Systemic Autoimmune Myopathies Research Articles

Exercise training attenuates skeletal muscle fat infiltration and improves insulin pathway of patients with immune-mediated necrotizing myopathies and dermatomyositis.

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). 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. 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 (AMPKβ2, AS160, INSR, PGC1-α, 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 (AMPKβ2, AS160, INSR, PGC1-α, PI3K, and RAB14) and in IMNM group (AKT2, AMPKβ2, RAB10, RAB14, and PGC1-α). 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.

Work situation, work ability and expectation of returning to work in patients with systemic autoimmune myopathies.

To document the work situation, the work ability and the expectation of returning to work among adult patients with systemic autoimmune myopathies (SAMs), and to identify the factors associated with each of these outcomes. Cross-sectional study. The work situation (performing paid work vs out of work) was ascertained via a structured questionnaire. For those who were working, we applied the Work Ability Index (WAI; scale 7-49); and for those who were out of work, we applied the Return-to-Work Self-Efficacy questionnaire (RTW-SE; scale 11-66). Of the 75 patients with SAMs included, 33 (44%) were doing paid work and 42 (56%) were out of work. The work situation was independently associated with physical function, assessed by the Health Assessment Questionnaire-Disability Index (HAQ-DI). A 1-point increase in the HAQ-DI (scale 0-3) decreased the chance of doing paid work by 66% (95% CI: 0.16, 0.74; P = 0.007). Patients performing paid work had a mean WAI of 33.5 (6.9). The following variables were associated with a decrease in the WAI score in the regression model: female sex (-5.04), diabetes (-5.94), fibromyalgia (-6.40), fatigue (-4.51) and severe anxiety (-4.59). Among those out of work, the mean RTW-SE was 42.8 (12.4). Cutaneous manifestations and >12 years of education were associated with an average increase of 10.57 and 10.9 points, respectively, in the RTW-SE. A 1-point increase in the HAQ-DI decreased the RTW-SE by 4.69 points. Our findings highlight the poor work participation in a well-characterized sample of working-age patients with SAMs. Strategies to improve work-related outcomes in these patients are urgently needed.

Improved skeletal muscle fatigue resistance in experimental autoimmune myositis mice following high-intensity interval training

BackgroundMuscle weakness and decreased fatigue resistance are key manifestations of systemic autoimmune myopathies (SAMs). We here examined whether high-intensity interval training (HIIT) improves fatigue resistance in the skeletal muscle of experimental autoimmune myositis (EAM) mice, a widely used animal model for SAM.MethodsFemale BALB/c mice were randomly assigned to control (CNT) or EAM groups (n = 28 in each group). EAM was induced by immunization with three injections of myosin emulsified in complete Freund’s adjuvant. The plantar flexor (PF) muscles of mice with EAM were exposed to either an acute bout or 4 weeks of HIIT (a total of 14 sessions).ResultsThe fatigue resistance of PF muscles was lower in the EAM than in the CNT group (P < 0.05). These changes were associated with decreased activities of citrate synthase and cytochrome c oxidase and increased expression levels of the endoplasmic reticulum stress proteins (glucose-regulated protein 78 and 94, and PKR-like ER kinase) (P < 0.05). HIIT restored all these alterations and increased the peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) and the mitochondrial electron transport chain complexes (I, III, and IV) in the muscles of EAM mice (P < 0.05).ConclusionsHIIT improves fatigue resistance in a SAM mouse model, and this can be explained by the restoration of mitochondria oxidative capacity via inhibition of the ER stress pathway and PGC-1α-mediated mitochondrial biogenesis.

Systemic autoimmune diseases and work outcomes in Brazil: a scoping review.

ABSTRACTOBJECTIVE To review articles that assessed work-related outcomes such as workability, work productivity, presenteeism, absenteeism, sick leave, return to work, and employment status of Brazilian patients with rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, Sjögren’s syndrome, and systemic autoimmune myopathies.METHODS This study was conducted in Medline databases (PubMed), SciELO, and Lilacs through a combination of descriptors of interest. Studies published until December 2020 were considered in the search strategy.RESULTS Eight out of 90 articles met the eligibility criteria and were included in this review. The studies are highly heterogeneous. Most of them are cross-sectional, and all of them address rheumatoid arthritis or systemic lupus erythematosus. A common denominator among these studies is the high proportion of patients outside the labor market.CONCLUSIONS In general, the studies show unfavorable labor outcomes and impaired participation in the Brazilian workforce among the samples of patients assessed. There is a need to better understand several topics about Brazilian patients with systemic autoimmune diseases and their work context, as well as to conduct studies focusing on rarer diseases and on the themes of return and reintegration to work.

