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Objective: The interplay between dysphagia, cancer, and mortality in idiopathic inflammatory myopathies (IIM) has not been carefully studied. The aim of this study was to investigate possible effect modification of cancer on the association between dysphagia and mortality in early IIM., Methods: A multi-center cohort of 230 adult IIM patients with dysphagia assessment within 6 months of disease onset was assembled. Crude mortality rates in IIM patients exposed or not to dysphagia were estimated for the 5-year period following cohort entry. To explore possible effect modification of cancer on the association between dysphagia and mortality, adjusted Cox models stratified on cancer status were performed as well as an interaction model., Results: Mortality rates per 100 person-years for IIM patients exposed to dysphagia were 2.3 (95 %CI 1.0 to 4.5) in those without cancer compared to 33.3 (95 %CI 16.6 to 59.5) in those with cancer. In stratified Cox models, the main effect of dysphagia was HR 0.5 (95 %CI 0.2 to 1.5) in non-cancer and 3.1 (95 %CI 1.0 to 10.2) in cancer patients. In the interaction model, the combination of dysphagia and cancer yielded a HR of 6.4 (1.2 to 35.1)., Conclusion: In this IIM cohort, dysphagia in non-cancer patients was not associated with increased mortality, while it was in presence of cancer, supporting effect modification of cancer on the association between dysphagia and mortality. This suggests that IIM patients with and without cancer differ and separate analyses for the two groups should be conducted when the outcome of interest is mortality., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Valerie Leclair reports financial support was provided by Börje Dahlin Foundation Fund. Valerie Leclair reports financial support was provided by Fonds de Recherche en Santé du Québec (FRSQ). Jiri Vencovsky reports financial support was provided by Project for Conceptual Development of Research Organization (00023728), Czech Republic Ministry of Health. Marie Holmqvist reports financial support was provided by Swedish Research Council. Marie Holmqvist reports financial support was provided by Stockholm Regional Council (ALF). Marie Holmqvist reports financial support was provided by Rheumatikerförbundet. Marie Holmqvist reports financial support was provided by Foundation King Gustaf V 80-årsfond. Ingrid E. Lundberg reports financial support was provided by Swedish Research Council. Ingrid E. Lundberg reports financial support was provided by Stockholm Regional Council (ALF). Ingrid E. Lundberg reports financial support was provided by Reumatikerförbundet. Ingrid E. Lundberg reports financial support was provided by Foundation King Gustaf V 80-årsfond. Herman Mann reports a relationship with Abbvie that includes: speaking and lecture fees and travel reimbursement. Herman Mann reports a relationship with Biogen that includes: speaking and lecture fees. Herman Mann reports a relationship with Bristol Myers Squibb Co that includes: speaking and lecture fees. Herman Mann reports a relationship with Eli Lilly that includes: speaking and lecture fees. Herman Mann reports a relationship with MSD that includes: speaking and lecture fees. Herman Mann reports a relationship with Janssen that includes: speaking and lecture fees. Herman Mann reports a relationship with Novartis that includes: speaking and lecture fees. Herman Mann reports a relationship with UCB that includes: speaking and lecture fees. Herman Mann reports a relationship with Pfizer that includes: speaking and lecture fees. Herman Mann reports a relationship with SOBI that includes: speaking and lecture fees. Jiri Vencovsky reports a relationship with Abbvie that includes: funding grants. Jiri Vencovsky reports a relationship with Argenx that includes: consulting or advisory. Jiri Vencovsky reports a relationship with Werfen that includes: speaking and lecture fees. Jiri Vencovsky reports a relationship with Octapharma that includes: consulting or advisory and speaking and lecture fees. Jiri Vencovsky reports a relationship with Horizon that includes: consulting or advisory. Jiri Vencovsky reports a relationship with Kezar that includes: consulting or advisory. Jiri Vencovsky reports a relationship with Boehringer that includes: consulting or advisory. Ingrid E. Lundberg reports a relationship with Corbus Pharmaceuticals Holdings Inc that includes: consulting or advisory. Ingrid E. Lundberg reports a relationship with AstraZeneca Pharmaceuticals LP that includes: consulting or advisory. Ingrid E. Lundberg reports a relationship with Bristol Myers Squibb Co that includes: consulting or advisory. Ingrid E. Lundberg reports a relationship with EMD Serono Research and Development Institute that includes: consulting or advisory. Ingrid E. Lundberg reports a relationship with Argenx that includes: consulting or