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Arthritis & Rheumatology (Hoboken, N.J.) Feb 2023Idiopathic inflammatory myopathies (IIMs) comprise a heterogeneous group of rare immune-mediated disorders that primarily affect muscles but also lead to dysfunction in... (Review)
Review
Idiopathic inflammatory myopathies (IIMs) comprise a heterogeneous group of rare immune-mediated disorders that primarily affect muscles but also lead to dysfunction in other organs. Five different clinical subphenotypes of IIM have been distinguished: dermatomyositis, polymyositis, inclusion body myositis, antisynthetase syndrome, and immune-mediated necrotizing myopathy. Excess mortality and morbidity associated with IIM are largely attributed to comorbidities, particularly cancer. The risk of malignancy is not equally distributed among IIM groups and is particularly high among patients with dermatomyositis. The cancer risk peaks around 3 years on either side of the IIM diagnosis and remains elevated even 10 years after the onset of the disease. Lung, colorectal, and ovarian neoplasms typically arise before the onset of IIM, whereas melanoma, cervical, oropharyngeal, and nonmelanoma skin cancers usually develop after IIM diagnosis. Given the close temporal proximity between IIM diagnosis and the emergence of malignancy, it has been proposed that IIM could be a consequence rather than a cause of cancer, a process known as a paramalignant phenomenon. Thus, a separate group of IIMs related to paramalignant phenomenon has been distinguished, known as cancer-associated myositis (CAM). Although the relationship between IIM and cancer is widely recognized, the pathophysiology of CAM remains elusive. Given that genetic factors play a role in the development of IIM, dissection of the molecular mechanisms shared between IIM and cancer presents an opportunity to examine the role of autoimmunity in cancer development and progression. In this review, the evidence supporting the contribution of genetics to CAM will be discussed.
Topics: Humans; Dermatomyositis; Myositis; Polymyositis; Myositis, Inclusion Body; Melanoma
PubMed: 36053262
DOI: 10.1002/art.42345 -
Ugeskrift For Laeger Aug 2023
Topics: Humans; Dermatomyositis; Eye Diseases; Angioedema; Edema
PubMed: 37615155
DOI: No ID Found -
Nature Communications Jan 2022Muscle cell death in polymyositis is induced by CD8 cytotoxic T lymphocytes. We hypothesized that the injured muscle fibers release pro-inflammatory molecules, which...
Muscle cell death in polymyositis is induced by CD8 cytotoxic T lymphocytes. We hypothesized that the injured muscle fibers release pro-inflammatory molecules, which would further accelerate CD8 cytotoxic T lymphocytes-induced muscle injury, and inhibition of the cell death of muscle fibers could be a novel therapeutic strategy to suppress both muscle injury and inflammation in polymyositis. Here, we show that the pattern of cell death of muscle fibers in polymyositis is FAS ligand-dependent necroptosis, while that of satellite cells and myoblasts is perforin 1/granzyme B-dependent apoptosis, using human muscle biopsy specimens of polymyositis patients and models of polymyositis in vitro and in vivo. Inhibition of necroptosis suppresses not only CD8 cytotoxic T lymphocytes-induced cell death of myotubes but also the release of inflammatory molecules including HMGB1. Treatment with a necroptosis inhibitor or anti-HMGB1 antibodies ameliorates myositis-induced muscle weakness as well as muscle cell death and inflammation in the muscles. Thus, targeting necroptosis in muscle cells is a promising strategy for treating polymyositis providing an alternative to current therapies directed at leukocytes.
Topics: Animals; Antibodies, Neutralizing; C-Reactive Protein; Fas Ligand Protein; Female; Gene Expression Regulation; Granzymes; HMGB1 Protein; Humans; Imidazoles; Indoles; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Muscle Fibers, Skeletal; Muscle Strength; Muscle, Skeletal; Myositis; Necroptosis; Perforin; Polymyositis; Signal Transduction; T-Lymphocytes, Cytotoxic
PubMed: 35013338
DOI: 10.1038/s41467-021-27875-4 -
Ugeskrift For Laeger Nov 2023Juvenile dermatomyositis (JDM) is a rare condition, which causes inflammation in children's skin and musculoskeletal systems. Symptoms include characteristic skin rashes...