Analysis of patient-physician discrepancy in global assessment of systemic autoimmune myopathy disease activity.

To compare the perception of disease activity (DA) between adult patients with systemic autoimmune myopathies (SAMs) and their physicians, and analyse possible sources of discordance. This cross-sectional study included 75 patients with SAMs. Patients and physicians rated the global DA on a 0-10 cm visual analogue scale. A discrepancy score was calculated by subtracting physician assessment from patient assessment. Three groups were defined: (I) no discrepancy: difference within -2.0 to +2.0; (II) negative discrepancy (ND): difference <-2.0 (patient underrated DA in relation to physcian); (III) positive discrepancy (PD): difference >+2.0 (patient overrated DA in relation to physician). Logistic regression was used to identify predictors of discordance. Discordance in patient-physician assessment of DA was found in 21 (28%) cases. ND was observed in 3 (4%), PD in 18 (24%), and no discrepancy in 54 (72%) assessments. Due to the small number, ND cases were excluded from the analysis. PD was associated with older age, personal history of depression, past joint involvement, higher MMT-8 and lower extramuscular DA. In the regression model, for each additional year of age, the chance of PD increases, on average, by 9% (OR 1.09; 95%CI 1.01-1.17, p=0.034). Personal history of depression increases the chance of PD by 829% (OR 9.29; 95%CI 1.52-56.89, p=0.016). Almost 30% of patients had discordance in DA assessment from their physicians. The majority of them overrated their DA. These patients tend to be older and are more likely to have personal history of depression, past joint involvement, and milder disease.

Incidence of systemic autoimmune myopathies and their risk of cancer in Leeds, UK: an 11-year epidemiological study.

ObjectivesThe aims were to identify all incident adult cases of systemic autoimmune myopathies (SAMs) in the city of Leeds, UK, and to estimate the risk of cancer in SAMs as compared with the general population.MethodsCases of SAMs were ascertained by review of all muscle biopsy reports from the Neuropathology Laboratory. A review of medical records was undertaken for each case to review the clinical diagnosis and collect epidemiological data such as age, ethnicity, sex and comorbidities, including cancer. Leeds denominator population numbers were publicly obtainable.ResultsA total of 206 biopsy reports were identified and, after review, 50 incident cases were included in the study between June 2010 and January 2021. Of the 50 cases, 27 were male and 23 were female. The mean incidence rate of SAMs in Leeds throughout the study period was 7.42/1 000 000 person-years. The proportion of SAMs cases with a confirmed malignancy was 22%. Compared with the general population, the relative risk of cancer was significantly greater in the SAMs population (31.56; P < 0.01).ConclusionsThe incidence rate of SAMs in Leeds was consistent with data from previous literature; however, disagreement exists between different methods of SAMs case inclusion due to varying clinical criteria and definitions. SAMs are associated with an increased risk of cancer, but the pathogenesis of this relationship still requires investigating. This study supports the practice of malignancy screening and long-term surveillance in patients with SAMs.

Pain and Fatigue Perceptions of Patients with Systemic Autoimmune Myopathies before and during the COVID-19 Pandemic Period

Objective: To assess general pain and fatigue and their association with the disease status of patients with systemic autoimmune myopathies (SAMs), in terms of the impact of the COVID-19 pandemic on these parameters. Methods: This is a cross-sectional and prospective cohort study that included 72 patients with SAMs who were matched by age and gender with 67 healthy individuals. The patients engaged in an interview via a validity survey to measure disease status, and assess a visual analog scale (VAS) for pain and fatigue in two periods: before (phase I) and during (phase II) of the Brazilian COVID-19 pandemic. For cross-sectional analysis, patients’ data from phase I were compared to healthy individuals’ information, whereas for prospective analysis, data of the patients who were assessed in phase II were compared to the same patients’ data from phase I. Results: The patients had significantly more pain perception, comparable fatigue perception and fatigue severity, when compared to the healthy individuals. During the COVID-19 pandemic period, the disease activity, pain and fatigue perceptions, and fatigue severity remained unchanged. Despite this, the pain and fatigue perceptions correlated significantly with patients’ VAS, the patient health outcome, and fatigue severity. In addition, the pain perception correlated to creatine phosphokinase, whereas fatigue perceptions correlated to physicians' VAS. Conclusions: The study showed that patients with SAMs have significantly increased pain perceptions compared to healthy individuals. During the COVID-19 pandemic period, the pain and fatigue perceptions remained unchanged in patients with SAMs but they correlated to several disease status parameters.

