Inclusion body myositis (ORPHA:611)
A rare degenerative inflammatory disorder of skeletal muscles characterized by late onset weakness, starting in either the quadriceps or finger flexors and slowly progressing to include other groups of limb muscles. Distinctive histopathological features include inflammatory and degenerative features.
Epidemiology
Inclusion body myositis (IBM) has a highly variable prevalence according to geographic, ethnic and age criteria. Prevalence in the general population ranges from 1/14,000-1,000,000 but a three-fold increase is observed when considering only a population over 50 years. Underdiagnosis may be an explanation for the high ethno-geographic variation. Male-to-female ratio is 2:1 on average (but varies between 0.5 to 6.5:1).
Clinical description
IBM onset is over 50 years but the disease may also occur earlier, in the 4th decade. Compared to other idiopathic inflammatory myopathies, the clinical phenotype is characteristic with distal and asymmetrical muscle involvement, amyotrophy, and no extramuscular manifestations. First signs are weakness or even atrophy of the quadriceps or of the finger flexors, leading to difficulties in rising from chairs or ground, climbing stairs, gripping, lifting and using tools, and thereby provoking falls. Flexor digitorum profundus and flexor pollicis longus are more severely involved than the forearm extensor muscles, especially during early stages of the disease. With disease progression, other groups of muscles are also involved, such as the elbow flexors, the hip, knee or neck flexors, and the ankle dorsiflexors, leading to footdrop. Patients frequently have a mild weakness of facial muscles, except for the extraocular muscles. Dysphagia may occur in approximately 66% of patients in advanced stages of the disease and can be severe in some cases.
Etiology
Etiology of IBM is poorly understood. No causal gene has been identified but genes encoding the major histocompatibility complex (MHC), HLA-DR3 and 8.1 ancestral haplotypes (HLA-A1, B8, DRB1*0301), have been shown to correlate with IBM susceptibility. Ageing and environmental factors are also surmised to play a triggering role. Whether IBM is primarily an immuno-inflammatory disorder leading to muscle degeneration or a degenerative disorder leading to muscle inflammation is still under debate. The pathogenic role of anti-cN1A, which is detected in 30-50% of patients, is also debated as it is not specific to IBM and may be found in patients with other autoimmune diseases as well as in healthy controls.
Diagnostic methods
Diagnosis is based on physical examination (especially the detection of finger flexor weakness), age of presentation and a duration of symptoms over 6 months. Muscle biopsy identifies the inflammatory (diffuse MHC class I sarcolemmal overexpression, endomysial inflammatory infiltrates including CD8+ T cells, T cell invasion of non-necrotic muscle fibers) and degenerative features (rimmed vacuoles, P62 and/or TDP43 aggregates and, occasionally, an abnormally elevated number of COX-negative fibers). Laboratory findings are not specific as serum creatine kinase is only slightly raised in some cases. Electromyography only helps in confirming the myopathic origin of the weakness or atrophy. Magnetic resonance imaging (MRI) helps delineating the characteristic pattern of muscle involvement.
Differential diagnosis
Differential diagnosis may include other idiopathic inflammatory myopathies and, in early stages of the disease, arthritis or any motor neuron disease.
Management and treatment
There is no curative treatment for IBM, and patients usually do not respond to anti-inflammatory or immunosuppressant therapies. The standard of care involves symptomatic treatments including exercise therapy, ergotherapy, and orthotic appliance. However, clinical trials are ongoing for new therapeutic strategies, of note for sirolimus, an inhibitor of mTOR.
Prognosis
No change in mean life expectancy has been observed. IBM patients present a progressive and continuous loss of muscle strength between 3.5-16.8% per year. There is a major impact of the disease on the daily activity. After 5 years, most patients require a walking aid and after 10, a wheelchair.

                            Last update: 
                            February 2021


                            - Expert reviewer(s): 
                            Dr Céline ANQUETIL  - Pr Olivier BENVENISTE