What is inclusion body myositis?

What is Inclusion Body Myositis?

Inclusion body myositis (IBM) is the most common acquired inflammatory myopathy in patients over age 50, characterized by insidious onset of asymmetric proximal and distal muscle weakness with distinctive involvement of finger flexors, wrist flexors, and quadriceps muscles, along with pathologic features of both inflammation and degeneration including rimmed vacuoles and abnormal protein accumulation. 1, 2

Epidemiology and Demographics

• IBM predominantly affects individuals after age 50 years with a male-to-female ratio of 3:1 1
• It is the most prevalent acquired myopathy above age 50, though frequently underdiagnosed or misdiagnosed as polymyositis 3, 4

Clinical Presentation

Characteristic Muscle Involvement Pattern

• Classic triad of weakness and atrophy: forearm flexors (finger flexors), wrist flexors (greater than wrist extensors), and quadriceps muscles 1
• Weakness is typically symmetric or asymmetric with insidious onset involving both proximal and distal muscles 1
• Progressive dysphagia is a prominent feature that can lead to aspiration pneumonia, recurrent aspiration, or feeding tube placement 1, 2

Disease Progression

• Slowly progressive disease course leading to severe disability, with most patients eventually losing ambulation 5
• Duration of illness typically longer than 6 months before diagnosis 1

Pathophysiology

Dual Nature: Inflammatory and Degenerative

• IBM exhibits both inflammatory features (similar to polymyositis) and degenerative characteristics, making it increasingly considered a degenerative myopathy with inflammatory features 6
• Inflammatory component: CD8+ cytotoxic T cells and macrophages in the endomysium surround and invade nonnecrotic muscle fibers expressing MHC class I, suggesting a cellular-mediated cytotoxic mechanism 6
• Degenerative component: muscle fiber vacuolization with abnormal accumulation of amyloid-β and phosphorylated tau proteins 3, 1

Pathologic Hallmarks

• Rimmed vacuoles visible on light microscopy 6, 2
• Nuclear and cytoplasmic inclusions detected on electron microscopy 6
• Congophilic amyloid deposits 6, 2
• Phosphorylated tau proteins 6
• 15-18 nm tubofilaments 7
• Endomysial inflammatory infiltrate with CD8+ T cells and macrophages 2

Inflammatory Mediators

• Proinflammatory cytokines circulate in IBM, including type 1 interferons (α/β) and TNF-α 6

Diagnostic Criteria

Clinical Criteria

• Age at onset older than 30 years 1
• Duration of illness longer than 6 months 1
• Weakness of proximal and distal muscles with finger flexor weakness, wrist flexor greater than wrist extensor weakness, or quadriceps weakness 1
• Serum creatine kinase (CK) level less than 12 times normal (minimal CK elevation is characteristic) 1, 2
• Characteristic muscle biopsy findings 1

Diagnostic Workup

• Muscle biopsy is essential when presentation is atypical or in the absence of classic clinical features, showing endomysial inflammatory infiltrate with rimmed vacuoles 2
• The diagnosis can be made exclusively on muscle biopsy when all characteristic histopathological findings are present (inflammation, rimmed vacuoles, protein deposits, and 15-18 nm tubofilaments), even in absence of typical clinical history 7
• Expert histopathological interpretation is required for accurate diagnosis 2

Laboratory and Imaging

• Initial laboratory evaluation must include CK levels, thyroid function tests (TSH, free T4), and inflammatory markers (ESR, CRP) if inflammatory myopathy is suspected 3
• Myositis-specific antibody panels (anti-Jo-1, anti-SRP) and electromyography (EMG) are essential 3
• MRI imaging can identify muscle inflammation patterns and guide biopsy site, as well as monitor disease progression 3, 2
• EMG may help differentiate IBM from neuropathy when diagnosis is uncertain 2

Common Diagnostic Pitfalls

• Frequently misdiagnosed as polymyositis and hence wrongly treated with steroids 4
• Treatment-resistant "polymyositis" in patients over 50 years of age is often IBM 4
• The diagnosis is sometimes missed because of the slow progression of the disease and lack of suspicion on the part of physicians 4
• If there is no histological confirmation, diagnostic criteria allow for a category of "possible IBM" 4

Prognosis and Complications

• Factors associated with poorer outcomes include advanced age, presence of dysphagia, cardiac involvement, and associated malignancy 1
• Progressive dysphagia represents a major cause of morbidity, with aspiration pneumonia risk requiring formal swallow assessment in every IBM patient 2
• Concurrent myocarditis or respiratory involvement should not be missed, as these can be life-threatening 2

Treatment Landscape

Current Evidence

• There is no known effective treatment for reversing or minimizing the progression of IBM 8
• Moderate-quality evidence shows that interferon beta-1a and methotrexate do not arrest or slow disease progression 8
• Although some immunomodulating therapies may exert transient and mild benefits, there is no effective treatment for IBM 7
• Treatment challenges in elderly patients include increased risk of complications from immunosuppressive therapy, requiring careful monitoring 1

Supportive Management Priorities

• Dysphagia management: formal swallow assessment is mandatory using speech and language therapy evaluation or videofluoroscopy; consider feeding tube placement when dysphagia becomes severe 2
• Functional monitoring: serial muscle strength testing using validated measures (MMT8, CMAS) is recommended for monitoring disease progression 2
• Cardiac surveillance: baseline ECG and echocardiography at diagnosis; repeat cardiac evaluation if hypertension, high disease activity, or chronic active disease develops 2
• Respiratory surveillance: pulmonary function tests, including CO diffusion, are necessary to assess for respiratory muscle involvement 2
• Physical therapy: referral to a physiatrist is essential early in the disease course to determine whether assistive devices are needed 6