Involvement In Idiopathic Inflammatory Myopathies Research Articles

Cardiovascular complications in patients with idiopathic inflammatory myopathies: does heart matter in idiopathic inflammatory myopathies?

This review presents a detailed study of original researches and previously published reviews concerning cardiovascular involvement in idiopathic inflammatory myopathies (IIM). We aimed to summarize the current knowledge on the cardiac involvement in IIM, evaluate its impact on mortality and indicate areas still awaiting to be investigated. We searched MEDLINE database (until January 2019) and the reference lists of articles. Selection criteria included only published data, available in English, both original researches and reviews. Articles related to cardiovascular involvement in IIM were selected and analysed. The references were also screened, and relevant articles were included. Cardiovascular involvement is frequent in IIM but typically remains subclinical. Among far less prevalent symptomatic forms, congestive heart failure is the most common. Myocardium and conduction system seems to be predominantly affected. High rate of left ventricular diastolic dysfunction was observed. Non-specific changes of ST-T segment were the most common abnormalities in electrocardiography. Patients with IIM were more frequently affected by atrial fibrillation as compared with other autoimmune diseases. Increased risk of myocardial infarction was observed; furthermore, patients often develop comorbidities that enhance cardiovascular risk. Since cardiovascular disorders remain one of the major causes of death and subclinical involvement is frequent, active screening is justified. Growing availability of the novel imaging techniques may facilitate diagnosis. Correlation between myocardial involvement and the type of autoantibodies and impact of different therapeutic options on the progression of cardiovascular lesions require further studies.

Cardiac involvement in idiopathic inflammatory myopathies detected by cardiac magnetic resonance imaging.

Cardiac involvement in idiopathic inflammatory myopathies (IIM) adversely affects prognosis but is commonly sub-clinical. Cardiac magnetic resonance imaging (CMR) is an effective imaging modality for detecting myocardial inflammation and fibrosis but its use as a screening tool for cardiac disease in IIM has not been fully explored. Nineteen patients with IIM without cardiac symptoms underwent CMR using a specific cardiomyopathy protocol including specific sequences detecting focal and diffuse myocardial fibrosis. 9/19 patients demonstrated late gadolinium enhancement (LGE (3/9 right ventricular insertion, 1/9 sub-endocardial, 7/9 mid-wall/sub-epicardial)). T1 mapping was performed in 15 patients. In total, 7/15 had elevated native T1 values, of which four had detected LGE. Myocardial fibrosis was frequently detected in IIM patients without cardiac history. Detection of LGE and elevated T1 values may have negative prognostic implications. Longitudinal studies determining whether early or augmented treatment has a role in patients with sub-clinical cardiac involvement are needed.Key Points• Cardiac involvement in myositis adversely affects prognosis.• Cardiac magnetic resonance imaging is an effective tool for detecting cardiac involvement.• T1 mapping is a technique which detects diffuse myocardial inflammation and fibrosis.• In our study, focal and diffuse myocardial fibrosis was frequently found in myositis patients without cardiac symptoms.

Novel Therapeutic Options in Treatment of Idiopathic Inflammatory Myopathies.

The purpose of this review is to update the audience on the recent progress in the treatment of idiopathic inflammatory myopathies, highlighting a myriad of treatment trials aimed at slowing down progression of muscle weakness and/or skin involvement in idiopathic inflammatory myopathies. Myositis continues to be an active area of clinical and translational research. Through the work of a number of investigators, we now have a much better understanding of the pathogenesis underlying the various myositides. The role of T cells, B cells, and dendritic cells has been better defined in dermatomyositis and inclusion body myositis. The role of autoantibodies has been better elucidated, with the recognition that autoantibodies play an important role in not only establishing the diagnosis but also helping with prognostication and choosing treatment paradigms. A number of new treatment trials were designed to alter the pathogenic factors, including T cell activation, docking, and signaling, cytokines, B cell signaling, B cell depletion, as well as targeting Toll-like receptors (TLRs). Myostatin inhibitors have been developed and tried in inclusion body myositis (IBM) in hopes that they would stop muscle atrophy and improve muscle strength and function. This review will outline the progress made to date in the treatment of idiopathic inflammatory myopathies.