Physical exercise for the management of systemic autoimmune myopathies: recent findings, and future perspectives.

The aim of this review is to present the main pieces of evidence, recent literature and to present future perspectives on the use of exercise/physical training in the treatment and improvement of the quality of life of patients with systemic autoimmune myopathies. In the last decades, knowledge about the relevance of physical exercise training in preventing and treating chronic diseases and improving quality of life has grown. Following the global trend exemplified by the expression 'exercise is medicine', the importance of exercise/physical training has also grown in myopathies. However, the science of exercise has a lot to collaborate on and improve patients' quality of life with myopathies by appropriating new technological tools, including accessible and low-cost devices and smartphone apps. Physical exercise, as already consolidated in the literature, is an effective, well tolerated, and low-cost strategy for patients with myopathies. The use of wearable devices, smartphone apps, and online training prescriptions must accompany the global scenario, bringing new research fields and expanding the options for access to training for the individualized basis, and prescribed by qualified professionals.

LB760 Statin use in patients with pre-existing inflammatory myopathies

Systemic autoimmune myopathies (SAM) are a group of rare rheumatic diseases associated with high morbidity and disability. Recent studies have shown a high prevalence of hyperlipidemia in patients with SAM. While statins are commonly used lipid-lowering medications, the safety of statin use in patients with SAM is still unclear. The objective of this study was to evaluate the safety of statin use in patients with pre-existing SAM. We performed a single-center retrospective cohort study of adult patients with clinically diagnosed SAM between 2008-2018.

Safety of Atorvastatin in Patients With Stable Systemic Autoimmune Myopathies: A Pilot Longitudinal Study.

Patients with systemic autoimmune myopathies (SAMs) have high prevalence of dyslipidemia and, consequently, possible endothelial dysfunction and vascular stiffness. Our objective was to evaluate the possible benefits on endothelial function and vascular stiffness, as well as adverse effects of atorvastatin in SAMs. A pilot longitudinal, double-blind, randomized, placebo-controlled study was conducted. Twenty-four of 242 patients were randomized at a 2:1 ratio to receive atorvastatin (20 mg/d) or placebo for a period of 12 weeks. Demographic data, comorbidities, and clinical and laboratory parameters, as well as endothelial function and arterial stiffness, were evaluated. Of the 24 randomized patients, 4 patients were excluded, with remaining 20 patients (14 in the atorvastatin group and 6 in the placebo group). The mean age of the patients was 49.0 years, and 75% of the patients were female. At baseline, the demographic data, disease status, treatment, cardiovascular comorbidities, and risk factors were comparable between the atorvastatin and placebo groups. After 12 weeks of follow-up of atorvastatin therapy, no improvements were observed for endothelial function and arterial stiffness in either group (p > 0.05). As expected, a significant reduction in total and low-density lipoprotein cholesterol levels was observed. During the study, no clinical intercurrences or disease relapses were observed in either group. The atorvastatin drug attenuated low-density lipoprotein cholesterol without worsening clinical outcomes in SAMs. No change was observed for endothelial function and arterial stiffness. Additional studies, with long-term follow-up time and different atorvastatin dosage, are needed to corroborate the results of this study.

The Brazilian Society of Rheumatology recommendations on investigation and diagnosis of systemic autoimmune myopathies

BackgroundThis research is recommended by the Myopathy Committee of the Brazilian Society of Rheumatology for the investigation and diagnosis of systemic autoimmune myopathies.BodyA systematic literature review was performed in the Embase, Medline (PubMed) and Cochrane databases, including studies published until October 2018. PRISMA was used for the review, and the articles were evaluated, based on the Oxford levels of evidence. Ten recommendations were developed addressing different aspects of systemic autoimmune myopathy investigation and diagnosis.ConclusionsThe European League Against Rheumatism/ American College of Rheumatology (EULAR/ACR) classification stands out for the diagnosis of systemic autoimmune myopathies. Muscular biopsy is essential, aided by muscular magnetic resonance images and electroneuromyography in complementary research. Analysis of the factors related to prognosis with the evaluation of extramuscular manifestations, and comorbidities and intense investigation regarding differential diagnoses are mandatory.