advisory. Ingrid E. Lundberg reports a relationship with Pfizer Inc that includes: consulting or advisory. Ingrid E. Lundberg reports a relationship with Janssen that includes: consulting or advisory. Ingrid E. Lundberg reports a relationship with Kezaar that includes: consulting or advisory. Ingrid E. Lundberg reports a relationship with Orphazyme that includes: consulting or advisory. Ingrid E. Lundberg reports a relationship with Chugai Pharmaceutical Co Ltd that includes: consulting or advisory. Ingrid E. Lundberg reports a relationship with Boehringer Ingelheim that includes: consulting or advisory. Ingrid E. Lundberg reports a relationship with Roche that includes: equity or stocks. Ingrid E. Lundberg reports a relationship with Novartis that includes: equity or stocks. co-author is an associate editor of this journal - IEL If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Objectives: We aimed to evaluate cardiovascular (CV) risk in patients with idiopathic inflammatory myopathies (IIM) compared with healthy controls (HC) and to assess its association with disease-specific features., Methods: Ninety IIM patients and 180 age-/sex-matched HC were included. Subjects with a history of CV disease (angina pectoris, myocardial infarction and cerebrovascular/peripheral arterial vascular events) were excluded. All participants were prospectively recruited and underwent examinations of carotid intima-media thickness (CIMT), pulse wave velocity (PWV), ankle-brachial index (ABI), and body composition. The risk of fatal CV events was evaluated by the Systematic COronary Risk Evaluation (SCORE) and its modifications., Results: Compared with HC, IIM patients had a significantly higher prevalence of traditional CV risk factors, carotid artery disease (CARD), abnormal ABI and PWV. After propensity score matching (using traditional CV risk factors), the prevalence of CARD and pathological PWV remained significantly higher in IIM than HC. No significant difference in SCORE was observed. The most unfavourable CV risk profile was observed in patients with necrotizing myopathy, especially in statin-induced anti-HMGCR+ patients. The calculated CV risk scores by SCORE, SCORE2 and SCORE multiplied by the coefficient 1.5 (mSCORE) were reclassified according to CIMT and the presence of carotid plaques. SCORE was demonstrated to be most inaccurate in predicting CV risk in IIM. Age, disease activity, lipid profile, body composition parameters and blood pressure were the most significant predictors of CV risk in IIM patients., Conclusion: Significantly higher prevalence of traditional risk factors and subclinical atherosclerosis was observed in IIM patients compared with HC., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Background: In patients with idiopathic inflammatory myopathies (IIM), autoantibodies are associated with specific clinical phenotypes suggesting a pathogenic role of adaptive immunity. We explored if autoantibody profiles are associated with specific HLA genetic variants and clinical manifestations in IIM., Methods: We included 1348 IIM patients and determined the occurrence of 14 myositis-specific or -associated autoantibodies. We used unsupervised cluster analysis to identify autoantibody-defined subgroups and logistic regression to estimate associations with clinical manifestations, HLA-DRB1, HLA-DQA1, HLA-DQB1 alleles, and amino acids imputed from genetic information of HLA class II and I molecules., Findings: We identified eight subgroups with the following dominant autoantibodies: anti-Ro52, -U1RNP, -PM/Scl, -Mi2, -Jo1, -Jo1/Ro52, -TIF1γ or negative for all analysed autoantibodies. Associations with HLA-DRB1∗11, HLA-DRB1∗15, HLA-DQA1∗03, and HLA-DQB1∗03 were present in the anti-U1RNP-dominated subgroup. HLA-DRB1∗03, HLA-DQA1∗05, and HLA-DQB1∗02 alleles were overrepresented in the anti-PM/Scl and anti-Jo1/Ro52-dominated subgroups. HLA-DRB1∗16, HLA-DRB1∗07 alleles were most frequent in anti-Mi2 and HLA-DRB1∗01 and HLA-DRB1∗07 alleles in the anti-TIF1γ subgroup. The HLA-DRB1∗13, HLA-DQA1∗01 and HLA-DQB1∗06 alleles were overrepresented in the negative subgroup. Significant signals from variations in class I molecules were detected in the subgroups dominated by anti-Mi2, anti-Jo1/Ro52, anti-TIF1γ, and the negative subgroup., Interpretation: Distinct HLA class II and I associations were observed for almost all autoantibody-defined subgroups. The associations support autoantibody profiles use for classifying IIM which would likely reflect underlying pathogenic mechanisms better than classifications based on clinical symptoms and/or histopathological features., Funding: See a detailed list of funding bodies in the Acknowledgements section at the end of the manuscript., Competing Interests: Declaration of interests Professor Lundberg has received consulting fees from Corbus Pharmaceuticals, Inc and research grants from Astra Zeneca