Pathology of skeletal muscle in mixed connective tissue disease

Abstract

To characterize the pathology of muscle involvement in mixed connective tissue disease (MCTD), skeletal muscle biopsies from 13 patients with MCTD were examined by routine light microscopy, histochemistry, and direct immunofluorescence. The histologic and histochemical changes observed corresponded closely to changes seen in idiopathic polymyositis and the myopathy associated with systemic lupus erythematosus. Eight of 13 cases examined by direct immunofluorescence demonstrated immunoglobulin deposition either within normal appearing vessels, within normal fibers, around or on the sarcoplasmic membrane, or within the perimysial connective tissue. The histologic findings support Sharp's observation of the high incidence of focal inflammatory lesions in skeletal muscle biopsies of patients with MCTD. Immunoglobulin deposition in these muscle biopsies suggests an immunologic basis for the muscular symptomatology in MCTD.

Transverse myelitis in mixed connective tissue disease

“…Other ANA patterns (diffuse and rim) probably result from antibody against deoxyribonucleoprotein (dNP) (6) particularly since the more sensitive Farr assay for anti-nDNA antibodies was negative. The immunofluorescent findings on muscle biopsy, although nonspecific, have previously been reported to occur in MCTD (7). The presence of epidermal nuclear staining by direct immunofluorescence has also been reported as a feature of this syndrome (8).…”

Mixed Connective Tissue Disease, a Roundabout to Rheumatic Diseases?

“…Myalgia occurs in approximately 50% of MCTD patients but frank myositis with weakness, elevated muscle enzymes and typical biopsy changes is fairly uncommon although asymptomatic focal inflammatory changes in muscle are a common histological feature [20]. In fact the only significant difference from that observed by Sharp and his collegues thirty years ago is that myositis is probably much less common than originally suggested and that the prognosis is worse than that SLE.…”

Myositis in mixed connective tissue disease: a unique syndrome characterized by immunohistopathologic elements of both polymyositis and dermatomyositis

“…The depletion of blood vessels has already been described on initial phase of DM 20 , which is also preceded by MAC deposition on blood vessels. Interestingly, vascular involvement associated to immunoglobulin deposition has been reported in a few MCTD patients more than 20 years ago 7 . In this regard, proliferative vascular lesions which are a consequence of intimal and medial thickening of blood vessel wall due to inflammatory cell infiltration were observed in the MCTD muscle of autopsy cases by Singsen et al 9 .…”

“…In contrast, there is a growing body of evidence that HLA class I-restricted cytotoxic T cells-mediated response against surface antigens expressed by muscle fibers is the primary pathogenic mechanism in PM and IBM 4 , whereas DM involves predominantly an antibody or immune-complex-mediated response against a vascular-endothelial component 5,6 . Moreover, the studies that have characterized the muscle involvement in MCTD 2,3,7 antedated the Kasukawa classification criteria 8 actually applied for this disease. According to some authors 2,3,[7][8][9] , the muscle involvement is a classic inflammatory myositis similar to that detected in PM when analyzed by histology and histochemistry.…”

“…Moreover, the studies that have characterized the muscle involvement in MCTD 2,3,7 antedated the Kasukawa classification criteria 8 actually applied for this disease. According to some authors 2,3,[7][8][9] , the muscle involvement is a classic inflammatory myositis similar to that detected in PM when analyzed by histology and histochemistry. Nonetheless, conventional light microscopy and staining techniques used in these studies could not distinguish the real significance of cellular infiltrates.…”