Using serum troponins to screen for cardiac involvement and assess disease activity in the idiopathic inflammatory myopathies.

ObjectivesLimitations in the methods available for identifying cardiac involvement and accurately quantifying disease activity in the idiopathic inflammatory myopathies (IIMs) may contribute to poor outcomes. We investigated the utility of different serum muscle damage markers [total creatine kinase (CK), cardiac troponin T (cTnT) and cardiac troponin I (cTnI)] to address these issues. MethodsWe assessed disease activity and cardiac involvement using the International Myositis Assessment and Clinical Studies Group core set measures in 123 participants with confirmed adult-onset IIM from the UK and Denmark. Total CK, cTnT and cTnI were measured. Associations were assessed using logistic regression and Spearman’s ranked correlation.ResultsCardiac involvement (n = 18) was associated with higher cTnI levels, independent of overall disease activity [adjusted odds ratio 1.03 (95% CI 1.01, 1.05); P = 0.002]. An abnormal cTnI had the highest specificity and positive predictive value for cardiac involvement (95% and 62%, respectively). In those with a normal CK but elevated cTnT or cTnI, an association with increased disease activity scores was observed. Serum cTnT correlated with the physician (ρ = 0.39) and patient-assessed (ρ = 0.28) global visual analogue scales and HAQ (ρ = 0.41) more strongly than CK or cTnI levels. cTnT was the only marker to correlate with manual muscle testing scores (ρ = −0.24).ConclusionSerum cTnI testing may have a role in screening for cardiac involvement in IIMs. Abnormal levels of serum cTnT and cTnI are associated with increased disease activity, including in those with a normal CK.

Diagnostic Approach to Cardiac Involvement in Idiopathic Inflammatory Myopathies.

Cardiac involvement in idiopathic inflammatory myopathies (IIMs) attracts more attention than it ever did because of its morbidity and impact on worse prognosis, although the accurate information needs further epidemiological studies. Early identification and intervention for the diseased heart may help improve the clinical outcomes of IIMs with cardiac involvement. Cardiac troponin assays, allowing for sensitive detection of minor myocardium injury, may provide a new way for early detection for heart involvement in IIMs. While elevated cardiac troponin I (cTnI) specifically indicates cardiomyocyte injury, the elevation of cardiac troponin T (cTnT) levels may not only derive from damaged heart but also diseased adult skeletal muscles in which cTnT could re-express in patients with IIMs. cTnI is the biomarker of choice for diagnosis of cardiac involvement and may also be a prognostic factor in IIMs. Meanwhile, electrocardiography (ECG), cardiac imaging (e.g., echocardiography, cardiac magnetic resonance) and histopathological techniques (e.g., endomyocardial biopsy) take on different degrees of importance for the diagnosis of cardiac involvement. We propose a diagnostic strategy combining the routine use of cTnI assay with other techniques (routine ECG and echocardiography, cardiac magnetic resonance, and or endomyocardial biopsy in necessity) and clinical investigation for early detection of heart involvement in IIMs. Future researches are required to validate the algorithm for performance.

Cardiovascular involvement in myositis.

The purpose of this review is to provide an update on cardiovascular involvement in idiopathic inflammatory myopathy (IIM). Studies from the past 18 months are identified and reviewed. Finally, the clinical impact of these findings is discussed. Epidemiological studies have revealed an increased risk of myocardial infraction and venous thromboembolism (VTE) - including deep venous thrombosis and pulmonary embolism - in adults with polymyositis or dermatomyositis compared to the general population, even after adjustment for potential confounders. This increased risk applies particularly within the initial year of diagnosis. In addition, cross-sectional studies have shown subclinical cardiac involvement in IIM effecting both heart function and rhythm, and conduction abnormalities, which in part might be because of myocarditis. The International Consensus Group on cardiac magnetic resonance (CMR) imaging suggests that CMR should be considered as a potentially viable diagnostic tool to evaluate the possibility of silent myocardial inflammation in IIM with normal routine noninvasive evaluation. Updated literature on cardiovascular involvement in IIM has identified an increased risk for subclinical and clinical cardiovascular disease in these rare inflammatory muscle diseases.

The clinical utility of serum IL-35 in patients with polymyositis and dermatomyositis.

