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The Journal of Applied Laboratory... Jan 2022Interstitial lung disease (ILD) comprises a heterogeneous group of inflammatory and fibrotic conditions, often resulting in progressive lung function decline and... (Review)
Review
BACKGROUND
Interstitial lung disease (ILD) comprises a heterogeneous group of inflammatory and fibrotic conditions, often resulting in progressive lung function decline and increased mortality. Connective tissue disease (CTD) should be considered in all patients with ILD, as distinguishing between CTD-ILD and other forms of fibrotic lung disease has important therapeutic and prognostic implications. The idiopathic inflammatory myopathies (IIM) represent a CTD subtype of growing interest to ILD experts. The expansion and availability of myositis-specific and myositis-associated antibody testing has allowed for improved disease detection and characterization.
CONTENT
In this review, we highlight the relationship between myositis antibodies and ILD. Select forms of IIM, such as the antisynthetase syndrome and clinically amyopathic dermatomyositis can present with rapidly progressive ILD, warranting timely disease diagnosis and management. Disease phenotypes, prevalence, laboratory testing, prognosis, and management strategies are described according to select myositis antibodies.
SUMMARY
Myositis antibodies provide valuable information for clinicians managing patients with ILD. This review aims to increase awareness of their role in disease detection, pathophysiology, and possibly therapeutics.
Topics: Autoantibodies; Dermatomyositis; Humans; Lung Diseases, Interstitial; Myositis; Prognosis
PubMed: 34996093
DOI: 10.1093/jalm/jfab108 -
Clinical and Experimental Immunology Mar 2014Dermatomyositis (DM), polymyositis (PM), necrotizing myopathy (NM) and inclusion body myositis (IBM) are four distinct subtypes of idiopathic inflammatory myopathies -... (Review)
Review
Dermatomyositis (DM), polymyositis (PM), necrotizing myopathy (NM) and inclusion body myositis (IBM) are four distinct subtypes of idiopathic inflammatory myopathies - in short myositis. Recent studies have shed some light on the unique pathogenesis of each entity. Some of the clinical features are distinct, but muscle biopsy is indispensable for making a reliable diagnosis. The use of magnetic resonance imaging of skeletal muscles and detection of myositis-specific autoantibodies have become useful additions to our diagnostic repertoire. Only few controlled trials are available to substantiate current treatment approaches for myositis and hopes are high that novel modalities will become available within the next few years. In this review we provide an up-to-date overview of the pathogenesis and diagnostic approach of myositis. We aim to present a guide towards therapeutic and general management.
Topics: Humans; Myositis
PubMed: 23981102
DOI: 10.1111/cei.12194 -
JAMA Neurology Dec 2018Idiopathic inflammatory myopathies are heterogeneous in their pathophysiologic features and prognosis. The emergence of myositis-specific autoantibodies suggests that... (Observational Study)
Observational Study
IMPORTANCE
Idiopathic inflammatory myopathies are heterogeneous in their pathophysiologic features and prognosis. The emergence of myositis-specific autoantibodies suggests that subgroups of patients exist.
OBJECTIVE
To develop a new classification scheme for idiopathic inflammatory myopathies based on phenotypic, biological, and immunologic criteria.
DESIGN, SETTING, AND PARTICIPANTS
An observational, retrospective cohort study was performed using a database of the French myositis network. Patients identified from referral centers for neuromuscular diseases were included from January 1, 2003, to February 1, 2016. Of 445 initial patients, 185 patients were excluded and 260 adult patients with myositis who had complete data and defined historical classifications for polymyositis, dermatomyositis, and inclusion body myositis were enrolled. All patients were tested for anti-histidyl-ARN-t- synthetase (Jo1), anti-threonine-ARN-t-synthetase (PL7), anti-alanine-ARN-t-synthetase (PL12), anti-complex nucleosome remodeling histone deacetylase (Mi2), anti-Ku, anti-polymyositis/systemic scleroderma (PMScl), anti-topoisomerase 1 (Scl70), and anti-signal recognition particle (SRP) antibodies. A total of 708 variables were collected per patient (eg, cancer, lung involvement, and myositis-specific antibodies).