and has been serving on the advisory board for Astra Zeneca, Bristol Myers Squibb, EMD Serono Research & Development Institute, Argenx, Octapharma, Kezaar, Orphazyme, Pfizer and Janssen and has stock shares in Roche and Novartis. Professor Vencovský has received speaker fees from Abbvie, Biogen, Boehringer, Eli Lilly, Gilead, MSD, Novartis, Pfizer, Roche, Sanofi, UCB, Werfen; and has received consulting fees from Abbvie, Argenx, Boehringer, Eli Lilly, Gilead, Octapharma, Pfizer, UCB. Professor Chinoy has received personal compensation for activities with Novartis, UCB, Eli Lilly, Biogen, Orphazyme, Astra Zeneca, Pfizer, Kezar Life Sciences, Galapagos, Argenx, GSK as a speaker, advisory board member or consultancy; grants via The University of Manchester from Eli Lilly and UCB; travel support from Abbvie and Janssen. Dr Mann has received honoraria from Abbvie, Biogen, BMS, Eli Lilly, MSD, Janssen, Novartis, UCB, Pfizer, SOBI and travel support by Abbvie. Dr Tansley received payment from Boehringer Ingelheim as a speaker. Dr Rönnblom received support from The Swedish Research Council (2018–02399), Reumatikerförbundet (R-939716) and GV:80 (FAI-2020-0658) foundation. Dr Holmqvist received support from The Swedish Research Council, Stockholm Regional Council (ALF), Reumatikerförbundet, Konung Gustaf V:80 year foundation, The Swedish Cancer Association and was a member of Medical Advisory Board of The Myositis Association. Dr Lamb received support from the Medical Research Council UK and Myositis UK. Other authors declare no competing interests., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Compelling evidence supports the health benefits of physical exercise on the immune system, possibly through the molecules secreted by the skeletal muscles known as myokines. Herein, we assessed the impact of exercise interventions on plasma Heat shock protein 90 (Hsp90) levels in 27 patients with idiopathic inflammatory myopathies (IIM) compared with 23 IIM patients treated with standard-of-care immunosuppressive therapy only, and in 18 healthy subjects undergoing strenuous eccentric exercise, and their associations with the traditional serum markers of muscle damage and inflammation. In contrast to IIM patients treated with pharmacotherapy only, in whom we demonstrated a significant decrease in Hsp90 over 24 weeks, the 24-week exercise program resulted in a stabilization of Hsp90 levels. These changes in Hsp90 levels were associated with changes in several inflammatory cytokines/chemokines involved in the pathogenesis of IIM or muscle regeneration in general. Strenuous eccentric exercise in healthy volunteers induced a brief increase in Hsp90 levels with a subsequent return to baseline levels at 14 days after the exercise, with less pronounced correlations to systemic inflammation. In this study, we identified Hsp90 as a potential myokine and mediator for exercise-induced immune response and as a potential biomarker predicting improvement after physiotherapy in muscle endurance in IIM.

Background: Heat shock proteins (Hsp) are chaperones playing essential roles in skeletal muscle physiology, adaptation to exercise or stress, and activation of inflammatory cells. We aimed to assess Hsp90 in patients with idiopathic inflammatory myopathies (IIM) and its association with IIM-related features., Methods: Hsp90 plasma levels were analyzed in a cross-sectional cohort (277 IIM patients and 157 healthy controls [HC]) and two longitudinal cohorts to assess the effect of standard-of-care pharmacotherapy (n=39 in early disease and n=23 in established disease). Hsp90 and selected cytokines/chemokines were measured by commercially available ELISA and human Cytokine 27-plex Assay., Results: Hsp90 plasma levels were increased in IIM patients compared to HC (median [IQR]: 20.2 [14.3-40.1] vs 9.8 [7.5-13.8] ng/mL, p<0.0001). Elevated Hsp90 was found in IIM patients with pulmonary, cardiac, esophageal, and skeletal muscle involvement, with higher disease activity or damage, and with elevated muscle enzymes and crucial cytokines/chemokines involved in the pathogenesis of myositis (p<0.05 for all). Plasma Hsp90 decreased upon pharmacological treatment in both patients with early and established disease. Notably, Hsp90 plasma levels were slightly superior to traditional biomarkers, such as C-reactive protein and creatine kinase, in differentiating IIM from HC, and IIM patients with cardiac involvement and interstitial lung disease from those without these manifestations., Conclusions: Hsp90 is increased systemically in patients with IIM. Plasma Hsp90 could become an attractive soluble biomarker of disease activity and damage and a potential predictor of treatment response in IIM., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Štorkánová, Oreská, Špiritović, Heřmánková, Bubová, Kryštůfková, Mann, Komarc, Slabý, Pavelka, Šenolt, Zámečník, Vencovský and Tomčík.)

