Inflammatory Myopathies - Myopathies, Inflammatory

  • Diagnosis
  • Algorithms
  • Screening
  • Monitoring
  • Background
  • Pediatrics
  • Lab Tests
  • References
  • Related Content

Indications for Testing

  • Progressive muscle weakness beginning with the proximal muscles
  • Symmetrical or asymmetrical proximal muscle weakness after more common etiologies have been ruled out

Criteria for Diagnosis

  • See Clinical Background section for inflammatory myopathies and definitions

Laboratory Testing

  • Myositis antibody testing

Histology

  • Muscle biopsy – gold standard for diagnosis
    • Usually performed on proximal leg muscles but should not be performed in end-stage muscles
      • MRI may be helpful in choosing muscle
    • Open biopsy preferred – larger sample

Other Testing

  • EMG – changes consistent with myopathy, including increased spontaneous and insertional activity with fibrillation potential, complex repetitive discharges, positive repetitive discharges, positive sharp waves, early recruitment and small polyphasic motor unit potentials
    • Abnormal in 70-90% of patients
    • Not specific for IIM
    • Amyopathic DM may have subtle myopathy on EMG

Imaging Studies

  • Ultrasound – muscle edema with alteration of normal architecture
    • May visualize subcutaneous calcifications
  • CT – fatty infiltration suggests chronic disease
  • MRI – very sensitive for detection of muscle edema; often used to guide biopsy site

Differential Diagnosis

Antinuclear Antibody Testing Algorithm

  • All adult patients with dermatomyositis (DM) should be evaluated for malignancy due to increased risk of malignancy
  • American Academy of Dermatology recommends reevaluation for malignancy every 6-12 months for first 2 years following diagnosis
  • Creatine kinase myoglobin, and lactate dehydrogenase (LD) levels are most useful in monitoring therapeutic response

Idiopathic inflammatory myopathies (IIM) are a group of chronic autoimmune disorders characterized by inflammation and degeneration of skeletal muscles. The original Bohan and Peter criteria classify inflammatory myopathies into dermatomyositis (DM), polymyositis (PM), and inclusion body myositis (IBM). Newer subtypes include necrotizing autoimmune myositis and overlap myositis (Dalakas, 2015).

Epidemiology

  • Incidence – 4-10/million (overall, all subtypes)
  • Age
    • DM – bimodal peaks
      • Childhood
      • 50-70 years
    • PM – age of onset typically >20 years
    • IBM – >50 years
    • Autoimmune necrotizing myositis – primarily adults, often older
  • Sex
    • DM and PM – M<F; 1:2
    • IBM – M>F; 2:1
  • Ethnicity
    • DM – unknown
    • PM – some studies suggest higher prevalence in African Americans compared to general U.S. population
    • IBM – higher prevalence in Caucasians

Pathophysiology

  • DM – microangiopathy affecting skin and muscle with deposition of complement-causing lysis of endomysial capillaries and muscle ischemia
  • PM and IBM – T-cells invade muscle fibers, leading to necrosis
  • Autoimmune necrotizing myositis – scattered necrotic myofiber with myophagocytosis, absence or paucity of T cells

Clinical Presentation

Clinical Background

Epidemiology

  • Incidence – 2-3/million (rare)
  • Age
    • Dermatomyositis (DM) – more common in children
      • Mean onset is 7 years (25% present at <4 years)
    • Polymyositis (PM) – rare in children
    • Juvenile myositis (JM) – children 2-18 years
  • Sex – M<F, 1:2.3
  • Ethnicity
    • JDM – Caucasians
    • JPM – African Americans

Classification

  • Juvenile dermatomyositis (JDM)
  • Juvenile polymyositis (JPM)
  • Juvenile connective tissue disease myositis (JCTM)

Clinical Presentation

Diagnosis

Indications for Testing

  • Symmetrical and proximal muscle weakness

Laboratory Testing

  • Initial screening tests – see adult laboratory testing
  • Muscle biopsy – less frequent in children so antibodies are important