The objectives of this study are to assess the levels of serum Interleukin-35 (IL-35) in patients with idiopathic inflammatory myopathies (IIMs) and to evaluate the association between IL-35 levels and IIM-related features. Serum IL-35 was detected in 76 patients with dermatomyositis (DM), 28 patients with polymyositis (PM), 98 disease controls (40 rheumatoid arthritis (RA), 34 systemic lupus erythematosus (SLE), 12 systemic sclerosis (SSc), and 12 sjogren syndrome (SS)), and 43 healthy controls by ELISA. Follow-up was conducted on 34 patients. Serum IL-35 was higher in myositis (PM/DM) patients than in healthy controls (median 76.6pg/ml [interquartile range (IQR) 57.9-136.2] vs. 29.9pg/ml (IQR 21.9-65.5), P<0.001) and disease controls. Serum IL-35 in IIM patients negatively correlated with disease duration moderately (r=-0.35, P<0.01). Patients with dysphagia had higher IL-35 than those without (median149.35pg/ml (IQR 87.97-267.32) vs. 70.72pg/ml (IQR 54.49-123.42), P=0.001). Cross-sectional correlation analysis showed a weak positive correlation between serum IL-35 and CK (r=0.293, P=0.003), moderate positive correlation with erythrocyte sedimentation rate (ESR) (r=0.304, P=0.002), serum ferritin (SF) (r=0.467, P=0.001) and LDH levels (r=0.401, P<0.001). Additionally, serum IL-35 was higher in patients who were positive for anti-HMGCR (median 292.04pg/ml (IQR 67.9-442.86) vs. 74.66pg/ml (IQR 57.24-131.32), P=0.038) and anti-SRP antibody (median 130.33pg/ml (IQR 88.04-481.28) vs. 73.06pg/ml (IQR 56.78-134.28), P=0.009) than in negative patients, respectively. Follow-up study showed that changes in IL-35 levels after treatment correlated with changes in MYOACT scores moderately (r=0.375, P=0.029). These data indicate that increased serum IL-35 could act as a disease activity marker and as a risk factor for esophageal involvement in IIM. IL-35 may participate in the pathophysiological processes of IIM, but it still needs further study to confirm.

Renal Involvement in Idiopathic Inflammatory Myopathies.

Renal involvement in idiopathic inflammatory myopathies is not as uncommon as was previously thought, as it develops in about one fifth of patients. Clinical presentation includes either acute kidney injury or chronic glomerulonephritis. The former usually develops abruptly during acute phases of rhabdomyolysis: in this case, kidney injury is caused by the toxic effects that myoglobinuria has on the kidney tubules, including cast formation and iron-induced oxidative stress and the development of a third space into the injured muscles. The latter instead has an autoimmune nature, a pleomorphic histological picture, and a more indolent course, with the exception of crescentic glomerulonephritis. Accurate diagnosis and management is crucial for these patients, as timely evaluation and treatment can prevent most of the complications. In the setting of rhabdomyolysis-induced acute kidney injury, the necessity of dialysis can be avoided through aggressive hydration and alkalinization, in order to force diuresis and avoid acidosis and hyperkalemia. In immune-mediated glomerulonephritis, renal biopsy is of undoubtedly value in the diagnostic process and can add prognostic and therapeutic information. In these forms, the development of chronic kidney disease can be prevented or at least delayed by the institution or modification of immunosuppressive treatment. Moreover, the use of drugs that inhibit the renin-angiotensin-aldosterone system and some lifestyle modifications, such as smoking cessation, weight loss, and salt restriction have also value in reducing proteinuria and the progression of kidney damage. In this review, we have summarized the currently available evidence and the different case series in an attempt to provide the readers with the most complete and practical notions that are needed to handle these delicate patients.

