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Mitochondrial alterations represent a common finding in muscle biopsy of sporadic inclusion body myositis (s-IBM) and in polymyositis with mitochondrial pathology (PM-Mito), although they have been occasionally reported in dermatomyositis (DM) and immune-mediated necrotizing myopathy (IMNM). However, while DM and IMNM usually show good treatment response, PM-Mito and s-IBM present a variable clinical course with poor response to therapy. The prevalence and significance of mitochondrial pathology in non-IBM myositis has not been deeply investigated, particularly if it could be a reliable marker of progression to IBM from PM-Mito and/or an index of treatment unresponsiveness and worse clinical outcome. We reviewed clinical and histopathological data from 22 patients, followed in 4 Italian and 1 French institutions, who presented with clinical and histological diagnosis of myositis showing COX-negative fibers at muscle biopsy. 16 patients [72,7%] were women; mean age was 65.7 years [range 39-78 years]. 4 patients had IMNM, 2 DM, 10 non-specific myositis (NSM), 6 Overlap myositis (OM). The mean number of COX-negative fibers was 3.5%. Mean age at muscle biopsy was 62,3 years. Only 5 patients [22,7 %] showed a complete recovery after treatment while the others had variable residual weakness. Treatment refractory and worst clinical outcome were observed in patients with higher percentage of COX-negative fibers. These findings suggest that skeletal muscle mitochondrial pathology might represent a marker of disease severity and predictor of worse treatment response in non-IBM myositis. [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibitor (ICI)-related inflammatory diseases, including polymyositis (PM) and dermatomyositis (DM), in patients suffering from neoplastic disorders represent a medical challenge. The treatment of these conditions has taken on new urgency due to the successful and broad development of cancer-directed immunological-based therapeutic strategies. While primary and secondary PM/DM phenotypes have been pathophysiologically characterized, a rational, stepwise approach to the treatment of patients with ICI-related disease is lacking. In the absence of high-quality evidence to guide clinical judgment, the available data must be critically assessed. In this literature review, we examine partially neglected immunological and clinical findings to obtain insights into the biological profiles of ICI-related PM/DM and potential treatment options. We show that differential diagnosis is essential to stratifying patients according to prognosis and therapeutic impact. Finally, we provide a comprehensive assessment of druggable targets and suggest a stepwise patient-oriented approach for the treatment of ICI-related PM/DM. [ABSTRACT FROM AUTHOR]