What is the approach to diagnosing and treating a patient with suspected myopathy, considering their demographic information, past medical history, and laboratory results?

Approach to Myopathy

Begin by distinguishing true muscle weakness from fatigue or asthenia through focused history, then use pattern recognition based on distribution of weakness, tempo of onset, and associated features to guide targeted diagnostic testing. 1, 2

Initial Clinical Assessment

Critical History Elements

Document the specific pattern and distribution of weakness:

• Proximal versus distal involvement (proximal weakness suggests inflammatory myopathy, distal suggests inclusion body myositis or certain genetic myopathies) 3, 4
• Symmetric versus asymmetric distribution 3
• Functional manifestations: difficulty rising from chair, climbing stairs, lifting objects, combing hair (proximal), versus difficulty with fine motor tasks (distal) 4

Establish temporal characteristics:

• Acute onset (days to 2 weeks): consider rhabdomyolysis, acute inflammatory myopathy, or drug-induced myopathy 3
• Subacute (>2 weeks to ≤2 months): typical for inflammatory myopathies 3, 4
• Insidious (>2 months to years): suggests genetic, metabolic, or inclusion body myositis 3

Identify red flag symptoms requiring urgent evaluation:

• Dysphagia or esophageal dysmotility (aspiration risk, suggests inflammatory myopathy) 3
• Respiratory muscle weakness (respiratory failure risk) 3
• Myoglobinuria (rhabdomyolysis) 5
• Cardiac symptoms (arrhythmias, heart failure in certain myopathies) 3

Physical Examination Priorities

Objectively document strength loss:

• Use manual muscle testing (MMT8) or validated strength assessment 3
• Test neck flexors versus extensors (neck flexors relatively weaker suggests inflammatory myopathy, scores 1.9 points in classification criteria) 3
• Compare proximal to distal strength in legs (proximal weaker than distal scores 0.9-1.2 points) 3

Search for diagnostic skin manifestations:

• Heliotrope rash (purple/lilac periorbital patches, scores 3.1-3.2 points) 3
• Gottron's papules (erythematous-violaceous papules over extensor joints, scores 2.1-2.7 points) 3
• Gottron's sign (erythematous macules over extensor joints, scores 3.3-3.7 points) 3

Assess for extramuscular involvement:

• Nailfold capillary abnormalities (perform capillaroscopy at diagnosis) 3
• Joint hypermobility 3
• Cardiac examination (perform ECG and echocardiogram at diagnosis) 3
• Respiratory assessment (pulmonary function tests including CO diffusion) 3

Essential Family and Medication History

Obtain 3-generation family pedigree looking for: 3

• Cardiomyopathy, heart failure, or sudden cardiac death
• Muscular dystrophy
• Pacemaker/defibrillator placement
• Unexplained deaths

Review all medications, particularly: 3

• Opioids (can cause myopathy and mask symptoms)
• Statins (drug-induced myopathy)
• Corticosteroids (steroid myopathy with chronic use)
• Hydroxychloroquine, tacrolimus, anabolic steroids (can cause LVH/myopathy) 3

Diagnostic Testing Algorithm

First-Tier Laboratory Studies (Obtain in All Patients)

Initial blood work: 3

• Complete blood count
• Comprehensive metabolic panel (electrolytes, renal function, liver transaminases)
• Creatine kinase (CK) - most sensitive marker, elevated in 90% of inflammatory myopathies 3
• Lactate dehydrogenase (LDH), AST, ALT 3
• Thyroid-stimulating hormone 3
• Fasting glucose 3
• Erythrocyte sedimentation rate 1

Interpretation of CK elevation:

• CK >10x upper limit of normal strongly suggests inflammatory myopathy 6
• Note: CK may be normal despite active disease in some cases 3

Second-Tier Studies (Based on Clinical Suspicion)

If inflammatory myopathy suspected (proximal weakness, elevated CK, subacute onset):

• Myositis-specific antibodies, particularly anti-Jo-1 (scores 3.9 points if positive) 3
• Antinuclear antibody 1
• Myositis antibody panel (anti-TIF1-γ, anti-NXP2, anti-MDA5) 3

