Inclusion Body Myositis

Inclusion body myositis (IBM) is the commonest age related muscle disease in the elderly and is an incurable disorder leading to severe disability. It is a slowly progressive inflammatory myopathy characterised by:

• Weakness of the proximal parts of the limbs
• Diminished deep tendon reflexes
• Dysphagia
• Mixed myopathic and neurogenic changes on electromyography

It is an underdiagnosed condition as it occurs mainly in the elderly with multiple comorbidities and is frequently misdiagnosed as polymyositis and wrongly treated with steroids. Treatment-resistant 'polymyositis' in the over 50s is often IBM.¹

Histologically, features include:

• Inflammatory infiltrate
• Cytoplasmic vacuolation
• Characteristic tubo-filamentous inclusions within the cytoplasm and nuclei of muscle cells

It occurs in both sporadic and inherited form (s-IBM and i-IBM respectively). I-IBM has autosomal recessive and dominant variants. Genetic susceptibility factors are thought to influence who develops s-IBM but this is poorly understood currently.² Familial and sporadic types share the same clinical, biological, MRI and histological features.³

The aetiology of IBM is largely unknown. Theories have proposed it as an autoimmune or viral-induced disorder. Others have suggested that it is a degenerative muscle disorder with deposition of substances in the muscles similar to those found in Alzheimer's disease, for example, amyloid pre-cursor proteins.⁴

Most cases present in patients over 50 years of age but it can occur much earlier, at any time between the 20s and 80s. Population studies from the Netherlands and Sweden suggest a population prevalence of 2.2-4.9 per million, with age-adjusted rates of 16 per million in the over 50s.¹ It is so rare that most GPs will never see a case.

Risk factors

Co-existent disease is quite common but this reflects the disease's association with aging:
Associated diseases are:

• Diabetes in 20%
• Autoimmune disease in 15%
• Peripheral neuropathy in 18%⁵

It is found in men more often than women with a ratio of 3:1 but muscle biopsy of related women may reveal pathology without clinical manifestation.

Complaint of muscle weakness is the usual presenting feature. It is painless and insidious, usually after the age of 50.⁵

• The distribution is variable and can be both proximal and distal. Characteristically, there is early involvement of quadriceps, ilio-psoas, ankle dorsiflexors and volar forearm muscles. This tends to present as loss of finger dexterity and poor grip and falling. Distal weakness occurs in about 50% but only in about 35% is it more marked than proximal weakness.
• Weakness is often asymmetrical in contrast to polymyositis.
• Fatigue and exercise intolerance are common but not with shortness of breath and the respiratory muscles are usually spared.
• Dysphagia is problematic in 40-50% patients.
• Limb weakness is not inevitable and weakness of erector spinae and "droopy neck" can be the presentation.
• Myalgia and cramping is uncommon and sensory or autonomic changes occur only if there is also a concurrent polyneuropathy, such as may occur with diabetes.

Strong indicators of IBM:

• Weakness of flexion of the wrist and fingers is disproportionate compared with any weakness of extension.
• Extension of the knee is weak compared with flexion of the hip.

Important negative findings to exclude differential diagnoses:

• Tendon reflexes are usually suppressed in myopathy and in this condition it is most marked at the knee.
• Sensation should be intact unless there is also a polyneuropathy.
• There should be no cognitive impairment, no abnormality in coordination and no evidence of upper motor neurone disease.
• Look for the rash of dermatomyositis to exclude it.

• Inherited and sporadic forms are differentiated by family history. Incomplete penetrance, death of a relative died before the age of onset of the disease or incorrect diagnosis can make pedigrees misleading.
• Dermatomyositis and polymyositis may show skin lesions and the creatine kinase level may be markedly elevated. It is rarely normal in active disease. In IBM it is normal or mildly elevated only.
• Oculopharyngeal dystrophy affects the external ocular muscles that are spared in this condition.
• Chronic atrophic sarcoid myopathy can be difficult to differentiate.
• Myasthenia gravis affects the external ocular muscles and muscle fatiguability is a key feature.
• Motor neurone disease usually shows features of upper motor neurone lesions.

Standard routine investigations should include:

• FBC
• Calcium and phosphate
• Creatine kinase
• ESR
• Fasting glucose
• Thyroid function tests

Specialist investigations include:

• Nerve conduction tests - should be normal.
• Electromyography may show a myopathic process. It may be necessary to test several muscles.
• Muscle biopsy as the final diagnostic procedure. Biopsy should be taken from a muscle that is moderately but not severely affected. Histological processing may require immunohistochemical staining (for beta-amyloid and ubiquitin) and electron microscopy.

There is no effective treatment for the disease but high quality RCTs are few.⁷ Many therapies have been tried, unsuccessfully.⁸Consensus is that steroids and conventional immunosuppressive therapies are not beneficial clinically. High-dose prednisolone paradoxically worsens strength whilst decreasing inflammation, possibly due to increased amyloid accumulation. Intravenous immunoglobulin is very expensive and ineffective.⁹ More specific immunotherapies require exploring.¹⁰

Without effective treatment, the role of the multi-disciplinary team to support and optimise function is critical:

• Speech and language therapy for assessment of dysphagia. A gastrostomy may be required if severe.
• Dietary support.
• Physio- and occupational therapy may help make the best of limited ability.

There tends to be very slow progression but those who develop symptoms at an older age tend to progress more rapidly. Progressive dysphagia is associated with a poorer prognosis and quality of life.