What is the differential diagnosis (Ddx) of myositis?

Differential Diagnosis of Myositis

The differential diagnosis of myositis must systematically distinguish inflammatory myopathies from noninflammatory myopathies, drug-induced conditions, metabolic disorders, infectious causes, and neuromuscular diseases that present with proximal weakness and elevated muscle enzymes.

Noninflammatory Myopathies

Muscular Dystrophies

• Late-onset muscular dystrophy and limb-girdle dystrophy (dysferlinopathies) can present in adult years with proximal weakness and elevated CK, mimicking inflammatory myositis 1
• Muscle biopsy shows reduction or absence of dystrophin with degenerating/regenerating fibers and replacement with fat or connective tissue; mononuclear cell invasion may occur, leading to confusion with polymyositis 1
• Genetic testing for the dystrophin gene should be performed when muscular dystrophy is suspected 1

Mitochondrial Myopathies

• Present with proximal weakness and can have elevated muscle enzymes 1
• Histopathology reveals subsarcolemmal and interfibrillar accumulation of mitochondria with "ragged red fibers" on Gomori trichrome stain and reduction/absence of cytochrome c oxidase 1

Adult-Onset Nemaline Myopathy

• Associated with monoclonal gammopathy and presents with proximal weakness 1

Myotonic Dystrophy Type 2

• Can present with proximal muscle weakness in adults 1

Drug-Induced Myopathies

Statin-Induced Myopathy

• Statins are much more likely than antipsychotics to cause muscle symptoms and should be considered first in patients on these medications 2
• Typically presents with myalgia and mild CK elevation that resolves with drug discontinuation 1

Immune Checkpoint Inhibitor-Associated Myositis

• More common with PD-1/PD-L1 inhibitors than ipilimumab 1
• Can present as reactivation of preexisting paraneoplastic polymyositis/dermatomyositis or de novo myositis 1
• May have fulminant necrotizing course with rhabdomyolysis and can involve myocardium, requiring urgent treatment 1
• CK is often markedly elevated 1

Corticosteroid-Induced Myopathy

• Should be considered in patients on chronic corticosteroid therapy 1
• Typically has normal CK levels, distinguishing it from inflammatory myositis 1

Endocrine and Metabolic Myopathies

Thyroid Disorders

• Both hypothyroidism and hyperthyroidism can cause proximal weakness 1

Hyperparathyroidism

• Can present with muscle weakness and should be excluded with calcium and PTH levels 1

Infectious Myopathies

Viral Myositis

• Benign self-limiting viral myositis is common and should be considered, especially with acute onset 2
• Usually resolves spontaneously within days to weeks 2

HIV-Associated Myopathy

• Shows strong resemblance to polymyositis 3

HTLV-1-Associated Myopathy

• Can present as inflammatory myopathy 3

Rheumatologic Mimics

Polymyalgia Rheumatica

• Presents with severe myalgia in proximal upper and lower extremities with severe fatigue 1
• Key distinguishing feature: patients have pain but NOT true weakness 1
• CK levels are within normal limits, differentiating from myositis 1
• RF and anti-CCP are negative, but inflammatory markers (ESR, CRP) are highly elevated 1
• MRI and EMG show no evidence of myopathy or muscle inflammation 1

Fibromyalgia

• Presents with diffuse pain and fatigue without true weakness 1
• Normal CK and inflammatory markers 1

Other Neuromuscular Conditions

Degenerative Joint Disease/Osteoarthritis

• Can cause pain mimicking myositis but without true proximal weakness 1

Soft Tissue Rheumatic Disorders

• Rotator cuff tendinitis and other soft tissue conditions can mimic myositis symptoms 1

Crystal Arthropathies

• Gout and pseudogout should be excluded 1

Septic Arthritis

• Must be ruled out in acute presentations 1

Critical Diagnostic Approach

Laboratory Evaluation

• Measure CK and repeat in 3-5 days; persistent and marked elevation (>10x normal) suggests necrotizing myopathy 2
• Inflammatory markers (ESR, CRP) are usually very elevated in inflammatory myositis 1
• Request specific myositis autoantibodies (anti-Jo-1, anti-Mi-2, anti-MDA5, anti-SRP) if elevated CK persists 2, 1

Imaging and Electrodiagnostic Studies

• EMG confirms myopathic process with polyphasic motor unit action potentials of short duration and low amplitude, increased insertional activity with fibrillation potentials 1
• MRI shows diffuse muscle edema in true myositis 2

Muscle Biopsy

• Muscle biopsy is the gold standard for confirming inflammatory myositis and distinguishing it from noninflammatory myopathies 1
• Choose a weak muscle demonstrated by EMG abnormalities; biopsy the same muscle on the opposite side 1

Common Pitfalls

• Do not confuse pain with weakness—true myositis causes proximal weakness (difficulty rising from chair, climbing stairs, lifting arms), not just myalgia 1, 2
• Normal CK essentially excludes active inflammatory myositis (except in some cases of dermatomyositis or polymyalgia rheumatica) 1
• Avoid sampling error by selecting an appropriately weak muscle for biopsy guided by EMG findings 1