What are the diagnostic approaches and treatment options for different types of myositis, including the role of imaging, such as Magnetic Resonance Imaging (MRI), and medications like corticosteroids (e.g. prednisone), methotrexate, and azathioprine?

Comprehensive Guide to Myositis: Diagnosis, Imaging, and Treatment

Diagnostic Approach

The diagnostic workup for myositis requires a systematic evaluation combining clinical assessment, laboratory testing, imaging, and often tissue diagnosis to differentiate between subtypes and guide treatment. 1

Clinical Evaluation

• Muscle weakness is the hallmark of myositis, not pain - this distinguishes it from other rheumatologic conditions 1
• Perform complete rheumatologic and neurologic examination including muscle strength testing, particularly of proximal muscles 1
• Examine skin carefully for dermatomyositis-specific findings (heliotrope rash, Gottron's papules) 1
• Assess for cardiac involvement (myocarditis) and respiratory muscle weakness, which significantly impact mortality 1

Laboratory Testing

Essential blood work includes: 1

• Creatine kinase (CK) - primary marker of muscle inflammation; CK ≥3× upper limit of normal indicates significant disease 1
• Aldolase - alternative muscle enzyme marker 1
• Transaminases (AST, ALT) and LDH - can be elevated but less specific 1
• Troponin and ECG/echocardiogram - mandatory to evaluate myocardial involvement, which requires permanent treatment discontinuation in immune checkpoint inhibitor contexts 1
• Inflammatory markers (ESR, CRP) - typically elevated 1
• Myositis-specific autoantibodies (anti-Jo-1, anti-Mi-2, anti-TIF1γ, anti-NXP2, anti-SRP, anti-HMGCR) - help classify subtypes and predict prognosis 1, 2
• Anti-acetylcholine receptor and anti-striational antibodies if myasthenia gravis overlap suspected 1
• Urinalysis for myoglobin to detect rhabdomyolysis 1

Imaging: MRI Characteristics

MRI of affected proximal limbs is the imaging modality of choice for myositis evaluation 1, 3

Key MRI findings that differentiate myositis: 3

• Active inflammation: T2-weighted and STIR sequences show hyperintense signal in affected muscles indicating edema
• Pattern of involvement: Typically symmetric, proximal muscle groups (thighs, shoulders)
• Fascial involvement: Perifascial and interfascial edema common in dermatomyositis
• Muscle atrophy and fatty replacement: Seen in chronic disease on T1-weighted sequences

MRI helps differentiate myositis from mimics: 3

• Denervation: Follows specific nerve distribution patterns
• Diabetic myonecrosis: Focal, asymmetric involvement with rim enhancement
• Deep venous thrombosis: Associated vascular findings
• Muscular dystrophies: Specific patterns of muscle involvement without significant edema
• Inclusion body myositis: Preferential involvement of quadriceps (especially vastus medialis) and finger flexors with early fatty replacement

Electromyography (EMG) and Muscle Biopsy

• EMG shows muscle fibrillations indicative of myopathy when diagnosis uncertain or neurologic overlap suspected 1
• Muscle biopsy is indispensable for definitive diagnosis when clinical and laboratory findings are equivocal 1, 2
• Biopsy helps distinguish between dermatomyositis (perivascular inflammation), polymyositis (endomysial inflammation), necrotizing myopathy (minimal inflammation with necrosis), and inclusion body myositis (rimmed vacuoles) 2

Major Myositis Subtypes and Differentiation

Dermatomyositis (DM)

• Characteristic skin findings (heliotrope rash, Gottron's papules, shawl sign) 2
• Perivascular and perifascial inflammation on biopsy 2
• Associated with anti-Mi-2, anti-TIF1γ, anti-NXP2 antibodies 2
• Higher malignancy association, especially with anti-TIF1γ 2

Polymyositis (PM)

• Pure muscle weakness without skin involvement 2
• Endomysial inflammation with CD8+ T cells on biopsy 2
• Associated with anti-Jo-1 and other anti-synthetase antibodies 2
• Often has interstitial lung disease component 2

Necrotizing Myopathy (NM)

