Ventricular arrhythmia predicts poor outcome in polymyositis/dermatomyositis with myocardial involvement.

OBJECTIVE: Myocardial involvement (MCI) is known to increase morbidity and mortality in polymyositis (PM) and dermatomyositis (DM). This study aims to investigate whether complicating with ventricular arrhythmia (VA) predicts poor outcomes in patients with PM/DM-related myocardial involvement (PM/DM-MCI). METHODS: We reviewed all PM/DM-MCI patients admitted to Peking Union Medical College Hospital from October 1997 to April 2019. VA and the other possible risk factors for the composite endpoint, including death from any cause and rehospitalization for cardiac causes, were analyzed. RESULTS: A total of 75 PM/DM-MCI patients (44 PM and 31 DM) were enrolled, of which 27 (36%) met the composite endpoint during a median follow-up of 24 months. Independent prognostic factors for the composite endpoint include VA [HR 4.215, 95% CI (1.737, 10.230)], NT-proBNP > 3415 pg/ml [HR 2.606, 95% CI (1.203, 5.646)], interstitial lung disease [HR 2.688, 95% CI (1.209, 5.978)], and anti-cardiac remodelling therapy [HR 0.302, 95% CI (0.115, 0.792)]. The 3-year event-free survival rate of patients without VA was significantly higher than that of patients with VA (63.3% vs 40.7%, P = 0.034). Skin lesions [OR 0.163, 95% CI (0.051, 0.523)] and positive antimitochondrial antibody [OR 3.484, 95% CI (1.192, 10.183)] were independent predictors of VA. CONCLUSION: VA provides prognostic insights for PM/DM-MCI patients and predicts poor outcome. Polymyositis and positive antimitochondrial antibody are closely associated with the presence of VA in PM/DM-MCI.

COVID-19 and myositis - unique challenges for patients.

OBJECTIVE: The COVID-19 pandemic and the subsequent effects on healthcare systems is having a significant effect on the management of long-term autoimmune conditions. The aim of this study was to assess the problems faced by patients with idiopathic inflammatory myopathies (IIM). METHODS: An anonymized eSurvey was carried out with a focus on effects on disease control, continuity of medical care, drug procurance and prevalent fears in the patient population. RESULTS: Of the 608 participants (81.1% female, median (s.d.) age 57 (13.9) years), dermatomyositis was the most frequent subtype (247, 40.6%). Patients reported health-related problems attributable to the COVID-19 pandemic (n = 195, 32.1%); specifically 102 (52.3%) required increase in medicines, and 35 (18%) required hospitalization for disease-related complications. Over half (52.7%) of the surveyed patients were receiving glucocorticoids and/or had underlying cardiovascular risk factors (53.8%), placing them at higher risk for severe COVID-19. Almost one in four patients faced hurdles in procuring medicines. Physiotherapy, critical in the management of IIM, was disrupted in 214 (35.2%). One quarter (159, 26.1%) experienced difficulty in contacting their specialist, and 30 (4.9%) were unable to do so. Most (69.6%) were supportive of the increased use of remote consultations to maintain continuity of medical care during the pandemic. CONCLUSION: This large descriptive study suggests that the COVID-19 pandemic has incurred a detrimental effect on continuity of medical care for many patients with IIM. There is concern that delays and omissions in clinical care may potentially translate to poorer outcomes in the future.

Patient-reported dermatomyositis and polymyositis flare symptoms are associated with disability, productivity loss, and health care resource use.

