Endocrine disorders

Hypothyroidism, hypercortisolemia, thyrotoxicosis, hypoparathyroidism, hyperparathyroidism

Testing: Endocrine blood testing

Metabolic disorders

GSDs (primarily McArdle disease [type V] but also III, VII, and XV), lysosomal storage disease (Pompe, previously known as GSD II), mitochondrial myopathy (TK2, MELAS, and other mtDNA mutations), primary systemic carnitine deficiency

Testing: Specific genetic testing (including mtDNA sequencing or nuclear-encoded gene testing, dry blood spot for Pompe disease, muscle histology and enzymatic testing (ie, PFK [GSD VII] and phosphorylase [GSD V]) 

Muscular dystrophy

Most common dystrophies to be mistaken for PM are Miyoshi myopathy due to dysferlin (DYSF) or ANO5 mutations, dystrophinopathy (mainly Becker), other limb girdle MDs (eg, sarcoglycanopathy, caveolin-3). Because nearly every one of >70 types of MD will meet probable criteria for PM (proximal weakness, high CK, myopathic EMG), careful history and examination are essential (medial calf atrophy is characteristic of Miyoshi myopathy and not PM/DM), muscle biopsy (inflammation is common as a secondary finding in MD but invasion is of necrotic fibers unlike in PM where they are nonnecrotic; immunohistochemistry can be classic: patchy or absent dystrophin staining in Becker)

Testing: Immunohistochemistry on muscle biopsy samples and specific genetic testing

Nerve disorders

Spinal muscular atrophy type III (EMG is usually characteristic, CK is normal or minimally elevated), amyotrophic lateral sclerosis (weakness is usually asymmetric but CK can be elevated [usually <1000 IU], EMG shows active changes but recruitment is different than in PM [reduced and large, long vs small duration, brief and early recruiting in PM/DM])

Testing: Genetic testing for SMA; history, examination, and EMG for ALS (El-Escorial criteria)

Neuromuscular junction

LEMS can present with proximal weakness but EMG is not characteristic of PM/DM and CK is usually not elevated. Diagnosis is established with incremental CMAP response post contraction and presence of antibodies to P/Q-type voltage-gated calcium channels. MG usually presents with ocular and bulbar symptoms and only rarely proximal weakness; CK is not usually elevated and EMG is normal. Diagnosis is established by single-fiber EMG, decremental response of CMAP to repetitive stimulation, and presence of specific antibodies (antiacetylcholine receptor, anti-MuSK)

Testing: EMG is suggestive but presence of antibodies is very specific

Infections

Viral, bacterial, parasitic (toxoplasmosis, trichinosis)

Testing: Virology, bacterial culture, and PCR-based testing

Electrolyte disturbances

Decreased or increased plasma levels of sodium, potassium, calcium, magnesium, or phosphate

Testing: Electrolyte analysis in blood

Granulomatous diseases

Sarcoidosis

Testing: Noncaseating granulomas in muscle biopsy, low ACE levels in blood

Drugs

Lipid-lowering agents (statins, rarely fibrates), antimalarial agents (chloroquine and hydroxychloroquine), amiodarone, quinidine, cimetidine, cyclosporine (INN ciclosporin), danazol, D-penicillamine, interferon alpha, interleukin 2, colchicine, epsilon-aminocaproic acid, phenylbutazone, phenytoin, glucocorticoids (common: type 2 muscle fiber atrophy, especially with doses >10 mg), hydralazine, levodopa, penicillin, procainamide, rifampicin, sulfonamides, L-tryptophan, valproic acid, vincristine, some anti-HIV drugs (zidovudine, ddI, ddC)

Toxic substances

Acute exposure to carbon monoxide, alcohol, heroin, cocaine; history and specific testing will easily differentiate these from PM/DM