Guidelines of the Brazilian Society of Rheumatology for the treatment of systemic autoimmune myopathies

BackgroundRecommendations of the Myopathy Committee of the Brazilian Society of Rheumatology for the management and therapy of systemic autoimmune myopathies (SAM).Main bodyThe review of the literature was done in the search for the Medline (PubMed), Embase and Cochrane databases including studies published until June 2018. The Prisma was used for the systematic review and the articles were evaluated according to the levels of Oxford evidence. Ten recommendations were developed addressing the management and therapy of systemic autoimmune myopathies.ConclusionsRobust data to guide the therapeutic process are scarce. Although not proven effective in controlled clinical trials, glucocorticoid represents first-line drugs in the treatment of SAM. Intravenous immunoglobulin is considered in induction for refractory cases of SAM or when immunosuppressive drugs are contra-indicated. Consideration should be given to the early introduction of immunosuppressive drugs. There is no specific period determined for the suspension of glucocorticoid and immunosuppressive drugs when individually evaluating patients with SAM. A key component for treatment in an early rehabilitation program is the inclusion of strength-building and aerobic exercises, in addition to a rigorous evaluation of these activities for remission of disease and the education of the patient and his/her caregivers.

Effects of Exercise Training on Endothelial Function, Arterial Structure, and Physical Conditioning in Patients with Systemic Autoimmune Myopathies: A Case Series Study

Introduction. Exercise training has been effective in improving endothelial function and decreasing arterial stiffness in several systemic autoimmune diseases. However, to date, no studies have assessed patients with systemic autoimmune myopathies (SAM). Methods. Five female patients with definite SAM (3 dermatomyositis and 2 polymyositis) who underwent a 12-week, twice-a-week, exercise training program were assessed prospectively. The following parameters were assessed: endothelial function measured by flow-mediated dilatation (FMD), carotid femoral by pulse wave velocity (PWV), disease status by International Myositis Assessment & Clinical Studies Group (IMACS) set score, the ventilatory anaerobic threefold (VAT), respiratory compensation point (RCP), maximum effort (ME), maximal oxygen uptake (VO2max) measured by ergospyrometer, and strength and muscle function. Results. Mean age of the patients and duration of disease were 43.9 and 10.5 years, respectively. The median FMD and PWV were 10.2% and 7.1 m/s. After exercise training, important FMD reduction was observed in 4 out of 5 patients, whereas the PWV parameters decreased in only 2 out of 5 patients. The exercise training was safe, without clinical intercurrences or disease relapses. Moreover, an increase in strength and functionality was observed. Concerning aerobic capacity, there was a decrease in the VAT and an increase in ME, without al-terations in the maximum oxygen consumption. Conclusions. In general, exercise training does not alter endothelial function and PWV values, but improves muscle strength and function and also, does not lead to disease reactivation (Clinical Trials (NCT03092167)).

Traditional and Non-Traditional Risk Factors Involved with Endothelial Dysfunction and Arterial Stiffness in Autoimmune Rheumatic Diseases

Autoimmune rheumatic diseases (ARDs) have been closely associated with accelerated plaque progression and the development of atherosclerosis, which lead to high morbidity and mortality rates for cardiovascular diseases. Endothelial dysfunction and arterial stiffness are greatly evidenced in several studies in the early phase of atherosclerosis. In ARDs, endothelial dysfunction and arterial stiffness are related to traditional and non-traditional risk factors. To date, no studies have clearly analyzed the main parameter involved in endothelial dysfunction and arterial stiffness. In this context, the present narrative review’s purpose was to describe the main factor in endothelial dysfunction and arterial stiffness in different ARDs. Endothelial dysfunction and arterial stiffness are related to traditional risk factors (i.e., hypertension, diabetes, dyslipidemia, metabolic syndrome, sedentary behavior) and non-traditional risk factors (linked to the immune mechanisms involved in these diseases). Moreover, in the present study, these associations were systemically analyzed in ankylosing spondylitis, antiphospholipid syndrome, rheumatoid arthritis, psoriatic arthritis, systemic autoimmune myopathies, systemic lupus erythematosus and systemic sclerosis. The present review shows that the relationship of traditional risk factors and non-traditional risk factors related to ARDs works in the worsening of function and structural properties of arterial vessels, leading to high cardiovascular morbidity and mortality.