BACKGROUND: Flare activity or worsening symptoms are not well defined for myositis. OBJECTIVES: To (a) characterize dermatomyositis (DM) and polymyositis (PM) flares from the patient perspective and (b) report the corresponding disability and rate of unplanned medical encounters. METHODS: Online survey data were collected from volunteer patients from The Myositis Association and Johns Hopkins Myositis Center. Flare frequency; Health Assessment Questionnaire Disability Index (HAQ-DI), HAQ-Pain Index, Work Productivity and Activity Impairment (WPAI) scales; emergency department/urgent care (ED/UC) visits; and hospital admissions during the past year were examined. RESULTS: 564 individuals with selfreported diagnoses of DM/PM were surveyed between December 2017 and May 2018. Recall of symptom flares was reported by 524 respondents (78.1% were female, mean age of 55 years). Among the respondents, 378 (72.1%) reported ≥ 1 flare in the past year. The pattern of flare frequency was similar for DM and PM respondents. The most common symptoms were muscle weakness (83%), extreme fatigue (78%), and muscle pain/discomfort (64%). Increasing flare frequency was associated with significantly (P < 0.01) greater mean HAQ-DI and HAQ-Pain scores, myositis-related ED/UC visits, hospital admissions, WPAI work productivity loss (among those employed), and WPAI nonwork activity impairment. CONCLUSIONS: DM/PM-related flares are common with exacerbations of muscle weakness and fatigue being the most common flare symptoms. Flare frequency was associated with greater disability, pain, work productivity loss, nonwork activity impairment, and increased ED/UC utilization. Higher frequency of patient-reported flares may serve as a marker of worsening physical functioning and intensifying health care needs and, therefore, suggests their importance in the clinical assessment of patients with DM/PM. DISCLOSURES: This study was supported by Mallinckrodt Pharmaceuticals (Bedminster, NJ) via grants to Vedanta Research and The Myositis Association. Christopher-Stine has received compensation from previous Mallinckrodt Advisory Board meetings, unrelated to this subject matter. Wan is an employee of Mallinckrodt Pharmaceuticals and is a stockholder of the company. Reed and Bostic received grant support from Mallinckrodt Pharmaceuticals for data collection and analysis. McGowan is an employee of The Myositis Foundation, which received grant funding to support study data collection. Kelly has no conflicts to disclose. This study was presented, in part or full, at the 2019 Annual American College of Rheumatology and Association of Rheumatology Professional Meeting (November 8-13, 2018; Atlanta, GA) and at the Third Global Conference on Myositis (March 27, 2019; Berlin, Germany).

An exploratory study of contractile force production in muscle fibers from patients with inflammatory myopathies.

INTRODUCTION: The mechanism by which weakness develops in idiopathic inflammatory myopathies (IIMs) is still unclear. In this study we investigated the maximum force of single muscle fibers from patients with IIMs. METHODS: Permeabilized single muscle fibers from patients with IIMs and healthy controls were subjected to contractility measurements. Maximum force and specific force production (maximum force normalized to fiber size) and fiber type were determined for each isolated fiber. RESULTS: A total of 178 fibers were studied from five patients with IIMs and 95 fibers from four controls. Specific force production was significantly lower in the IIM group for all fiber types. DISCUSSION: The findings from this exploratory study suggest that weakness in IIMs may, in part, be caused by dysfunction of the contractile apparatus. These findings provide a basis for further studies into the mechanisms underlying weakness in IIMs.

Identification of a novel autoantigen eukaryotic initiation factor 3 associated with polymyositis.

OBJECTIVES: To describe the prevalence and clinical associations of autoantibodies to a novel autoantigen, eukaryotic initiation factor 3 (eIF3), detected in idiopathic inflammatory myositis. METHODS: Sera or plasma from 678 PM patients were analysed for autoantigen specificity by radio-labelled protein immunoprecipitation (IPP). Samples immunoprecipitating the same novel autoantigens were further analysed by indirect immunofluorescence and IPP using pre-depleted cell extracts. The autoantigen was identified through a combination of IPP and MALDI-TOF mass spectrometry, and confirmed using commercial antibodies and IPP-western blots. Additional samples from patients with DM (668), DM-overlap (80), PM-overlap (191), systemic sclerosis (150), systemic lupus erythematosus (200), Sjogren's syndrome (40), rheumatoid arthritis (50) and healthy controls (150) were serotyped by IPP as disease or healthy controls. RESULTS: IPP revealed a novel pattern in three PM patients (0.44%) that was not found in disease-specific or healthy control sera. Indirect immunofluorescence demonstrated a fine cytoplasmic speckled pattern for all positive patients. Mass spectrometry analysis of the protein complex identified the target autoantigen as eIF3, a cytoplasmic complex with a role in the initiation of translation. Findings were confirmed by IPP-Western blotting. The three anti-eIF3-positive patients had no history of malignancy or interstitial lung disease, and had a favourable response to treatment. CONCLUSION: We report a novel autoantibody in 0.44% of PM patients directed against a cytoplasmic complex of proteins identified as eIF3. Although our findings need further confirmation, anti-eIF3 appears to correlate with a good prognosis and a favourable response to treatment.

Polymyositis with mitochondrial pathology or atypical form of sporadic inclusion body myositis: case series and review of the literature.

