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Journal of Internal Medicine Jul 2016The idiopathic inflammatory myopathies are characterized by muscle weakness, skin disease and internal organ involvement. Autoimmunity is known to have a role in... (Review)
Review
The idiopathic inflammatory myopathies are characterized by muscle weakness, skin disease and internal organ involvement. Autoimmunity is known to have a role in myositis pathogenesis, and myositis-specific autoantibodies, targeting important intracellular proteins, are regarded as key biomarkers aiding in the diagnosis of patients. In recent years, a number of novel myositis autoantibodies including anti-TIF1, anti-NXP2, anti-MDA5, anti-SAE, anti-HMGCR and anti-cN1A have been identified in both adult and juvenile patients. These autoantibodies correlate with distinct clinical manifestations and importantly are found in inclusion body, statin-induced, clinically amyopathic and juvenile groups of myositis patients, previously believed to be mainly autoantibody negative. In this review, we will describe the main myositis-specific and myositis-associated autoantibodies and their frequencies and clinical associations across different ages and ethnic groups. We will also discuss preliminary studies investigating correlations between specific myositis autoantibody titres and clinical markers of disease course, collectively demonstrating the utility of myositis autoantibodies as both diagnostic and prognostic markers of disease.
Topics: Autoantibodies; Dermatomyositis; Humans; Inclusion Bodies; Ligases; Myositis; Necrosis
PubMed: 26602539
DOI: 10.1111/joim.12451 -
The New England Journal of Medicine Apr 2015
Review
Topics: Autoimmune Diseases; Biopsy; Glucocorticoids; Humans; Inclusion Bodies; Magnetic Resonance Imaging; Muscle, Skeletal; Myositis; Physical Therapy Modalities
PubMed: 25923553
DOI: 10.1056/NEJMra1402225 -
Autoimmunity Reviews 2014Autoantibodies are a hallmark in the diagnosis of many systemic autoimmune rheumatic diseases (SARD) including idiopathic inflammatory myopathies (IIM). Based on their... (Review)
Review
Autoantibodies are a hallmark in the diagnosis of many systemic autoimmune rheumatic diseases (SARD) including idiopathic inflammatory myopathies (IIM). Based on their specificity, autoantibodies in IIM are grouped into myositis specific (MSA) and myositis associated autoantibodies (MAA). Among the MSA, autoantibodies against aminoacyl-tRNA synthetases (ARS) represent the most common antibodies and can be detected in 25-35% of patients. The presence of ARS and other autoantibodies has become a key feature for classification and diagnosis of IIM and is increasingly used to define clinically distinguishable IIM subsets. For example, anti-ARS autoantibodies are the key features of what has become known as anti-synthetase syndrome (aSS), characterized by multiple organ involvement, primarily interstitial lung disease, often accompanied by myositis, non-erosive arthritis, Raynaud's phenomenon, fever, and "mechanic's hands". Autoantibodies directed to eight different ARS have been described: Jo-1 (histidyl), PL-7 (threonyl), PL-12 (alanyl), OJ (isoleucyl), EJ (glycyl), KS (asparaginyl), Zo (phenylalanyl) and Ha (tyrosyl). Each anti-ARS antibody seems to define a distinctive clinical phenotype. Although several research methods and commercial tests are available, routine testing for anti-ARS autoantibodies (other than anti-Jo-1/histidyl-tRNA synthetase) is not widely available, sometimes leading to delays in diagnosis and poor disease outcomes.
Topics: Amino Acyl-tRNA Synthetases; Arthritis; Autoantibodies; Humans; Myositis; Ribonucleoproteins
PubMed: 24424190
DOI: 10.1016/j.autrev.2014.01.022 -
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 -
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 -
Pediatric Endocrinology Reviews : PER Jun 2013Fibrodysplasia ossificans progressiva (FOP), a rare and disabling genetic condition characterized by congenital malformations of the great toes and progressive... (Review)
Review
Fibrodysplasia ossificans progressiva (FOP), a rare and disabling genetic condition characterized by congenital malformations of the great toes and progressive heterotopic endochondral ossification (HEO) which is the most catastrophic of HEO disorders in humans. Flare-ups of FOP are episodic; immobility is cumulative. Heterozygous activating mutations in activin receptor IA/activin-like kinase-2 (ACVRI/ ALK2), a bone morphogenetic protein (BMP) type I receptor, exist in all sporadic and familial cases of FOP. The discovery of the FOP gene established a critical milestone in our understanding of FOP, and revealed a highly conserved therapeutic target in the BMP signaling pathway. This discovery has advanced efforts to develop novel therapies for this disabling disorder of tissue metamorphosis. While effective treatment of FOP will likely be based on interventions that modulate overactive ACVR1/ALK2 signaling, or that specifically block postnatal HEO, current management is focused on early diagnosis, assiduous avoidance of injury or iatrogenic harm, symptomatic amelioration of painful flare-ups, and optimization of residual function.
Topics: Animals; Disease Models, Animal; Humans; Myositis Ossificans
PubMed: 23858627
DOI: No ID Found -
Arthritis Care & Research Nov 2011
Review
Measures of adult and juvenile dermatomyositis, polymyositis, and inclusion body myositis: Physician and Patient/Parent Global Activity, Manual Muscle Testing (MMT), Health Assessment Questionnaire (HAQ)/Childhood Health Assessment Questionnaire (C-HAQ), Childhood Myositis Assessment Scale (CMAS),...