Abstract 14014: Early Detection of Myocardial Involvement in Idiopathic Inflammatory Myopathies Assessed by Cardiac Magnetic Resonance Imaging

Background: Idiopathic inflammatory myopathies are heterogeneous autoimmune systemic diseases characterized by chronic progressive muscle weakness and inflammatory infiltrates in skeletal muscle. The frequency of cardiac involvement varies between 9% and 72%, mainly dependent on patient selection, definition and diagnostic tools applied. Heart failure is the most frequent finding. Cardiac magnetic resonance imaging (CMR) has been shown to provide reliable and valuable information about cardiac function and inflammatory process in one examination. Hypothesis: Aim of our prospective study was to characterize cardiac involvement using a comprehensive CMR protocol. Methods: Fifty-three consecutive patients with histologically proven idiopathic inflammatory myopathy were enrolled into the study. Blood levels of Creatine kinase (CK) and myocardial CK (CK-MB) were analyzed from each patient. All patients underwent CMR examination in a 1.5-T whole body scanner. 3D short-axis functional steady-state free precession and late gadolinium enhancement (LGE) sequences were acquired in all patients covering the entire left and right ventricle. CMR images were analyzed by two experienced and blinded readers in consensus. Besides functional analysis LGE images were analyzed for hyperenhancement and quantified as LGE percentage of myocardial mass. Results: Reduced left ventricular function (ejection fraction &lt; 60%) was present in 9 (17%) patients. These patients exhibited significantly higher blood levels of CK-MB (283±193 vs. 175±221 U/l, p=0.02) than patients with preserved LVEF. Early myocardial enhancement (&gt;45% signal intensity increase) was more often present (6 out of 9 [66.7%] vs. 25 out of 44 [56.8%], p=.014) as well as LGE patterns consistent with myocardial inflammation (9 out of 9 [100%] vs. 24 out of 44 [54.5%], p=.001). LGE was most often observed in the inferior and lateral segments. Conclusion: The results of this study show that CMR is able to detect cardiac involvement in idiopathic inflammatory myopathies. Early diagnosis using CMR could result in early therapy of heart failure, leading to beneficial ventricular remodeling and thus improving living quality and survival in these patients.

The role of microRNAs in the idiopathic inflammatory myopathies.

The idiopathic inflammatory myopathies (IIMs) are a group of rare autoimmune disorders characterized by skeletal muscle weakness and inflammation. MicroRNAs (miRNAs) regulate a wide range of developmental and physiological cellular processes. New approaches to investigating the mechanisms involved in IIM, such as investigating the role of miRNAs, are vital for the development of novel therapeutics and/or better diagnostic tools. Identification of dysregulated miRNAs has led to a greater understanding of inflammation, muscle weakness/wasting and extra-muscular organ involvement in IIM. Up-regulation of immune-related miRNAs in muscle, for example, miR-155 and miR-146, is associated with autoimmunity, whereas down-regulation of myogenic miRNAs, including miR-1 and miR-206, is associated with inhibition of muscle regeneration. Disease mechanisms have been explored by altering in-vitro conditions and monitoring miRNA levels of interest, or, alternatively, changing miRNA levels and monitoring possible targets. For example, higher levels of cytokines appear to inhibit myogenic miRNAs in muscle and artificially reducing levels of miR-223 increases protein kinase C-epsilon (PKCε) levels in keratinocytes. The exciting expansion of the miRNA field adds to our understanding of IIM pathogenesis and may provide future clinical potential either as diagnostic tools or as therapeutics via use of anti-miRNAs or synthetic miRNAs.

Early diagnosis of cardiac involvement in idiopathic inflammatory myopathy by cardiac magnetic resonance tomography.

The aim of this study was to investigate cardiac involvement in patients with idiopathic inflammatory myopathies excluding inclusion body myositis with cardiac magnetic resonance tomography (CMR). A case series of 53 patients with polymyositis, dermatomyositis, or non-specific myositis underwent CMR including functional imaging, T1-weighted, and late gadolinium enhancement (LGE) imaging. T1-weighted and LGE images were analyzed for myocardial enhancement. Reduced left ventricular function (LVF) was found in 9 (7%) patients. Patients with reduced LVF more often presented with early and late myocardial enhancement (p = 0.014 and p = 0.001). In 33 (62.3%) patients, LGE was observed by CMR. These patients had significantly lower left ventricular ejection fractions (p < 0.001) compared to patients without LGE. LGE was mainly present in the lateral (p < 0.01) and inferior (p < 0.02) segments. No correlations of LGE presence or reduced LVF to cardiovascular risk factors were found. Myocardial inflammation is very frequent in polymyositis, dermatomyositis, and non-specific myositis. In our patient, cohort CMR demonstrated signs of myocardial inflammation in 62.3%. CMR seems to offer a measurable and quantifiable diagnostic tool for cardiac involvement of idiopathic inflammatory myopathies and can thus be used to monitor disease progress and therapeutic success in these patients.

