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Current Opinion in Pulmonary Medicine Sep 2023In idiopathic inflammatory myopathies (IIMs), interstitial lung disease (ILD) is common and the autoantibody profile, made up of myositis-specific and... (Review)
Review
PURPOSE OF REVIEW
In idiopathic inflammatory myopathies (IIMs), interstitial lung disease (ILD) is common and the autoantibody profile, made up of myositis-specific and myositis-associated (MSA and MAA) antibodies, can predict the clinical phenotype and progression over time. This review will focus on the characteristics and management of antisynthetase syndrome related ILD and anti-MDA5 positive ILD, which are the most clinically relevant subtypes.
RECENT FINDINGS
The prevalence of ILD in IIM has been estimated in Asia, North America and Europe at 50, 23 and 26%, respectively, and is increasing. In antisynthetase syndrome related ILD, the clinical presentation, progression and prognosis varies among anti-ARS antibodies. ILD is more common and severe in patients with anti-PL-7/anti-PL-12 antibodies when compared with anti Jo-1 patients. The prevalence of anti-MDA5 antibodies is higher in Asians (11-60%) than in whites (7-16%). Sixty-six percent of antisynthetase syndrome patients had 'chronic ILD' compared with the more rapidly progressive ILD (RP-ILD) seen in 69% of patients with anti-MDA5 antibodies.
SUMMARY
ILD is most common in the antisynthetase subtype of IIM and can be a chronic indolent or RP- ILD. The MSA and MAAs are associated with different clinical phenotypes of ILD. Treatments typically involve combinations of corticosteroids and other immunosuppressants.
Topics: Humans; Myositis; Autoantibodies; Lung Diseases, Interstitial; Immunosuppressive Agents
PubMed: 37435671
DOI: 10.1097/MCP.0000000000001000 -
Medicina (Kaunas, Lithuania) Apr 2021Idiopathic inflammatory myopathies, including polymyositis (PM), dermatomyositis (DM), and clinically amyopathic DM (CADM), are a diverse group of autoimmune diseases... (Review)
Review
Idiopathic inflammatory myopathies, including polymyositis (PM), dermatomyositis (DM), and clinically amyopathic DM (CADM), are a diverse group of autoimmune diseases characterized by muscular involvement and extramuscular manifestations. Interstitial lung disease (ILD) has major pulmonary involvement and is associated with increased mortality in PM/DM/CADM. The management of PM-/DM-/CADM-associated ILD (PM/DM/CADM-ILD) requires careful evaluation of the disease severity and clinical subtype, including the ILD forms (acute/subacute or chronic), because of the substantial heterogeneity of their clinical courses. Recent studies have highlighted the importance of myositis-specific autoantibodies' status, especially anti-melanoma differentiation-associated gene 5 (MDA5) and anti-aminoacyl tRNA synthetase (ARS) antibodies, in order to evaluate the clinical phenotypes and treatment of choice for PM/DM/CADM-ILD. Because the presence of the anti-MDA5 antibody is a strong predictor of a worse prognosis, combination treatment with glucocorticoids (GCs) and calcineurin inhibitors (CNIs; tacrolimus (TAC) or cyclosporin A (CsA)) is recommended for patients with anti-MDA5 antibody-positive DM/CADM-ILD. Rapidly progressive DM/CADM-ILD with the anti-MDA5 antibody is the most intractable condition, which requires immediate combined immunosuppressive therapy with GCs, CNIs, and intravenous cyclophosphamide. Additional salvage therapies (rituximab, tofacitinib, and plasma exchange) should be considered for patients with refractory ILD. Patients with anti-ARS antibody-positive ILD respond better to GC treatment, but with frequent recurrence; thus, GCs plus immunosuppressants (TAC, CsA, azathioprine, and mycophenolate mofetil) are often needed in order to achieve favorable long-term disease control. PM/DM/CADM-ILD management is still a therapeutic challenge for clinicians, as evidence-based guidelines do not exist to help with management decisions. A few prospective clinical trials have been recently reported regarding the treatment of PM/DM/CADM-ILD. Here, the current knowledge on the pharmacologic managements of PM/DM/CADM-ILD was mainly reviewed.
