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Current Opinion in Rheumatology Nov 2023Imaging techniques such as MRI, ultrasound and PET/computed tomography (CT) have roles in the detection, diagnosis and management of myositis or idiopathic inflammatory... (Review)
Review
PURPOSE OF REVIEW
Imaging techniques such as MRI, ultrasound and PET/computed tomography (CT) have roles in the detection, diagnosis and management of myositis or idiopathic inflammatory myopathy (IIM). Imaging research has also provided valuable knowledge in the understanding of the pathology of IIM. This review explores the latest advancements of these imaging modalities in IIM.
RECENT FINDINGS
Recent advancements in imaging of IIM have seen a shift away from manual and qualitative analysis of the images. Quantitative MRI provides more objective, and potentially more sensitive characterization of fat infiltration and inflammation in muscles. In addition to B-mode ultrasound changes, shearwave elastography offers a new dimension to investigating IIM. PET/CT has the added advantage of including IIM-associated findings such as malignancies.
SUMMARY
It is evident that MRI, ultrasound and PET/CT have important roles in myositis. Continued technological advancement and a quest for more sophisticated applications help drive innovation; this has especially been so of machine learning/deep learning using artificial intelligence and the developing promise of texture analysis.
Topics: Humans; Positron Emission Tomography Computed Tomography; Artificial Intelligence; Myositis; Inflammation; Muscle, Skeletal
PubMed: 37656661
DOI: 10.1097/BOR.0000000000000975 -
Nature Reviews. Disease Primers Dec 2021Idiopathic inflammatory myopathies (IIM), also known as myositis, are a heterogeneous group of autoimmune disorders with varying clinical manifestations, treatment...
Idiopathic inflammatory myopathies (IIM), also known as myositis, are a heterogeneous group of autoimmune disorders with varying clinical manifestations, treatment responses and prognoses. Muscle weakness is usually the classical clinical manifestation but other organs can be affected, including the skin, joints, lungs, heart and gastrointestinal tract, and they can even result in the predominant manifestations, supporting that these are systemic inflammatory disorders. Different myositis-specific autoantibodies have been identified and, on the basis of clinical, histopathological and serological features, IIMs can be classified into several subgroups — dermatomyositis (including amyopathic dermatomyositis), antisynthetase syndrome, immune-mediated necrotizing myopathy, inclusion body myositis, polymyositis and overlap myositis. The prognoses, treatment responses and organ manifestations vary among these groups, implicating different pathophysiological mechanisms in each subtype. A deeper understanding of the molecular pathways underlying the pathogenesis and identifying the autoantigens of the immune reactions in these subgroups is crucial to improve outcomes. New, more homogeneous subgroups defined by autoantibodies may help define disease mechanisms, and will also be important in future clinical trials to develop targeted therapies and in identifying biomarkers to guide treatment decisions for the individual patient.
Topics: Humans; Myositis
PubMed: 34857780
DOI: 10.1038/s41572-021-00325-7 -
Brain Pathology (Zurich, Switzerland) May 2021
Topics: Autoantibodies; Humans; Muscle, Skeletal; Myopathies, Nemaline; Myositis
PubMed: 34043261
DOI: 10.1111/bpa.12966 -
The Oncologist Apr 2019Immune checkpoint inhibitors (ICIs) initiate antitumor immunity by blocking the action of immune inhibitor-signaled cytotoxic proteins, such as cytotoxic... (Review)
Review
Immune checkpoint inhibitors (ICIs) initiate antitumor immunity by blocking the action of immune inhibitor-signaled cytotoxic proteins, such as cytotoxic T-lymphocyte-associated protein 4, programmed cell death protein 1, and programmed cell death ligand 1. However, in rare cases (∼1%-12% of patients), ICI treatment causes neurologic immune-related adverse events (irAEs). These include, but are not limited to, headache, encephalitis, neuropathies, myasthenia gravis, and myositis. The symptoms associated with irAEs can range from mild (grade 1-2) to severe (grade 3-4); however, they are often challenging to diagnose because they may present as generalized symptoms, such as fatigue and weakness, that can also be caused by the cancer itself. Here, we present an illustrative case of a 67-year-old woman who presented with signs of a neurologic irAE, including progressive dysphagia and weakness leading to falls, which started during treatment