Juvenile dermatomyositis (JDM) is a rare condition, which causes inflammation in children's skin and musculoskeletal systems. Symptoms include characteristic skin rashes on the face and extremities, muscle pain and weakness. This is a case report of a ten-year-old boy initially suspected of having lupus erythematosus. He was later diagnosed with JDM by dermatologists. Treatment with methotrexate and prednisolone proved to be effective.
Topics: Male; Child; Humans; Dermatomyositis; Methotrexate; Skin; Inflammation; Prednisolone
PubMed: 37987452
DOI: No ID Found -
Best Practice & Research. Clinical... Jun 2022Idiopathic inflammatory myopathies (IIM) are heterogeneous autoimmune diseases. There are distinct subgroups, including antisynthetase syndrome, dermatomyositis,... (Review)
Review
Idiopathic inflammatory myopathies (IIM) are heterogeneous autoimmune diseases. There are distinct subgroups, including antisynthetase syndrome, dermatomyositis, polymyositis, immune-mediated necrotizing myopathy, and sporadic inclusion body myositis. In patients with IIM, autoantibodies are present in up to 80% of the patients. These autoantibodies are often characterized as myositis-specific autoantibodies (MSA) or myositis-associated autoantibodies (MAA). The recognition of the importance of autoantibodies, especially MSA, is increasing in recent years. In this chapter, we provide an overview of the MSAs, including some new autoantibodies of interest as they target mainly muscle-specific autoantigen, in clinical classification, the measurement of the disease activity, and a possible role in the pathogenesis in the patients with IIM.
Topics: Autoantibodies; Autoantigens; Autoimmune Diseases; Dermatomyositis; Humans; Myositis; Myositis, Inclusion Body
PubMed: 35810122
DOI: 10.1016/j.berh.2022.101767 -
Continuum (Minneapolis, Minn.) Dec 2016This article provides guidelines for diagnosing and treating the different subtypes of autoimmune myopathies. (Review)
Review
PURPOSE OF REVIEW
This article provides guidelines for diagnosing and treating the different subtypes of autoimmune myopathies.
RECENT FINDINGS
The most common subtypes of autoimmune myopathies are dermatomyositis, immune-mediated necrotizing myopathy, antisynthetase syndrome, and overlap syndromes; isolated polymyositis is an exceptionally rare disease. Specific autoantibodies are associated with unique clinical phenotypes and may be used for diagnostic and prognostic purposes, such as to assess the risk of coexisting malignancy.
SUMMARY
Diagnosing the specific subtype of autoimmune myopathy can be achieved by combining relevant features of the history, neuromuscular examination, muscle biopsy, and serologic studies.
Topics: Aged; Autoantibodies; Autoimmune Diseases; Dermatomyositis; Electromyography; Female; Humans; Male; Middle Aged; Muscular Diseases; Myositis
PubMed: 27922497
DOI: 10.1212/01.CON.0000511070.50715.ab -
Biochimica Et Biophysica Acta Apr 2015Dermatomyositis, polymyositis and immune-mediated necrotising myopathy are major forms of idiopathic inflammatory myopathy. We review here recent developments in... (Review)
Review
Dermatomyositis, polymyositis and immune-mediated necrotising myopathy are major forms of idiopathic inflammatory myopathy. We review here recent developments in understanding the pathology and pathogenesis of these diseases, and characterisation of autoantibody biomarkers. Dermatomyositis is traditionally considered to be due to a complement-mediated microangiopathy but the factors responsible for complement activation remain uncertain. Recent studies have emphasised the importance of the type I interferon pathway in the pathogenesis of the disease and have identified autoantibodies with specificities for different clinical subgroups of patients. Polymyositis is characterised by a cytotoxic T cell response targeting as yet unidentified muscle antigens presented by MHC Class I molecules, and can occur in isolation but is more often part of a multi-systemic overlap syndrome. The immune-mediated necrotising myopathies are heterogeneous and are distinguished from polymyositis by the sparseness of inflammatory infiltrates and recognition of an association with specific autoantibodies such as anti-SRP and anti-HMGCR in many cases. This article is part of a Special Issue entitled: Neuromuscular Diseases: Pathology and Molecular Pathogenesis.