Objectives: To date, there is almost no information concerning the sexual health of patients with idiopathic inflammatory myopathies (IIM). This cross-sectional study aimed to compare sexual function in patients with IIM to age-/sex-matched healthy controls (HC) and determine the potential impact of clinical features on sexual function., Methods: In total, 122 women (61 with IIM, 61 age-matched HC) and 22 men (11 with IIM, 11 age-matched HC) aged 18-80 years completed gender-specific selection of 7 well-established and validated questionnaires assessing sexual health and function (Female Sexual Function Index, Brief Index of Sexual Function for Women, Sexual Function Questionnaire, Sexual Quality of Life Questionnaire-Female, International Index of Erectile Function, Male Sexual Health Questionnaire, Sexual Quality of Life Questionnaire-Male). Results were compared between patients and HC and correlated with selected disease-related features., Results: The prevalence of sexual dysfunction in IIM was 59% in women (vs 40% in HC), and 64% (vs 9% in HC) in men. Men and women with IIM reported significantly impaired sexual function compared with sex-/age-matched HC. Decreased sexual function was associated with muscle weakness, disability, physical inactivity, fatigue, depression and decreased quality of life., Conclusions: Our results suggest that sexual dysfunction is common among IIM patients and more attention should be paid to this aspect of the disease., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Objectives: The aim of this cross-sectional study was to explore the circulating and skeletal muscle expression of clusterin (CLU) in inflammatory myopathies (IIM) and its potential implication in pathogenetic mechanisms of the disease., Methods: A total of 85 IIM patients and 86 healthy controls (HC) were recruited. In addition, 20 IIM patients and 21 HC underwent a muscle biopsy. Circulating CLU was measured by ELISA. Serum cytokine profile of patients and HC was assessed by Cytokine 27-plex Assay. Immunohistochemical localisation of CLU was assessed in 10 IIM and 4 control muscle tissue specimens. The expression of CLU and myositis related cytokines in muscle was determined by qPCR., Results: Serum levels of CLU were significantly increased in IIM patients compared to controls (86.2 (71.6-99.0) vs. 59.6 (52.6-68.4) μg/mL, p<0.0001) and positively correlated with myositis disease activity assessment (MYOACT) (r=0.337, p=0.008), myositis intention-to-treat activity index (MITAX) (r=0.357, p=0.004) and global disease assessment evaluated by physician (r=0.309, p=0.015). Moreover, serum CLU correlated with cytokines and chemokines involved in IIM and their combined effect on disease activity was revealed by multivariate redundancy analysis. In muscle tissue, CLU mRNA was increased in IIM patients compared to controls (p=0.032) and CLU accumulated in the cytoplasm of regenerating myofibres., Conclusions: We suggest that the up-regulation of clusterin in circulation and skeletal muscle of IIM patients may be an inflammation and atrophy induced response of the organism intended to limit the environment, favouring further muscle damage.

Background: The structural and functional changes of the skeletal muscles in idiopathic inflammatory myopathies (IIM) caused by inflammation and immune changes can be severely disabling. The objective of this study was to assess the effect of a 24-week program combining a supervised training of activities of daily living (ADL), resistance, and stability with home exercise for improving muscle function, compared to a daily home-based exercise representing the regular outpatient care., Methods: Fifty-seven patients with IIM were consecutively and non-selectively enrolled in an intervention (IG, n = 30) or control (CG, n = 27) group. Both groups were provided a standard-of-care pharmacological treatment and follow-up. Only the IG underwent the supervised intervention twice a week for 1 h per session. At baseline, 12, 24, and 48 weeks, all patients were assessed by an assessor blinded to the intervention for primary outcomes: muscle strength (Manual Muscle Testing of eight muscle groups [MMT-8]) and endurance (Functional Index-2 [FI-2]), and secondary outcomes: stability and body composition. Secondary outcomes also included questionnaires evaluating disability (Health Assessment Questionnaire [HAQ]), quality of life (Short Form 36 [SF-36]), depression (Beck's Depression Inventory-II [BDI-II]), and fatigue (Fatigue Impact Scale [FIS]), and analysis of the systemic and local inflammatory response and perceived exertion to assess the safety of the intervention., Results: Twenty-seven patients in the IG and 23 in the CG completed the entire program and follow-up. At week 24, compared to deterioration in the CG, we found a significant improvement in the IG in muscle strength (mean % improvement compared to baseline by 26%), endurance (135%), disability (39%), depression (26%), stability (11%), and basal metabolism (2%) and a stabilization of fitness for physical exercise. The improvement was clinically meaningful (a 24-week change by >20%) in most outcomes in a substantial proportion of patients. Although the improvement was still present at 48 weeks, the effect was not sustained during follow-up. No significant increase in the systemic or local expression of inflammatory markers was found throughout the intervention., Conclusions: This 24-week supervised intervention focused on ADL training proved to be safe and effective. It not only prevented the progressive deterioration, but also resulted in a significant improvement in muscle strength, endurance, stability, and disability, which was clinically meaningful in a substantial proportion of patients., Trial Registration: ISRCTN35925199 (retrospectively registered on 22 May 2020).

