Comparison of clinical features between patients with anti-synthetase syndrome and dermatomyositis: Results from the MYONET registry.

OBJECTIVES: To compare clinical characteristics, including the frequency of cutaneous, extramuscular manifestations, and malignancy, between adults with anti-synthetase syndrome (ASyS) and dermatomyositis (DM). METHODS: Using data regarding adults from the MYONET registry, a cohort of DM patients with anti-Mi2/-TIF1É£/-NXP2/-SAE/-MDA5 autoantibodies, and a cohort of ASyS patients with anti-tRNA synthetase autoantibodies (anti-Jo1/-PL7/-PL12/-OJ/-EJ/-Zo/-KS) were identified. Patients with DM sine dermatitis or with discordant dual autoantibody specificities were excluded. Sub-cohorts of patients with ASyS with or without skin involvement were defined based on presence of DM-type rashes (heliotrope rash, Gottron's papules/sign, violaceous rash, shawl sign, V sign, erythroderma, and/or periorbital rash). RESULTS: In total 1,054 patients were included (DM, n = 405; ASyS, n = 649). In ASyS cohort, 31% (n = 203) had DM-type skin involvement (ASyS-DMskin). A higher frequency of extramuscular manifestations, including Mechanic's hands, Raynaud's phenomenon, arthritis, interstitial lung disease, and cardiac involvement differentiated ASyS-DMskin from DM (all p< 0.001), whereas higher frequency of any of four DM-type rashes: heliotrope rash (n = 248, 61% vs n = 90, 44%), violaceous rash (n = 166, 41% vs n = 57, 9%), V sign (n = 124, 31% vs n = 28, 4%), and shawl sign (n = 133, 33% vs n = 18, 3%) differentiated DM from ASyS-DMskin (all p< 0.005). Cancer-associated myositis (CAM) was more frequent in DM (n = 67, 17%) compared with ASyS (n = 21, 3%) and ASyS-DMskin (n = 7, 3%) cohorts (both p< 0.001). CONCLUSION: DM-type rashes are frequent in patients with ASyS; however, distinct clinical manifestations differentiate these patients from classical DM. Skin involvement in ASyS does not necessitate increased malignancy surveillance. These findings will inform future ASyS classification criteria and patient management.

Myositis-specific autoantibodies and QTc changes by ECG in idiopathic inflammatory myopathies.

OBJECTIVES: The aim of this study was to investigate cardiac involvement detected by ECG in patients with idiopathic inflammatory myopathies (IIMs) and to evaluate possible associations between the autoantibody profile and ECG changes in these patients. METHODS: In a Scandinavian cross-sectional study, patients were included from two Danish centres and one Swedish centre. Resting 12-lead ECG was investigated in 261 patients with IIM compared with 102 patients with systemic sclerosis (SSc) and 48 healthy controls (HCs). ECG changes were correlated to clinical manifestations and myositis-specific and myositis-associated autoantibodies (MSAs and MAAs, respectively). RESULTS: Patients with IIM had a longer mean corrected QT (QTc) duration and more frequently presented with prolonged QTc (≥450 ms; P = 0.038) compared with HCs. A longer QTc duration was recorded in SSc compared with IIM [433 ms (s.d. 23) vs 426 (24); P = 0.011], yet there was no significant difference in the fraction with prolonged QTc (SSc: 22%, IIM: 16%; P = 0.19). In multivariable regression analyses, anti-Mi2 (P = 0.01, P = 0.035) and anti-Pl-7 (P = 0.045, P = 0.014) were associated with QTc duration and prolonged QTc in IIM. Elevated CRP was associated with prolonged QTc (P = 0.041). CONCLUSION: The presence of QTc abnormalities was as common in patients with IIM as in patients with SSc, including prolonged QTc seen in almost one-fifth of the patients. Anti-Mi2, anti-Pl-7 and elevated CRP may serve as biomarkers for cardiac disease in IIM, but needs to be confirmed in a larger prospective study.

Effects of blood-flow restricted resistance training on mechanical muscle function and thigh lean mass in sIBM patients.

Sporadic inclusion body myositis (sIBM) is an idiopathic inflammatory muscle disease associated with skeletal muscle inflammation and a parallel progressive decline in muscle strength and physical function. Eventually, most sIBM patients require use of wheelchair after about 10 years of diagnosis and assistance to perform activities of daily living. This study presents data from a randomized controlled intervention trial (NCT02317094) that examined the effect of 12 weeks low-load blood-flow restricted (BFR) resistance training on maximal muscle strength, power, rate of force development (RFD), thigh lean mass (TLM), and voluntary muscle activation (VA) in sIBM patients. A time-by-group interaction in knee extensor strength was observed in the stronger leg (p ≤ 0.033) but not the weaker leg. Within-group changes were observed with BFR training (BFR) manifested by increased knee extensor strength in the strongest leg (+13.7%, p = 0.049), whereas non-exercising patients (CON) showed reduced knee extensor strength (-7.7%, p = 0.018). Maximal leg extensor power obtained for the stronger leg remained unchanged following BFR training (+9.5%, p = 0.37) while decreasing in CON (-11.1%, p = 0.05). No changes in TLM were observed. VA declined post-training (p = 0.037) in both BFR (-6.3% points) and CON (-7.5% points). The present data indicate that BFR resistance training can attenuate the rate of decline in mechanical muscle function typically experienced by sIBM patients. The preservation of muscle mass and mechanical muscle function with BFR resistance training may be considered of high clinical importance in sIBM patients to countermeasure the disease-related decline in physical function.

