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

Abstract

-Objective: To characterize the inflammatory cells, the expression pattern of adhesion molecules (ICAM-1 and VCAM-1), membrane attack complex (C5b-9), and major histocompatibility complex (MHC) antigens in muscle biopsy of mixed connective tissue disease (MCTD). Method: We studied 14 patients with MCTD, and compared to 8 polimyositis (PM) patients, 5 dermatomyositis (DM) and 4 dystrophies. Inflammatory cells were examined for CD4 + , CD8 + , memory and naïve T cells, natural killer cells, and macrophages. Expression of MHC-I and -II, ICAM-1, VCAM-1 and C5b -9 were characterized on muscle fibers and vessels. Results: Morphological analysis displayed a pattern of PM. Immunohistochemical study revealed a decreased number of capillaries, predominance of CD4 + and B cells in perivascular regions and predominance of CD8 + and CD45RO + in endomysial regions. The expression of MHC-I on vessels and on degenerated muscle fibers, MHC-II expression on vessels and perifascicular muscle fibers, and the expression of ICAM-1 / VCAM-1 on endothelial cells indicated both vascular and cellular-immune mediated processes causing the muscular lesion. Conclusion: Our findings revealed a mixed mechanism in MCTD, both vascular involvement as DM, and cell-mediated like PM.KEY WORDS: mixed connective tissue disease, myositis, major histocompatibility complex, adhesion molecules, membrane attack complex, lymphocyte phenotyping.Miosite na doença mista do tecido conectivo: achados imunopatológicos de polimiosite e dermatomiosite RESUMO -Objetivo: Caracterizar as células do infiltrado inflamatório, o padrão de expressão das molécu-las de adesão (ICAM-1 e VCAM-1), complexo de ataque à membrana (C5b-9) e antígenos de histocompatibilidade maior (MHC) em biópsias musculares de patientes com doença mista do tecido conectivo (DMTC). Método: Foram estudados14 pacientes com DMTC e comparadas com 8 pacientes com polimiosite (PM), 5 com dermatomiosite (DM) e 4 com distrofias. As células inflamatórias foram caracterizadas como CD4 + , CD8 + , células T de memória (CD45RO + ) e virgens, células "natural killer" e macrófagos. As expressões de MHC-I e -II, ICAM-1, VCAM-1 e C5b-9 foram caracterizadas em fibras musculares e vasos. Resultados: A análise morfológica demonstrou um padrão tipo PM. O estudo imuno-histoquímico revelou diminuição do número de capilares, predomínio de células CD4 + e B nas regiões perivasculares e predomínio de CD8 + e CD45RO + nas regiões endomisiais. A expressão de MHC-I nos vasos e nas fibras degeneradas, MHC-II nos vasos e fibras perifasciculares e expressão de ICAM-1 / VCAM-1 no endotélio indicaram uma associação de processos vascular e imune-celular mediando a lesão muscular. Conclusão: Os achados revelaram duplo mecanismo na DMTC, imune-celular como na PM e vascular como na DM. PALAVRAS-CHAVE: doença mista do tecido conectivo, miosite, complexo de histocompatibilidade maior, moléculas de adesão, complexo de ataque à membrana, fenotipagem linfocitária.

Clinical Course, Prognosis, and Causes of Death in Mixed Connective Tissue Disease

“…Organ involvement is often more extensive than was previously thought; neurological expression and pulmonary disease, erosive arthritis, various skin signs, and vasculitis have been added to the clinical picture 3,4,5,6,7,8,9,10,11,12,13,14,15 . Organ involvement is often more extensive than was previously thought; neurological expression and pulmonary disease, erosive arthritis, various skin signs, and vasculitis have been added to the clinical picture 3,4,5,6,7,8,9,10,11,12,13,14,15 .…”

Severe and refractory myositis in mixed connective tissue disease: a description of a rare case

“…4 There is clinical evidence of this association, although this association is generally subclinical and defined by symmetric proximal weakness, abnormal electromyography or modified muscle enzymes. 3 It is believed that this association may be similar to that observed in other inflammatory myopathies in its clinical presentation, being distinguished by the paucity of clinical symptoms and its excellent response to corticotherapy. 4 However, there is only one previous description of a pediatric patient that presented a condition of severe myositis associated with MCTD.…”

“…The vascular involvement associated with the deposition of immunoglobulin was reported more than 20 years ago in some patients with MCTD. 3,10,11 As a consequence, the proliferative vascular lesions have a thicker intima and media layer of the blood vessel walls due to an inflammatory cell infiltrate that was observed during the autopsies of muscles in patients with MCTD, as described by Singsen et al 3,11 In the literature no previous report was found that describes a severe and refractory case of myositis in adults with MCTD. One report from Japan described the case of a 13-year-old child with MCTD who presented muscle weakness and an elevated level of CK.…”

Polymyositis as a manifestation of chronic graft‐versus‐host disease after allo‐HSCT

“…The immunohistochemical staining suggested that the cellular dysimmunity played a key role in the development of GVHD‐associated myositis in the two cases. Activation of complement system might have contributed to the pathogenesis since the necrotic myofibers were positive for MAC, which is a marker for complement system activation …”