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Background/objective: The aim of this study was to evaluate the effects of exercise training on the ubiquitin-proteasome system (UPS) and genes related to autophagy on the skeletal muscle of patients with dermatomyositis (DM) and immune-mediated necrotizing myopathies (IMNMs)., Methods: Seven DM patients and 6 IMNM patients were treated for 12 weeks with a twice-weekly aerobic and resistance training exercise program. Aerobic capacity, muscle strength, and expression of genes in the skeletal muscle related to UPS and to autophagy were evaluated at the baseline and after the intervention. Moreover, only at the baseline, 10 healthy control individuals were also evaluated., Results: The age of DM and IMNM patients was 49.8 and 58.5 years, respectively. Genes related to UPS were upregulated, whereas genes related to autophagy and antioxidative systems were downregulated only in the DM group when compared with control group. After completion of the exercise training program, several genes related to UPS were downregulated, whereas genes related to autophagy, mitochondrial pathways, and antioxidative systems were upregulated in both the DM and IMNM groups., Conclusions: Exercise training can increase genes related to autophagy, mitophagy, and lysosomal biogenesis in the skeletal muscle of patients. These results suggest an increase in the recycling of damaged proteins and organelles, which may also contribute to the performance and endurance of skeletal muscles in these patients. Furthermore, in patients with myositis, exercise training led to a decrease in genes related to UPS and an increase in genes related to antioxidative capacity. Therefore, this may also contribute to an attenuation of skeletal muscle loss and of the deleterious effects of oxidative stress on the skeletal muscle of these patients., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction/objectives: To assess the effects of exercise training on insulin resistance and β-cell function in patients with systemic autoimmune myopathies (SAMs)., Method: This quasi-experimental, prospective study includes 9 patients with SAMs (six with dermatomyositis, two with antisynthetase syndrome, and one with polymyositis). Patients were submitted to a 12-week, twice a week, exercise training program comprising aerobic and resistance exercises. Baseline and after the intervention, we evaluated disease status, aerobic capacity, muscle strength, body composition, insulin resistance, and β-cell function parameters., Results: The patients have a mean age of 46.7 years and stable disease. No clinical or laboratory parameter impairment was observed after the intervention. Compared with baseline, aerobic capacity, muscle strength, and function increased after 12 weeks (P < 0.05), while no changes were observed for body composition. Data from the oral glucose tolerance test showed that exercise did not change glucose area under the curve (AUC), whereas insulin and C-peptide AUC decreased significantly (P < 0.05). Furthermore, Matsuda index and HOMA2 percentage (both surrogates of insulin resistance) also improved (P < 0.05)., Conclusion: Exercise training improved aerobic capacity, muscle strength, and muscle function in patients with SAMs. In addition, exercise training led to an attenuation of insulin resistance and improvements in β-cell function parameters. These data indicate that exercise training can mitigate metabolic impairments, attenuating the cardiovascular risk in SAMs.Key Points• Exercise training improved aerobic capacity, muscle strength, and function without disease impairment• Exercise training was capable of improve insulin resistance and β-cell function in patients with SAM• These results suggest that exercise can mitigate metabolic impairments in patients with SAM, attenuating the cardiovascular risk.

Objectives: To evaluate the feasibility, safety and efficacy of exercise training in patients with immune-mediated necrotising myopathies (IMNM)., Methods: Eight consecutive sedentary patients with IMNM (5 anti-signal recognition particle and 3 anti-hydroxy-methyl-glutaryl coenzyme A reductase) were engaged in this study. Disease status was based on International Myositis Assessment and Clinical Studies Group (IMACS) core set measures. Physical performance was evaluated by cardiopulmonary exercise test, repetition maximum (RM) protocol, handgrip dynamometry, sit-to-stand (STS) and timed up-and-go (TUG) tests. All these parameters were measured at baseline and after a 12-week, twice-a-week, supervised exercise training comprising aerobic and strength exercises., Results: Patients (aged 61 years on average) were very disabled at the beginning of the disease (mean duration of 17.7 months), but after being aggressively treated with a treat-to-target approach, they presented only mild symptoms that were well-controlled with oral immunosuppression and low disease status scores by the time of the exercise intervention. No disease relapsing, worsening of the IMACS set scores or adverse events were observed throughout the training period. Patients also increased aerobic capacity (e.g. time to achieve anaerobic threshold and time to achieve exhaustion), muscle strength (e.g. 1RM bench press) and function (e.g. STS test)., Conclusions: Supervised exercise training did not impair disease status and seemed to be feasible, safe and effective in patients with IMNM. Moreover, exercise training increased aerobic capacity, muscle strength and function, suggesting that this could be a novel potential coadjuvant therapy in IMNM.

Systemic autoimmune myopathies (SAMs) are a heterogeneous group of rare systemic autoimmune diseases that primarily affect skeletal muscles. Patients with SAMs show progressive skeletal muscle weakness and consequent functional disabilities, low health quality, and sedentary lifestyles. In this context, exercise training emerges as a non-pharmacological therapy to improve muscle strength and function as well as the clinical aspects of these diseases. Because many have feared that physical exercise exacerbates inflammation and consequently worsens the clinical manifestations of SAMs, it is necessary to evaluate the possible benefits and safety of exercise training among these patients. The present study systematically reviews the evidence associated with physical training among patients with SAMs.