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

Objectives: Limitations 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. Methods: We 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. Results: Cardiac 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). Conclusion: Serum 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.

Cardiovascular involvement in myositis.

PURPOSE OF REVIEW: 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. RECENT FINDINGS: 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. SUMMARY: Updated literature on cardiovascular involvement in IIM has identified an increased risk for subclinical and clinical cardiovascular disease in these rare inflammatory muscle diseases.

Physical function and muscle strength in sporadic inclusion body myositis.

INTRODUCTION: In this study, self-reported physical function, functional capacity, and isolated muscle function were investigated in sporadic inclusion body myositis (sIBM) patients. METHODS: The 36-item Short Form (SF-36) Health Survey and 2-min walk test (2MWT), timed up & go test (TUG), and 30-s chair stand performance were evaluated. In addition, patients were tested for knee extensor muscle strength (isokinetic dynamometer) and leg extension power (Nottingham power rig). RESULTS: TUG performance was the strongest predictor of self-reported physical function (r2 = 0.56, P < 0.05). Knee extension strength and between-limb strength asymmetry were the strongest multi-regression indicators of TUG performance (r2 = 0.51, P < 0.05). Strength asymmetry showed the strongest single-factor (negative) association with 2MWT performance (r2 = 0.49, P < 0.05). DISCUSSION: TUG assessment appears to sensitively predict self-perceived physical function in sIBM patients. Notably, between-limb asymmetry in lower limb muscle strength had a substantial negative impact on motor tasks involving gait function. Muscle Nerve 56: E50-E58, 2017.

Quality of life in patients with myositis is associated with functional capacity, body composition, and disease activity-Baseline data from a randomized controlled trial.

OBJECTIVE: To investigate the potential associations between functional capacity, muscle strength, body composition, and disease-related measures and quality of life in patients with myositis. METHODS: Baseline measures of functional capacity (functional index 3 (FI3), 2-minute walk test (2MWT), timed up and go (TUG) and 30-s sit-to-stand (30-STS)), muscle strength (incl. leg and handgrip strength), maximal leg extensor power, body composition (appendicular lean mass, fat percentage/mass) and disease-related measures (disease activity & damage core sets) were examined for their associations with quality of life (physical- and mental component summary scores, Short Form 36 questionnaire (SF-36)) by means of Spearman's correlation analysis. RESULTS: A total of 32 patients with myositis were included. Positive correlations between SF-36 physical component summary score (PCS) and FI3, 30-STS, TUG, 2MWT, leg extensor power, leg strength, bench press strength, and handgrip strength were observed. In contrast, fat percentage and fat mass correlated negatively with PCS. In disease-related measures, Extramuscular global assessment, health assessment questionnaire, physician global damage, and patient global damage scores were negatively associated with SF-36 PCS. No correlations to the mental component summary score of SF-36 were observed. CONCLUSION: All measures of functional capacity were positively related to the SF-36 physical component summary score, indicating higher functional capacity positively affects quality of life in patients with myositis. Health assessment questionnaire and patient global damage scores demonstrated the strongest correlations with SF-36 physical component summary scores, further supporting these patient-reported outcomes as viable monitoring tools in patients with myositis.

Cardiac arrest in anti-mitochondrial antibody associated inflammatory myopathy.

Insight into predictors of cardiac involvement in inflammatory myopathies is sparse. A negative prognostic role of anti-mitochondrial antibodies (AMA) has been noticed and is supported by the current case. We describe a male patient who at the age 40 suffered a cardiac arrest and over the following months experienced progressive heart failure, arrhythmias and proximal muscle weakness. Clinical, genetic and serologic testing and repeated imaging- and histopathological investigations resulted in a diagnosis of AMA-associated, necrotizing, inflammatory myositis with cardiac involvement. Besides a cardiac resynchronization therapy defibrillator, heart failure and antiarrhythmic drugs the patient received successive immunosuppressants, which improved skeletal muscle strength but not cardiac disease progression. At age 45 he died from end-stage heart failure. Clinicians must be aware of AMA-associated myositis as a cause of unclarified heart disease, even in patients with initially sparse extra-cardiac manifestations. Further knowledge of treatment strategies is highly needed for this disease entity.

