Familial Inclusion Body Myositis (FIBM): Update (original) (raw)
Related papers
Inclusion body myositis. Genetics, biomarkers and muscle biopsy
International Journal of Neuroscience, 2023
Sporadic inclusion body myositis is the most common idiopathic inflammatory myopathy over the age of 50, with a male-to-female ratio of 3:1. Symptoms onset before age of 60 occurs in 18-20% of patients, with a delay in diagnosis of 5 to 8 years. The classic clinical presentation of SIBM consists of proximal leg and distal arm weakness, and most commonly patients present early slowly progressive quadriceps weakness which leads to falls and to difficulties in climbing stairs, while less common the initial complaints refer to finger flexor weakness and atrophy, foot drop, or dysphagia, and rare presentations include prominent forearm weakness, sparing the quadriceps. The aetiopathogenesis of the disease remains unclear and despite some preliminary promising results, to the day there is no effective treatment. A c c e p t e d M a n u s c r i p t The diagnosis of SIBM is based on the clinical presentation and the histopathological findings in muscle biopsy, however increasing evidence on genetics and paraclinical biomarkers has recently come to light giving new insights on the pathogenesis, the diagnosis and the potential treatment of the disease. In the present study we aim to review the histopathological findings, genetics and blood biomarkers, and to review the role of muscle biopsy in the diagnosis of SIBM.
Inclusion body myositis: current pathogenetic concepts and diagnostic and therapeutic approaches
The Lancet Neurology, 2007
Inclusion body myositis is the most common acquired muscle disease in older individuals, and its prevalence varies among countries and ethnic groups. The aetiology and pathogenesis of sporadic inclusion body myositis are still poorly understood; however genetic factors, ageing, and environmental triggers might all have a role. Unlike other infl ammatory myopathies, sporadic inclusion body myositis causes slowly progressing muscular weakness and atrophy, it has a distinctive pattern of muscle involvement, and is unresponsive to conventional forms of immunotherapy. This review covers the clinical presentation, diagnosis, treatment, and the latest information on genetic susceptibility and pathogenesis of sporadic inclusion body myositis.
Sporadic inclusion body myositis: a continuing puzzle
Neuromuscular Disorders, 2008
There is now compelling evidence that sporadic inclusion body myositis (sIBM) is a muscle-specific autoimmune disease in which both T and B-cells play a part and in which both cytotoxic muscle fibre necrosis and degeneration occur. However the factors responsible for breakdown of immune tolerance and the nature of the target antigens expressed by muscle fibres remain unknown. Genetic factors are known to contribute to susceptibility, in particular MHC haplotyes which may influence antigenic presentation, and could also operate through genetic variations in muscle fibre constituents or immune effector mechanisms. Viral infection may act as a trigger mechanism, as in cases of HIV-associated sIBM. Our understanding of the mechanisms leading to the degenerative changes in muscle fibres is still incomplete. Protein misfolding and proteasomal dysfunction rather than defective transcriptional control is likely to underlie the abnormal accumulation of multiple proteins in the muscle fibre inclusions. However, aberrant transcription is thought to be the basis for the accumulation of potentially toxic mutant protein forms (e.g. UBB +1 ). The origin of the multiple clonally expanded somatic mtDNA mutations in COX-negative segments of muscle fibres remains uncertain but may be linked to the effects of oxidative stress. It is proposed that the disproportionate involvement of certain muscles in sIBM may be due to the existence of muscle group-specific transcriptomes which are differentially affected by the disease process and that the male predominance of the disease may indicate the influence of genes preferentially expressed in males. There is a need to develop better animal models of sIBM in which the relationship between the inflammatory and degenerative components of the disease as well as the gender difference in susceptibility and differential vulnerability of different muscle groups can be more critically investigated.
Ongoing Developments in Sporadic Inclusion Body Myositis
Current Rheumatology Reports, 2014
Sporadic inclusion body myositis (IBM) is an acquired muscle disorder associated with ageing, for which there is no effective treatment. Ongoing developments include: genetic studies that may provide insights regarding the pathogenesis of IBM, improved histopathological markers, the description of a new IBM autoantibody, scrutiny of the diagnostic utility of clinical features and biomarkers, the refinement of diagnostic criteria, the emerging use of MRI as a diagnostic and monitoring tool, and new pathogenic insights that have led to novel therapeutic approaches being trialled for IBM, including treatments with the objective of restoring protein homeostasis and myostatin blockers. The effect of exercise in IBM continues to be investigated. However, despite these ongoing developments, the aetiopathogenesis of IBM remains uncertain. A translational and multidisciplinary collaborative approach is critical to improve the diagnosis, treatment, and care of patients with IBM.
