Department of Neurology, Thomas Jefferson University, Philadelphia, PA, United States; Neuroimmunology Unit National and Kapodistrian University of Athens Medical School, Athens, Greece.
Handb Clin Neurol. 2023;195:425-460. doi: 10.1016/B978-0-323-98818-6.00023-6.
The autoimmune inflammatory myopathies constitute a heterogeneous group of acquired myopathies that have in common the presence of endomysial inflammation and moderate to severe muscle weakness. Based on currently evolved distinct clinical, histologic, immunopathologic, and autoantibody features, these disorders can be best classified as dermatomyositis, necrotizing autoimmune myositis, antisynthetase syndrome-overlap myositis, and inclusion body myositis. Although polymyositis is no longer considered a distinct subset but rather an extinct entity, it is herein described because its clinicopathologic information has provided over many years fundamental information on T-cell-mediated myocytotoxicity, especially in reference to inclusion body myositis. Each inflammatory myopathy subset has distinct immunopathogenesis, prognosis, and response to immunotherapies, necessitating the need to correctly diagnose each subtype from the outset and avoid disease mimics. The paper describes the main clinical characteristics that aid in the diagnosis of each myositis subtype, highlights the distinct features on muscle morphology and immunopathology, elaborates on the potential role of autoantibodies in pathogenesis or diagnosis , and clarifies common uncertainties in reference to putative triggering factors such as statins and viruses including the 2019-coronavirus-2 pandemic. It extensively describes the main autoimmune markers related to autoinvasive myocytotoxic T-cells, activated B-cells, complement, cytokines, and the possible role of innate immunity. The concomitant myodegenerative features seen in inclusion body myositis along with their interrelationship between inflammation and degeneration are specifically emphasized. Finally, practical guidelines on the best therapeutic approaches are summarized based on up-to-date knowledge and controlled studies, highlighting the prospects of future immunotherapies and ongoing controversies.
自身免疫性炎症性肌病是一组获得性肌病，其共同特征为存在肌内膜炎症和中重度肌无力。基于目前已明确的独特临床、组织学、免疫病理学和自身抗体特征，这些疾病最好分类为皮肌炎、坏死性自身免疫性肌炎、抗合成酶综合征重叠性肌炎和包涵体肌炎。虽然多发性肌炎不再被认为是一个独特的亚型，而是一个已灭绝的实体，但在此仍有描述，因为其临床病理信息多年来为 T 细胞介导的肌细胞毒性提供了基本信息，特别是在包涵体肌炎方面。每种炎症性肌病亚型都有独特的免疫发病机制、预后和对免疫治疗的反应，因此需要从一开始就正确诊断每种亚型，并避免疾病模拟。本文描述了有助于每种肌炎亚型诊断的主要临床特征，强调了肌肉形态和免疫病理学上的独特特征，阐述了自身抗体在发病机制或诊断中的潜在作用，并澄清了与假定触发因素（如他汀类药物和病毒，包括 2019 年冠状病毒 2 大流行）相关的常见不确定性。它广泛描述了与自身侵入性肌毒性 T 细胞、活化 B 细胞、补体、细胞因子相关的主要自身免疫标志物，并阐明了先天免疫的可能作用。包涵体肌炎中同时存在的肌退行性特征及其与炎症和退行性变之间的相互关系特别强调。最后，根据最新知识和对照研究总结了最佳治疗方法的实用指南，突出了未来免疫治疗的前景和持续存在的争议。