Background: Interleukin-35 (IL-35) is a recently described heterodimeric cytokine that belongs to the IL-12 family and consists of p35 (IL-12a) and EBI3 (IL-27b) subunits. The expression of IL-35 in humans is inducible in response to inflammatory stimuli. Increased IL-35 levels were documented in several autoimmune inflammatory diseases, suggesting a possible immunomodulatory role in their pathogenesis., Objectives: The aim of this study was to explore a potential role of IL-35 in the pathogenesis of idiopathic inflammatory myopathies (IIM) by studying the expression of IL-35 subunits in muscle biopsy samples and by evaluating serum levels of IL-35 and their association with disease activity in IIM patients., Methods: The expression of IL-35 subunits was studied in serial sections of 9 muscle biopsy samples [4 polymyositis (PM), 5 dermatomyositis (DM)] and in 7 non-inflammatory control muscle biopsies. Serum levels of IL-35 were measured in 23 PM, 28 DM and 15 cancer associated myositis (CAM) patients as well as in 40 healthy controls. Disease activity was evaluated using the Myositis Disease Activity Assessment Tool (MDAAT) and by serum muscle enzymes., Results: Expression of both IL-35 subunits was evident in the inflammatory infiltrates in IIM muscle biopsies, while no IL-35 expression was observed in control muscle samples. IL-35 serum levels were increased in all IIM patients compared to healthy controls [median 119.5 (range 32.1-1074.5) vs 36.2 (range 1.5-86.5) pg/ml, P < 0.001]. There were no differences in IL-35 serum levels between myositis subgroups (DM, PM or CAM). Serum IL-35 levels correlated significantly with physician's assessment of global (r = 0.29, p = 0.021), muscle (r = 0.30, p = 0.017) and extramuscular (r = 0.30, p = 0.016) disease activity as well as creatine kinase (r = 0.26, p = 0.044) and lactate dehydrogenase (r = 0.40, p = 0.003) levels. There was a significant correlation with pulmonary activity in patients with interstitial lung disease (r = 0.39, p = 0.037). Serum IL-35 correlated negatively with duration of treatment (r = -34, p = 0.009)., Conclusions: IL-35 is overexpressed in inflammatory infiltrates in muscle tissue and serum in IIM patients and there is correlation with several disease activity parameters. These data suggest potential role of locally produced IL-35 in the pathogenesis of inflammatory myopathies., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objectives: The aim of this study was to investigate the systemic and skeletal muscle levels of atrophy-associated myokines in patients with idiopathic inflammatory myopathies (IIM) and their association with clinical characteristics of myositis., Methods: A total of 94 IIM patients and 162 healthy controls were recruited. Of those, 20 IIM patients and 28 healthy controls underwent a muscle biopsy. Circulating concentrations of myostatin, follistatin, activin A and TGF-β1 were assessed by ELISA. The expression of myokines and associated genes involved in the myostatin signalling pathway in muscle tissue was determined by real-time PCR., Results: We report decreased levels of circulating myostatin (median 1817 vs 2659 pg/ml; P = 0.003) and increased follistatin (1319 vs 1055 pg/ml; P = 0.028) in IIM compared with healthy controls. Activin A levels were also higher in IIM (414 vs 309 pg/ml; P = 0.0005) compared with controls. Myostatin was negatively correlated to muscle disease activity assessed by physician on visual analogue scale (MDA) (r = -0.289, P = 0.015) and positively to manual muscle testing of eight muscles (r = 0.366, P = 0.002). On the other hand, follistatin correlated positively with MDA (r = 0.235, P = 0.047). Gene expression analysis showed higher follistatin (P = 0.003) and myostatin inhibitor follistatin-like 3 protein (FSTL3) (P = 0.008) and lower expression of activin receptor type 1B (ALK4) (P = 0.034), signal transducer SMAD3 (P = 0.023) and atrophy marker atrogin-1 (P = 0.0009) in IIM muscle tissue compared with controls., Conclusion: This study shows lower myostatin and higher follistatin levels in circulation and attenuated expression of myostatin pathway signalling components in skeletal muscle of patients with myositis, a newly emerging pattern of the activin A-myostatin-follistatin system in muscle wasting diseases., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Purpose of Review: To summarize recent findings and progression in the field of imaging of inflammatory myopathies. The most commonly used method is magnetic resonance imaging, and the article focuses on this technique, but covers also several other less frequently used or emerging methods., Recent Findings: A relatively good agreement exists regarding some technical parameters, area of investigation, and assessment of inflammatory activity and chronic damage using magnetic resonance imaging. There are inconsistent data available with respect to distribution of involvement in individual IIM subtypes. Ultrasound and other imaging methods lack the validation and still face many unresolved problems. Imaging plays a crucial role in the evaluation of impairment in patients with IIMs. The future research should be focused on standardization of each method in order to obtain comparable results and on defining the most appropriate indications of their use.

