Inclusion body myositis (IBM) is the most common 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. There is debate as to whether it is primarily a T cell-mediated inflammatory myopathy or a myodegenerative disease. Interest has been stimulated by the finding that substances deposited in muscle are similar to those found in the brain in Alzheimer's disease - for example, amyloid precursor proteins.^4,5

Epidemiology

Most cases present in patients aged over 50 years but it can occur much earlier, at any time between the 20s and 80s. Reported prevalence figures (for the over-50s) suggest a range of 4.9 per million in the Netherlands to 10.7 per million in the USA. 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

Coexistent 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%.⁶

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.

History⁷

Complaint of muscle weakness is the usual presenting feature. It is painless and insidious, usually after the age of 50.⁶

• The distribution is variable and can be both proximal and distal. Characteristically, there is early involvement of quadriceps, iliopsoas, 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% of patients.
• Limb weakness is not inevitable and weakness of erector spinae and 'droopy neck' can be the presentation.
• Myalgia and cramping are uncommon and sensory or autonomic changes occur only if there is also a concurrent polyneuropathy, such as may occur with diabetes.

Examination

Strong indicators of inclusion body myositis (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 co-ordination and no evidence of upper motor neurone disease.
• Look for the rash of dermatomyositis to exclude it.

Differential diagnosis⁷

• Inherited and sporadic forms are differentiated by family history. Incomplete penetrance, death of a relative who 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 inclusion body myositis (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.

Investigations

Standard routine investigations should include:

• Full blood count.
• Calcium and phosphate.
• Creatine kinase.
• Erythrocyte sedimentation rate.
• Fasting glucose.
• Thyroid function tests.

Specialist investigations include:

• Nerve conduction tests - these should be normal.
• Electromyography - this 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.

Management

There is no effective treatment for the disease but high-quality randomised controlled trials are few.⁸ Many therapies have been tried, unsuccessfully.⁹

The consensus 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.¹⁰ More specific immunotherapies require exploring.¹¹

Without effective treatment, the role of the multidisciplinary 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.
• Physiotherapy and occupational therapy may help make the best of limited ability.

Prognosis

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 a poorer quality of life.

Document references

1. Munshi SK, Thanvi B, Jonnalagadda SJ, et al; Inclusion body myositis: an underdiagnosed myopathy of older people. Age Ageing. 2006 Jan;35(1):91-4. [abstract]
2. Needham M, Mastaglia FL, Garlepp MJ; Genetics of inclusion-body myositis. Muscle Nerve. 2007 May;35(5):549-61. [abstract]
3. Ranque-Francois B, Maisonobe T, Dion E, et al; Familial inflammatory inclusion body myositis. Ann Rheum Dis. 2005 Apr;64(4):634-7. [abstract]
4. Finch CE; A perspective on sporadic inclusion-body myositis: the role of aging and inflammatory processes. Neurology. 2006 Jan 24;66(2 Suppl 1):S1-6. [abstract]
5. Askanas V, Engel WK; Inclusion-body myositis: muscle-fiber molecular pathology and possible pathogenic Acta Neuropathol. 2008 Dec;116(6):583-95. Epub 2008 Oct 31. [abstract]
6. Lotz BP, Engel AG, Nishino H, et al; Inclusion body myositis. Observations in 40 patients. Brain. 1989 Jun;112 ( Pt 3):727-47. [abstract]
7. Lin HC, Inclusion Body Myositis, eMedicine, Jun 2010
8. Choy EH, Hoogendijk JE, Lecky B, et al; Immunosuppressant and immunomodulatory treatment for dermatomyositis and polymyositis. Cochrane Database Syst Rev. 2005 Jul 20;(3):CD003643. [abstract]
9. Griggs RC; The current status of treatment for inclusion-body myositis. Neurology. 2006 Jan 24;66(2 Suppl 1):S30-2. [abstract]
10. Helmers SB, Dastmalchi M, Alexanderson H, et al; Limited effects of high-dose intravenous immunoglobulin (IVIG) treatment on molecular expression in muscle tissue of patients with inflammatory myopathies. Ann Rheum Dis. 2007 Oct;66(10):1276-83. Epub 2007 Feb 2. [abstract]
11. Needham M, Mastaglia FL; Inclusion body myositis: current pathogenetic concepts and diagnostic and therapeutic approaches. Lancet Neurol. 2007 Jul;6(7):620-31. [abstract]

Internet and further reading

• Inclusion Body Myositis, Online Mendelian Inheritance in Man (OMIM)
• Inclusion Body Myositis, National Institute of Neurological Disorders and Stroke

Acknowledgements