How do you diagnose or differentiate steroid-induced myopathy from other types of myopathy in a patient with a history of corticosteroid (e.g. prednisone) use?

Diagnosing and Differentiating Steroid-Induced Myopathy

Steroid-induced myopathy is primarily a clinical diagnosis distinguished from inflammatory myopathies by normal or minimally elevated CK levels, absence of inflammatory markers, and characteristic muscle biopsy findings showing type II fiber atrophy without inflammation. 1, 2

Key Diagnostic Features of Steroid-Induced Myopathy

Clinical Presentation

• Painless, progressive proximal muscle weakness affecting hip flexors and shoulder girdle, developing insidiously over weeks to months in chronic cases 3
• Acute steroid myopathy can develop within 1-3 days of initiation, even after a single dose, though this is rare and unpredictable 4
• No muscle pain or tenderness distinguishes it from inflammatory myositis, which typically presents with myalgia 3
• Functional impairment in activities of daily living (difficulty rising from chair, climbing stairs, lifting arms overhead) 2

Laboratory Findings That Differentiate Steroid Myopathy

• CK levels are normal or only minimally elevated (typically <2x normal), contrasting sharply with inflammatory myositis where median CK is approximately 2650 IU/L 5, 2, 3
• ESR and CRP remain normal, whereas inflammatory myopathies show elevated inflammatory markers 6, 5
• Other muscle enzymes (LDH, aldolase, AST) show minimal changes 2, 3
• Absence of myositis-specific antibodies (anti-Jo-1, anti-HMGCR, anti-SRP, anti-Mi2) rules out autoimmune inflammatory myopathy 6, 7

Electromyography Findings

• EMG may show nonspecific myopathic changes (short duration, low amplitude polyphasic potentials) but these are variable and not diagnostic 3
• Unlike inflammatory myositis, there are no fibrillation potentials or spontaneous activity suggesting active muscle inflammation 6
• EMG is most useful to exclude neuropathy or neuromuscular junction disorders 6

Muscle Biopsy Characteristics

• Selective type II (fast-twitch) fiber atrophy is the pathognomonic finding 1, 3
• Complete absence of inflammatory infiltrates, distinguishing it from polymyositis/dermatomyositis which show perivascular and endomysial inflammation 6
• No necrosis or regenerating fibers (unlike inflammatory myopathies) 3
• In severe acute cases, selective loss of thick filaments (myosin) may be seen 8

Diagnostic Algorithm

Step 1: Establish Corticosteroid Exposure

• Document dose ≥5 mg prednisone equivalent daily for ≥3 months for chronic myopathy 1
• For acute myopathy, any dose and duration (even single dose) is possible 4
• Higher risk with fluorinated steroids (dexamethasone, triamcinolone) and in patients with neuromuscular transmission disorders 1, 8

Step 2: Measure CK and Inflammatory Markers

• If CK >3x normal with weakness: This suggests inflammatory myositis, not steroid myopathy; initiate urgent evaluation for life-threatening complications including myocarditis 5
• If CK normal or <2x normal: Consistent with steroid myopathy 2, 3
• Check ESR, CRP (should be normal in steroid myopathy) 6, 5

Step 3: Test for Autoimmune Myositis

• Obtain myositis-specific antibodies (anti-Jo-1, anti-HMGCR, anti-SRP, anti-Mi2, anti-MDA5) 6, 7
• Positive antibodies indicate immune-mediated myopathy, not steroid-induced 7, 9
• Consider that immune-mediated necrotizing myopathy (anti-HMGCR positive) can paradoxically worsen with steroids 9

Step 4: Rule Out Other Causes

• Thyroid function tests to exclude hypothyroid myopathy 6
• Electrolytes, calcium, vitamin D to exclude metabolic myopathies 6
• Statin use history (statin myopathy requires statin discontinuation, not immunosuppression) 7
• Consider muscular dystrophy (check dystrophin gene) if family history or early onset 6
• Consider mitochondrial myopathy if "ragged red fibers" on biopsy 6

Step 5: Consider MRI and Biopsy

• MRI with T2-weighted/STIR sequences shows muscle edema and inflammation in inflammatory myositis but is typically normal or shows only atrophy in steroid myopathy 6
• Muscle biopsy is indicated when:
  • Diagnosis remains uncertain after above workup 6
  • CK is elevated and inflammatory myositis cannot be excluded 5
  • Atypical features suggest alternative diagnosis 6
• Biopsy should target a weak muscle identified by clinical exam or MRI, avoiding the contralateral muscle used for EMG 6

Critical Pitfalls to Avoid

Do Not Assume All Weakness on Steroids is Steroid Myopathy

• Immune-mediated necrotizing myopathy (anti-HMGCR, anti-SRP positive) presents with marked CK elevation (often >10x normal) and requires immunosuppression, not steroid withdrawal 7, 9
• Checkpoint inhibitor myositis has 20% mortality and requires immediate high-dose steroids, opposite of steroid myopathy management 5

Do Not Overlook Acute Steroid Myopathy

• Can develop within 1-3 days, particularly in patients with myasthenia gravis or those receiving neuromuscular blocking agents 4, 8
• May involve respiratory muscles causing quadriparesis and respiratory failure 1, 8
• CK may be elevated in acute cases with rhabdomyolysis, unlike chronic steroid myopathy 10

Do Not Delay Steroid Discontinuation

• Once steroid myopathy is confirmed, taper or discontinue steroids as the primary treatment 2, 3
• Recovery may take weeks to years after steroid cessation 1
• Irreversibility can occur if steroids are continued 4

Do Not Confuse with Polymyalgia Rheumatica

• Polymyalgia rheumatica presents with severe myalgia and fatigue but normal CK, distinguishing it from both steroid myopathy (which has weakness without pain) and inflammatory myositis (which has elevated CK) 5

Management Implications

• If steroid myopathy is confirmed: Reduce steroid dose to minimum effective level, initiate physical therapy and resistance exercise, ensure adequate protein intake 2, 3
• If inflammatory myositis is confirmed: Continue or escalate immunosuppression; consider IVIG for refractory cases 7, 9
• If diagnosis remains uncertain: Muscle biopsy is the gold standard to differentiate inflammatory from non-inflammatory myopathy 6