The diagnosis depends on the clinical features and is supported by the muscle biopsy. There are structural abnormalities of muscle fibers and inflammatory changes. The latter are similar to, but usually of lesser severity than, those observed in idiopathic PM. (The infiltrating cells are mainly T cells of the CD8 type.) The denominative finding is of intracytoplasmic, subsarcolemmal vacuoles, and eosinophilic inclusions in both the cytoplasm and nuclei of degenerating muscle fibers. The vacuoles contain, and are rimmed by, basophilic granular material, called “rimmed vacuoles.” Special stains, particularly Gomori trichrome on frozen sections, and extensive inspection of biopsy specimens are required to disclose the rimmed vacuoles, for they are infrequent, widely dispersed, and easily overlooked. The inclusions may be congophilic, and often stain for TDP-43, p62, SM1-31, and, particularly, beta amyloid. As noted in subsequent sections similar inclusions are found in a number of other muscle diseases and are not in and of themselves diagnostic, especially without the destructive and mildly inflammatory changes of IBM. Moreover, the clinical context of these other diseases usually causes little difficulty in identifying the inclusions as ancillary and minor abnormalities on the biopsy.
Of clinical utility has been the recent introduction of testing for cytosolic antibodies (anti-cN1; NT5C1A) that are found in two-thirds of patients with IBM. They appear to be specific and assist in particular by differentiating this disease from the other inflammatory myopathies and in its detection when there is a pattern of weakness that is not typical of an inflammatory myopathy. Testing other antibodies such as anti-Jo is probably suited to confirming cases that have the elements of a larger syndrome that includes, for example, interstitial lung disease.
Ultrastructural studies show that the protein inclusions accumulate at or near foci of abnormal tubulofilamentous structures in both the nuclei and cytoplasm. The nature of these diverse changes is obscure. The tubulofilamentous inclusions suggested to earlier investigators a viral origin, but an agent has never been isolated and serologic studies have failed to substantiate an infectious causation.
IBM has not responded in any consistent fashion to treatment with corticosteroids or other immunosuppressive drugs. Indeed, the disease should be suspected in recalcitrant cases of apparent PM or DM. The level of CK and the degree of leukocyte infiltration of muscle often diminish with corticosteroid treatment despite a lack of clinical improvement. On this basis, Barohn and coworkers suggested that the inflammatory response is not a primary cause of muscle destruction. In a few cases there has been brief improvement in response to glucocorticoids or IVIg, especially in weakened muscles involved in swallowing, but the gains have been unsustained and serial histopathologic examinations have detected no change. Two controlled trials have failed to show a benefit of IVIg. Plasma exchange and leukocytapheresis have also been tried, with generally discouraging results. In a preliminary trial of bimagrumab, an antibody directed to signaling of TGF-β receptor, has shown some improvement of muscle mass but a definitive clinical demonstration of effect has not been tested (Amato et al, 2014).
The disease in most patients is relentlessly progressive over many years, sometimes very slowly, and no method of treatment has so far altered the long-term prognosis. Sometimes, the process remains fairly restricted in scope or severity for up to a decade, thereby creating less disability than in cases that become generalized.
Problems in Diagnosis of Inflammatory Myopathy