Extended Myositis Panel Recommendations
Myositis-specific autoantibodies (MSAs) such as anti-TIF1-γ, anti-NXP2, anti-MDA5, and anti-SRP should be included in the extended myositis panel, along with myositis-associated antibodies (MAAs) like anti-PmScl, anti-U1-RNP, anti-La, anti-Ro, and anti-Sm when overlap features are present. 1
Core Components of Extended Myositis Panel
Myositis-Specific Autoantibodies (MSAs)
- Anti-TIF1-γ (p155): Associated with severe dermatomyositis and increased risk of malignancy 1, 2
- Anti-NXP2 (p140/MJ): Associated with calcinosis, severe disease course, and persistent disease activity 1
- Anti-MDA5: Associated with interstitial lung disease, skin/oral ulceration, arthritis, and milder muscle disease 1, 2
- Anti-SRP: Associated with necrotizing autoimmune myopathy 1
- Anti-Jo-1: Part of antisynthetase syndrome, associated with lung involvement 1
- Anti-Mi-2α/β: Associated with classic dermatomyositis 2
- Anti-SAE1: Associated with dermatomyositis 2
- Anti-synthetases: Anti-PL-7, Anti-PL-12, Anti-EJ, Anti-OJ 2
Myositis-Associated Antibodies (MAAs)
For patients with overlap features, include:
- Anti-PmScl (PM-Scl75, PM-Scl100)
- Anti-U1-RNP
- Anti-La (SSB)
- Anti-Ro (SSA)
- Anti-Sm
- Anti-Ku 1
Clinical Context for Testing
High Risk Factors for Cancer Association
Testing for specific MSAs is particularly important for risk stratification in patients with:
- Dermatomyositis
- Age >40 years at disease onset
- Persistent high disease activity despite immunosuppression
- Moderate to severe dysphagia
- Cutaneous necrosis or ulceration 1
Low Risk Factors for Cancer Association
- Antisynthetase syndrome
- Overlap myositis with connective tissue disease
- Anti-SRP positivity
- Anti-Jo-1 or other antisynthetase antibody positivity
- Raynaud phenomenon
- Inflammatory arthropathy
- Interstitial lung disease 1
Diagnostic Value and Interpretation
The extended myositis panel has high specificity (94-95% for MSAs) but lower sensitivity (20-22%), making it more valuable for confirmation than screening 3, 4. Consider these important points when interpreting results:
- Strength of positivity matters: Weak positive antibody levels generally show less diagnostic accuracy compared to strong positives, with the exception of anti-NXP2 5
- Multiple positivity warning: Multiple MSA positivity on line blot assays (occurring in ~17% of cases) should be interpreted with caution as this is rare with gold standard immunoprecipitation methods 6
- Clinical correlation is essential: Antibody results should always be interpreted in conjunction with clinical features, muscle enzymes, imaging, and sometimes biopsy findings 7
Additional Recommended Testing
Beyond the extended myositis panel, a comprehensive evaluation should include:
Laboratory Tests
- Muscle enzymes: CPK, LDH, AST, ALT, aldolase 1, 2
- Inflammatory markers: ESR, CRP 1, 2
- Complete blood count and blood film 2
- Troponin (for cardiac involvement) 1, 2
- Urinalysis (to evaluate for rhabdomyolysis when relevant) 1
Imaging and Functional Studies
- MRI of muscles with T2-weighted/STIR sequences 1, 2
- Nailfold capillaroscopy 1, 2
- Pulmonary function tests with CO diffusion 1, 2
- Echocardiogram and ECG 1, 2
- EMG (when diagnosis is uncertain) 1
Common Pitfalls to Avoid
- Relying solely on ANA testing: ANA has low specificity for myositis and may miss specific myositis subtypes 2
- Overlooking cardiac involvement: Cardiac manifestations can be life-threatening and occur more frequently than previously recognized 2
- Missing associated conditions: Particularly malignancy and interstitial lung disease 1, 2
- Misinterpreting multiple antibody positivity: This may represent technical issues rather than true multiple autoimmunity 6
- Over-reliance on antibody testing alone: Diagnosis should integrate clinical, laboratory, imaging, and sometimes histopathological findings 7
By following these comprehensive recommendations for extended myositis panel testing, clinicians can better characterize myositis subtypes, predict disease complications, and guide appropriate management strategies.