Inflammatory Myopathies - Myopathies, Inflammatory


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
  • Bohan and Peter criteria for the diagnosis of polymyositis (PM) and dermatomyositis (DM)

    Bohan and Peter Criteria for the Diagnosis of Polymyositis (PM) and Dermatomyositis (DM)

    • Proximal muscle weakness, usually symmetrical
    • Elevated serum muscle enzymes – creatine kinase (CK), aldolase
    • Electromyographic abnormalities
      • Common – myopathic potential (low amplitude, short duration and polyphasic action potentials)
      • Characteristic triad – myopathic potentials, fibrillations, positive sharp waves, increased insertional activity, complex repetitive discharges
    • Muscle biopsy findings typical of PM or DM – necrosis, phagocytosis, regeneration, inflammation
    • Dermatological features of DM, Gottron’s sign or papules, or heliotrope rash

    Definite diagnosis requires 4 criteria with rash for DM and without rash for PM

    Probable diagnosis requires 3 criteria with rash for DM and without rash for PM

    Kahn, 2011

  • Criteria supporting inflammatory myopathy subtypes

    Criteria Supporting Inflammatory Myopathy Subtypes




    Necrotizing Autoimmune


    Pattern of muscle weakness




    Rash present




    Rash present


    Proximal with severe weakness

    Acute or subacute

    Rash absent


    Distal>proximal with atrophy

    Slow onset

    Rash absent





    Children (rare)

    Adult (elderly common)Adult (usually >50 yrs)
    CK levelsHighHigh, may linger in spite of treatmentVery high

    Lower levels

    Normal level not uncommon


    Active and chronic

    Myopathic units

    Active and chronic

    Myopathic units

    Active myopathic units

    Active and chronic

    Myopathic units

    Some mixed large-size potentials






    Antisynthetase antibodies



    Anti-CN1A (uncertain pathologic significance)
    Dalakas, 2015

Laboratory Testing

  • Initial screening tests
    • Creatine kinase (CK) – elevated in most idiopathic inflammatory myopathies (IIM)
      • Most sensitive muscle-derived enzyme test
      • Consider other causes for elevations >100-fold
    • C-reactive protein (CRP)
      • Often unnecessary but frequently performed in evaluation
    • Thyroid stimulating hormone (TSH) – use to evaluate for thyroid disease as etiology of muscle weakness
    • Antinuclear antibodies (ANA)
      • Use to rule out underlying connective tissue disease (CT) or overlap diseases
      • Staining pattern leads to reflex testing
      • Positive in 50-80% of patients with inflammatory myopathies
    • Aldolase, aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LD), serum myoglobin
      • Not usually recommended
      • Variably elevated
      • Highly nonspecific
  • Myositis antibody testing
    • Myositis-specific antibodies

      Antisynthetase Antibodies



      Target autoantigen



      Frequency (%)/Comments


      Histidyl-tRNA synthetase


      Interstitial lung disease (ILD)

      Moderate-to-severe disease

      Adults – 15-20

      Most common antisynthetase antibody

      More common in PM

      Relationship between Jo-1 antibody titer and disease activity reported but not confirmed


      Threonyl-tRNA synthetase


      Severe arthritis

      Adults – <5


      Alanyl-tRNA synthetase

      Raynaud phenomenon

      Pulmonary hypertension

      Adults – <5


      Glycyl-tRNA synthetase

      Mechanic’s hands


      Adults – <5


      Isoleucyl-tRNA synthetase



      Adults – <5


      Asparaginyl -tRNA synthetase


      Adults –<5


      Tyrosyl-tRNA synthetase


      Adults –<1


      Phenylalanyl-tRNA synthetase


      Adults –<1

      Other Myositis-Specific Antibodies


      Signal recognition particle (SRP)

      Necrotizing myopathy

      Severe cardiac involvement

      Adults – 5-10

      JDM – <3


      Nucleosome remodeling deacetylase complex (NuRD)


      Not associated with increased malignancy risk


      Adults – <10

      JDM – 4-10


      Transcriptional intermediary factor 1 gamma (TIF1-γ)

      JDM – DM and ulceration

      Adults – DM, increased malignancy risk

      Adults – 13-21

      JDM – 22-29


      Melanoma differentiation-associated gene 5 (MDA5)


      Rapidly progressive ILD

      Adults – 50-73 CADM (not in Caucasians)

      JDM – not known


      Nuclear matrix protein 2 (NXP2)

      JDM –DM and calcinosis

      Adults – DM, increased malignancy risk, ILD

      Adults – <5

      JDM – 23


      Small ubiquitin-like modifier activating enzyme (SAE)


      Adults – <5

      JDM – <1



      Necrotizing myopathy

      Response to short-term statin withdrawal

      Adults – <10 necrotizing myopathy

      JDM – not known

      *Less common anti-synthetase antibodies (not currently available for testing)

      Myositis-associated antibodies – usually associated with CT diseases and overlap syndromes
      • Anti-PM-Scl – scleroderma-polymyositis
      • Anti-U1-RNP
      • Anti-Ku
      • Anti-Ro (SSA)


  • 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


  • 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

Clinical Background

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).