MAIN OUTCOMES AND MEASURES
Unsupervised multiple correspondence analysis and hierarchical clustering analysis to aggregate patients in subgroups.
RESULTS
Among 260 participants (163 [62.7%] women; mean age, 59.7 years; median age [range], 61.5 years [48-71 years]), 4 clusters of patients emerged. Cluster 1 (n = 77) included patients who were male, white, and older than 60 years and had finger flexor and quadriceps weakness and findings of vacuolated fibers and mitochondrial abnormalities. Cluster 1 regrouped patients who had inclusion body myositis (72 of 77 patients [93.5%]; 95% CI, 85.5%-97.8%; P < .001). Cluster 2 (n = 91) regrouped patients who were women and had high creatine phosphokinase levels, necrosis without inflammation, and anti-SRP or anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) antibodies corresponding to immune-mediated necrotizing myopathy (53 of 91 [58.2%]; 95% CI, 47.4%-68.5%; P < .001). Cluster 3 (n = 52) regrouped patients who had dermatomyositis rash and anti-Mi2, anti-melanoma differentiation-associated protein 5 (MDA5), or anti-transcription intermediary factor-1γ (TIF1γ) antibodies, mainly corresponding with patients who had dermatomyositis (43 of 52 [82.7%]; 95% CI, 69.7%-91.8%; P < .001). Cluster 4 (n = 40) was defined by the presence of anti-Jo1 or anti-PL7 antibodies corresponding to antisynthetase syndrome (36 of 40 [90.0%]; 95% CI, 76.3%-97.2%; P < .001). The classification of an independent cohort (n = 50) confirmed the 4 clusters (Cohen κ light, 0.8; 95% CI, 0.6-0.9).
CONCLUSIONS AND RELEVANCE
These findings suggest a classification of idiopathic inflammatory myopathies with 4 subgroups: dermatomyositis, inclusion body myositis, immune-mediated necrotizing myopathy, and antisynthetase syndrome. This classification system suggests that a targeted clinical-serologic approach for identifying idiopathic inflammatory myopathies may be warranted.
Topics: Aged; Autoantibodies; Classification; Databases, Factual; Dermatomyositis; Female; Humans; Male; Middle Aged; Myositis; Myositis, Inclusion Body; Retrospective Studies
PubMed: 30208379
DOI: 10.1001/jamaneurol.2018.2598 -
Expert Review of Clinical Immunology 2023Idiopathic inflammatory myopathies (IIMs) represent a diverse group of systemic autoimmune disorders with variable clinical manifestations and disease course. Currently,... (Review)
Review
INTRODUCTION
Idiopathic inflammatory myopathies (IIMs) represent a diverse group of systemic autoimmune disorders with variable clinical manifestations and disease course. Currently, the challenges of IIMs are multifold, including difficulties in timely diagnosis owing to clinical heterogeneity, limited insights into disease pathogenesis, as well as a restricted number of available therapies. However, advances utilizing myositis-specific autoantibodies have facilitated the definition of subgroups as well as the prediction of clinical phenotypes, disease course, and response to treatment.
AREAS COVERED
Herein we provide an overview of the clinical presentations of dermatomyositis, anti-synthetase syndrome, immune-mediated necrotizing myopathy, and inclusion body myositis. We then provide an updated review of available and promising therapies for each of these disease groups. We synthesize current treatment recommendations in the context of case-based construct to facilitate application to patient care. Finally, we provide high-yield, clinical pearls relevant to each of the subgroups that can be incorporated into clinical reasoning.
EXPERT OPINION
There are many exciting developments on the horizon for IIM. As insights into pathogenesis evolve, the therapeutic armamentarium is expanding with many novel therapies in development, holding promise for more targeted treatment approaches.