Purpose of Review: Arthritis is a well-recognized symptom of idiopathic inflammatory myopathies (IIM). We provide a summary of available data regarding the epidemiology, clinical characteristics, and autoantibody associations of joint involvement in various forms of IIM., Recent Findings: Arthritis is reported in 18-55% of patients with IIM. It is particularly frequent (20-70%) in those with antisynthetase syndrome (ASS); highest prevalence is associated with anti-Jo-1 positivity. Most common manifestation is non-erosive polyarthritis. X-ray erosions may be found occasionally in ASS, particularly in patients with overlap with rheumatoid arthritis (RA). Arthritis is often present at the time of IIM diagnosis and it may even precede the onset of muscle weakness. Arthritis may in some cases be the main disease manifestation responsible for the disease burden in patients with IIM. Arthritis is a frequent symptom of IIM. Polyarthritis of small joints of the hands is the most frequent clinical manifestation. Arthritis may be the first or dominant symptom in IIM and therefore patients may be initially misdiagnosed as having RA. Particularly in seronegative RA patients with interstitial lung disease or Raynaud's phenomenon, the possibility of IIM should be considered.

Objectives: To describe imaging modalities for diagnosing and monitoring of patients with idiopathic inflammatory myopathies., Methods: A detailed literature search summarising recent data documenting the contribution of different imaging techniques to current management of idiopathic inflammatory myopathies was performed., Results: An overview of methods most frequently used for evaluation of inflammatory myopathies and the description of their role in the diagnostic and monitoring process is presented., Conclusions: MRI is currently the most useful method capable of demonstrating both inflammatory and post-inflammatory changes in the muscles and surrounding soft tissue. Several studies have documented potential usefulness of other imaging techniques, such as ultrasonography, positron emission tomography, scintigraphy, and dual-energy x-ray absorptiometry.

Purpose of Review: MRI is a promising imaging method commonly used to assess muscle involvement in patients with idiopathic inflammatory myopathies (IIM). MRI enables evaluation of both activity and damage and is therefore an ideal noninvasive diagnostic and monitoring tool. Despite its widespread use, there is no universally accepted method for scoring and reporting of MRI findings. The aim of this review is to provide an overview of systems used in the evaluation of MR images in patients with IIM., Recent Findings: A number of semi-quantitative and quantitative methods have been used to evaluate and record the severity of myopathy on MRI. These scoring systems differ in the number and type of parameters assessed and in their complexity; furthermore, they were evaluated in different patient populations, all of which make comparisons between them difficult., Summary: There is a need to create a standardized and validated protocol for evaluation of pathological changes in muscle MRI in IIM. The most appropriate number and distribution of muscle groups as well as evaluated pathological features need to be determined. Based on this literature search, the future scoring system should include assessment of muscle oedema, fatty infiltration, muscle atrophy and possibly the presence of fascial and subcutaneous inflammation. Whether the quantitative methods provide more reliable information regarding disease activity remains unclear.

Objectives: To analyse the expression regulation of two inducible HSP70 genes - HSPA1A and HSPA1B - located within the major histocompatibility complex (MHC) in patients with various systemic autoimmune diseases and to prove the reliability of MHC-located HSP70 genes as molecular markers reflecting the autoimmune process., Methods: 94 adult patients with idiopathic inflammatory myopathy (IIM, n=31), systemic lupus erythematosus (SLE, n=31) or systemic sclerosis (SSc, n=32) and 37 healthy individuals were analysed. The mRNA expression level was determined using quantitative real-time PCR method. The expression of intracellular HSP70 was established by flow cytometry, the extracellular HSP70 protein was measured in plasma samples using a commercially available sandwich enzyme-linked immunosorbent assay (ELISA)., Results: The expression of HSPA1A gene was significantly up-regulated in patients with autoimmune diseases (SLE: p<0.01; SSc: p<0.01; IIM: p<0.0001) compared to healthy controls. The expression of HSPA1B gene was increased only in patients with myositis (p<0.05). Furthermore, the HSPA1B gene expression is associated with the HLA-DRB1*03 risk allele in patients with IIM. In addition, we have found a relation between HSPA1A gene expression regulation and the presence of disease specific autoantibodies in patients with SLE and myositis. The level of intracellular HSP70 was not increased; however, the level of extracellular HSP70 protein was increased in patients suffering from SSc and IIM as compared to controls., Conclusions: The results suggest an involvement of the MHC-linked HSP70 genes in the pathology of studied autoimmune disorders. Therefore, the HSPA1A and HSPA1B genes might serve as an interesting candidate molecule for development of distinct types of autoimmunities.