Early detection of myocardial involvement in idiopathic inflammatory myopathies detected by cardiac magnetic resonance imaging

Background Idiopathic inflammatory myopathies are heterogeneous systemic autoimmune diseases that are characterized by progressive muscle weakness and typical inflammatory infiltration in skeletal muscle. It is known that a cardiac involvement may occur; the frequency varies between 9% and 72%, mainly depending on patient selection and diagnostic procedures applied. Most common finding is a progressive (systolic) heart failure. Diagnosis may be difficult in patients that exhibit exercise limitation due to peripheral muscle weakness. It has been shown that cardiac magnetic resonance imaging (CMR) is reliably able to provide important information concerning cardiac function and inflammatory processes in a single exam. Therefore, objective of our prospective study was to assess and characterize myocardial involvement in patients with histological defined idiopathic inflammatory myopathies by a comprehensive CMR protocol.

Cardiac and muscular involvement in idiopathic inflammatory myopathies: noninvasive diagnostic assessment and the role of cardiovascular and skeletal magnetic resonance imaging.

Idiopathic inflammatory myopathies (IIMs) are rare autoimmune diseases and include dermatomyositis, polymyositis, necrotizing myopathy and inclusion body myositis; they are characterized by inflammation of skeletal muscle and other internal organs and may potentially lead to irreversible damage and death. Only a small percentage of IIM has clinically overt cardiac disease; however, heart involvement is one of the leading causes of death and therefore, early detection remains a challenge. Biochemical markers and non-invasive methods such as the electrocardiogram and echocardiography have a role in diagnosis, but lack sensitivity in identifying patients with early, sublinical cardiac abnormalities. Endomyocardial and skeletal muscle biopsies are very useful, but invasive techniques and cannot be used for routine follow-up. Cardiac and skeletal magnetic resonance imaging, due to their capability to perform tissue characterization, has emerged as novel techniques for the early detection and follow-up of myocardial and skeletal muscle tissue changes (oedema, inflammation, fibrosis) in IIM. However, the clinical implications of using these approaches and their cost /benefit ratio require further evaluation.

SAT0200 Abnormal Cardiac SPECT/CT in Newly Diagnosed, Untreated Patients with Idiopathic Inflammatory Myopathies

BackgroundKnowledge of cardiac involvement in idiopathic inflammatory myopathies (IIM) is limited and a matter of debate with reported frequencies between 6% and 75%. Although clinically overt disease is rare, cardiac...