Polymyositis with mitochondrial pathology (PM-Mito) is a rare form of idiopathic inflammatory myopathy with no definite diagnostic criteria and similarities to both PM and sporadic inclusion body myositis (s-IBM). The aim of this study is to address the dilemma of whether PM-Mito is a subtype of inflammatory myopathy or represents a disease falling into the spectrum of s-IBM. Herein, we report four female patients diagnosed with PM-Mito, highlighting their rather atypical clinical and histopathological characteristics that seem to indicate a diagnosis away from s-IBM. Muscle weakness was rather proximal and symmetrical and lacked the selective pattern observed in s-IBM. Patients had large-scale deletions in mtDNA, reflecting the mitochondrial component in the pathology of the disease. Conclusively, our study adds to the limited data in the literature on whether PM-Mito is a distinct form of myositis or represents a prodromal stage of s-IBM. Although the latter seems to be supported by a substantial body of evidence, there are, however, important differences, such as the different patterns of muscle weakness, and the good response to treatment observed in some patients. Larger-scale studies are certainly needed to clarify pathogenesis and clinical characteristics of PM-Mito patients, especially in therapeutic and prognostic terms.

Mitochondrial dysfunction and role of harakiri in the pathogenesis of myositis.

The etiology of myositis is unknown. Although attempts to identify viruses in myositis skeletal muscle have failed, several studies have identified the presence of a viral signature in myositis patients. Here we postulate that in individuals with susceptible genetic backgrounds, viral infection alters the epigenome to activate the pathological pathways leading to disease onset. To identify epigenetic changes, methylation profiling of Coxsackie B infected human myotubes and muscle biopsies from polymyositis (PM) and dermatomyositis (DM) patients were compared to changes in global transcript expression induced by in vitro Coxsackie B infection. Gene and protein expression analysis and live cell imaging were performed to examine the mechanisms. Analysis of methylation and gene expression changes identified that a mitochondria-localized activator of apoptosis - harakiri (HRK) - is upregulated in myositis skeletal muscle cells. Muscle cells with higher HRK expression have reduced mitochondrial potential and poor ability to repair from injury as compared to controls. In cells from myositis patient toll-like receptor 7 (TLR7) activates and sustains high HRK expression. Forced over expression of HRK in healthy muscle cells is sufficient to compromise their membrane repair ability. Endurance exercise that is associated with improved muscle and mitochondrial function in PM and DM patients decreased TLR7 and HRK expression identifying these as therapeutic targets. Increased HRK and TLR7 expression causes mitochondrial damage leading to poor myofiber repair, myofiber death and muscle weakness in myositis patients and exercise induced reduction of HRK and TLR7 expression in patients is associated with disease amelioration. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Long-term pulmonary outcomes and mortality in idiopathic inflammatory myopathies associated with interstitial lung disease.

OBJECTIVE: To study prognostic factors in different types of idiopathic inflammatory myopathies (IIM) associated with interstitial lung disease (ILD). PATIENTS AND METHODS: Multicenter retrospective study of a Spanish cohort of patients diagnosed with IIM. Patients were classified into four categories: polymyositis (PM), dermatomyositis (DM), antisynthetase syndrome (ASS), and overlap myositis (OM). Sociodemographic data, clinical characteristics, antibodies, and treatments were collected. Cox regression models were calculated to identify factors associated with mortality, the necessity for long-term oxygen therapy (LTOT), and deterioration in respiratory function tests (RFT). RESULTS: The number of patients included was 478, of whom 112 (23.4%) suffered from ILD: 17% PM, 16% DM, 45% ASS, and 22% OM. Factors associated with mortality in the multivariate analysis were clinically meaningful progression of ILD after 3 months (CMP 3m) (hazard ratio (HR) 9.48, p = 0.005), severe infections (HR 6.41, p = 0.016), heliotrope erythema (HR 31.1, p = 0.002), delay in diagnosis (HR 1.29; p = 0.011), and Raynaud's phenomenon (HR 11.9, p = 0.007). However, being female (HR 0.19, p = 0.044) and positivity solely for ANAs (HR 0.08, p = 0.008) presented a protective effect. CMP 3m (HR 22.7, p = 0.027) was associated with the need for LTOT, while basal aldolase (HR 0.90; p = 0.049) had a protective effect. Likewise, joint manifestations (HR 0.04, p = 0.034) were shown to reduce risk of deterioration in RFT. CONCLUSIONS: CMP 3m, severe infections, delay in diagnosis, heliotrope erythema, and Raynaud's phenomenon were identified as factors of poor prognosis in different IIM associated with ILD.

[The effect of interferon-gamma on skeletal muscle cell biology]. / 15es JSFM : Prix Master 2017* - Effet de l'interféron-gamma sur la biologie des cellules musculaires squelettiques.