Objectives: The aim of this study was to evaluate serum levels of visfatin in anti-Jo-1-positive myositis patients, its expression in muscle tissue and to investigate potential relationships between visfatin, B-cell activating factor of the TNF family (BAFF), disease activity and anti-Jo-1 autoantibody levels., Methods: Serum levels of visfatin and BAFF were measured in 38 anti-Jo-1 positive myositis patients and 35 healthy subjects. Disease activity was evaluated by myositis disease activity assessment tool (MYOACT) using visual analogue scales (VAS) and by serum muscle enzymes. Visfatin expression was evaluated by immunohistochemistry in muscle tissue of myositis patients (n=10) and compared with non-inflammatory control muscle tissue samples from patients with myasthenia gravis (n=5)., Results: Serum visfatin and BAFF levels were significantly higher in myositis patients compared to healthy subjects and were associated with clinical muscle activity assessed by VAS. Only serum BAFF levels, but not visfatin levels, positively correlated with muscle enzyme concentrations and anti-Jo1 antibody levels. There was a positive correlation between visfatin and BAFF serum levels in myositis patients but a negative correlation was observed in healthy subjects. Visfatin expression was up-regulated in endomysial and perimysial inflammatory infiltrates of muscle tissue from myositis patients., Conclusions: Up-regulation of visfatin in myositis muscle tissue and an association between increased visfatin levels and muscle disease activity evaluated by MYOACT in anti-Jo-1 positive myositis patients could support possible role of visfatin in the pathogenesis of myositis.

Introduction: The aim was to evaluate S100A4 protein as a biomarker of disease activity and potential cancer development in patients with myositis., Methods: Serum levels of S100A4 were determined in 43 dermatomyositis (DM), 39 polymyositis (PM) and 22 cancer associated myositis (CAM) patients as well as in 77 healthy controls. The associations between S100A4 levels, inflammation, disease activity, muscle strength and cancer development were evaluated., Results: All myositis patients had significantly higher serum levels of S100A4 protein compared to healthy controls (median (IQR): 31.5 (17.4 to 59.5) versus 23.8 (14.5 to 33.7) ng/ml, P <0.05). In patients with PM, serum levels of S100A4 protein were significantly higher than in healthy controls (41.6 (24.2 to 123.1) versus 23.8 (14.5 to 33.7) ng/ml; P <0.001) as well as in patients with DM (26.7 (11.3 to 47.5) ng/ml; P <0.05). The levels of S100A4 were comparable between myositis with and without cancer. In all myositis patients, serum S100A4 levels correlated with MYOsitis disease ACTivity assessment (MYOACT) score (r = 0.34; P = 0.001), constitutional (r = 0.30; P = 0.003), pulmonary (r = 0.43; P = 0.0001) and extramuscular disease activity (r = 0.36; P = 0.0001), as well as with creatine phosphokinase (r = 0.27; P = 0.015) and lactate dehydrogenase (r = 0.37; P = 0.002) or c-reactive protein (CRP) levels (r = 0.24; P = 0.038). Multiple regression analysis showed significant association between S100A4 serum levels and extramuscular disease activity (β = 0.552; P = 0.002) in PM patients and with MYOACT (β = 0.557; P = 0.003) and CRP levels (β = 0.391; P = 0.029) in DM patients., Conclusions: Circulating levels of S100A4 are elevated in patients with myositis and associate with several disease activity parameters, particularly with extramuscular components. No relation between S100A4 levels and presence of cancer associated myositis was found.

Objective: To determine the prevalence, distribution, and clinical manifestations of arthritis in a cohort of patients with idiopathic inflammatory myopathies (IIM). Associations with autoantibody status and HLA genetic background were also explored., Methods: Consecutive patients with IIM treated in a single center were included in this cross-sectional study (n = 106). History of arthritis, 68-joint and 66-joint tender and swollen joint index, clinical features of IIM, and autoantibody profiles were obtained by clinical examination, personal interview, and review of patient records. High-resolution genotyping in HLA-DRB1 and HLA-DQB1 loci was performed in 71 and 73 patients, respectively., Results: A combination of patients' medical history and cross-sectional physical examination revealed that arthritis at any time during the disease course had occurred in 56 patients (53%). It was present at the beginning of the disease in 39 patients (37%) including 23 cases (22%) with arthritis preceding the onset of muscle weakness. On physical examination, 29% of patients had at least 1 swollen joint. The most frequently affected areas were wrists, and metacarpophalangeal and proximal interphalangeal joints. Twenty-seven out of the 29 anti-Jo1-positive patients had arthritis at any time during the course of their illness; this prevalence was significantly higher compared to patients without the anti-Jo1 autoantibody (p < 0.0001). No association of arthritis with individual HLA alleles was found., Conclusion: Our data suggest that arthritis is a common feature of myositis. It is frequently present at the onset of disease and it may even precede muscular manifestations of IIM. The most common presentation is a symmetrical, nonerosive polyarthritis affecting particularly the wrists, shoulders, and small joints of the hands. We have confirmed a strong association of arthritis with the presence of the anti-Jo1 antibody.

