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Inclusion body myositis, or myopathy, is the third major form of idiopathic in ammatory myopathy and, depending on the care taken with histologic diagnosis, is found to be as common as PM and DM Its de ning features, the intracytoplasmic and intranuclear inclusions, were rst described in 1965 by Adams and colleagues, who also drew attention to a number of clinical attributes now considered characteristic By 1994, more than 240 sporadic cases and 59 familial ones had been recorded in the medical literature (Mikol and Engel), but the diagnosis is now made so frequently that this low number almost certainly re ects the misidenti cation of IBM as PM in the past Garlepp and Mastaglia concluded that over one-third of cases of in ammatory myopathy, especially in men, are of this type A set of clinical and pathologic diagnostic criteria for the disease has been proposed by Griggs and coworkers and are useful for research purposes The disease predominates in males (in a ratio of 3:1) and has its onset in middle or late adult life Practically all instances occur sporadically but an unrelated inherited form, either autosomal recessive or dominant, is well known (Cole et al, Neville et al) Many, but not all of these forms of autosomal recessive IBM are caused by a mutation on chromosome 9p1-q1 (Argov et al, Eisenberg et al) An autosomal recessive distal myopathy with rimmed vacuoles (a central feature of IBM; see later) has also been described in Japan The process has been shown to be allelic to the same 9p chromosomal abnormality which in turn gives rise to most cases of hereditary IBM The mutation involves an unusual bifunctional protein that is both a kinase and an epimerase, defects of which reduce the number of sugar and sialic acid residues on muscle proteins These chemical changes increase the susceptibility of the muscle membrane to injury, similar in a general way to the circumstances in the muscular dystrophies One must express some skepticism about the validity of linking sporadic and familial cases on the basis of a single histopathologic nding (the inclusions) Diabetes, any one of a variety of autoimmune diseases, and a
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DISEASES OF SPINAL CORD, PERIPHERAL NERVE, AND MUSCLE
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both the nuclei and cytoplasm The nature of these diverse changes is obscure The tubulo lamentous inclusions have suggested a viral origin, but one has never been isolated and serologic studies have failed to substantiate a viral causation except perhaps for one patient in whom adenovirus type 2 was isolated from a biopsy specimen (Mikol and Engel) No evidence has emerged to date to suggest an autoimmune mechanism, and the in ammatory component, although similar to PM, is thought to be possibly a secondary phenomenon as noted later Treatment Inclusion body myositis 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 Despite this, because a few patients improve slightly or cease worsening with steroids, a severalmonth trial is often recommended (Lotz et al) The level of CK and the degree of leukocyte in ltration of muscle often diminish with corticosteroid treatment despite a lack of clinical improvement On this basis, Barohn and coworkers have suggested, as alluded to earlier, that the in ammatory response is not a primary cause of muscle destruction Sayres and colleagues concluded in a review of 32 patients that low-dose methotrexate and corticosteroids may slow the progression of disease, but this regimen has not been widely adopted In a few cases there has been brief improvement in response to IVIG, especially in the weakened muscles involved in swallowing, but the gains have been unsustained and serial histopathologic examinations have detected no change Plasma exchange and leukocytopheresis have been tried, also with generally discouraging results The disease in most patients is relentlessly progressive over many years, sometimes very slowly, and no method of treatment has altered the long-term prognosis Sometimes, the process remains fairly restricted for up to a decade, thereby creating less disability than in cases that generalize
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