Dysimmune and inflammatory myopathies (DIMs) affect around 14/100,000 people worldwide. Based on immupour nopathological criteria, DIMs are divided in four groups: (1) polymyositis (PM)/inclusion body myositis (IBM), (2) dermatomyositis (DM), (3) immune-mediated necrotizing myopathies (IMNM) and (iv) overlapping myositis including anti-synthetase syndrome (ASS). ASS and PM/IBM are characterized by the activation of inflammation with lymphocytic infiltrations. Recently, we showed that an expression of the major histocompatibility complex class 2 (MHC2) was present in myofibers from ASS and IBM muscle biopsies. Interestingly, MHC2 expression is known to be stimulated by Interferon-gamma (IFNγ) in myogenic cells. LTCD8 cells, which are well-known producers of IFNγ, are commonly found in close vicinity to MHC2 positive myofibers. This inflammatory cytokine also inhibits myogenic differentiation in vitro by CIITA-myogenin interaction. The mechanisms involved in the lymphocyte-driven muscle toxicity in DIMs are unclear. The objectives of this project are to characterize IFNγ effects on the biology of human myogenic cells by morphological, molecular and cellular approaches. Then, we aim to investigate the role of IFNγ in these myopathies and its impact during muscular regeneration. In vitro preliminary studies have been performed using human and mouse myoblasts treated or not with IFNγ. Our results should lead to a better understanding of the role of IFNγ in the pathophysiology of DIMs, and would hopefully help identify new therapeutic targets.

Piomiositis del músculo pectíneo. Descripción de un caso y revisión bibliográfica / Pectineus muscle pyomyositis. A case report and review of the literature

La piomiositis (PM) es una infección aguda bacteriana que afecta al músculo estriado, generalmente causada por Staphylococcus aureus y suele acompañarse de la formación de un absceso en el músculo. Esta entidad clínica fue descrita por primera vez en 1885 por Scriba1 como enfermedad endémica en los trópicos. En las últimas dos décadas se ha observado un incremento notable del número de casos en países de clima templado, probablemente asociado a un aumento de pacientes inmunodeprimidos. Las infecciones profundas de músculos pélvicos son difíciles de diagnosticar por ocasionar signos clínicos inespecíficos y que hacen pensaren otras patologías más comunes. Comunicamos el caso de una paciente de 33 años diabética que consultó por dolor inguinal acompañado de tumoración en la misma zona y fiebre de 4 días de evolución. Recibió tratamiento sintomático sin respuesta. La resonancia nuclear magnética pélvica fue compatible con piomiositis de músculo pectíneo. Recibió tratamiento antibiótico, evolucionando satisfactoriamente. La piomiositis es una entidad poco frecuente, que requiere un elevado índice de sospecha, para un adecuado diagnóstico y tratamiento, siendo la terapia antibiótica y drenaje en caso de absceso los pilares de éste último. Este tratamiento debe instaurarse de forma precoz, ya que su evolución puede ser potencialmente letal

Pyomyositis (PM) is an acute bacterial infection of skeletal muscle, usually caused by Staphilococcus Aureus and it is frenquently associated to a muscle abcess. This clinical entity was first described by Scriba1 at 1885 as a tropic endemic pathology. In the past two decades the number of cases at countries of temperate climate has rised notably due to the number of patients with inmunosuppression. Unfortunately, diagnosis of deep pelvic muscle infection is often delayed since they usually present with non-specific physical signs suggesting other more common diseases. The authors communicate a case of a diabetic33-year-old female who suffered inguinal acute pain and mass with history of fever since 4 days before. She initially received symptomatic treatment with no success. Pelvis magnetic resonance imaging showed pyomyositis of the piriformis muscle. Antibacterial treatment was administered, resulting in a good outcome. Pyomyositis is a rare condition that demands a high index of suspicion to make an adequate diagnosis and prompt treatment, including antibacterial treatment and drainage, particularly in case of abscess formation. This treatment should be established promptly since its outcome may be potentially lethal

Musculoskeletal Manifestations of Non-RA Connective Tissue Diseases: Scleroderma, Systemic Lupus Erythematosus, Still's Disease, Dermatomyositis/Polymyositis, Sjögren's Syndrome, and Mixed Connective Tissue Disease.

The most common systemic rheumatologic conditions are connective tissue diseases (including rheumatoid arthritis [RA]) followed by spondyloarthropathy. With the advent of biotherapies and imaging biomarkers, development in the imaging of RA and spondyloarthropathies has received substantial attention in the literature. This article details the various musculoskeletal imaging features of the other connective tissue diseases such as scleroderma and progressive systemic sclerosis, systemic lupus erythematosus, Still's disease, dermatomyositis and polymyositis, Sjögren's syndrome, and mixed connective tissue disease.