with pembrolizumab and worsened following initiation of ipilimumab. Following neurological and pathological evaluation, she was diagnosed with myositis. She was treated with steroids and improved rapidly. In this article, we review previous literature to provide guidance to frequently asked questions concerning the diagnosis and management of neurologic irAEs in patients with advanced cancer. With prompt and effective treatment, most patients will achieve a complete recovery. KEY POINTS: Neurologic immune-related adverse events (irAEs) affect approximately 1% of patients treated with immune checkpoint inhibitor (ICI) monotherapy and 2%-3% treated with combination therapy. These irAEs can affect any portion of the nervous system, although peripheral nerve system manifestations are most common. Overlap syndromes with multiple neurologic irAEs or other affected organ systems frequently exist.Diagnosis of neurologic irAEs can be challenging. Routine testing may be unremarkable and symptoms frequently mimic those from cancer or side effects of other therapies. Optimal management is currently unknown. A systematic, highly coordinated, and multidisciplinary approach is critical.Outcomes from neurologic irAEs are typically favorable with the current practice of holding the ICI and starting corticosteroids. Some patients are even successfully retreated with an ICI. A subset of patients, however, have a fulminant and potentially fatal course.Improved risk assessments and targeted therapies are needed.
Topics: Aged; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Disease Management; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Ipilimumab; Myositis; Neoplasms; Neurotoxicity Syndromes; Prognosis
PubMed: 30482825
DOI: 10.1634/theoncologist.2018-0359 -
Frontiers in Immunology 2023Idiopathic inflammatory myopathies (IIMs) are common autoimmune diseases that affect skeletal muscle quality and function. The lack of an early diagnosis and treatment... (Review)
Review
Idiopathic inflammatory myopathies (IIMs) are common autoimmune diseases that affect skeletal muscle quality and function. The lack of an early diagnosis and treatment can lead to irreversible muscle damage. Non-coding RNAs (ncRNAs) play an important role in inflammatory transfer, muscle regeneration, differentiation, and regulation of specific antibody levels and pain in IIMs. ncRNAs can be detected in blood and hair; therefore, ncRNAs detection has great potential for diagnosing, preventing, and treating IIMs in conjunction with other methods. However, the specific roles and mechanisms underlying the regulation of IIMs and their subtypes remain unclear. Here, we review the mechanisms by which micro RNAs and long non-coding RNA-messenger RNA networks regulate IIMs to provide a basis for ncRNAs use as diagnostic tools and therapeutic targets for IIMs.
Topics: Humans; Myositis; RNA, Untranslated; Autoimmune Diseases; MicroRNAs; Muscle, Skeletal
PubMed: 37744337
DOI: 10.3389/fimmu.2023.1227945 -
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 -
Der Nervenarzt Jun 2023Inflammatory diseases of the skeletal muscle are important, often severe diseases with a considerable impact on the quality of life. In addition to muscle weakness there... (Review)
Review
BACKGROUND
Inflammatory diseases of the skeletal muscle are important, often severe diseases with a considerable impact on the quality of life. In addition to muscle weakness there is often involvement of other organs, such as the heart, lungs and esophagus with symptoms such as dyspnea or dysphagia.
PURPOSE
A fast and effective treatment is only possible by an early and reliable diagnosis according to current national and international standards.
METHODS
The diagnostic repertoire includes autoantibody testing, imaging, muscle biopsy, detection of extramuscular manifestations, e.g., by high-resolution lung computed tomography (CT) and an individualized tumor search. An optimal treatment and the avoidance of irreversible damage, such as a loss of walking ability, are only possible through a good interdisciplinary cooperation including neurology or pediatrics, rheumatology, dermatology, neuropathology, pulmonology and cardiology.
RESULTS
In addition to standard immunosuppression with glucocorticosteroids, azathioprine or methotrexate, escalation treatment with rituximab is now well established. Interdisciplinary treatment according to national and international standards, such as guidelines on myositis, should be coordinated at qualified centers of excellence.
DISCUSSION
Helpful resources are the MYOSITIS NETZ ( www.myositis-netz.de ) and the International Myositis Society (iMyoS; www.imyos.org ).