Topics: Humans; Myositis; Myositis, Inclusion Body; Autoimmune Diseases; Autoantibodies; Disease Progression
PubMed: 37158055
DOI: 10.1080/1744666X.2023.2212162 -
Frontiers in Immunology 2022Systemic sclerosis and autoimmune myositis are both associated with decreased quality of life and increased mortality. Their prognosis and management largely depend on... (Review)
Review
Systemic sclerosis and autoimmune myositis are both associated with decreased quality of life and increased mortality. Their prognosis and management largely depend on the disease subgroups. Indeed, systemic sclerosis is a heterogeneous disease, the two predominant forms of the disease being limited and diffuse scleroderma. Autoimmune myositis is also a heterogeneous group of myopathies that classically encompass necrotizing myopathy, antisynthetase syndrome, dermatomyositis and inclusion body myositis. Recent data revealed that an additional disease subset, denominated "scleromyositis", should be recognized within both the systemic sclerosis and the autoimmune myositis spectrum. We performed an in-depth review of the literature with the aim of better delineating scleromyositis. Our review highlights that this concept is supported by recent clinical, serological and histopathological findings that have important implications for patient management and understanding of the disease pathophysiology. As compared with other subsets of systemic sclerosis and autoimmune myositis, scleromyositis patients can present with a characteristic pattern of muscle involvement (i.e. distribution of muscle weakness) along with multisystemic involvement, and some of these extra-muscular complications are associated with poor prognosis. Several autoantibodies have been specifically associated with scleromyositis, but they are not currently integrated in diagnostic and classification criteria for systemic sclerosis and autoimmune myositis. Finally, striking vasculopathic lesions at muscle biopsy have been shown to be hallmarks of scleromyositis, providing a strong anatomopathological substratum for the concept of scleromyositis. These findings bring new insights into the pathogenesis of scleromyositis and help to diagnose this condition, in patients with subtle SSc features and/or no autoantibodies (i.e. "seronegative" scleromyositis). No guidelines are available for the management of these patients, but recent data are showing the way towards a new therapeutic approach dedicated to these patients.
Topics: Humans; Quality of Life; Myositis; Autoimmune Diseases; Scleroderma, Systemic; Myositis, Inclusion Body
PubMed: 36776390
DOI: 10.3389/fimmu.2022.974078 -
Current Pharmaceutical Design 2022Inflammatory myopathies, in short, myositis, are heterogeneous disorders that are characterized by inflammation of skeletal muscle and weakness of arms and legs.... (Review)
Review
Inflammatory myopathies, in short, myositis, are heterogeneous disorders that are characterized by inflammation of skeletal muscle and weakness of arms and legs. Research over the past few years has led to a new understanding regarding the pathogenesis of myositis. The new insights include different pathways of the innate and adaptive immune response during the pathogenesis of myositis. The importance of non-inflammatory mechanisms such as cell stress and impaired autophagy has been recently described. New target-specific drugs for myositis have been developed and are currently being tested in clinical trials. In this review, we discuss the mechanisms of action of pharmacological standards in myositis and provide an outlook of future treatment approaches.
Topics: Dermatomyositis; Humans; Inflammation; Muscle, Skeletal; Myositis; Myositis, Inclusion Body
PubMed: 34781868
DOI: 10.2174/1381612827666211115165353 -
Acta Myologica : Myopathies and... Dec 2020Giant cell myositis (GCMm) and giant cell myocarditis (GCMc) are two rare autoimmune conditions. Among these, GCMc is a life-threatening disease with a 1-year mortality... (Review)
Review
Giant cell myositis (GCMm) and giant cell myocarditis (GCMc) are two rare autoimmune conditions. Among these, GCMc is a life-threatening disease with a 1-year mortality rate of 70%. Lethal ventricular arrhythmias, rapid evolution to heart failure and sudden death risk makes GCMc an emergency condition. It is thought to be mediated by T-cells and characterized by the presence of myofiber necrosis and giant cells in biopsies. Most commonly co-manifesting conditions with GCMm and/or GCMc are thymoma, myasthenia gravis and orbital myositis, all of which are treatable. As suspicion is the key approach in diagnosis, the physician following patients with thymoma with or without myasthenia gravis and with orbital myositis should always be alert. The fatal nature of GCMc associated with these relatively benign diseases deserves a special emergency attention with prompt institution of combined immunosuppressive treatment and very early inclusion of heart failure teams.
