Inflammatory Myositis: Comprehensive Overview
Definition and Classification
Inflammatory myositis encompasses a group of rare, systemic autoimmune diseases characterized by proximal muscle weakness, elevated muscle enzymes, and potential extramuscular manifestations. 1
The major subtypes include:
- Polymyositis (PM): Symmetric proximal muscle weakness with CD8+ cytotoxic T cells invading nonnecrotic muscle fibers on biopsy 1
- Dermatomyositis (DM): Characteristic skin manifestations (heliotrope rash, Gottron papules, periorbital edema) combined with muscle weakness 1
- Immune-mediated necrotizing myopathy (IMNM): Severe myopathy with minimal inflammatory infiltrate, often triggered by statins, viral infections, or malignancy 1
- Juvenile dermatomyositis (JDM): Affects children under 18 years with additional features of calcinosis cutis, cutaneous vasculitis, and gastrointestinal vasculopathy 1
Clinical Presentation and Diagnosis
Key Clinical Features
The hallmark presentation involves proximal muscle weakness developing over weeks to months, manifesting as difficulty standing from a seated position, climbing stairs, or lifting arms overhead 1. Patients may experience severe fatigue and, in severe cases, myalgia 1.
In dermatomyositis specifically, the rash typically precedes or accompanies muscle weakness, involving photosensitive erythema with poikiloderma, periungual telangiectasias, and characteristic involvement of the face, neck, torso, and extensor surfaces 1.
Diagnostic Workup
The diagnostic evaluation must include measurement of muscle enzymes (especially creatine kinase, which is often markedly elevated), inflammatory markers (ESR, CRP), and myositis-specific autoantibodies 1.
Advanced diagnostic modalities include:
- Electromyography (EMG): Shows muscle fibrillations indicative of myopathy, with polyphasic motor unit action potentials of short duration and low amplitude 1
- Magnetic resonance imaging (MRI): T1-weighted, T2-weighted, and fat suppression sequences (STIR) demonstrate increased intensity and edema in affected muscles, useful for identifying biopsy sites and monitoring treatment response 1
- Muscle biopsy: Confirms diagnosis and differentiates subtypes based on immunohistopathologic patterns 1
Critical Differential Diagnoses
Clinicians must exclude polymyalgia rheumatica (pain without true weakness, normal CK), statin-induced myopathy, fibromyalgia, generalized fatigue, muscle dystrophies, and corticosteroid-induced myopathy 1. The key distinguishing feature is that most alternative diagnoses have normal CK levels 1.
Treatment Approach
First-Line Therapy for Uncomplicated Disease
For adult patients with idiopathic inflammatory myositis, initiate high-dose corticosteroids (prednisone 1 mg/kg/day orally or methylprednisolone IV for severe cases) concurrent with a steroid-sparing agent from the outset 1, 2, 3. This dual approach allows better disease control while reducing long-term glucocorticoid-related complications 1.
The recommended steroid-sparing agents include:
- Methotrexate: 15-25 mg weekly (first choice due to faster onset and greater efficacy) 1, 2, 4
- Azathioprine: 2-3 mg/kg/day 1, 2
- Mycophenolate mofetil: 2-3 g/day 1, 2
Avoid methotrexate in patients with anti-Jo-1 antibodies or existing interstitial lung disease due to increased risk of pulmonary toxicity 4.
Pediatric Dosing for Juvenile Dermatomyositis
For uncomplicated juvenile dermatomyositis, begin corticosteroids at 2 mg/kg up to a maximum of 60 mg/day with tapering after 2-4 weeks depending on response, and add subcutaneous methotrexate at 15 mg/m² once weekly from treatment onset 1.
Management of Severe or Refractory Disease
For patients with severe myositis, extensive extramuscular organ involvement (especially cardiac or pulmonary), or inadequate response to initial therapy, administer high-dose intravenous methylprednisolone plus intravenous immunoglobulin (IVIG) at 2 g/kg divided over 2-5 days 1, 2.
Additional options for refractory cases include:
- Plasmapheresis: Reserved for cases with poor response to corticosteroids or life-threatening situations 1, 2
- Cyclophosphamide or cyclosporine: For severe or refractory disease 1, 2
- Rituximab: Emerging evidence supports efficacy in patients with certain myositis-specific autoantibodies 5
Special Consideration: Immune Checkpoint Inhibitor-Induced Myositis
Myositis associated with PD-1/PD-L1 inhibitors can be severe and fatal, requiring immediate discontinuation of the offending agent and urgent treatment with high-dose corticosteroid bolus 1. This form is more common with PD-1/PD-L1 inhibitors than ipilimumab and can have a fulminant necrotizing course with rhabdomyolysis 1.
Patients with concomitant myocarditis and/or myasthenia gravis have particularly poor prognosis with high mortality rates, necessitating aggressive management with plasmapheresis and IVIG 1, 2.
Monitoring and Long-Term Management
Serial measurements of creatine kinase and inflammatory markers guide treatment adjustments, with regular assessment of muscle strength using standardized manual muscle testing 1, 2. MRI can monitor treatment response objectively 1, 2.
The corticosteroid taper should begin only after satisfactory clinical response is obtained (usually 4-10 days for allergic and collagen diseases), with the goal of reaching the lowest effective maintenance dose 3. Alternate-day corticosteroid therapy may reduce side effects in patients requiring long-term treatment 3.
Common Pitfalls and Complications
Long-term corticosteroid use carries significant risks including osteoporosis, compression fractures, avascular necrosis, excessive weight gain, hypertension, diabetes, dyslipidemia, cataracts, and paradoxically, corticosteroid-induced myopathy 1. This underscores the critical importance of concurrent steroid-sparing agents from treatment initiation 1.
Disease relapse is common even with appropriate treatment, requiring vigilant monitoring and willingness to escalate therapy when muscle enzymes rise or clinical symptoms worsen 6.
Prognostic Factors
Myositis-specific autoantibodies define clinical subsets, predict extramuscular organ involvement (particularly pulmonary and cardiac systems), and offer prognostic information 1. Emerging biomarkers including interleukin-6 and type 1 interferon-regulated genes may serve as indicators of disease activity in both adult and juvenile myositis 1.
The combination of pharmacological treatment with individualized, supervised exercise programs improves muscle performance and should be incorporated into the treatment plan 5.