Topics: Humans; Child; Quality of Life; Myositis; Muscle, Skeletal; Autoantibodies; Treatment Outcome
PubMed: 37222759
DOI: 10.1007/s00115-023-01490-8 -
Current Rheumatology Reports Aug 2020To highlight new and emerging treatment targets in myositis. (Review)
Review
PURPOSE OF REVIEW
To highlight new and emerging treatment targets in myositis.
RECENT FINDINGS
The landscape of novel therapeutics in myositis has vastly changed in the past 5 years. This is largely due to a greater understanding of the pathogenesis of myositis and validation of more robust outcome measures that standardize the ability to assess treatment response. Clinical trials in dermatomyositis are leading the way with ongoing multicenter, international phase 3 clinical trials. Proof-of-concept studies targeting the JAK/STAT pathway have also showed early promise in treating refractory dermatomyositis in adults and children. This review highlights that the future armamentarium of therapeutic drugs will likely be larger and more selective in treating different subgroups of myositis.
Topics: Clinical Trials, Phase III as Topic; Dermatomyositis; Humans; Multicenter Studies as Topic; Myositis
PubMed: 32845402
DOI: 10.1007/s11926-020-00943-2 -
Clinical Rheumatology Oct 2023Cardiovascular involvement in idiopathic inflammatory myopathies (IIM) is an understudied area which is gaining increasing recognition in recent times. Recent advances... (Review)
Review
Cardiovascular involvement in idiopathic inflammatory myopathies (IIM) is an understudied area which is gaining increasing recognition in recent times. Recent advances in imaging modalities and biomarkers have allowed the detection of subclinical cardiovascular manifestations in IIM. However, despite the availability of these tools, the diagnostic challenges and underestimated prevalence of cardiovascular involvement in these patients remain significant. Notably, cardiovascular involvement remains one of the leading causes of mortality in patients with IIM. In this narrative literature review, we outline the prevalence and characteristics of cardiovascular involvement in IIM. Additionally, we explore investigational modalities for early detection of cardiovascular involvement, as well as newer approaches in screening to facilitate timely management. Key points • Cardiac involvement in IIM in majority cases is subclinical and a major cause of mortality. • Cardiac magnetic resonance imaging is sensitive for detection of subclinical cardiac involvement.
Topics: Humans; Myositis; Heart; Magnetic Resonance Imaging; Biomarkers
PubMed: 37148365
DOI: 10.1007/s10067-023-06599-4 -
Frontiers in Immunology 2022The idiopathic inflammatory myopathies (IIM) are rare, heterogeneous systemic autoimmune disorders, characterized by inflammation of skeletal muscle and multi-organ... (Review)
Review
The idiopathic inflammatory myopathies (IIM) are rare, heterogeneous systemic autoimmune disorders, characterized by inflammation of skeletal muscle and multi-organ involvement. Studies to identify genetic risk factors and dysregulated gene expression in IIM aim to increase our understanding of disease pathogenesis. Genome-wide association studies have confirmed the HLA region as the most strongly associated region in IIM, with different associations between clinically-defined subgroups. Associated genes are involved in both the innate and adaptive immune response, while identification of variants reported in other autoimmune disorders suggests shared biological pathways. Targeted imputation analysis has identified key associated amino acid residues within HLA molecules that may influence antigen recognition. These amino acids increase risk for specific clinical phenotypes and autoantibody subgroups, and suggest that serology-defined subgroups may be more homogeneous. Recent data support the contribution of rare genetic variation to disease susceptibility in IIM, including mitochondrial DNA variation in sporadic inclusion body myositis and somatic mutations and loss of heterozygosity in cancer-associated myositis. Gene expression studies in skeletal muscle, blood and skin from individuals with IIM has confirmed the role of interferon signalling and other dysregulated pathways, and identified cell-type specific signatures. These dysregulated genes differentiate IIM subgroups and identify potential biomarkers. Here, we review recent genetic studies in IIM, and how these inform our understanding of disease pathogenesis and provide mechanistic insights into biological pathways.
Topics: Autoantibodies; Autoimmune Diseases; Genome-Wide Association Study; Humans; Myositis; Myositis, Inclusion Body
PubMed: 35693792
DOI: 10.3389/fimmu.2022.886290