Differential Diagnosis

Indications for Laboratory Testing

Tests generally appear in the order most useful for common clinical situations.
Click on number for test-specific information in the ARUP Laboratory Test Directory

Creatine Kinase, Total, Serum or Plasma 0020010
Method: Quantitative Enzymatic

Anti-Nuclear Antibodies (ANA), IgG by ELISA with Reflex to ANA, IgG by IFA 0050080
Method: Qualitative Enzyme-Linked Immunosorbent Assay/Semi-Quantitative Indirect Fluorescent Antibody

Limitations

ANA ELISA assays have been reported to have lower sensitivities for antibodies associated with nucleolar and speckled ANA-IFA patterns

Follow Up

Recommend cutaneous direct immunofluorescence testing of active edge of new lesion (lesional biopsy) if dermatologic manifestations are present

Myositis-Specific Antibody Panel 2010862
Method: Qualitative Immunoprecipitation/Semi-Quantitative Multiplex Bead Assay

Limitations

Results by themselves are not diagnostic; strong clinical correlation is recommended

Myositis Antibody Comprehensive Panel 2010851
Method: Qualitative Immunoprecipitation/Semi-Quantitative Multiplex Bead Assay

Limitations

Results by themselves are not diagnostic; strong clinical correlation is recommended

Additional Tests Available

Thyroid Stimulating Hormone with reflex to Free Thyroxine 2006108
Method: Quantitative Electrochemiluminescent Immunoassay

Comments

Use to assess thyroid function

Reflex pattern – if the Thyroid Stimulating Hormone is outside the reference interval, then Thyroxine, Free (Free T4) testing will be added

Thyroid Stimulating Hormone 0070145
Method: Quantitative Chemiluminescent Immunoassay

Comments

Preferred test for screening and monitoring of thyroid function

Aldolase, Serum 0020012
Method: Quantitative Enzymatic

Comments

Do not use as a standalone test; this non-specific test has been replaced by more specific markers for muscle or liver damage (eg, CK, alanine aminotransferase [ALT], and aspartate aminotransferase [AST])

Alanine Aminotransferase, Serum or Plasma 0020008
Method: Quantitative Enzymatic

Comments

Evaluate liver function

Aspartate Aminotransferase, Serum or Plasma 0020007
Method: Quantitative Enzymatic

Comments

Evaluate liver function

Lactate Dehydrogenase, Serum or Plasma 0020006
Method: Quantitative Enzymatic

Comments

Monitor therapeutic response

C-Reactive Protein 0050180
Method: Quantitative Immunoturbidimetry

Comments

Preferred test to detect inflammatory processes

Sedimentation Rate, Westergren (ESR) 0040325
Method: Visual Identification

Comments

Evaluate for inflammation

Calcium, Serum or Plasma 0020027
Method: Quantitative Spectrophotometry

Comments

Rule out hypercalcemia as etiology of muscle weakness

If elevated, indicator of active disease

Myoglobin, Serum 0020224
Method: Quantitative Electrochemiluminescent Immunoassay

Comments

Not a standalone test

May be useful in monitoring therapy

Jo-1 Antibody, IgG 0099592
Method: Semi-Quantitative Multiplex Bead Assay

Comments

Screen for inflammatory myopathies

RNP (U1) (Ribonucleic Protein) (ENA) Antibody, IgG 0050470
Method: Semi-Quantitative Multiplex Bead Assay

Signal Recognition Particle (SRP) Antibody 2002098
Method: Immunoprecipitation

PM/Scl-100 Antibody, IgG by Immunoblot with Reflex to ANA IFA 2003040
Method: Semi-Quantitative Immunoblot/Semi-Quantitative Indirect Fluorescent Antibody

Comments

Reflex pattern – if PM/Scl-100 is 11 units or greater, then Anti-Nuclear Antibody (ANA) by IFA, IgG will be added