Topics: Autoantibodies; Dermatomyositis; Humans; Lung Diseases, Interstitial; Myositis
PubMed: 33916864
DOI: 10.3390/medicina57040347 -
Current Opinion in Neurology Oct 2019Idiopathic inflammatory myopathies (IIM) are rare diseases with heterogenous clinicopathological features. In recent years, new classification systems considering... (Review)
Review
PURPOSE OF REVIEW
Idiopathic inflammatory myopathies (IIM) are rare diseases with heterogenous clinicopathological features. In recent years, new classification systems considering various combinations of clinical, serological, and pathological information have been proposed. This review summarizes recent clinicoseropathological development in major subgroups of IIM.
RECENT FINDINGS
Considering clinicoseropathological features, IIM are suggestively classified into four major subgroups: dermatomyositis, immune-mediated necrotizing myopathy (IMNM), antisynthetase syndrome (ASS), and inclusion body myositis (IBM). Many historically diagnosed polymyositis have been mainly reclassified as IBM, IMNM, and ASS. Different types of myositis-specific antibodies (MSA) suggest distinct clinicopathological subsets of IIM. Excluding IBM, at least one-third of the IIMs have no known associated MSA.
SUMMARY
MSA are crucial for IIM classification but can be negative. Thus, IIM should be universally classified using stepwise or integrated information on clinical, serological, and pathological findings.
Topics: Autoantibodies; Dermatomyositis; Humans; Myositis; Myositis, Inclusion Body
PubMed: 31369423
DOI: 10.1097/WCO.0000000000000740 -
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 -
Nature Reviews. Rheumatology Jun 2023The childhood-onset or juvenile idiopathic inflammatory myopathies (JIIMs) are a heterogenous group of rare and serious autoimmune diseases of children and young people... (Review)
Review
The childhood-onset or juvenile idiopathic inflammatory myopathies (JIIMs) are a heterogenous group of rare and serious autoimmune diseases of children and young people that predominantly affect the muscles and skin but can also involve other organs, including the lungs, gut, joints, heart and central nervous system. Different myositis-specific autoantibodies have been identified that are associated with different muscle biopsy features, as well as with different clinical characteristics, prognoses and treatment responses. Thus, myositis-specific autoantibodies can be used to subset JIIMs into sub-phenotypes; some of these sub-phenotypes parallel disease seen in adults, whereas others are distinct from adult-onset idiopathic inflammatory myopathies. Although treatments and management have much improved over the past decade, evidence is still lacking for many of the current treatments and few validated prognostic biomarkers are available with which to predict response to treatment, comorbidities (such as calcinosis) or outcome. Emerging data on the pathogenesis of the JIIMs are leading to proposals for new trials and tools for monitoring disease.
Topics: Humans; Myositis; Autoantibodies; Autoimmune Diseases; Phenotype; Prognosis
PubMed: 37188756
DOI: 10.1038/s41584-023-00967-9 -
Seminars in Arthritis and Rheumatism Feb 2021The aim of the study was to summarize current knowledge on antisynthetase syndrome (ASS), including its epidemiology, pathogenesis, proposed so far diagnostic criteria,... (Review)
Review
The aim of the study was to summarize current knowledge on antisynthetase syndrome (ASS), including its epidemiology, pathogenesis, proposed so far diagnostic criteria, heterogeneity of clinical manifestations, prognostic factors and therapeutic possibilities. PubMed database was screened for "antisynthetase syndrome" OR "antisynthetase antibodies" between February and April 2020. Aminoacyl-tRNA synthetases participate in the immune system activation as antigens, but also serve chemoattractive and cytokine-resembling roles, initiating innate and adaptive pathways. Exposure to various inhaled antigens may induce the autoimmune cascade leading to ASS. NK cells with its impaired INF-y production as well as formation of NETs by neutrophils contribute to pathogenesis. The prevalence of symptoms vary significantly depending on the study with muscular, articular and pulmonary involvement being the most frequently observed. Although classified as subtype of idiopathic inflammatory myopathies, myositis may not necessarily be the prominent manifestation. Since clinical presentation is heterogeneous and symptoms can emerge gradually, ASS could be considered as a heterogeneous spectrum rather than a homogenous disease entity. The currently available classification criteria do not fully correspond with the clinical patterns of the disease. Therapy is based on glucocorticosteroids and other immunosuppressive agents. Randomized controlled trials, dedicated for patients with ASS, are needed to form treatment algorithms.