• Severe, rapidly progressive weakness 2
• Minimal inflammation but extensive muscle fiber necrosis on biopsy 2
• Associated with anti-SRP and anti-HMGCR antibodies 2
• Anti-HMGCR type often statin-associated 2

Inclusion Body Myositis (IBM)

• Late-onset (>50 years), slowly progressive 2, 4
• Distinctive pattern: Asymmetric weakness of quadriceps (especially vastus medialis) and finger/wrist flexors 2, 4
• Rimmed vacuoles and protein aggregates on biopsy 2
• Refractory to immunosuppressive therapy - this is the critical differentiating feature 4

Treatment Approach by Severity

Mild Disease (Grade 1)

For mild weakness with or without pain: 1

• Continue monitoring if CK normal
• If CK elevated with weakness: initiate prednisone 0.5 mg/kg/day 1
• Offer acetaminophen or NSAIDs for myalgia if no contraindications 1
• Consider holding statins to eliminate confounding myopathy 1

Moderate Disease (Grade 2)

For moderate weakness limiting instrumental activities of daily living: 1

• If CK ≥3× upper limit: initiate prednisone 0.5-1 mg/kg/day 1
• Early referral to rheumatologist or neurologist 1
• Obtain EMG and MRI of affected limbs 1
• Most patients require combination therapy: high-dose prednisone plus azathioprine or methotrexate to facilitate early steroid tapering and reduce glucocorticoid-related side effects 5, 6

Severe Disease (Grade 3-4)

For severe weakness limiting self-care or with life-threatening complications: 1

• Initiate prednisone 1 mg/kg/day orally 1
• For severe compromise (respiratory involvement, dysphagia, rhabdomyolysis, cardiac involvement): use methylprednisolone 1-2 mg/kg IV or higher-dose pulse therapy 1
• Urgent referral to rheumatologist and/or neurologist 1
• Consider hospitalization for severe weakness 1

Escalation therapy if no improvement after 2 weeks or worsening: 1

• Plasmapheresis - consider in acute or severe disease (acts rapidly) 1
• IVIG therapy - slower onset of action; note that plasmapheresis immediately after IVIG removes immunoglobulin 1
• Biologic agents: Rituximab, TNF-α antagonists, or IL-6 antagonists 1

Maintenance immunosuppression if symptoms persist after 4 weeks: 1

• Methotrexate, azathioprine, or mycophenolate mofetil 1
• Rituximab has evidence for efficacy in patients with certain myositis-specific autoantibodies 5

Special Considerations for Inclusion Body Myositis

IBM is fundamentally different and refractory to standard immunosuppression 4

• No proven effective treatment exists for reversing or minimizing IBM progression 4
• A trial of oral prednisone combined with methotrexate may be attempted in select patients, but expectations should be tempered 6
• Focus on supportive care, physical therapy, and management of complications (dysphagia, falls) 4

Critical Pitfalls and Caveats

Cardiac Involvement

• Myocardial involvement is a medical emergency with high mortality 1
• Always check troponin and obtain ECG/echocardiogram in all myositis cases 1
• Cardiac involvement requires permanent discontinuation of immune checkpoint inhibitors if that is the etiology 1

Overlap Syndromes

• Myositis can occur with myasthenia gravis - this combination has ominous prognosis with high mortality 1
• Test for anti-acetylcholine receptor antibodies when neurologic overlap suspected 1

Monitoring Treatment Response

• Serial CK levels, ESR, and CRP are essential for monitoring disease activity 1
• Do not restart immune checkpoint inhibitors until CK normalizes and clinical manifestations resolve 1

Steroid-Sparing Strategy

• Early combination with steroid-sparing agents (azathioprine, methotrexate) is recommended to reduce glucocorticoid toxicity 5, 6
• If unable to taper prednisone below 10 mg/day after 3 months, escalate to disease-modifying agents 1

Pre-Treatment Screening

• Test for hepatitis B, C, and latent/active tuberculosis before initiating DMARDs or biologics 1

IL-6 Inhibitor Caution

• IL-6 antagonists can cause intestinal perforation (though extremely rare) and should not be used in patients with concomitant colitis 1

Exercise Therapy

• Combining pharmacological treatment with individualized, supervised exercise is recommended based on evidence showing improved muscle performance 5