Topics: Adult; Child; Dermatology; Dermatomyositis; Health Status; Humans; Muscle Strength Dynamometer; Myositis, Inclusion Body; Parents; Patient Satisfaction; Physician's Role; Polymyositis; Quality of Life; Surveys and Questionnaires
PubMed: 22588740
DOI: 10.1002/acr.20532 -
Autoimmunity Reviews Mar 2019Idiopathic inflammatory myopathies (IIM) are a group of diseases characterized by immune-mediated muscular lesions that may be associated with extra-muscular... (Review)
Review
Idiopathic inflammatory myopathies (IIM) are a group of diseases characterized by immune-mediated muscular lesions that may be associated with extra-muscular manifestations involving skin, lungs, heart or joints. Four main groups of IIM can be distinguished: dermatomyositis (DM), overlap myositis including mainly anti-synthetase syndrome (ASS), immune mediated necrotizing myopathy (IMNM), and inclusion body myositis (IBM). Myositis-specific autoantibodies (MSA) are increasingly recognized as valuable tools for diagnosis, classification and prognosis of IIM. For example, ASS is associated with anti-aminoacyl tRNA synthetase antibodies (anti-Jo-1, PL-7, PL-12, …), IMNM with anti-SRP and anti-HMGCR; IBM with anti-cytosolic 5'nucleotidase 1A (cN1A), and DM with anti-Mi-2, anti-MDA-5, anti-TIF-1γ, anti-NXP-2 and anti-SAE. Moreover, anti-MDA-5 is associated with amyopathic myositis and interstitial lung disease and anti-TIF-1γ and anti-NXP-2 with juvenile DM as well as malignancy in patients >40 years. Most MSA have initially been discovered by immunoprecipitation. In routine laboratories, however, MSA are screened for by indirect immunofluorescence and identified by (automated) monospecific immunoassays or by multispecific immunoassays (mainly line/dot immunoassays). Validation of these (multispecific) assays is a challenge as the antibodies are rare and the assays diverse. In this review, we give an overview of the (clinical) performance characteristics of monospecific assays as well as of multispecific assays for detection of MSA. Although most assays are clinically useful, there are differences between techniques and between manufacturers. We discuss that efforts are needed to harmonize and standardize detection of MSA.
Topics: Autoantibodies; Humans; Immunoassay; Myositis
PubMed: 30639643
DOI: 10.1016/j.autrev.2018.10.004 -
Continuum (Minneapolis, Minn.) Dec 2013To discuss the clinical, laboratory, and histopathologic features and presumed pathogenic mechanisms of the four major categories of idiopathic inflammatory myopathy,... (Review)
Review
PURPOSE OF REVIEW
To discuss the clinical, laboratory, and histopathologic features and presumed pathogenic mechanisms of the four major categories of idiopathic inflammatory myopathy, namely dermatomyositis, polymyositis, immune-mediated necrotizing myopathy, and inclusion body myositis.
RECENT FINDINGS
Dermatomyositis, polymyositis, necrotizing myopathy, and inclusion body myositis are clinically, histologically, and pathogenically distinct. Polymyositis is a T cell-mediated disorder directed against muscle fibers. The pathogenesis of dermatomyositis, necrotizing myopathy, and inclusion body myositis are unknown. Dermatomyositis, polymyositis, and necrotizing myopathy are generally, but not always, responsive to immunosuppressive therapy, in contrast to inclusion body myositis, which is generally refractory to therapy.
SUMMARY
The pattern of muscle weakness, other clinical features (eg, rash, concurrent interstitial lung disease), laboratory features (creatine kinase, autoantibodies), and muscle biopsies are useful in distinguishing subtypes of inflammatory myopathy and in guiding treatment. More research is necessary to unravel the exact pathogenic bases of these myopathies and identify better treatments.
Topics: Dermatomyositis; Humans; Myositis; Myositis, Inclusion Body; Polymyositis
PubMed: 24305450
DOI: 10.1212/01.CON.0000440662.26427.bd -
Missouri Medicine 2016Idiopathic inflammatory myopathies are relatively rare diseases. Polymyositis and dermatomyositis are more common in women than men (2:1 ratio), while inclusion body... (Review)
Review
Idiopathic inflammatory myopathies are relatively rare diseases. Polymyositis and dermatomyositis are more common in women than men (2:1 ratio), while inclusion body myositis is twice as common in men. Inflammatory myopathies are a heterogeneous group of chronic systemic autoimmune diseases with an annual incidence of two to five cases per million, characterized by muscle inflammation and progressive muscle weakness. There are three major diseases which includes Dermatomyositis (DM) including a distinct juvenile subtype (JDM), Polymyositis (PM), and Inclusion Body Myositis. DM is a compliment mediated microangiopathy affecting skin and muscle. PM and IBM are T-cell mediated disorders, where CD8 positive cytotoxic T cells invade muscle fibers expressing MHC class I antigens, this leading to fiber necrosis. In IBM, vacuolar formation with amyloid deposits are also present. This article summarizes the clinical, histochemical and immunological features as well as the treatment options of the inflammatory myopathies.
Topics: Humans; Myositis
PubMed: 27311223
DOI: No ID Found