Inclusion body myositis.
IBM has emerged as a clinicopathological entity during the past 25 years but with increasing complexity. It occurs primarily in elderly persons (over the sixth decade of life, with 3:1 male preponderance), but young adults or children may also be affected in some families. FIBM is by and large non-inflammatory though some autosomal dominant FIBM cases have inflammatory cell infiltrates. In IBM, slowly progressive weakness of proximal as well as distal muscle groups occurs and is usually not associated with skin rash or malignancy. The incidence of associated collagen-vascular disease is thought to be lower than in DM or PM but is reported to be as high as 15%. It is generally refractory to treatment with corticosteroids or other immunosuppressants. Muscle biopsy and electromyography may suggest a neurogenic process mixed with myopathic features. None of the histopathological features is specific enough to be a diagnostic criterion. The diagnostic criteria have to be collective, encompassing both clinical and pathological criteria in different combinations. The presence of eosinophilic intranuclear or cytoplasmic inclusions immunoreactive for both beta-amyloid and ubiquitin in affected myofibres may facilitate the diagnosis of IBM. The diagnosis no longer depends on the ultrastructural demonstration of characteristic microtubular filaments as previously thought. The identification of both beta-amyloid and ubiquitin may provide a new concept for the disease process in IBM. A chronic persistent intracytoplasmic synthesis of abnormal amyloid protein in IBM is suspected to be similar to that in Alzheimer's disease. IBM is considered to be intimately related to a heterogenous group of non-inflammatory IBMD, including DMY, OPMD, and both autosomal recessive and dominant FIBM. An inflammatory response has been seen, however, in muscles of both OPMD and autosomal dominant FIBM. The pathogenesis in IBM and in IBMD may not be the same. Unlike IBM, there is no abnormal sarcolemmal expression of MHC-I antigen in IBMD as a sign of T-cell-mediated cytotoxicity causing myofibre destruction. The prion theory derived from identification of amyloidogenic protein in the filament inclusions in the rimmed vacuoles is provocative. If one believes in the contention that the amyloidogenic filaments are the primary pathogen of either IBM or IBMD, one must account for the fact that these filaments are originally derived from sarcolemmal nuclei and not from autophagic vacuoles. Until this is clarified, the possibility that the filaments represent either abnormal or defective 'slow' virus nucleocapsids cannot be completely ruled out.
Chou
S M
SM
ALS and Neuromuscular Research Foundation, San Francisco, CA 94115.
D006801:Humans; D002479:Inclusion Bodies / Q000648:ultrastructure*; D009132:Muscles / Q000648:ultrastructure; D009220:Myositis / Q000473:pathology* / Q000628:therapy