What are the steps for investigating inclusion body myositis (IBM)?

Investigation of Inclusion Body Myositis (IBM)

The diagnostic investigation of inclusion body myositis requires a comprehensive approach including clinical assessment, laboratory testing, electrophysiological studies, imaging, and muscle biopsy, with muscle biopsy being the definitive test revealing characteristic inflammatory infiltrates with rimmed vacuoles and congophilic deposits.

Clinical Assessment

• Age and demographics: IBM typically occurs after age 50 with a male to female ratio of 3:1 1
• Pattern of weakness: Look specifically for:
  • Asymmetric or symmetric weakness
  • Selective involvement of quadriceps, forearm flexors (finger and wrist), and biceps/triceps 1, 2
  • Early depression of knee reflexes 2
  • Distal weakness in approximately 50% of cases 2
  • Dysphagia (may be a prominent feature) 1

Laboratory Investigations

• Muscle enzymes:

  • Creatine kinase (CK): Normal or mildly elevated (less than 12 times normal) 1, 2
  • Comprehensive muscle enzyme panel including transaminases and LDH 3
  • Aldolase levels

• Inflammatory markers:

  • Erythrocyte sedimentation rate (ESR)
  • C-reactive protein (CRP) 3

• Autoantibody testing:

  • Myositis-specific antibodies 1
  • Anti-nuclear antibodies (ANA)
  • Screen for associated autoimmune disorders (present in 15% of cases) 2

Electrophysiological Studies

• Electromyography (EMG):

  • No specific pattern that reliably distinguishes IBM from other inflammatory myopathies 2
  • May show myopathic features in about 80% of patients 4
  • Look for short- or long-duration complex motor unit potentials (MUPs) 5

• Nerve conduction studies:

  • Generally normal in most cases 4
  • Rule out peripheral neuropathy (present in 18% of cases) 2

Imaging

• Magnetic resonance imaging (MRI):
  • T1-weighted, T2-weighted, and sequences using fat suppression techniques 1
  • Useful to identify a muscle site for biopsy 1
  • Look for characteristic pattern of muscle involvement (quadriceps, forearm flexors)

Muscle Biopsy

• Key histopathological features (all three present in 88% of specimens) 2:

  • Vacuoles containing membranous material (100%)
  • Groups of atrophic fibers (96%)
  • Endomysial inflammatory exudate (92%)

• Electron microscopy:

  • Confirms presence of filamentous inclusions 2
  • Examine minimum of three vacuolated fibers to detect inclusions with confidence 2

• Immunohistochemistry:

  • Inflammatory infiltrates predominantly composed of T8 cells 4
  • Rimmed vacuoles (100% of patients) 4

Diagnostic Criteria

The EULAR/ACR classification criteria for idiopathic inflammatory myopathies can be applied, with specific features for IBM subclassification 1:

• For IBM classification, one of the following is required:
  • Finger flexor weakness and no response to treatment
  • Muscle biopsy showing rimmed vacuoles 1

Differential Diagnosis Considerations

• Other inflammatory myopathies (polymyositis, dermatomyositis)
• Immune-mediated necrotizing myopathy
• Hereditary myopathies
• Muscular dystrophies with inflammation 1
• Peripheral neuropathies
• Metabolic myopathies

Associated Conditions to Screen For

• Other autoimmune disorders (15% of cases) 2
• Diabetes mellitus (20% of cases) 2
• Diffuse peripheral neuropathy (18% of cases) 2
• Cardiac involvement (evaluate with troponin, ECG, and echocardiogram) 3
• Respiratory function (assess with negative inspiratory force and vital capacity measurements) 3

Pitfalls to Avoid

• Misdiagnosis: IBM is often misdiagnosed as polymyositis due to similar inflammatory features 1
• Inadequate biopsy sampling: Multiple sites may need to be sampled as pathological features can be patchy
• Overreliance on CK levels: Unlike other inflammatory myopathies, CK is often only mildly elevated or normal 2
• Delayed diagnosis: The insidious onset and slow progression may delay seeking medical attention
• Treatment expectations: Unlike other inflammatory myopathies, IBM is generally refractory to immunosuppressive therapy 2, 4

By following this systematic approach to investigating IBM, clinicians can establish an accurate diagnosis and provide appropriate counseling regarding prognosis and management options.