Introduction: In a recent study, we have shown that atorvastatin is clinically safe for dermatomyositis (DM) and antisynthetase syndrome (ASS) patients with dyslipidemia. Herein, we showed in an unprecedented way, the safety of atorvastatin on the muscular tissues of these patients., Methods: Transcriptome analysis was performed on samples of the vastus lateralis muscle obtained at baseline and after 12 weeks of atorvastatin (20 mg/day) intervention in DM or ASS patients with dyslipidemia [6DM and 5ASS received atorvastatin, and 2DM and 3ASS received placebo]. The results were analyzed considering differences in expression fold change before and after treatment. Histological and histochemical analyses were also performed., Results: In both groups, no significant changes were observed in genes related to the mitochondrial, oxidative, insulin, lipid, and fibrogenic pathways. Histological analysis showed a slight variability in the fiber size that was preserved after the intervention. In addition, the mosaic of muscle fibers was preserved in the internal architecture of the fibers and all histological regions. No fiber necrosis or atrophy, focal failures, subsarcolemmal accumulation, lipids, areas of fibrosis, or alterations in mitochondrial activity were observed. All muscle fibers were labeled for MHC I., Conclusion: Atorvastatin did not promote significant changes in the expression of genes related to mitochondrial, oxidative, insulin, lipid, and fibrogenic pathways in the muscle tissues of DM and ASS patients with dyslipidemia. Atorvastatin did not also promote histological and histochemical changes in muscle tissues. Our results reinforce the safety of the administration of atorvastatin to treat dyslipidemia in patients with DM and ASS., (© 2023 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

Idiopathic inflammatory myopathies (IIM) are rare diseases affecting skeletal muscles and leading to progressive muscle weakness and disability. Thanks to the better understanding of their pathogenesis, the management of IIM has been noteworthily implemented in recent years. Current therapeutic strategies include pharmacological and non-pharmacological interventions, among which physical exercise represents a useful option, able to ameliorate disease activity without worsening muscle inflammation. The aim of this narrative review is therefore to provide an updated overview of the benefits of physical exercise in patients with IIM and to suggest plausible training programs to be applied in patients with dermatomyositis, polymyositis, necrotizing myopathy, and inclusion body myositis. In this regard, a combined strategy mixing aerobic and resistance exercises could positively affect the pro-inflammatory and metabolic pathways occurring in skeletal muscles, while promoting muscle fiber regeneration and repair., (© 2021. International League of Associations for Rheumatology (ILAR).)

The idiopathic inflammatory myopathies (IIMs) are chronic disorders characterized by inflammation in skeletal muscle but also in other organs such as the skin, lungs, joints, gastrointestinal tract, and heart. The effect of immunosuppressive treatment varies between individual patients and between organ manifestations within the same individual. Many patients respond poorly to first-line treatment with glucocorticoids and other immunosuppressive agents such as methotrexate or azathioprine, with symptoms persisting in the muscles, skin, and lungs, leading to refractory disease. Management of refractory IIM is a clinical challenge, and a systematic approach is proposed to better understand the lack of treatment response, in order to guide disease management. The first step in the management of refractory IIM is to recognize whether remaining symptoms are caused by persistent inflammation in the affected tissue or whether the symptoms may be attributable to damage preceding inflammation. Thus, a second diagnostic examination is recommended. Second, in particular for patients with remaining muscle weakness, it is important to ascertain whether the diagnosis of myositis is correct or whether another underlying muscle disorder could explain the symptoms. Third, with confirmation of remaining inflammation in the tissues, a strategy to change treatment needs to be undertaken. Few controlled trials are available to guide our treatment strategies. Furthermore, different subgroups of patients may benefit from different therapies, and different organ manifestations may respond to different therapies. In this context, subgrouping of patients with IIM based on autoantibody profile may be helpful, as there are emerging data from open studies and case series to support the notion of a varying treatment response in different autoantibody-defined subgroups of IIM patients., (© 2021 The Authors. Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Idiopathic inflammatory myopathy (IIM) is a term used for a heterogeneous group of diseases characterized by severe muscle weakness. In addition to pharmacological treatment options, non-pharmacological methods such as exercising are essential for proper management of myositis. The present article aimed to provide an insight into the potential pathophysiological mechanisms underlying exercise-related benefits in myositis. A systematic search was performed on PubMed/MEDLINE, Scopus, Web of Science, and Google Scholar using the following keywords and their combinations: "idiopathic inflammatory myopathy", "inflammatory myopathy", "myositis", "polymyositis", "dermatomyositis", "inclusion body myositis", and "exercise". Current literature indicates that exercising has impact on both immune and non-immune pathways in patients with IIM. Exercise-related benefits include (a) increased mitochondrial biogenesis/enzyme activity, (b) reconditioning of immune/inflammatory pathways, (c) decreased endoplasmic reticulum stress, (d) modulation of gene expression, (e) increased protein synthesis and cytoskeletal remodeling, and (f) decreased muscle fibrosis and non-muscle area infiltrates. With its certain benefits, exercise stands as a precious non-pharmacological treatment option for patients with IIM., (© 2021 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