A10.3 Arthritis in Patients with Idiopathic Inflammatory Myopathies

<h3>Background and Objectives</h3> Arthritis in idiopathic inflammatory myopathies (IIM) is frequently observed in clinical practise, but, to our knowledge, there is lack of systemic reports of prevalence and/or characteristics of arthritis in myositis patients. The aim of this study is to determine prevalence of arthritis in IIM patients; it’s relation to the course of the muscle disease; characteristics of arthritis with respect to seriousness, distribution and extent as well as it’s relation to autoantibody profiles and others disease’s characteristics. <h3>Materials and Methods</h3> In this cross-sectional study, clinical aspects of disease, history of arthritis and autoantibody profiles were obtained from 106 consecutive patients with definite diagnosis of IIM. In all of them the 68-joint index was investigated. In 55 IIM patients and in 60 control patients with rheumatoid arthritis (RA) German Ultrasound Score 7 (US-7) was performed. <h3>Results</h3> Arthritis at any time of course of myositis occurred in 65 patients (61.3%); 42 had arthritis at the beginning of myositis (in 22 patients before and in 16 together with onset of muscle weakness). 52 patients presented arthritis at clinical examination (25 poly-, 17 oligo-, and 10 with monoarthritis). Most frequently affected joints were wrists (21.7%) and shoulders, metacarpophalangeal, and proximal interphalangeal joints (20.8%). From 29 anti-Jo-1 positive patients 28 had arthritis and significant association between arthritis and anti-Jo-1 positivity was found <i>(p</i> &lt; 0.0001<i>)</i>. 39 out of 55 (70.9%) patients had Gray-Scale (GS) synovitis on ultrasound; in 34 of them also Power-Doppler (PD) positivity was found. Only 4 patients had ultrasonographic tenosynovitis and 3 had bony erosions. From 60 RA patients 57 (95%) had GS synovitis, which was PD-active in 54. Tenosynovitis was found in 25 patients. 25 RA patients had one or more joint erosions. Mean US-7 score as well as scores of individual joints or modality subscores were significantly lower in IIM than in RA, but, when compared only those patients with positive findings, the differences were found in total US-7 score, and GS-synovitis and PD-tenosynovitis subscores, but not in PD-synovitis, GS-tenosynovitis as well as in scores of individual joints. <h3>Conclusions</h3> Our data suggest that arthritis is common feature of myositis. It is often present at the beginning of muscular manifestation of disease, or it even precedes the onset of muscle weakness. Most common presentation is symmetrical, non erosive polyarthritis affecting particularly wrists, shoulders, metacarpophalangeal and proximal interphalangeal joints of the hands. We confirmed strong association of arthritis with anti-Jo-1 antibody. Ultrasound investigation of joint involvement in IIM shows less frequent involvement than in RA, but comparable activity of synovitis measured by PD in affected joints. IIMs have less erosions and tenosynovitis than RA.

Myocarditis during acute inflammatory myopathies: Evaluation using clinical criteria and cardiac magnetic resonance imaging

Polymyositis (PM)/dermatomyositis (DM) are inflammatory myopathies (IM) that may be complicated by myocarditis. To diagnose myocarditis in IM remains a challenge, due to a high risk for death and a lack of standardized diagnostic criteria [ [1] Lundberg I.E. The heart in dermatomyositis and polymyositis. Rheumatology. 2006; 45: iv18-iv21 Crossref PubMed Scopus (156) Google Scholar ]. Cardiac magnetic resonance (CMR) has been successfully used in myocarditis detection [ 2 Mavrogeni S. Spargias C. Bratis C. et al. Myocarditis as a precipitating factor for heart failure: evaluation and 1-year follow-up using cardiovascular magnetic resonance and endomyocardial biopsy. Eur J Heart Fail. 2011; 13: 830-837 Crossref PubMed Scopus (69) Google Scholar , 3 Friedrich M.G. Sechtem U. Schulz-Menger J. et al. International Consensus Group on Cardiovascular Magnetic Resonance in Myocarditis. Cardiovascular magnetic resonance in myocarditis: a JACC white paper. J Am Coll Cardiol. 2009; 53: 1475-1487 Abstract Full Text Full Text PDF PubMed Scopus (1667) Google Scholar , 4 Mavrogeni S. Spargias K. Markussis V. et al. Myocardial inflammation in autoimmune diseases: investigation by cardiovascular magnetic resonance and endomyocardial biopsy. Inflamm Allergy Drug Targets. 2009; 8: 390-397 Crossref PubMed Scopus (67) Google Scholar ]. However, studies about IM are scarce [ 5 Mavrogeni S. Douskou M. Manoussakis M.N. Contrast-enhanced CMR imaging reveals myocardial involvement in idiopathic inflammatory myopathy without cardiac manifestations. JACC Cardiovasc Imaging. 2011; 4: 1324-1325 Abstract Full Text Full Text PDF PubMed Scopus (39) Google Scholar , 6 Allanore Y. Vignaux O. Arnaud L. et al. Effects of corticosteroids and immunosuppressors on idiopathic inflammatory myopathy related myocarditis evaluated by magnetic resonance imaging. Ann Rheum Dis. 2006; 65: 249-252 Crossref PubMed Scopus (100) Google Scholar ]. Currently, IM myocarditis documentation is based on ECG, laboratory and echocardiographic findings, but these criteria are of limited value [ [1] Lundberg I.E. The heart in dermatomyositis and polymyositis. Rheumatology. 2006; 45: iv18-iv21 Crossref PubMed Scopus (156) Google Scholar ]. Our aim was to evaluate the possibility of myocarditis in acute IM by clinical and CMR criteria.