Safety of statin drugs in patients with dyslipidemia and stable systemic autoimmune myopathies.

Recent studies have shown a high prevalence of dyslipidemia in patients with systemic autoimmune myopathies (SAM). However, little is known about the safety of the use of statins in these patients, and this gap in research motivated the accomplishment of the present study. In a retrospective cohort study conducted from 2004 to 2018, 250 patients with SAM were evaluated, and 24 patients had stable forms of SAM (16 dermatomyositis, 1 polymyositis and 7 antisynthetase syndrome) but had dyslipidemia and had received statins. Patients with clinically amyopathic dermatomyositis, immune-mediated necrotizing myopathy, dermatomyositis, or polymyositis induced by statins were excluded. The mean age of the patients was 50.6years, and they were predominantly women. The median duration of the disease was 5.0years. Twelve patients received simvastatin (10-60mg/day), and 11 patients received atorvastatin (20-40mg/day), and 1 patient received atorvastatin (10mg/day) which was later replaced by simvastatin (20mg/day). The median time of exposure to the statin was 22.5months. The follow-up appointments showed that the patients' lipid profiles had improved and that there had been no recurrences of disease activity or clinical intercurrences. Despite the small sampling, the data showed that the use of statins in patients with SAM was safe. New studies with a larger sample and patients with different degrees of disease activity are necessary to corroborate the results of the present study.

Mycophenolate mofetil in patients with refractory systemic autoimmune myopathies: case series

BackgroundCurrently, there are only few studies (mostly case reports or case series) on mycophenolate mofetil (MMF) in patients with systemic autoimmune myopathies (SAM). Therefore, the goal of the present study was to evaluate the safety and efficacy of MMF (monotherapy or coadjuvant drug) in a specific sample of patients with refractory SAM: dermatomyositis, polymyositis, anti-synthetase syndrome or clinically amyopathic dermatomyositis.MethodsA case series including 20 consecutive adult patients with refractory SAM from 2010 to 2016 was conducted. After the introduction of MMF, associated or not with other drugs, the patients were followed for 6 consecutive months.ResultsIn 17 out of 20 patients MMF was introduced without any intolerance. The clinical symptoms evaluated in these patients were muscular, cutaneous and/or pulmonary activity. During the 6-month follow-up, 11 out of 17 patients had clinical and laboratory activities response with MMF, allowing significant tapering of the prednisone median dose (15 vs. 5 mg/day, P=0.005). On the other hand, in three out of 20 patients; MMF was discontinued in less than two months, because of gastrointestinal intolerance. There were no cases of serious infection or death.ConclusionsMMF was relatively well-tolerated, safe and effective in patients with refractory SAM. Further studies are needed to confirm the data found.

P3487The role of high-sensitivity troponin I for risk prediction in patients with systemic autoimmune myopathies

P3487The role of high-sensitivity troponin I for risk prediction in patients with systemic autoimmune myopathies

O11 Outcome measures in idiopathic inflammatory myositis

Systemic autoimmune myopathies (or idiopathic inflammatory myopathies) are a wide group of rare rheumatic diseases characterized by muscle weakness due to muscle inflammation. Recent evidence has continually reinforced the relevance of the perception of pain and fatigue as parameters of notable contribution to reducing the quality of life of these patients. However, due to the multidimensional characteristic of these variables, few studies address the effects of pharmacological and non-pharmacological therapies, such as exercise training on these variables. With regard to patients with systemic autoimmune myopathies, the outcomes related to the effects of exercise training are focused on muscle strength and endurance, few explore the effects on the perception of pain and fatigue. Given this, studies that review systematically the available evidence of the effects of exercise training on these perceptions can contribute to management of this parameter in clinical practice. Given this context, the present study aims to review systematically the effectiveness of exercise training specifically on the perception of pain and fatigue.