What is the recommended evaluation and treatment plan for inflammatory myositis?

Evaluation and Treatment of Inflammatory Myositis

Initial Diagnostic Evaluation

Begin high-dose corticosteroids (prednisone 1 mg/kg/day, typically 60-80 mg daily) immediately upon diagnosis, concurrent with a steroid-sparing agent such as methotrexate, azathioprine, or mycophenolate mofetil. 1, 2

Essential Laboratory Testing

• Creatine kinase (CK) is the single most important test, elevated in the majority of patients with a median level of 2650 IU/L (range 335-20,270 IU/L) 2
• Measure aldolase, AST, ALT, and LDH as additional muscle enzyme markers 2
• Check inflammatory markers (ESR and CRP) 2, 3
• Obtain myositis-specific antibodies including anti-Jo1, anti-SRP, anti-PL-7, anti-PL12, anti-PM/Scl, anti-TIF1 gamma, or anti-SM, though these are negative in most cases 2
• Cardiac troponin and echocardiogram are mandatory if any cardiac symptoms or signs are present, as myocardial involvement is life-threatening 3

Clinical Assessment Focus

• Document proximal muscle weakness pattern: difficulty standing from seated position, lifting arms overhead, and ambulation 2
• Examine for dermatomyositis rash: heliotrope rash, Gottron papules, periorbital edema, periungual telangiectasias, and photosensitive erythema on face, neck, torso, and extensor surfaces 1
• Assess for ptosis and diplopia, which occur commonly and may indicate associated myasthenia gravis (present in 12.5% of cases) 2
• Evaluate for dropped head syndrome 2
• Note that myalgia without weakness suggests polymyalgia rheumatica rather than myositis 2

Diagnostic Imaging

• MRI with T1-weighted, T2-weighted, and fat suppression techniques (STIR sequences) should be obtained to confirm diagnosis, identify optimal biopsy site, and establish baseline for monitoring treatment response 1, 3
• T2-weighted images show muscle edema as increased signal intensity and correlate with disease activity 1
• T1-weighted images demonstrate muscle atrophy and chronic damage 1

Muscle Biopsy and EMG

• Muscle biopsy remains the gold standard for confirming diagnosis and differentiating inflammatory from non-inflammatory myopathy 1
• Select a weak muscle demonstrated by EMG abnormalities; biopsy the contralateral side of the same muscle 1
• EMG shows polyphasic motor unit action potentials of short duration and low amplitude with increased insertional activity, fibrillation potentials, and sharp waves 1

Malignancy Screening (Adults Only)

Perform age-appropriate cancer screening in all adult patients with dermatomyositis, as malignancy occurs in 25% within 0-5 years of diagnosis 1:

• Mammography and pelvic examination in women
• Colonoscopy
• Prostate-specific antigen and prostate examination in men
• Consider CA-125 in women with dermatomyositis (elevated levels predict ovarian or peritoneal malignancy) 1
• Common associated cancers: breast, ovarian, lung, prostate, pancreatic, gastric, colorectal, bladder, and non-Hodgkin lymphoma 1

Treatment Algorithm

First-Line Treatment for Newly Diagnosed Adult Myositis

Initiate prednisone 0.5-1 mg/kg/day (typically 60-80 mg daily as single dose) PLUS a steroid-sparing immunosuppressive agent on day one 1, 2, 3:

Steroid-sparing agent options (no superiority of one over another):

• Methotrexate 1, 3
• Azathioprine 1, 3
• Mycophenolate mofetil 1, 3

Rationale: Steroid-sparing agents take 3-6 months to reach full efficacy, so concurrent initiation reduces cumulative steroid exposure and side effects 1

Corticosteroid Tapering Schedule

Follow this specific taper after 2-4 weeks of clinical improvement 1:

1. Decrease by 10 mg every 2 weeks until reaching 30 mg/day
2. Then decrease by 5 mg every 2 weeks until reaching 20 mg/day
3. Then decrease by 2.5 mg every 2 weeks until reaching 10 mg/day
4. Finally decrease by 1 mg every 2-4 weeks until completion

Treatment for Juvenile Dermatomyositis

Begin prednisone 2 mg/kg/day (maximum 60 mg/day) with taper after 2-4 weeks based on response, PLUS subcutaneous methotrexate 15 mg/m² once weekly initiated at onset 1

Treatment for Severe or Refractory Disease

For patients with severe weakness, extensive extramuscular involvement, or refractory disease, escalate immediately to 1, 2, 3:

• High-dose intravenous methylprednisolone pulse therapy (1-2 mg/kg or higher-dose bolus) 1, 2
• PLUS intravenous immunoglobulin (IVIG) - used in up to 20% of severe cases 1, 2, 3
• AND/OR plasmapheresis - performed in approximately 10% of patients, especially with poor corticosteroid response or life-threatening situations 1, 2
• Consider cyclophosphamide, rituximab, or cyclosporine 1, 3

Immune Checkpoint Inhibitor-Related Myositis

This is a distinct clinical scenario requiring immediate action 1, 3:

Grade 2 (moderate weakness, CK elevated ≥3x normal):

• Hold checkpoint inhibitor until Grade 1 or less
• Initiate prednisone 0.5-1 mg/kg/day 1
• May require permanent discontinuation in most patients with objective findings 1

Grade 3-4 (severe weakness limiting self-care):

• Permanently discontinue checkpoint inhibitor if ANY evidence of myocardial involvement 1, 3
• Hold checkpoint inhibitor and consider hospitalization 1
• Initiate prednisone 1 mg/kg or methylprednisolone IV 1-2 mg/kg (or higher-dose bolus if severe compromise) 1
• Consider plasmapheresis and IVIG 1
• Add methotrexate, azathioprine, or mycophenolate mofetil if no improvement after 4-6 weeks 1
• Caution with rituximab due to long biologic duration 1
• Extreme caution with rechallenge 1, 3

Monitoring Treatment Response

• Measure CK and inflammatory markers (ESR, CRP) regularly 2, 3
• Repeat MRI to assess treatment response 1, 3
• Monitor for corticosteroid-related complications including osteoporosis and opportunistic infections 4

Critical Pitfalls to Avoid

Cardiac involvement is life-threatening and easily missed - maintain high suspicion and obtain troponin/echocardiogram liberally 3

Failure to screen for malignancy in adult dermatomyositis patients - this is mandatory, not optional 3

Inadequate initial corticosteroid dosing - underdosing leads to treatment failure 3

Delaying steroid-sparing agent initiation - start on day one, not after corticosteroid failure 3

Confusing polymyalgia rheumatica with myositis - pain without weakness is not myositis 2