Key Points: Regular exercise improves muscle functional capacity and clinical state of patients with idiopathic inflammatory myopathy (IIM). In our study, we used an in vitro model of human primary muscle cell cultures, derived from IIM patients before and after a 6-month intensive supervised training intervention to assess the impact of disease and exercise on lipid metabolism dynamics. We provide evidence that muscle cells from IIM patients display altered dynamics of lipid metabolism and impaired adaptive response to saturated fatty acid load compared to healthy controls. A 6-month intensive supervised exercise training intervention in patients with IIM mitigated disease effects in their cultured muscle cells, improving or normalizing their capacity to handle lipids. These findings highlight the putative role of intrinsic metabolic defects of skeletal muscle in the pathogenesis of IIM and the positive impact of exercise, maintained in vitro by yet unknown epigenetic mechanisms., Abstract: Exercise improves skeletal muscle function, clinical state and quality of life in patients with idiopathic inflammatory myopathy (IIM). Our aim was to identify disease-related metabolic perturbations and the impact of exercise in skeletal muscle cells of IIM patients. Patients underwent a 6-month intensive supervised training intervention. Muscle function, anthropometric and metabolic parameters were examined and muscle cell cultures were established (m. vastus lateralis; Bergström needle biopsy) before and after training from patients and sedentary age/sex/body mass index-matched controls. [ 14 C]Palmitate was used to determine fat oxidation and lipid synthesis (thin layer chromatography). Cells were exposed to a chronic (3 days) and acute (3 h) metabolic challenge (the saturated fatty acid palmitate, 100 μm). Reduced oxidative (intermediate metabolites, -49%, P = 0.034) and non-oxidative (diglycerides, -38%, P = 0.013) lipid metabolism was identified in palmitate-treated muscle cells from IIM patients compared to controls. Three days of palmitate exposure elicited distinct regulation of oxidative phosphorylation (OxPHOS) complex IV and complex V/ATP synthase (P = 0.012/0.005) and adipose triglyceride lipase in patients compared to controls (P = 0.045) (immunoblotting). Importantly, 6 months of training in IIM patients improved lipid metabolism (CO 2 , P = 0.010; intermediate metabolites, P = 0.041) and activation of AMP kinase (P = 0.007), and nearly normalized palmitate-induced changes in OxPHOS proteins in myotubes from IIM patients, in parallel with improvements of patients' clinical state. Myotubes from IIM patients displayed altered dynamics of lipid metabolism and impaired response to metabolic challenge with saturated fatty acid. Our observations suggest that metabolic defects intrinsic to skeletal muscle could represent non-immune pathomechanisms, which can contribute to muscle weakness in IIM. A 6-month training intervention mitigated disease effects in muscle cells in vitro, indicating the existence of epigenetic regulatory mechanisms., (© 2020 The Authors. The Journal of Physiology © 2020 The Physiological Society.)

Objectives: This study aims to evaluate the effects of exercise training on intramuscular lipid content and genes related to insulin pathway in patients with systemic autoimmune myopathies (SAMs). Patients and methods: Between January 2016 and May 2019, a total of seven patients with dermatomyositis (DM; 3 males, 4 females; mean age: 49.8±2.3 years; range, 43 to 54 years), six with immune mediated necrotizing myopathy (IMNM; 3 males, 3 females; mean age: 58.5±10.6 years; range, 46 to 74 years), and 10 control individuals (CTRL group; 4 males, 6 females; mean age: 48.7±3.9 years; range, 41 to 56 years) were included. The muscle biopsy before and after the intervention was performed to evaluate the intramuscular lipid content. Patients underwent a combined exercise training program for 12 weeks. Skeletal muscle gene expression was analyzed and the DM versus CTRL group, DM pre- and post-, and IMNM pre- and post-intervention were compared. Results: The DM group had a higher intramuscular lipid content in type II muscle fibers compared to the CTRL group. After the intervention, there was a reduction of lipid content in type I and II fibers in DM and IMNM group. The CTRL group showed a significantly higher expression of genes related to insulin and lipid oxidation pathways (AMPKb2, AS160, INSR, PGC1-a, PI3K, and RAB14) compared to the DM group. After exercise training, there was an increase gene expression related to insulin pathway and lipid oxidation in DM group (AMPKb2, AS160, INSR, PGC1-a, PI3K, and RAB14) and in IMNM group (AKT2, AMPKb2, RAB10, RAB14, and PGC1-a). Conclusion: Exercise training attenuated the amount of fat in type I and II muscle fibers in patients with DM and IMNM and increased gene expression related to insulin pathways and lipid oxidation in DM and IMNM. These results suggest that exercise training can improve the quality and metabolic functions of skeletal muscle in these diseases. [ABSTRACT FROM AUTHOR]