Conventional ultrasound and elastography as imaging outcome tools in autoimmune myositis: A systematic review by the OMERACT ultrasound group.

AIMS: To analyze whether there is sufficient data from published literature to demonstrate that ultrasound, including elastography, present good metric properties (truth, discrimination and feasibility) in autoimmune myositis (AIM). METHODS: A population, intervention, comparator and outcome-structured (PICO) search was performed in Medline, Cochrane Library and Embase database from 01/01/1973 to 08/05/2019. The inclusion criteria required original research involving adult humans, reported in English, assessing ultrasound and elastography in patients with an AIM. Conference abstracts and computer-assisted diagnostics that focused on technique and not ultrasound domains were excluded. RESULTS: Approximately 2670 articles were identified. Forty-one full-text articles were included in the final analysis. There were 551 AIM patients studied. Eighteen studies (43.9%) had a control group, of which 15 (63.3%) were healthy controls. The age of participants (including controls) varied from 18 to 86 years, and most were females (59%). Diagnosis of AIM was largely biopsy-proven, although some were derived through clinical presentation, positive clinical imaging (ultrasound or otherwise) and/or electromyography and steroid responsiveness. The features examined with ultrasound in the 41 included articles consisted of: muscle echogenicity, bulk, atrophy, architecture, power Doppler, perfusion characteristics, shear wave modulus, shear wave velocity, elasticity index and fasciculations. Twelve studies (29.2%) used quantitative methods to assess these characteristics, whilst others used semi-quantitative, dichotomous/binary and descriptive scoring systems. Criterion validity was met in 14 studies (12/14, 85.7%) and construct validity in 22 studies (22/25, 88.0%). Most published articles reported Level 3b to Level 5 evidence with varying degrees of bias. There was only one longitudinal study examining discrimination. Reliability and feasibility were under-reported. CONCLUSION: This is the first systematic review studying the utility of ultrasound, including elastography, in AIM. There is some evidence for criterion and construct validity, suggesting that ultrasound may be a promising outcome measurement instrument in AIM. Agreement on the standardization of acquisition, and the definitions of target domains, is required. Additionally, further validation studies are required to determine discrimination, reliability and feasibility.

Quality of life correlates with muscle strength in patients with dermato- or polymyositis.

The aim of this study was to compare health-related quality of life (HQoL) in adults with dermatomyositis (DM) or polymyositis (PM) with a healthy control group and to assess whether muscle strength was associated with HQoL in patients with DM or PM. A cross-sectional study was performed and included 75 patients with DM or PM and 48 healthy controls. HQoL was assessed by the Short Form 36 questionnaire (SF-36). Muscle strength of the patients was assessed using the Manual Muscle Test-8 (MMT8). Covariables and possible confounding factors were collected by validated tools. Associations were determined in multiple linear regression models. The patients had significantly lower HQoL than the control group in both the physical component summary score (PCS) and the mental component summary score (MCS). Thus, the PCS-difference between groups was 32% (p < 0.001), whereas the MCS-difference was 14% (p < 0.001). Muscle strength was associated with one domain in the patients; Physical Function (ß = 1.2; 95% confidence interval 0.37 to 2.1). No statistically significant associations were found between muscle strength and HQoL in the remaining domains. Patients with DM or PM have reduced HQoL compared to healthy controls. Notably, muscle strength was associated with scores of the domain reflecting perceived physical function in patients. These findings corroborate the validity of including selected patient reported outcomes in the evaluation and monitoring of patients with DM or PM.

Traditional cardiovascular risk factors and coronary artery calcification in adults with polymyositis and dermatomyositis: a Danish multicenter study.

OBJECTIVE: To determine the occurrence of traditional cardiovascular (CV) risk factors and coronary artery calcification (CAC) in adults with polymyositis (PM) or dermatomyositis (DM) compared to healthy controls and to assess the association between CV risk factors, PM/DM, and CAC score. METHODS: Traditional CV risk factors were assessed in a cross-sectional, observational study of 76 patients with PM/DM and in 48 sex- and age-matched healthy controls. CAC was quantified by means of cardiac computed tomography scan and expressed in Agatston units. The associations between CV risk factors, PM/DM, and CAC were studied by multivariate analyses. RESULTS: Thirty-three percent of the patients were obese compared to 11% of the controls (P = 0.005). Hypertension and diabetes mellitus were more frequent in patients (71% versus 42%; P = 0.002, and 13% versus 0%; P = 0.007), and patients had higher levels of triglycerides (P = 0.0009). High CAC score occurred more frequently in patients (20% versus 4%; P = 0.04). In multivariate analysis of patient factors associated with CAC were age (P = 0.02) and smoking (P = 0.02). CONCLUSION: In this study, traditional CV risk factors and severe CAC were commonly found in patients with PM/DM. However, severe CAC was not associated with PM/DM per se, but rather with age and smoking in these patients.