Guidelines

American Society for Clinical Pathology. Choosing Wisely - Five Things Physicians and Patients Should Question. An initiative of the ABIM Foundation. [Last revision Feb 2015; Accessed: Jan 2016]

General References

Carstens P, Schmidt J. Diagnosis, pathogenesis and treatment of myositis: recent advances. Clin Exp Immunol. 2014; 175(3): 349-58. PubMed

Casciola-Rosen L, Mammen A. Myositis autoantibodies. Curr Opin Rheumatol. 2012; 24(6): 602-8. PubMed

Catalán M, Selva-O'Callaghan A, Grau J. Diagnosis and classification of sporadic inclusion body myositis (sIBM). Autoimmun Rev. 2014; 13(4-5): 363-6. PubMed

Chatterjee S, Prayson R, Farver C. Antisynthetase syndrome: not just an inflammatory myopathy. Cleve Clin J Med. 2013; 80(10): 655-66. PubMed

Dalakas M. Inflammatory muscle diseases. N Engl J Med. 2015; 372(18): 1734-47. PubMed

Dimachkie M, Barohn R, Amato A. Idiopathic inflammatory myopathies. Neurol Clin. 2014; 32(3): 595-628, vii. PubMed

Ernste F, Reed A. Idiopathic inflammatory myopathies: current trends in pathogenesis, clinical features, and up-to-date treatment recommendations. Mayo Clin Proc. 2013; 88(1): 83-105. PubMed

Ernste F, Reed A. Recent advances in juvenile idiopathic inflammatory myopathies. Curr Opin Rheumatol. 2014; 26(6): 671-8. PubMed

Feldman B, Rider L, Reed A, Pachman L. Juvenile dermatomyositis and other idiopathic inflammatory myopathies of childhood. Lancet. 2008; 371(9631): 2201-12. PubMed

Harris B, Mohila C. Essential muscle pathology for the rheumatologist. Rheum Dis Clin North Am. 2011; 37(2): 289-308, vii. PubMed

Huber A. Idiopathic inflammatory myopathies in childhood: current concepts. Pediatr Clin North Am. 2012; 59(2): 365-80. PubMed

Khan S, Christopher-Stine L. Polymyositis, dermatomyositis, and autoimmune necrotizing myopathy: clinical features. Rheum Dis Clin North Am. 2011; 37(2): 143-58, v. PubMed

Lazarou I, Guerne P. Classification, diagnosis, and management of idiopathic inflammatory myopathies. J Rheumatol. 2013; 40(5): 550-64. PubMed

Lynch M, Cohen J. A primer on electrophysiologic studies in myopathy. Rheum Dis Clin North Am. 2011; 37(2): 253-68, vii. PubMed

Mahler M, Miller F, Fritzler M. Idiopathic inflammatory myopathies and the anti-synthetase syndrome: a comprehensive review. Autoimmun Rev. 2014; 13(4-5): 367-71. PubMed

Nasr R, Reed A, Peterson E. Update: biomarkers for idiopathic inflammatory myopathies. Curr Opin Rheumatol. 2012; 24(6): 609-15. PubMed

Solorzano G, Phillips L. Inclusion body myositis: diagnosis, pathogenesis, and treatment options. Rheum Dis Clin North Am. 2011; 37(2): 173-83, v. PubMed

van der Kooi A, de Visser M. Idiopathic inflammatory myopathies. Handb Clin Neurol. 2014; 119: 495-512. PubMed

References from the ARUP Institute for Clinical and Experimental Pathology®

Jaskowski T, Schroder C, Martins T, Mouritsen L, Hill H. Comparison of three commercially available enzyme immunoassays for the screening of autoantibodies to extractable nuclear antigens. J Clin Lab Anal. 1995; 9(3): 166-72. PubMed

Medical Reviewers

Last Update: December 2015