Statins are well-established lipid-lowering drugs that reduce morbidity and mortality due to cardiovascular disease and cause adverse effects relatively rarely. It is still unclear whether statins are capable of inducing an immune-mediated response directed against skeletal muscle. Here, we present the cases of three patients who developed inflammatory myopathy in the course of statin treatment. Moreover, multiple mitochondrial DNA deletions were found in two of them. The ability of statins to induce an immune-mediated response and their interactions with mitochondrial metabolism pathways are discussed.

Introduction: The purpose of this study was to evaluate and compare the serum levels and local expression of resistin in patients with idiopathic inflammatory myopathies to controls, and to determine the relationship between resistin levels, inflammation and disease activity., Methods: Serum resistin levels were determined in 42 patients with inflammatory myopathies and 27 healthy controls. The association among resistin levels, inflammation, global disease activity and muscle strength was examined. The expression of resistin in muscle tissues from patients with inflammatory myopathies and healthy controls was evaluated. Gene expression and protein release from resistin-stimulated muscle and mononuclear cells were assessed., Results: In patients with inflammatory myopathies, the serum levels of resistin were significantly higher than those observed in controls (8.53 ± 6.84 vs. 4.54 ± 1.08 ng/ml, P < 0.0001) and correlated with C-reactive protein (CRP) levels (r = 0.328, P = 0.044) and myositis disease activity assessment visual analogue scales (MYOACT) (r = 0.382, P = 0.026). Stronger association was observed between the levels of serum resistin and CRP levels (r = 0.717, P = 0.037) as well as MYOACT (r = 0.798, P = 0.007), and there was a trend towards correlation between serum resistin and myoglobin levels (r = 0.650, P = 0.067) in anti-Jo-1 positive patients. Furthermore, in patients with dermatomyositis, serum resistin levels significantly correlated with MYOACT (r = 0.667, P = 0.001), creatine kinase (r = 0.739, P = 0.001) and myoglobin levels (r = 0.791, P = 0.0003) and showed a trend towards correlation with CRP levels (r = 0.447, P = 0.067). Resistin expression in muscle tissue was significantly higher in patients with inflammatory myopathies compared to controls, and resistin induced the expression of interleukins (IL)-1β and IL-6 and monocyte chemoattractant protein (MCP)-1 in mononuclear cells but not in myocytes., Conclusions: The results of this study indicate that higher levels of serum resistin are associated with inflammation, higher global disease activity index and muscle injury in patients with myositis-specific anti-Jo-1 antibody and patients with dermatomyositis. Furthermore, up-regulation of resistin in muscle tissue and resistin-induced synthesis of pro-inflammatory cytokines in mononuclear cells suggest a potential role for resistin in the pathogenesis of inflammatory myopathies.

Objective: To investigate serum levels of B cell activating factor (BAFF) in patients with myositis and correlate these to autoantibody profile, clinical phenotype and treatment., Methods: BAFF levels in sera from 49 patients with dermatomyositis, 44 with polymyositis, 6 with inclusion body myositis and 30 matched controls were measured by ELISA. Specific autoantibodies were detected by line blot and western blot assays., Results: Serum levels of BAFF were significantly higher in patients compared to healthy controls (p = 0.003). Patients with anti-Jo-1 autoantibodies had higher BAFF levels than control individuals (p<0.003) or patients without any specific autoantibodies (p<0.05). Patients with dermatomyositis had higher BAFF levels compared to polymyositis (p<0.05). Patients with interstitial lung disease (ILD) had higher BAFF levels than patients without ILD (p<0.05) or controls (p<0.01) but this could be explained by presence of anti-Jo-1 autoantibodies. BAFF levels correlated with serum creatine kinase (CK) (rs = 0.365, p = 0.0005) but not with C-reactive protein (CRP) levels. A negative correlation of BAFF levels with glucocorticoid daily dose for all patients (rs = -0.292, p = 0.003) and with cumulative glucocorticoid doses in early myositis cases (rs = -0.659, p<0.001) was recorded., Conclusion: Our finding of elevated serum levels of BAFF in patients with myositis with described phenotypes together with the correlations between levels of BAFF and CK and a negative correlation with dose of glucocorticoids, indicate that BAFF could be a potential therapeutic target in such cases.