Inflammatory Myopathies - Myopathies, Inflammatory

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

Indications for Testing

  • Progressive muscle weakness (usually proximal) 
  • 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
    • Myositis-specific antibodies

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
    • Findings on muscle biopsy are usually diagnostic for specific subtypes

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

  • 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
  • Creatinine kinase myoglobin, and lactate dehydrogenase (LD) levels are most useful in monitoring therapeutic response
  • Necrotizing autoimmune myopathy
    • Decline in anti-HMGCR antibodies associated with treatment 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

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

3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase (HMGCR) Antibody, IgG 2013101
Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay

Limitations

Diagnostic relevance in a minor subset of patients with inflammatory myopathy

Results should be used in conjunction with clinical findings, muscle biopsy and other relevant laboratory tests for disease evaluation

Related Tests

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

Ancuta C, Ancuta E, Chirieac R. Aminoacyl-tRNA Synthetases in Idiopathic Inflammatory Myopathies: An Update on Immunopathogenic Significance, Clinical and Therapeutic Implications. In: Idiopathic Inflammatory Myopathies - Recent Developments, Gran, JT, editor. InTech. [Accessed: Jan 2016]

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 AL. Myositis autoantibodies. Curr Opin Rheumatol. 2012; 24(6): 602-8. PubMed

Catalán M, Selva-O'Callaghan A, Grau JM. 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 MC. Inflammatory muscle diseases. N Engl J Med. 2015; 372(18): 1734-47. PubMed

Dimachkie MM, Barohn RJ, Amato AA. Idiopathic inflammatory myopathies. Neurol Clin. 2014; 32(3): 595-628, vii. PubMed

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

Feldman BM, Rider LG, Reed AM, Pachman LM. Juvenile dermatomyositis and other idiopathic inflammatory myopathies of childhood. Lancet. 2008; 371(9631): 2201-12. PubMed

Gunawardena H, Betteridge ZE, McHugh NJ. Myositis-specific autoantibodies: their clinical and pathogenic significance in disease expression. Rheumatology (Oxford). 2009; 48(6): 607-12. PubMed

Hamann PD H, Cooper RG, McHugh NJ, Chinoy H. Statin-induced necrotizing myositis - a discrete autoimmune entity within the "statin-induced myopathy spectrum". Autoimmun Rev. 2013; 12(12): 1177-81. PubMed

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

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

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

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

Mammen AL, Chung T, Christopher-Stine L, Rosen P, Rosen A, Doering KR, Casciola-Rosen LA. Autoantibodies against 3-hydroxy-3-methylglutaryl-coenzyme A reductase in patients with statin-associated autoimmune myopathy. Arthritis Rheum. 2011; 63(3): 713-21. PubMed

Mammen AL, Gaudet D, Brisson D, Christopher-Stine L, Lloyd TE, Leffell MS, Zachary AA. Increased frequency of DRB1*11:01 in anti-hydroxymethylglutaryl-coenzyme A reductase-associated autoimmune myopathy. Arthritis Care Res (Hoboken). 2012; 64(8): 1233-7. PubMed

Mammen AL. Statin-Associated Autoimmune Myopathy. N Engl J Med. 2016; 374(7): 664-9. PubMed

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

Solomon J, Swigris JJ, Brown KK. Myositis-related interstitial lung disease and antisynthetase syndrome. J Bras Pneumol. 2011; 37(1): 100-9. PubMed

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

van der Kooi AJ, 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 TD, Schroder C, Martins TB, Mouritsen L, Hill HR. 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: April 2016