Topics: Giant Cells; Humans; Myocarditis; Myositis
PubMed: 33458585
DOI: 10.36185/2532-1900-033 -
Best Practice & Research. Clinical... Feb 2016Knowledge on idiopathic inflammatory myopathy (IIM) has evolved with the identification of myositis-associated and myositis-specific antibodies, development of... (Review)
Review
Knowledge on idiopathic inflammatory myopathy (IIM) has evolved with the identification of myositis-associated and myositis-specific antibodies, development of histopathological classification and the recognition of how these correlate with clinical phenotype and response to therapy. In this paper, we outline key advances in diagnosis and histopathology, including the more recent identification of antibodies associated with immune-mediated necrotising myopathy (IMNM) and inclusion body myositis (IBM). Ongoing longitudinal observational cohorts allow further classification of these patients with IIM, their predicted clinical course and response to specific therapies. Registries have been developed worldwide for this purpose. A challenging aspect in IIM, a multisystem disease with multiple clinical subtypes, has been defining disease status and clinically relevant improvement. Tools for assessing activity and damage are now recognised to be important in determining disease activity and guiding therapeutic decision-making. The International Myositis Assessment and Clinical Studies (IMACS) group has developed such tools for use in research and clinical settings. There is limited evidence for specific treatment strategies in IIM. With significant development in the understanding of IIM and improved classification, longitudinal observational cohorts and trials using validated outcome measures are necessary, to provide important information for evidence-based care in the clinical setting.
Topics: Humans; Myositis; Myositis, Inclusion Body
PubMed: 27421222
DOI: 10.1016/j.berh.2016.04.007 -
Current Opinion in Rheumatology Sep 2001Idiopathic inflammatory myositis in children includes multiple disease entities, but is primarily made up of juvenile dermatomyositis and, to a lesser degree, juvenile... (Review)
Review
Idiopathic inflammatory myositis in children includes multiple disease entities, but is primarily made up of juvenile dermatomyositis and, to a lesser degree, juvenile polymyositis. Much new information has been published in the last few years about these diseases, including the epidemiology, pathogenesis, clinical diagnosis, and outcomes and treatment. This includes information on onset of symptoms, potential inciting agents, and regional differences. Exciting data have emerged in our understanding of the immune response gene associations and the description of chimerism in children with these disorders. Finally, new advances in clinical evaluations and outcomes have been described as well as new treatment protocols to provide a more effective therapy with less toxicity. Continued investigation is needed to further understand these diseases, but great strides are being made in our understanding and ability to care for children with idiopathic inflammatory myositis.
Topics: Adolescent; Child; Child, Preschool; Genetic Predisposition to Disease; HLA Antigens; Histocompatibility Testing; Humans; Myositis
PubMed: 11604600
DOI: 10.1097/00002281-200109000-00015 -
Myositis-associated interstitial lung disease: a comprehensive approach to diagnosis and management.Clinical and Experimental Rheumatology Feb 2022Interstitial lung disease (ILD) frequently complicates the inflammatory myopathies and at times is the most prominent clinical feature. Over the years, there has been a... (Review)
Review
Interstitial lung disease (ILD) frequently complicates the inflammatory myopathies and at times is the most prominent clinical feature. Over the years, there has been a growing recognition for the strong association between seropositivity of several myositis-specific antibodies (MSAs) and lung involvement. Growing literature suggests that individual MSAs may influence the risk of developing ILD and are associated with pulmonary disease severity and various clinical sub-phenotypes. The presence of ILD in patients with myositis correlates with increased morbidity and mortality. As such, it presents a unique treatment challenge for both the rheumatology and pulmonary communities and requires a multidisciplinary approach to management. This review will discuss the role of serologies and invasive and non-invasive testing modalities utilised to diagnose and monitor patients with myositis-ILD. Current studies pertaining to the wide array of immunomodulatory therapies utilised in cases of progressive disease are also highlighted in detail.
Topics: Autoantibodies; Humans; Lung Diseases, Interstitial; Myositis; Phenotype; Retrospective Studies; Rheumatology
PubMed: 33769263
DOI: 10.55563/clinexprheumatol/brvl1v