Topics: Animals; Autoantibodies; Autoimmune Diseases; Complement Activation; Dermatomyositis; Histocompatibility Antigens Class I; Humans; T-Lymphocytes; Vascular Diseases
PubMed: 24907561
DOI: 10.1016/j.bbadis.2014.05.034 -
Rheumatic Diseases Clinics of North... Feb 2016Idiopathic inflammatory myopathies (IIMs) involve inflammation of the muscles and are classified by the patterns of presentation and immunohistopathologic features on... (Review)
Review
Idiopathic inflammatory myopathies (IIMs) involve inflammation of the muscles and are classified by the patterns of presentation and immunohistopathologic features on skin and muscle biopsy into 4 categories: dermatomyositis, polymyositis, inclusion body myositis, and immune-mediated necrotizing myopathy. Systemic corticosteroid (CS) treatment is the standard of care for IIM with muscle and organ involvement. The extracutaneous features of systemic sclerosis are frequently treated with CS; however, high doses have been associated with scleroderma renal crisis in high-risk patients. Although CS can be effective first-line agents, their significant side effect profile encourages concomitant treatment with other immunosuppressive medications to enable timely tapering.
Topics: Adrenal Cortex Hormones; Biopsy; Dermatomyositis; Glucocorticoids; Humans; Immunosuppressive Agents; Muscle, Skeletal; Myositis; Myositis, Inclusion Body; Polymyositis; Scleroderma, Systemic; Skin
PubMed: 26611554
DOI: 10.1016/j.rdc.2015.08.011 -
Discovery Medicine Feb 2018The inflammatory myopathies, which include dermatomyositis, polymyositis, and the immune-mediated necrotizing myopathies, are a heterogeneous group of autoimmune... (Review)
Review
The inflammatory myopathies, which include dermatomyositis, polymyositis, and the immune-mediated necrotizing myopathies, are a heterogeneous group of autoimmune diseases that manifest with muscle, skin, or lung damage. Collectively, these autoimmune diseases result from loss of tolerance to a select group of self-antigens, although the precise mechanism through which this occurs is not known. Infection, malignancy, and certain medications including statins and the immune checkpoint inhibitors used in cancer therapy have been identified as potential immunologic triggers of the inflammatory myopathies. Some of these triggers are classically associated with specific myositis-specific autoantibodies (MSAs). The strong association between certain triggers and MSAs provides insights into how an immunologic event can lead to loss of tolerance to specific self-antigens, resulting in autoimmune disease. In this review, we discuss the proposed triggers of the inflammatory myopathies and their associations with MSAs, and provide insights into how these triggers may result in the inflammatory myopathies.
Topics: Animals; Antineoplastic Agents; Autoantibodies; Autoantigens; Autoimmune Diseases; Dermatomyositis; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Lung; Muscles; Polymyositis; Skin
PubMed: 29579414
DOI: No ID Found -
Briefings in Bioinformatics Nov 2023Idiopathic inflammatory myopathies (IIMs) are a heterogeneous group of muscle disorders including adult and juvenile dermatomyositis, polymyositis, immune-mediated... (Review)
Review
Idiopathic inflammatory myopathies (IIMs) are a heterogeneous group of muscle disorders including adult and juvenile dermatomyositis, polymyositis, immune-mediated necrotising myopathy and sporadic inclusion body myositis, all of which present with variable symptoms and disease progression. The identification of effective biomarkers for IIMs has been challenging due to the heterogeneity between IIMs and within IIM subgroups, but recent advances in machine learning (ML) techniques have shown promises in identifying novel biomarkers. This paper reviews recent studies on potential biomarkers for IIM and evaluates their clinical utility. We also explore how data analytic tools and ML algorithms have been used to identify biomarkers, highlighting their potential to advance our understanding and diagnosis of IIM and improve patient outcomes. Overall, ML techniques have great potential to revolutionize biomarker discovery in IIMs and lead to more effective diagnosis and treatment.
Topics: Adult; Humans; Myositis; Dermatomyositis; Autoimmune Diseases; Biomarkers; Disease Progression
PubMed: 38243695
DOI: 10.1093/bib/bbad514