  • 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


  • 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

  • General features of IIM
    • Musculoskeletal – progressive muscle weakness (usually symmetrical and proximal)
      • Pharyngeal and neck flexion muscles frequently involved, leading to dysphagia and/or myalgia
      • Sparing of ocular muscles
    • Arthralgias/arthritis – wrists, knees, small joints of hands
    • Constitutional – fever, weight loss
    • Pulmonary – fibrosing alveolitis, aspiration pneumonia
    • Gastrointestinal – esophageal dysfunction, dysphagia
    • Cardiovascular – myocarditis, pericarditis, valvular disease, rhythm disturbances
    • Renal – glomerulonephritis, myoglobinuria (rare)
    • Dermatologic – Raynaud phenomenon, rashes, calcinosis over bony prominences
    Antisynthetase syndrome
    • Found almost exclusively in middle-aged women
    • Characterized by
      • Low-grade fevers
      • Interstitial pneumonitis – major determinant of morbidity and mortality
      • Hyperkeratosis, cracking of lateral and palmar aspects of the fingers (mechanic’s hands)
      • Raynaud phenomena
      • Inflammatory polyarthritis, myalgias
    • Presence of antinuclear antibodies known as antisynthetases
    • Characteristic photosensitive rash often accompanied by symmetrical, subacute, proximal muscle weakness
      • Rash usually precedes muscle symptoms
      • Blue-purple rash – symmetrical distribution
      • Violaceous discoloration of upper eyelids with periorbital edema (heliotrope rash)
      • Erythema of metacarpophalangeal proximal and distal joints
        • Raised violaceous rash (Gottron sign) or scaly erythematous plaques over dorsal surface of bony prominences (Gottron papules) – considered pathognomonic for DM
      • Macular erythema over the lower neck and upper chest in a V-distribution (V-sign), over upper back (Shawl sign), or over upper thighs (Holster sign)
      • Telangiectasias at base of fingernails, cuticular overgrowth and periungual erythema
      • Vasculitic skin changes
        • Subcutaneous nodules, periungual infarcts, digital ulcerations
    • Cancer-associated myositis
      • Most commonly associated with DM, but can be found in PM
      • May be diagnosed prior to, simultaneous with, or after myopathy
      • Increased risk of malignancy (20-25%) in adults for the following types (highest risk in first 3-5 years after diagnosis)
    • Amyopathic DM
      • Characteristic cutaneous findings of DM >6 months without muscle involvement
      • May progress to DM
      • Some risk for lung disease, malignancy
      • Electromyography (EMG) may demonstrate subtle myopathy
    • Dominated by muscular presentation
      • No rash
    • Usually subacute presentation
    • May be associated with other autoimmune diseases
    • Diagnosis of exclusion –  must rule out the following
      • Neuromuscular disease
      • Endocrinopathy
      • Muscular dystrophy
      • Known biochemical muscle disorder or familial biochemical disorder
      • Drug-induced myopathy
    • Two types – sporadic, hereditary
    • Small muscles in hand frequently involved
      • Distal weakness is most common – deep finger flexors and foot extensors common
        • Proximal muscles less frequently involved
        • Muscle atrophy early in disease
      • Quadriceps involvement common – associated with frequent falls
      • Facial muscles frequently involved
      • Asymmetric distribution common
    • Extramuscular disease rare – dysphagia is the exception (>50% of patients)
    • May be misdiagnosed as PM, adult-onset muscular dystrophy, or motor neuron disease
    • Associated with other autoimmune diseases
    Necrotizing autoimmune myositis
    • Acute or subacute presentation
    • Severe proximal muscle weakness – clinically indistinguishable from PM
    • May occur in association with cancer, other CT diseases, or drug use (eg, statins)
    • Diagnosis of exclusion
    Overlap syndromes
    • Most common in DM, but can occur with other inflammatory myopathies
    • Myositis in conjunction with connective tissue disease (CT)
      • Most common – systemic sclerosis, mixed connective tissue disease, SLE
    • Rash – faint or transient
    • Frequent association with antisynthetase antibodies
    • Myopathy varies from mild to dominant presentation


