What is the treatment for proximal myopathy?

Treatment of Proximal Myopathy

Treatment of proximal myopathy depends entirely on identifying and addressing the underlying cause—remove offending drugs (especially statins), correct endocrine/metabolic abnormalities, or initiate aggressive immunosuppression for inflammatory myopathies. 1, 2

Immediate Priority: Identify Life-Threatening Causes

Before initiating any treatment, you must urgently assess for conditions requiring immediate intervention:

• Checkpoint inhibitor-induced myositis: If the patient is on anti-PD-1/PD-L1 therapy, immediately check cardiac troponin and obtain ECG, as concurrent myocarditis carries 20% mortality risk. 3 Withdraw immunotherapy immediately if myositis is confirmed, and initiate high-dose glucocorticoids, IVIG, and/or plasma exchange for life-threatening manifestations (dysphagia, dysarthria, dyspnoea). 3

• Assess for bulbar symptoms and respiratory involvement: Dysphagia, dysarthria, dysphonia, or dyspnoea indicate severe disease requiring urgent high-dose methylprednisolone. 3

• Screen for malignancy in dermatomyositis: Adults with dermatomyositis have substantial malignancy risk and require immediate cancer screening. 1

Drug-Induced Myopathy: Remove the Offending Agent

Statins are the most common drug cause of proximal myopathy and produce two distinct patterns requiring different management approaches: 1

• Statin-associated myopathy: Discontinue the statin immediately. Most cases resolve within weeks to months after cessation. 1

• Immune-mediated necrotizing myopathy (IMNM): This statin-triggered autoimmune condition does NOT resolve with statin cessation alone and requires aggressive immunosuppression with high-dose corticosteroids, IVIG, and methotrexate. 1

Other drugs to discontinue: Corticosteroids (which paradoxically cause myopathy with chronic use), SGLT2 inhibitors, and alcohol. 1, 4

Endocrine and Metabolic Causes: Correct the Abnormality

Initial laboratory evaluation must include: 1, 2

• Thyroid function tests (TSH, free T4): Treat hypothyroidism or hyperthyroidism appropriately
• 25-OH vitamin D levels: Supplement if osteomalacia is present
• Cortisol assessment: Both Cushing's syndrome and adrenal insufficiency cause myopathy 3, 4

For Cushing's disease-related myopathy: The pathology is multifactorial, involving protein degradation through the FOXO3 pathway and intramuscular fat accumulation. 3 Definitive treatment requires addressing the hypercortisolism through transsphenoidal surgery. 3 Note that post-remission growth hormone deficiency may contribute to persistent myopathy, and lower 6-month postoperative IGF-I levels strongly predict more severe long-term muscle atrophy. 3

Idiopathic Inflammatory Myopathies: Aggressive Immunosuppression

For newly diagnosed uncomplicated inflammatory myopathy, initiate high-dose corticosteroids immediately (typically prednisone 1 mg/kg/day). 3

Standard Treatment Protocol:

• First-line: High-dose corticosteroids concurrent with methotrexate, azathioprine, or mycophenolate mofetil as steroid-sparing agents. 3

• Severe myositis: Administer high-dose methylprednisolone PLUS IVIG, cyclophosphamide, rituximab, or cyclosporine. 3

• Polymyositis: Characterized by symmetric proximal weakness with CD8+ T cell invasion on biopsy; responds to corticosteroids and immunosuppressants. 1

• Dermatomyositis: Requires immediate cancer screening in adults due to malignancy association, then treat with corticosteroids and immunosuppressants. 1

Critical Monitoring During Corticosteroid Therapy:

Corticosteroids are a major cause of morbidity in long-term management, with primary adverse outcomes being osteoporosis, compression fractures, and avascular necrosis. 3

Implement these preventive measures: 3

• Monitor bone health with routine dual-energy x-ray absorptiometry
• Prescribe calcium and vitamin D supplements
• Add bisphosphonate if osteoporosis develops
• Use Pneumocystis prophylaxis (trimethoprim-sulfamethoxazole) if taking ≥20 mg corticosteroids for ≥4 weeks

Beware of corticosteroid-induced myopathy: Prolonged corticosteroid use itself causes proximal myopathy, creating a treatment paradox. 3 This necessitates aggressive steroid-sparing strategies with early introduction of immunosuppressants.

Diagnostic Workup to Guide Treatment

Creatine kinase (CK) is the single most important initial test: 1, 2

• Normal CK: Consider polymyalgia rheumatica, fibromyalgia, or non-inflammatory causes
• Markedly elevated CK (>2000 IU/L): Suggests inflammatory myositis, IMNM, or rhabdomyolysis 3
• Mildly elevated CK: May indicate statin myopathy or metabolic disorders

Further evaluation when no toxic, metabolic, or endocrine cause is identified: 2

• Myositis-specific antibody panels (anti-Jo-1, anti-SRP) to identify IIM subtypes 1
• Electromyography (EMG) to detect myotonic discharges and confirm myopathy 1
• Muscle MRI to identify inflammation and guide biopsy site 1
• Muscle biopsy as the gold standard to distinguish IIM subtypes 1, 5

Special Populations

Inclusion body myositis (IBM): The most prevalent acquired myopathy above age 50, characterized by vacuolization and abnormal protein accumulation. 1, 4 Unlike other inflammatory myopathies, IBM responds poorly to immunosuppression; focus on physical therapy and rehabilitation. 2

Juvenile dermatomyositis: Occurs in children <18 years with calcinosis cutis and potential gastrointestinal vasculopathy requiring aggressive early treatment. 1