Inclusion body myositis: Clinical and pathological boundaries
Annals of Neurology, 1996
Inclusion body myositis, polymyositis, and dermatomyositis are three distinct categories of inflammatory myopathy. Some authorities commented on the selective early weakness of the volar forearm muscles, quadriceps, and ankle dorsiflexors in inclusion body myositis. The most important feature distinguishing inclusion body myositis from the other two inflammatory myopathies is the lack of responsiveness to immunosuppressive treatment. Although most patients with inclusion body myositis have characteristic muscle biopsy findings, some cannot be distinguished histologically early from polymyositis. Predicting responsiveness to immunosuppressive medications, independent of muscle histology, would be valuable to clinicians. We retrospectively reviewed the pattern of weakness and other clinical features of 46 patients newly diagnosed with either inclusion body myositis, polymyositis, or dermatomyositis. Asymmetrical muscle weakness with prominent wrist flexor, finger flexor, and knee extensor involvement was specific for inclusion body myositis and unresponsive polymyositis. Male sex, lower creatine kinase levels, slower rate of progression, and peripheral neuropathy were also more common in inclusion body myositis and unresponsive polymyositis than in responsive polymyositis and dermatomyositis patients. Repeat muscle biopsy in 2 patients in the unresponsive polymyositis group demonstrated histological features of inclusion body myositis. We suspect that patients with clinical features of inclusion body myositis but lacking histological confirmation may nonetheless have inclusion body myositis. Our study supports the recently proposed criteria for definite and possible inclusion body myositis.
Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology, 2015
Sporadic inclusion body myositis is the most frequent acquired myopathy of middle and later life and is distinguished from other inflammatory myopathies by its selective pattern of muscle involvement and slowly progressive course, and by the combination of inflammatory and degenerative muscle pathology and multi-protein deposits in muscle tissue. This review summarises the findings of recent studies that provide a more complete picture of the clinical phenotype and natural history of the disease and its global prevalence and genetic predisposition. Current diagnostic criteria, including the role of electrophysiological and muscle imaging studies and the recently identified anti-5'-nucleotidase (anti-cN1A) antibody in diagnosis are also discussed as well as current trends in the treatment of the disease.
Inclusion body myositis: from genetics to clinical trials
Journal of Neurology
Inclusion body myositis (IBM) belongs to the group of idiopathic inflammatory myopathies and is characterized by a slowly progressive disease course with asymmetric muscle weakness of predominantly the finger flexors and knee extensors. The disease leads to severe disability and most patients lose ambulation due to lack of curative or disease-modifying treatment options. Despite some genes reported to be associated with hereditary IBM (a distinct group of conditions), data on the genetic susceptibility of sporadic IBM are very limited. This review gives an overview of the disease and focuses on the current genetic knowledge and potential therapeutic implications.
C URRENT OPINION Inclusion body myositis: update
2014
Purpose of review To examine new developments in sporadic inclusion body myositis (IBM), including updated clinical and prognostic factors, novel autoantibody associations, unique histopathologic findings, proposed new clinical diagnostic criteria, and novel therapeutic agents. Recent findings IBM is a slowly progressive disease, leading to wheelchair use, on average, 12-20 years after onset of symptoms; however, it does not appear to interfere with life expectancy. Older age at the onset of first symptoms as well as immunosuppressive therapy are likely associated with more rapid disease progression. Quantitative muscle strength of knee extensor and the IBM functional rating scale seem to be sensitive disease progression markers and may be useful clinical trial outcome measures. Newly proposed diagnostic criteria utilize data-driven approaches with very high sensitivity and specificity. A novel autoantibody, as well as unique proteins seen histopathlogically, may help hone in on diagnosis as well as to deepen our understanding of IBM pathophysiology. Novel treatments, including follistatin and bimagrumab, are directed at potential therapeutic targets. Summary We have observed an explosion of knowledge in IBM in the recent past, which challenges traditional dogma and ushers in a new era of understanding with potential clinical implications for those who suffer with IBM.