Characteristics and Treatment of Muscle Diseases
Muscle diseases encompass a diverse group of disorders characterized by muscle weakness, elevated muscle enzymes, and specific histopathological changes, with treatment approaches varying based on disease type, severity, and underlying pathophysiology. 1
Major Categories of Muscle Diseases
Idiopathic Inflammatory Myopathies (IIMs)
- Clinical presentation: Symmetric proximal muscle weakness, elevated muscle enzymes, extramuscular manifestations (fever, weight loss, rash) 1
- Subtypes:
- Polymyositis (PM): CD8+ T-cell infiltration of non-necrotic muscle fibers
- Dermatomyositis (DM): Characteristic skin rashes with muscle weakness
- Immune-mediated necrotizing myopathy (IMNM): Severe myopathy with minimal inflammatory infiltrate
- Sporadic inclusion body myositis (sIBM): Degenerative features with amyloid-β and phosphorylated tau protein accumulation 1
Muscular Dystrophies
- Characteristics: Progressive loss of muscle fibers leading to increasing weakness and reduced VO₂max 2
- Examples: Duchenne muscular dystrophy and Becker's muscular dystrophy, characterized by absent or reduced dystrophin protein 3
Congenital Myopathies (CM)
- Presentation: Hypotonia and weakness from birth with static or slowly progressive course
- Features: Facial weakness, ptosis, generalized hypotonic posture, hyporeflexia, poor muscle bulk, proximal weakness
- Structural abnormalities: Nemaline rods, cores, central nuclei, hyaline bodies
- Cardiac involvement: Rare but can include hypertrophic, dilated cardiomyopathy and LVNC phenotypes 1
Metabolic Myopathies
- Characteristics: Preserved muscle bulk and resting strength with exercise intolerance
- Symptoms: Exertional muscle pain, cramping, weakness, fatigue
- Examples: Pompe disease (glycogen storage disease type II), disorders of glycolysis, mitochondrial myopathies 3, 2
Diagnostic Approach
Clinical Assessment
- Evaluate distribution, symmetry, and progression of muscle weakness 4
- Assess for associated symptoms (myoglobinuria, contractures, myotonia, cardiac disease, respiratory insufficiency) 5
Laboratory Testing
- Muscle enzymes: CPK, LDH, AST (often elevated)
- Complete blood count and metabolic panel
- Inflammatory markers: ESR, CRP
- Autoantibody testing: ANA, myositis-specific antibodies 4
- Specific biomarkers: Glucose tetrasaccharide (Glc4) in urine for Pompe disease 1
Imaging and Electrophysiology
- MRI: Important for assessment of muscle inflammation 1
- EMG: Useful to document presymptomatic myopathy 1
- ECG: May show specific abnormalities (e.g., short PR interval in infantile Pompe disease) 1
Muscle Biopsy
- Gold standard for diagnosis of many muscle diseases
- Reveals specific histopathological patterns:
- Inflammatory infiltrates in IIMs
- Dystrophic changes in muscular dystrophies
- Specific structural abnormalities in congenital myopathies 1
Treatment Approaches
Inflammatory Myopathies
Initial Treatment
- Moderate disease: Prednisone 0.5-1 mg/kg/day
- Severe disease: Prednisone 1 mg/kg/day or IV methylprednisolone 1-2 mg/kg
- Life-threatening manifestations: IV pulse methylprednisolone (500-1000 mg/day for 3-5 days) 4
Steroid-Sparing Agents
- First-line: Methotrexate (15-25 mg weekly)
- Alternatives: Azathioprine, mycophenolate mofetil 4
Refractory Disease
- IVIG: For patients with inadequate response to first-line therapies
- Rituximab: Effective in approximately 62% of IMNM cases, particularly anti-SRP antibody-positive cases
- Biologic agents: TNF-α or IL-6 antagonists in selected refractory cases 4
Muscular Dystrophies
- Currently no curative treatments
- Supportive care and management of complications 3
Metabolic Myopathies
- Disease-specific treatments (e.g., enzyme replacement therapy for Pompe disease)
- Dietary modifications and exercise adaptations 2
Monitoring and Supportive Care
Disease Monitoring
- Regular assessment of muscle strength
- Serial creatine kinase measurements
- Functional status improvement
- Annual assessment of disease damage using validated indices 4
Supportive Measures
- Pain management with acetaminophen or NSAIDs if no contraindications
- Appropriate exercise program monitored by a physiotherapist
- Sun protection for patients with dermatomyositis
- Calcium and vitamin D supplementation to prevent steroid-induced osteoporosis 4, 6
Complications and Cautions
- Steroid therapy: Risk of adrenal insufficiency with abrupt discontinuation, osteoporosis, gastrointestinal complications 6
- Cardiac complications: Progressive atrioventricular or intraventricular conduction defects and tachyarrhythmias in certain muscle diseases 1
- Respiratory complications: May be life-threatening in some muscle diseases 1
Disease-Specific Considerations
Pompe Disease
- Differential diagnosis includes limb girdle muscular dystrophy, Becker muscular dystrophy, myasthenia gravis
- Infantile form typically presents with hypertrophic cardiomyopathy
- Late-onset form presents as proximal myopathy 1
Juvenile Dermatomyositis
- Affects children younger than 18 years
- Characterized by proximal muscle weakness and distinctive cutaneous manifestations 1
By understanding the specific characteristics of different muscle diseases, clinicians can develop targeted diagnostic and treatment approaches to improve outcomes for patients with these complex disorders.