Differential Diagnosis of Myositis

Noninflammatory Myopathies

Late-onset muscular dystrophy and limb-girdle dystrophy 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 is associated with monoclonal gammopathy and presents with proximal weakness 1
Myotonic dystrophy type 2 can present with proximal muscle weakness in adults 1

Statins are more likely to cause muscle symptoms than antipsychotics and should be considered first in patients on these medications 2
Statin-induced myopathy typically presents with myalgia and mild CK elevation that resolves with drug discontinuation 3
Immune checkpoint inhibitor-associated myositis is more common with PD-1/PD-L1 inhibitors than ipilimumab 3, 4
Immune checkpoint inhibitor-associated myositis can present as reactivation of preexisting paraneoplastic polymyositis/dermatomyositis or de novo myositis 3, 4
Corticosteroid-induced myopathy should be considered in patients on chronic corticosteroid therapy 3
Corticosteroid-induced myopathy typically has normal CK levels, distinguishing it from inflammatory myositis 3

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

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

Polymyalgia rheumatica presents with severe myalgia in proximal upper and lower extremities with severe fatigue 3, 4
Polymyalgia rheumatica is distinguished by pain but not true weakness, normal CK levels, and highly elevated inflammatory markers (ESR, CRP) 3, 4
Fibromyalgia presents with diffuse pain and fatigue without true weakness 3
Fibromyalgia is characterized by normal CK and inflammatory markers 3

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 4
Request specific myositis autoantibodies (anti-Jo-1, anti-Mi-2, anti-MDA5, anti-SRP) if elevated CK persists 1, 2
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 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

Do not confuse pain with weakness—true myositis causes proximal weakness (difficulty rising from chair, climbing stairs, lifting arms), not just myalgia 2, 4
Normal CK essentially excludes active inflammatory myositis (except in some cases of dermatomyositis or polymyalgia rheumatica) 3
Avoid sampling error by selecting an appropriately weak muscle for biopsy guided by EMG findings 1