Diagnosis of Inflammatory Myopathies

The diagnosis of the exact subtype of inflammatory myopathy is based on the combination of clinical history, tempo of disease progression, pattern of muscle involvement, muscle enzyme levels, electromyographic findings, muscle-biopsy analysis, and for some conditions, the presence of certain autoantibodies.

Criteria Supporting the Diagnosis of Inflammatory Myopathies

Criterion Dermatomyositis Polymyositis Necrotizing Autoimmune Myositis Inclusion-Body Myositis
Pattern of muscle weakness Subacute onset of proximal symmetric weakness with characteristic skin rash in patients of any age Subacute onset of proximal symmetric weakness in adults (diagnosis is made when other causes have been ruled out)* Acute or subacute onset of proximal, often severe weakness in adults Slow onset of proximal and distal weakness; atrophy of quadriceps and forearms; frequent falls; mild facial muscle weakness in people older than 50 years of age
Creatine kinase level High, up to 50 times the upper limit of normal; can at times be normal High, up to 50 times the upper limit of normal in early active disease; may linger at up to 10 times the upper limit of normal Very high; more than 50 times the upper limit of normal in early active disease Up to 10 times the upper limit of normal; can be normal or slightly elevated
Electro- myography Myopathic units (active and chronic) Myopathic units (active and chronic) Active myopathic units Myopathic units (active and chronic) with some mixed large-size potentials
Muscle biopsy Perivascular, perimysial, and perifascicular inflammation; necrotic fibers in “wedge-like” infarcts; perifascicular atrophy; reduced capillaries† CD8+ cells invading healthy fibers; widespread expression of MHC class I antigen; no vacuoles; ruling out of inflammatory dystrophies Scattered necrotic fibers with macrophages; no CD8+ cells or vacuoles; deposits of complement on capillaries‡ CD8+ cells invading healthy fibers; widespread expression of MHC class I antigen; autophagic vacuoles,§ ragged-red or ragged-blue fibers; congophilic amyloid deposits¶
Autoantibodies Autoantibodies Anti-MDA-5, anti-Mi-2; anti-TIF-1 and anti-NXP-2 (implicated in cancer- associated dermatomyositis) Antisynthetase antibodies (often seen in overlap myositis) associated with interstitial lung disease, arthritis, fever, and “mechanic’s hands” Anti-SRP and anti-HMGCR, specific for necrotizing autoimmune myositis Anti-cN1A (of uncertain pathologic significance)
Magnetic resonance imaging May show active inflammation May show active inflammation; could guide biopsy site May show active inflammation; could guide biopsy site Shows selective muscle involvement, but might be difficult to distinguish atrophy from chronic inflammation

* Drug-induced myopathies (e.g., penicillamine, statins, or antiretrovirals), inflammatory dystrophies (such as those due to mutations in the genes encoding dysferlin, calpain, or anoctamin; Becker’s muscular dystrophy; facioscapulohumeral muscular dystrophy; or myofibrillar myopathies), inclusion-body myositis, necrotizing autoimmune myositis, metabolic myopathies, and fasciitis or fibromyalgia need to be ruled out.
† Similar pathologic changes in the perifascicular, perimysial, and interfascicular areas (to a lesser degree of severity) can be seen in overlap myositis (without skin lesions) or the antisynthetase syndrome.
‡ Metabolic muscle diseases presenting as myoglobinuria and toxic or drug-induced myopathies need to be ruled out.
§ In clinical inclusion-body myositis, when patients have the typical inclusion-body myositis phenotype, vacuoles are absent; such patients are erroneously thought to have polymyositis because of polymyositis-like inflammation; ragged-red fibers or cytochrome oxidase–negative fibers are frequently present and are helpful in diagnosis.
¶TDP43 and p62 deposits, detected with the use of immunostaining, have been proposed as tissue biomarkers.
Abbreviations:

  • MHC: Major histocompatibility complex
  • anti-MDA-5: Anti–melanoma differentiation–associated protein-5
  • Anti-Mi-2: Autoantibody directed against a nuclear DNA helicase involved in transcriptional activation
  • Anti-TIF-1: Anti–transcriptional intermediary factor 1
  • Anti-NXP-2: Anti–nuclear matrix protein 2
  • Anti-SRP: Anti–signal recognition particle
  • Anti-HMGCR: Anti–3-hydroxy-3-methylglutaryl–coenzyme A reductase
  • Anti-cN1A, or anti-NT5C1A: Anti–cytosolic 5-nucleotidase 1A

 
 
References:

  1. Dalakas MC. Inflammatory muscle diseases. N Engl J Med. 2015 Apr 30;372(18):1734-47. [Medline]
  2. Dalakas MC. Inflammatory muscle diseases: a critical review on pathogenesis and therapies. Curr Opin Pharmacol. 2010 Jun;10(3):346-52. [Medline]
Created May 13, 2015.
print