Topics: Amino Acyl-tRNA Synthetases; Autoantibodies; Humans; Muscular Diseases; Myositis
PubMed: 33360231
DOI: 10.1016/j.semarthrit.2020.09.020 -
Handbook of Clinical Neurology 2024This chapter reviews the association between cancer and the idiopathic inflammatory myopathies (IIM), which includes dermatomyositis (DM), antisynthetase syndrome... (Review)
Review
This chapter reviews the association between cancer and the idiopathic inflammatory myopathies (IIM), which includes dermatomyositis (DM), antisynthetase syndrome (ASyS), immune-mediated necrotizing myopathy (IMNM), and inclusion body myositis (IBM). Accumulating evidence shows that the risk of a coexisting malignancy is high in patients with DM, especially among those with anti-Tif1γ autoantibodies. Patients with IMNM and no defined autoantibodies also have an increased risk of malignancy. Recent evidence demonstrates that many IBM patients have increased numbers of circulating CD57+ CD8+ T cells, consistent with a diagnosis of large granular lymphocytic leukemia. In contrast, IMNM patients with anti-SRP or anti-HMGCR autoantibodies as well as patients with ASyS syndrome do not have a definitively increased risk of cancer. Patients who have a cancer treated with one of the immune checkpoint inhibitors can develop myositis (ICI-myositis), sometimes along with myasthenia gravis and/or myocarditis.
Topics: Humans; Myositis; Myositis, Inclusion Body; Autoantibodies; Myasthenia Gravis; Muscle, Skeletal
PubMed: 38494286
DOI: 10.1016/B978-0-12-823912-4.00022-0 -
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 -
Nature Reviews. Rheumatology Dec 2023Adult-onset idiopathic inflammatory myopathy (IIM) is associated with an increased cancer risk within the 3 years preceding and following IIM onset. Evidence- and... (Review)
Review
International Guideline for Idiopathic Inflammatory Myopathy-Associated Cancer Screening: an International Myositis Assessment and Clinical Studies Group (IMACS) initiative.
Adult-onset idiopathic inflammatory myopathy (IIM) is associated with an increased cancer risk within the 3 years preceding and following IIM onset. Evidence- and consensus-based recommendations for IIM-associated cancer screening can potentially improve outcomes. This International Guideline for IIM-Associated Cancer Screening provides recommendations addressing IIM-associated cancer risk stratification, cancer screening modalities and screening frequency. The international Expert Group formed a total of 18 recommendations via a modified Delphi approach using a series of online surveys. First, the recommendations enable an individual patient's IIM-associated cancer risk to be stratified into standard, moderate or high risk according to the IIM subtype, autoantibody status and clinical features. Second, the recommendations outline a 'basic' screening panel (including chest radiography and preliminary laboratory tests) and an 'enhanced' screening panel (including CT and tumour markers). Third, the recommendations advise on the timing and frequency of screening via basic and enhanced panels, according to risk status. The recommendations also advise consideration of upper or lower gastrointestinal endoscopy, nasoendoscopy and F-FDG PET-CT scanning in specific patient populations. These recommendations are aimed at facilitating earlier IIM-associated cancer detection, especially in those who are at a high risk, thus potentially improving outcomes, including survival.
Topics: Adult; Humans; Early Detection of Cancer; Positron Emission Tomography Computed Tomography; Neoplasms; Myositis; Autoantibodies
PubMed: 37945774
DOI: 10.1038/s41584-023-01045-w -
Continuum (Minneapolis, Minn.) Dec 2019This article summarizes the clinical features, diagnostic evaluation, and management of the common immune-mediated myopathies: dermatomyositis, antisynthetase syndrome,... (Review)
Review
PURPOSE OF REVIEW
This article summarizes the clinical features, diagnostic evaluation, and management of the common immune-mediated myopathies: dermatomyositis, antisynthetase syndrome, immune-mediated necrotizing myopathy, and overlap myositis.
RECENT FINDINGS
The identification of myositis-specific autoantibodies has improved the characterization of the subtypes of myositis and associated clinical phenotypes, as the severity of muscle involvement, extramuscular manifestations, and risk of malignancy may vary among the subtypes of autoimmune myopathies.
SUMMARY
The understanding and diagnostic accuracy of the subtypes of autoimmune myopathies have been enhanced with careful attention to the key clinical features, the emergence of myositis-specific autoantibodies, the characterization of histopathologic hallmark features, and the aid of muscle imaging. Several immunotherapeutic options now exist that can be selected to target a specific subtype, often with a favorable prognosis, especially when treatment starts early in the disease course.
Topics: Autoimmune Diseases; Female; Humans; Immunologic Factors; Immunotherapy; Male; Middle Aged; Myositis
PubMed: 31794460
DOI: 10.1212/CON.0000000000000789