitamin K) 2
• Minerals: Iron, ferritin, B12, red blood cell folate, selenium, zinc, and copper 2

Autoantibody Testing

When to Order Autoantibodies

• Request myositis-specific antibodies if inflammatory myopathy is suspected based on elevated CK, proximal weakness, or skin findings 1, 2
• Anti-Jo-1 and anti-synthetase panel: For patients with suspected polymyositis/dermatomyositis, especially with interstitial lung disease 2, 1
• Anti-Mi-2, anti-SRP, anti-TIF1-γ, anti-NXP2: For dermatomyositis subtyping and malignancy risk stratification 1
• Anti-HMGCR antibody: For suspected statin-induced immune-mediated necrotizing myopathy 2, 3

Connective Tissue and Paraneoplastic Antibodies

• Scleroderma antibodies: Anti-centromere, anti-Scl70, anti-M3R 2
• General autoimmune screen: ANA, ANCA, anti-DNA, anti-SMA 2
• Paraneoplastic antibodies (if autonomic dysfunction or rapid progression): ANNA-1 (anti-Hu), anti-CRMP-5 (anti-CV2), ganglionic AChR antibody, anti-VGKC-complex antibodies 2

Advanced Diagnostic Testing

Electromyography (EMG)

• Proceed to EMG when diagnosis remains uncertain after initial workup, or to confirm myopathic versus neuropathic process 1, 5
• Myopathic EMG findings include: Polyphasic motor unit action potentials of short duration and low amplitude, increased insertional activity, spontaneous activity with fibrillation potentials, positive sharp waves, and repetitive discharges 2, 5
• Use EMG to target muscle for biopsy and differentiate from neuromuscular junction disorders 1

Magnetic Resonance Imaging (MRI)

• Order MRI of proximal muscles with STIR sequences to detect muscle edema and inflammation 5, 1
• Active inflammatory myositis shows: T2 hyperintensity and edema on STIR sequences 5
• Use MRI to identify the optimal muscle for biopsy: Choose muscles with edema but not end-stage fatty replacement 1, 5

Muscle Biopsy

• Muscle biopsy is the gold standard for definitive diagnosis when inflammatory versus non-inflammatory myopathy cannot be distinguished 1, 5
• Biopsy an affected proximal muscle that shows abnormalities on MRI or EMG, but avoid muscles that are severely atrophied 5, 1
• Request specific stains and analyses: Routine histology, immunohistochemistry for dysferlin and dystrophin, Gomori trichrome stain for ragged red fibers (mitochondrial myopathy), and inflammatory markers 5
• Inflammatory myopathy findings: Endomysial mononuclear inflammatory infiltrate (polymyositis), perivascular inflammation (dermatomyositis), rimmed vacuoles with congophilic deposits (inclusion body myositis), or necrotizing myopathy with minimal inflammation (immune-mediated necrotizing myopathy) 2

Screening for Complications and Associated Conditions

Pulmonary Assessment

• Obtain pulmonary function tests including CO diffusion capacity to screen for interstitial lung disease, particularly in patients with anti-synthetase antibodies 1
• Measure negative inspiratory force and vital capacity if respiratory muscle symptoms are present 5

Cardiac Evaluation

• Check troponin, ECG, and echocardiogram to exclude cardiac involvement, which can occur in inflammatory myopathies and some muscular dystrophies 5

Malignancy Screening

• Screen for malignancy in adult patients with dermatomyositis, particularly those with anti-TIF1-γ or anti-NXP2 antibodies 1
• Obtain chest X-ray or CT/PET-CT for thymoma or other neoplastic conditions (small cell carcinoma of lung) 2

Swallowing and Gastrointestinal Assessment

• Perform swallow assessment if dysphagia is present, as cricopharyngeal dysfunction is common in dermatomyositis and inclusion body myositis 2, 1

Specialized Testing for Specific Myopathies

Mitochondrial Disorders

• Test plasma and urine thymidine and deoxyuridine, and white blood cell thymidine phosphorylase if mitochondrial myopathy is suspected 2
• Consider TYMP gene testing and screening for related diseases like MELAS (m.3243A>G mutation) 2
• Muscle biopsy with Gomori trichrome stain to identify ragged red fibers, and mitochondrial genome sequencing if indicated 2, 4

Diagnostic Algorithm Based on CK Levels

Elevated CK (>10 times upper limit of normal)

• If symptomatic with muscle pain/weakness: Discontinue statins or other potentially offending medications immediately 2, 3
• Pursue inflammatory myopathy workup: Autoantibodies, EMG, MRI, and consider muscle biopsy 1, 2
• Consider immune-mediated necrotizing myopathy if CK remains markedly elevated despite stopping statins 2, 3

Moderately Elevated CK (3-10 times upper limit of normal)

• If symptomatic: Follow symptoms and CK levels weekly; consider dose reduction or temporary discontinuation of statins 2
• If asymptomatic: Can usually continue treatment with careful monitoring, but consider stopping if CK continues to rise 2

Normal or Minimally Elevated CK

• Check aldolase: If elevated, consider dermatomyositis, glycogen storage diseases, or mitochondrial myopathies 1, 4
• Consider steroid myopathy if patient has been on prolonged corticosteroids with proximal weakness and normal/low-normal CK 5
• Consider inclusion body myositis if insidious onset after age 50 with distal and proximal weakness and only minimally elevated CK 2
• Proceed to EMG and MRI to guide further workup 1, 5

Common Pitfalls to Avoid

• Do not assume normal CK excludes myopathy: Aldolase may be elevated when CK is normal, and some myopathies (steroid myopathy, inclusion body myositis) have minimal CK elevation 1, 4, 5
• Do not attribute elevated AST/ALT solely to liver disease: These enzymes are also released from damaged muscle 1
• Do not continue statins in patients with CK >10 times upper limit of normal and muscle symptoms: This increases risk of rhabdomyolysis and acute kidney injury 2, 3
• Do not overlook drug-induced myopathy: Always review medication list, especially statins, corticosteroids, opioids, and cyclizine 2, 3
• Do not forget malignancy screening in dermatomyositis: Particularly in adults with new-onset disease 1
• Remember that autoantibodies are absent in 20-30% of inflammatory myopathies: Negative antibodies do not exclude the diagnosis 5