Pathogenesis
Mechanisms and Contributing Factors
The pathogenesis of Dermatomyositis (DM) is multifactorial, and influenced by genetic, environmental, and immunological factors. Inflammatory mediators may play a role in DM pathogenesis. Type I interferons, which regulate both innate and adaptive immune responses, play a key role in DM pathogenesis. DM is thought to be caused by a humoral mediated attack against the muscle capillaries and the endothelium of arterioles (Figure 1-1). Activation of complement mediators is followed by formation and deposition of the membrane attack complex on vascular walls, leading to inflammation, endothelial cell death and ischemic muscle fiber damage. Increased release of proinflammatory cytokines and chemokines upregulate the expression of adhesion molecules on the endothelial cell membrane, facilitating the migration of activated CD4+ T cells, B cells, and macrophages to the endomysial tissue. Hypoxic injury to the muscle fibers results in atrophy of muscle fibers,…
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Mechanisms and Contributing Factors
The pathogenesis of Dermatomyositis (DM) is multifactorial, and influenced by genetic, environmental, and immunological factors. Inflammatory mediators may play a role in DM pathogenesis. Type I interferons, which regulate both innate and adaptive immune responses, play a key role in DM pathogenesis. DM is thought to be caused by a humoral mediated attack against the muscle capillaries and the endothelium of arterioles (Figure 1-1). Activation of complement mediators is followed by formation and deposition of the membrane attack complex on vascular walls, leading to inflammation, endothelial cell death and ischemic muscle fiber damage. Increased release of proinflammatory cytokines and chemokines upregulate the expression of adhesion molecules on the endothelial cell membrane, facilitating the migration of activated CD4+ T cells, B cells, and macrophages to the endomysial tissue. Hypoxic injury to the muscle fibers results in atrophy of muscle fibers, particularly those at the periphery furthest from the vascular supply. Over time, the capillary density reduces, and muscle fibers experience necrosis and degeneration.
Adults and children with DM show similar distributions of CD4 and CD8-positive cells in muscle, though children have more CD4 in perimysium while adults had more CD20 and CD68-positive cells.
References
- Aggarwal, R., Schessl, J., Charles-Schoeman, C. et al. Safety and tolerability of intravenous immunoglobulin in patients with active dermatomyositis: results from the randomised, placebo-controlled ProDERM study. Arthritis Res Ther 26, 27 (2024).
- ArgenX Press Release. Argenx Advances Clinical Development of Efgartigimod SC in Idiopathic Inflammatory Myopathies. November 20, 2024. https://argenx.com/content/dam/argenx-corp/newsroom/press-release-pdfs/PressRelease_argenx_ALKIVIA_Ph2_20241120.pdf.coredownload.inline.pdf