If metabolic/storage disease suspected (exercise intolerance, myoglobinuria, family history):

• Plasma lactate and pyruvate 3
• Carnitine profile 3
• Urine organic acids and amino acids 3
• Creatine phosphokinase (elevated in metabolic disorders like Danon disease) 3

If infiltrative disease suspected (cardiac involvement, neuropathy, older age):

• Serum immunoglobulin free light chains 3
• Serum and urine protein electrophoresis (for amyloidosis) 3
• Plasma/leucocyte alpha-galactosidase A in men >30 years (for Fabry disease) 3

Electrodiagnostic Studies

Electromyography (EMG) indications: 1

• Confirm presence of myopathy versus neuropathy or neuromuscular junction disorder
• Differentiate myopathy from neuropathy when diagnosis unclear 3
• Note: EMG does not reliably detect metabolic myopathies 3

Nerve conduction studies:

• Perform if suspicion of neuropathy or neuromuscular junction disorder 3

Imaging Studies

Muscle MRI with T2-weighted/STIR sequences: 3

• Aids diagnosis by detecting muscle inflammation
• Guides biopsy site selection
• Can monitor disease activity
• Must be interpreted by expert radiologist 3

Cardiac imaging (all patients with confirmed myopathy): 3

• Echocardiography and ECG at diagnosis
• Repeat if high disease activity, hypertension, or chronic active disease 3

Pulmonary imaging (if interstitial lung disease suspected):

• Chest X-ray initially 3
• High-resolution CT if pulmonary function tests abnormal 3

Muscle Biopsy

Indications for biopsy: 3, 4

• Atypical presentation, especially absence of rash
• Diagnosis remains unclear after non-invasive testing
• Required for definitive diagnosis of many myopathies

Biopsy technique:

• Insufficient evidence to recommend needle versus open biopsy in children 3
• Use standardized scoring tools (e.g., JDM biopsy score) 3
• Requires expert histopathological interpretation 3

Histologic features to assess: 3

• Endomysial infiltration of mononuclear cells (scores 1.7 points)
• Perimysial/perivascular infiltration
• Perifascicular atrophy
• Necrosis and regeneration patterns

Age-Specific Considerations

Pediatric patients (<18 years):

• Represent 25.5% of inflammatory myopathy cases 7
• Use z-scores >2 standard deviations for LV wall thickness diagnosis 3
• Adjust muscle strength thresholds for children <9 years 7
• Additional metabolic screening often required (lactate, pyruvate, ammonia, ketones, free fatty acids) 3

Adults 18-40 years:

• Age of onset scores 1.3-1.5 points in classification criteria 3, 7

Adults ≥40 years:

• Age of onset scores 2.1-2.2 points (higher diagnostic weight) 3, 7
• Median age of onset is 44 years for inflammatory myopathies 7
• Must screen for malignancy (3-8 times increased risk in dermatomyositis) 7

Common Diagnostic Pitfalls

Mistaking weakness for fatigue or asthenia:

• True weakness involves objective loss of strength on examination 1
• Fatigue is subjective tiredness without demonstrable weakness 1

Overlooking drug-induced myopathy:

• Always review medication list, particularly statins, corticosteroids, and immunosuppressants 3, 8
• Corticosteroid-induced myopathy can occur with chronic use and presents with proximal weakness 8

Missing extramuscular manifestations:

• Cardiac involvement may be subclinical but life-threatening 3
• Interstitial lung disease requires proactive screening 3
• Dysphagia increases aspiration risk and requires formal assessment 3

Inadequate family history:

• Many genetic myopathies have incomplete penetrance 3
• Update family history periodically as relatives may develop symptoms later 3

Relying solely on CK levels:

• CK may be normal in active inflammatory myopathy 3
• Conversely, CK elevation alone does not confirm myopathy diagnosis 1

Specialized Referral Indications

Refer to comprehensive myopathy/neuromuscular center when: 3

• Diagnosis remains uncertain after initial workup
• Complex disease-related management decisions required
• Considering muscle biopsy or genetic testing
• Severe or rapidly progressive weakness
• Significant cardiac or pulmonary involvement