What are the causes of proximal muscle weakness of the upper extremities?

Causes of Proximal Muscle Weakness of Upper Extremities

The most common causes of proximal upper extremity muscle weakness include inflammatory myopathies, endocrine disorders, toxic/drug-induced myopathies, metabolic conditions, and hereditary myopathies, with idiopathic inflammatory myopathies being the most significant cause requiring prompt diagnosis and treatment. 1, 2

Inflammatory Causes

Idiopathic Inflammatory Myopathies (IIMs)

• Polymyositis: Characterized by symmetric progressive weakness of proximal upper extremities, elevated muscle enzymes, and minimal skin involvement 1
• Dermatomyositis: Features proximal weakness with characteristic skin manifestations:
  • Heliotrope rash (purple/lilac-colored patches over eyelids)
  • Gottron's papules (erythematous papules over extensor surfaces of joints)
  • Gottron's sign (erythematous macules over joint surfaces) 1
• Inclusion Body Myositis (IBM): Most prevalent acquired myopathy in patients over 50 years 3
• Anti-synthetase syndrome: Features myositis, interstitial lung disease, arthritis, Raynaud's phenomenon, and "mechanic's hands" 1

Autoimmune Connective Tissue Disorders

• Systemic Lupus Erythematosus (SLE)
• Sjögren's Syndrome
• Overlap syndromes 3
• Sarcoidosis with muscle involvement 3

Endocrine and Metabolic Causes

Thyroid Disorders

• Hypothyroidism: Often presents with proximal weakness, myalgia, and elevated CK
• Hyperthyroidism: Can cause proximal myopathy 2, 3

Other Endocrine Disorders

• Hyperparathyroidism
• Adrenal dysfunction (both Cushing's syndrome and Addison's disease)
• Pituitary disorders 3

Metabolic Disorders

• Vitamin D deficiency (Osteomalacia)
• Glycogen storage diseases (e.g., McArdle disease)
• Lipid deposition myopathies 2, 3

Toxic and Drug-Induced Causes

Medications

• Corticosteroids: Long-term use can cause steroid myopathy 4, 3
• Statins: Can cause proximal weakness with elevated CK
• Antimalarials
• SGLT2 inhibitors 3

Toxins

• Alcohol: Chronic consumption can lead to myopathy
• Other environmental toxins 3

Hereditary Myopathies

Muscular Dystrophies

• Limb-girdle muscular dystrophies
• Facioscapulohumeral muscular dystrophy
• Duchenne and Becker muscular dystrophy (primarily affects males)
• Oculopharyngeal muscular dystrophy: Can present with proximal weakness before developing ptosis and dysphagia 5
• Proximal myotonic myopathy 3

Infectious Causes

• Viral myositis: HIV, dengue, influenza, hepatitis B/C, SARS-CoV-2
• Bacterial and parasitic infections affecting muscle 3

Diagnostic Approach

Initial Laboratory Evaluation

• Muscle enzymes: CK, LDH, AST, ALT
• Inflammatory markers: ESR, CRP
• Thyroid function tests
• 25(OH) vitamin D levels
• Complete blood count
• Comprehensive metabolic panel 6, 2

Autoantibody Testing

• Anti-Jo-1 and other myositis-specific antibodies
• ANA and other rheumatologic markers 1, 6

Electrodiagnostic Studies

• EMG to confirm myopathic process and guide muscle biopsy site selection
• Nerve conduction studies to rule out neuropathic processes 1, 6

Imaging

• MRI of affected muscles can show edema in inflammatory conditions
• Chest imaging if interstitial lung disease is suspected 6

Muscle Biopsy

• Gold standard for diagnosis of inflammatory myopathies
• Key findings in IIMs:
  • Endomysial infiltration of mononuclear cells
  • Perimysial/perivascular infiltration
  • Perifascicular atrophy (in dermatomyositis)
  • Rimmed vacuoles (in inclusion body myositis) 1

Common Pitfalls and Caveats

1. Misdiagnosis: Proximal myopathy can be mistaken for other neurological conditions like motor neuron disease or neuropathies.

2. Overlooking treatable causes: Always check for endocrine and metabolic causes before pursuing invasive testing.

3. Respiratory involvement: Monitor for respiratory muscle weakness in progressive myopathies.

4. Cardiac involvement: Some myopathies affect cardiac muscle; consider cardiac evaluation.

5. Medication review: Always perform thorough medication review as many drugs can cause or exacerbate myopathy.

6. Age considerations: In patients over 50, consider inclusion body myositis which may be resistant to immunosuppressive therapy 3.

7. Malignancy screening: Consider malignancy screening in patients with dermatomyositis, as it can be paraneoplastic 2.