Red blood cell distribution width and neutrophil to lymphocyte ratio are correlated with disease activity of dermatomyositis and polymyositis.

BACKGROUND: Previous studies indicated that both red blood cell distribution width (RDW) and neutrophil to lymphocyte ratio (NLR) were useful indices in assessing the disease activity of autoimmune diseases. However, the evidence for the association between RDW, NLR and dermatomyositis (DM) and polymyositis (PM) is limited. The aim of this study is to investigate the association between the disease activity of PM/DM and both RDW and NLR. METHODS: Medical records of 114 PM/DM patients and 114 healthy controls were retrospectively reviewed, and their RDW, NLR and myositis disease activity assessment visual analogue scale (MYOACT) on admission were extracted. The correlations between RDW, NLR and MYOACT were analyzed using the Spearman approach and multivariable model. RESULTS: PM/DM patients had significantly higher RDW and NLR. Increased RDW in PM/DM patients was not completely attributed to decreased hemoglobin or therapeutic agents. Both RDW and NLR are independently and positively correlated MYOACT. CONCLUSION: Both RDW and NLR are useful indices in assessing the disease activity of PM/DM.

Risk factors for the recurrence of interstitial lung disease in patients with polymyositis and dermatomyositis: a retrospective cohort study.

To identify risk factors for the recurrence of interstitial lung disease (ILD) in patients with polymyositis (PM)/dermatomyositis (DM). Forty-four PM/DM-ILD patients who had been treated with glucocorticoid and/or immunosuppressive agents as a remission induction therapy were enrolled. The patients were first classified into two groups: the early recurrence group that recurred within 52 weeks, and the non-early recurrence group, which was further classified into the late recurrence group that recurred after 52 weeks, and the non-recurrence group. The characteristics and treatment regimen between the groups were compared. Recurrence was experienced by 15 of 44 patients. The pulmonary vital capacity of the early recurrence group was significantly lower than the non-early recurrence group (46 vs 76%, p = 0.0003), and 60% of the early recurrence group was treated with glucocorticoid alone as a maintenance therapy in contrast to 10% in the non-early recurrence group (p = 0.004). The late recurrence was only related with a positivity for autoantibodies against aminoacyl-tRNA synthetases (anti-ARS antibodies, odds ratio 8.4, p = 0.02), but calcineurin inhibitors tended to decrease the relapse incidence in patients with anti-ARS antibodies. Low pulmonary vital capacity at disease onset and anti-ARS antibodies positivity are the risk factors for the recurrence of ILD with PM/DM. Calcinuerin inhibitors are important in preventing relapse.

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.

2016 American College of Rheumatology/European League Against Rheumatism Criteria for Minimal, Moderate, and Major Clinical Response in Adult Dermatomyositis and Polymyositis: An International Myositis Assessment and Clinical Studies Group/Paediatric Rheumatology International Trials Organisation Collaborative Initiative.

OBJECTIVE: To develop response criteria for adult dermatomyositis (DM) and polymyositis (PM). METHODS: Expert surveys, logistic regression, and conjoint analysis were used to develop 287 definitions using core set measures. Myositis experts rated greater improvement among multiple pairwise scenarios in conjoint analysis surveys, where different levels of improvement in 2 core set measures were presented. The PAPRIKA (Potentially All Pairwise Rankings of All Possible Alternatives) method determined the relative weights of core set measures and conjoint analysis definitions. The performance characteristics of the definitions were evaluated on patient profiles using expert consensus (gold standard) and were validated using data from a clinical trial. The nominal group technique was used to reach consensus. RESULTS: Consensus was reached for a conjoint analysis-based continuous model using absolute percent change in core set measures (physician, patient, and extramuscular global activity, muscle strength, Health Assessment Questionnaire, and muscle enzyme levels). A total improvement score (range 0-100), determined by summing scores for each core set measure, was based on improvement in and relative weight of each core set measure. Thresholds for minimal, moderate, and major improvement were ≥20, ≥40, and ≥60 points in the total improvement score. The same criteria were chosen for juvenile DM, with different improvement thresholds. Sensitivity and specificity in DM/PM patient cohorts were 85% and 92%, 90% and 96%, and 92% and 98% for minimal, moderate, and major improvement, respectively. Definitions were validated in the clinical trial analysis for differentiating the physician rating of improvement (P < 0.001). CONCLUSION: The response criteria for adult DM/PM consisted of the conjoint analysis model based on absolute percent change in 6 core set measures, with thresholds for minimal, moderate, and major improvement.

Polimiositis secundaria a un linfoma no Hodgkin / Polymyositis secondary to a non-Hodgkins lymphoma

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