Inclusion body myositis (IBM) is classified as an inflammatory muscle disease. It however stands out from all other muscle diseases, inflammatory or not. IBM has quite unique, and often unexplained, characteristics. These features mark it out as an enigma, and the mystery deepens the more neurologists research it.
IBM continues to throw up new and challenging riddles for neurologists, and here are my 6 puzzling things about IBM.
6. Unique muscle distribution
Muscle diseases in adults almost always start in the upper or proximal parts of the limbs. IBM however bucks the trend with a specific predilection for muscles of the middle part of the limbs, the knee extensors in the legs, and the long finger flexors in the arms. This unique pattern of muscle involvement results in a characteristic or pathognomonic clinical picture of IBM: marked wasting of the muscles of the forearms, and of the quadriceps. People with IBM therefore complain of a weak grip, and a tendency to fall. The reason for this unique muscle specificity has me dumbfounded.
5. Unusual muscle biopsy features
The classical inflammatory muscle diseases are polymyositis (PM) and dermatomyositis (DM), and the inflammation in these conditions is easily detected on muscle biopsy. This is however not the case with IBM which shows very little inflammation, and this paucity of inflammation underlies IBM’s unresponsiveness to anti-inflammatory treatment with steroids. IBM muscle biopsy specimens however show typical eosinophilic cytoplasmic inclusions and rimmed vacuoles. The unwary neuropathologist however easily misses these specific but elusive landmarks, making IBM notoriously difficult to diagnose, or worse still, easily misdiagnosed as PM or DM.
4. Association with strange bedfellows
IBM is typically an isolated disease, preferring to roam in solitude. Or so I thought until I came across a paper in Neurology which introduced me to the concept of multisystem proteinopathy. This is the association of IBM with Paget’s disease of the bone (PDP), motor neurone disease (MND), or frontotemporal dementia (FTD). Why IBM should associate with these strange and unrelated diseases leaves me totally baffled.
3. Genetic underpinnings
Neurologists like to keep the geneticists busy with every disease they study, and IBM is no exception. It is not clear exactly when, how or why neurologists went gene-hunting in a condition that is typically sporadic. But hunt they did, and their perseverance paid off; we now know that IBM may also be hereditary or familial. And the genetic spectrum of IBM continues to grow. Take this paper in Neurology Genetics which reports two families with abnormalities in the hnRNPA1 gene. Another genetic association of IBM is GNE. To muddy things up a bit more, IBM has been linked to HLA-DRB1*03. Why any disease should decide to have sporadic and genetic forms leaves me very befuddled.
2. Association with hepatitis C virus (HCV)
Just when you start adjusting your mindset to a disease that may be genetic, sporadic and inflammatory, the neurologists do it again. This time in cahoots with the infectious disease specialists. They ask you once more to adjust your mindset, and see IBM as a possible fallout of a viral invasion, the culprit here being hepatitis C virus (HCV). Writing in Neurology, the authors boldly suggest a possible pathomechanistic link between the 2 conditions. Mindset tuning in progress.
1. Autoimmune pathogenesis
Just before you lose it all, the neurologists take you gently back to familiar territory, autoimmunity. But even here there are strange undertones. The autoimmune antibody associated with IBM is rather unique, as you have now learnt to expect. The reported association of anti cN-1A and IBM comes from the Annals of the Rheumatic Diseases, letting the neurologist off this time. The authors looked at autoantibodies to cytosolic 5′-nucleotidase 1A in sporadic IBM. The significance of the association is still not clear. One thing is however obvious-neurologists need to start working on the reasons they will give to their immunologists to justify sending off that blood sample for anti cN-1A. I foresee a drawn-out battle!
These and many other things go to show why IBM is such a conundrum for neurologists. It has the neurologists vigorously scratching their heads, wishing for an enigma cipher machine. In the meantime all they can do is assure their patients of the therapeutic advances in IBM. As with all mysteries however, it shall all be revealed in time… and neurologists and their patients will be all smiles!