Clinical Background


  • 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


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

Clinical Presentation

  • JDM
    • ~85% of juvenile idiopathic inflammatory myopathy (JIIM)
    • Symmetrical and proximal muscle weakness
    • Gottron papules
    • Heliotrope rash
    • Periungual telangiectasia
    • Vasculitis – more common than in adults
    • Other organs
      • Cardiac
      • Joints
      • Gastrointestinal
      • Pulmonary
    • May have family history of other autoimmune diseases
    • Amyopathic (hypomyopathic form)
      • Inflammatory rashes without muscle weakness
      • ~25% develop full blown dermatomyositis (Ernste, 2014)
    • 6-11% of JIIM
    • Occurs in conjunction with another connective tissue (CT) disease
    • Raynaud phenomenon
    • Arthritis
    • Malar rash
    • Intestinal lung disease (ILD)
    • 4-8% 
    • Proximal and distal muscle weakness
    • Frequent falling episodes
    • Cardiac damage


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
  • JIIM subsets of myositis-associated and myositis-specific antibodies (Ernste, 2014)

    JIIM Subsets of Myositis-Associated and Myositis-Specific Antibodies


    JIIM Subgroup

    Clinical Appearance


    • JDM
    • JCTM
    • Cutaneous ulcers
    • Severe DM rashes
    • No malignancy risk
    • Low CK levels
    • Chronic course


    Anti-MJ (NXP-2)JDM
    • Muscle cramps
    • Calcinosis
    • Dysphonia
    • Monocyclic course


    • JCTM (more common)
    • JPM
    • Raynaud phenomenon
    • Sclerodactyly
    • Arthritis


    • JDM
    • JCTM
    • Classic DM rash
    • Mild disease
    • More common in Hispanic patients


    Antisynthetases (eg, anti-Jo1)
    • JPM (more common)
    • JDM
    • JCTM
    • Fever
    • Raynaud phenomenon
    • Arthritis
    • Mechanics hands
    • Interstitial lung disease (ILD)


    • JPM
    • JCTM
    • Raynaud phenomenon
    • Arthritis
    • ILD
    • Dysphagia


    • Severe muscle weakness
    • Chronic falls
    • High CK levels
    • More common in African American populations


    Ernste, 2014

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
Test Name and Number Recommended Use Limitations Follow Up
Creatine Kinase, Total, Serum or Plasma 0020010
Method: Quantitative Enzymatic

Nonspecific indicator of muscle inflammation or damage

Monitor therapeutic response

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

Aid in evaluation of connective tissue disease

Reflex pattern – if ANA are detected by ELISA, then ANA by IFA titer is added

ANA ELISA screen is designed to detect antibodies against dsDNA, histone, SS-A (Ro), SS-B (La), Smith, snRNP/Sm, Scl-70, Jo-1, centromere, and an extract of lysed HEp-2 cells

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

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

Aid in differential diagnosis of inflammatory myopathies in conjunction with muscle biopsy and clinical presentation

Components include Jo-1 antibody, IgG; myositis-specific antibody, Mi-2; myositis-specific antibody, PL-7; myositis-specific antibody, PL-12; myositis-specific antibody, P155/140; myositis-specific antibody, EJ; myositis-specific antibody, SRP; myositis-specific antibody, OJ

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

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

Most useful if general suspicion for inflammatory myopathy exists, including overlap syndromes

Components include PM/Scl-100; SSA 52 and 60 (Ro) (ENA) IgG; RNP (U1) (ribonucleic protein) (ENA) IgG; Jo-1 IgG; Mi-2; PL-7; PL-12; P155/140; EJ; SRP; Ku; U2; and OJ

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

Additional Tests Available
Click the plus sign to expand the table of additional tests.
Test Name and NumberComments
Thyroid Stimulating Hormone with reflex to Free Thyroxine 2006108
Method: Quantitative Electrochemiluminescent Immunoassay

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

Preferred test for screening and monitoring of thyroid function

Aldolase, Serum 0020012
Method: Quantitative Enzymatic

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

Evaluate liver function

Aspartate Aminotransferase, Serum or Plasma 0020007
Method: Quantitative Enzymatic

Evaluate liver function

Lactate Dehydrogenase, Serum or Plasma 0020006
Method: Quantitative Enzymatic

Monitor therapeutic response

C-Reactive Protein 0050180
Method: Quantitative Immunoturbidimetry

Preferred test to detect inflammatory processes

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

Evaluate for inflammation

Calcium, Serum or Plasma 0020027
Method: Quantitative Spectrophotometry

Rule out hypercalcemia as etiology of muscle weakness

If elevated, indicator of active disease

Myoglobin, Serum 0020224
Method: Quantitative Electrochemiluminescent Immunoassay

Not a standalone test

May be useful in monitoring therapy

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

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

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