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BMJ Case Reports Jan 2024A diagnosis of polymyositis can readily be made when there is a typical history of proximal muscle weakness together with clinical findings, and there is corroboratory...
A diagnosis of polymyositis can readily be made when there is a typical history of proximal muscle weakness together with clinical findings, and there is corroboratory evidence in the form of elevated creatine kinase lactate dehydrogenase, aldolase, and serum glutamic-oxaloacetic transaminase (aspartate aminotransferase). A muscle biopsy usually helps in making the confirmatory diagnosis. A female in her 50s presented with non-healing multiple deep necrotic ulcers with muscle weakness. The initial possibility of vasculitis ulcers remained. Later, this proved to be a case of polymyositis with mildly elevated creatine kinase (which is usually not the case), atypical skin manifestations (usually there is no skin involvement), and negative extended myositis specific antibody panel with the growth of (perhaps the triggering factor). Hence, polymyositis can present with a myriad of atypical findings. Thus, thorough clinical examination and an integrated approach are necessary for early identification and treatment of the disease.
Topics: Humans; Female; Burkholderia; Ulcer; Polymyositis; Muscle Weakness; Creatine Kinase
PubMed: 38232996
DOI: 10.1136/bcr-2023-255782 -
Nature Medicine Dec 2023Immune checkpoint inhibitors (ICI) have transformed the therapeutic landscape in oncology. However, ICI can induce uncommon life-threatening autoimmune T-cell-mediated... (Meta-Analysis)
Meta-Analysis
Immune checkpoint inhibitors (ICI) have transformed the therapeutic landscape in oncology. However, ICI can induce uncommon life-threatening autoimmune T-cell-mediated myotoxicities, including myocarditis and myositis. The thymus plays a critical role in T cell maturation. Here we demonstrate that thymic alterations are associated with increased incidence and severity of ICI myotoxicities. First, using the international pharmacovigilance database VigiBase, the Assistance Publique Hôpitaux de Paris-Sorbonne University data warehouse (Paris, France) and a meta-analysis of clinical trials, we show that ICI treatment of thymic epithelial tumors (TET, and particularly thymoma) was more frequently associated with ICI myotoxicities than other ICI-treated cancers. Second, in an international ICI myocarditis registry, we established that myocarditis occurred earlier after ICI initiation in patients with TET (including active or prior history of TET) compared to other cancers and was more severe in terms of life-threatening arrythmias and concurrent myositis, leading to respiratory muscle failure and death. Lastly, we show that presence of anti-acetylcholine-receptor antibodies (a biological proxy of thymic-associated autoimmunity) was more prevalent in patients with ICI myocarditis than in ICI-treated control patients. Altogether, our results highlight that thymic alterations are associated with incidence and seriousness of ICI myotoxicities. Clinico-radio-biological workup evaluating the thymus may help in predicting ICI myotoxicities.
Topics: Humans; Immune Checkpoint Inhibitors; Myocarditis; Antineoplastic Agents, Immunological; Myotoxicity; Myositis; Neoplasms
PubMed: 37884625
DOI: 10.1038/s41591-023-02591-2 -
Brain and Nerve = Shinkei Kenkyu No... May 2024Dermatomyositis (DM) is distinguished from other idiopathic inflammatory myopathies by the characteristic skin rashes, muscle pathology, and muscle symptoms. Five... (Review)
Review
Dermatomyositis (DM) is distinguished from other idiopathic inflammatory myopathies by the characteristic skin rashes, muscle pathology, and muscle symptoms. Five myositis-specific autoantibodies have been identified in DM, and the correlation between each antibody and the clinical picture is clear. Pathological analysis has also identified DM as a type I interferonopathy of the skeletal muscle. Consideration of treatment strategies requires careful evaluation of muscle strength, systemic inflammatory findings, muscle pathology, muscle imaging, and complications such as malignancy and interstitial lung disease. Corticosteroids are administered as first-line treatment, and immunosuppressive agents and intravenous immunoglobulins are employed as important second-line treatments. Some patients exhibit resistance to these therapies. Currently, treatment strategies for refractory cases are not well established, necessitating further development of treatment methods.
Topics: Dermatomyositis; Humans; Autoantibodies; Immunosuppressive Agents; Immunoglobulins, Intravenous; Adrenal Cortex Hormones
PubMed: 38741507
DOI: 10.11477/mf.1416202654 -
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 -
Ophthalmic Plastic and Reconstructive...VEXAS (Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic) syndrome is an adult-onset autoinflammatory disorder characterized by systemic inflammation (vasculitis,...
VEXAS (Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic) syndrome is an adult-onset autoinflammatory disorder characterized by systemic inflammation (vasculitis, arthritis, chondritis, dermatosis) and hematologic abnormalities (thrombosis, cytopenia, vacuolization of marrow precursors). The patient demonstrated some of the adult-onset inflammatory and hematologic features, in addition to recurrent eye pain, chemosis and orbital inflammation. This case describes an instance of VEXAS syndrome in a patient with uncommon orbital symptoms such as scleritis and myositis.
Topics: Adult; Humans; Inflammation; Eye Pain; Myelodysplastic Syndromes; Myositis; Mutation
PubMed: 37405738
DOI: 10.1097/IOP.0000000000002450 -
The Lancet. Rheumatology Feb 2024Idiopathic inflammatory myopathies are a group of autoimmune diseases with a broad spectrum of clinical presentations, primarily characterised by immune-mediated muscle... (Review)
Review
Idiopathic inflammatory myopathies are a group of autoimmune diseases with a broad spectrum of clinical presentations, primarily characterised by immune-mediated muscle injury. Until recently, there was little insight into the pathogenesis of idiopathic inflammatory myopathies, which challenged the recognition of the breadth of heterogeneity of this group of diseases as well as the development of new therapeutics. However, the landscape of idiopathic inflammatory myopathies is evolving. In the past decade, advances in diagnostic tools have facilitated an enhanced understanding of the underlying disease mechanisms in idiopathic inflammatory myopathies, enabling the expansion of therapeutic trials. The fields of transcriptomics, prot§eomics, and machine learning offer the potential to gain greater insights into the underlying pathophysiology of idiopathic inflammatory myopathies. Harnessing insights gained from these sophisticated tools could contribute to the identification of differences at a molecular level among patients, accelerating the development of targeted, tailored therapies. Bolstered by the validation and standardisation of robust outcome measures, many promising therapies are in clinical trial development. Although challenges remain, there is great optimism in the field due to the progress in innovative diagnostics, outcome measures, and therapeutic approaches. In this Review, we discuss the expanding landscape of idiopathic inflammatory myopathies as the frontier of precision medicine becomes imminent.
Topics: Humans; Myositis; Autoimmune Diseases; Gene Expression Profiling; Machine Learning; Optimism
PubMed: 38267098
DOI: 10.1016/S2665-9913(23)00322-3 -
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 -
Current Neurology and Neuroscience... May 2024Immune-mediated necrotizing myopathy (IMNM), characterized by acute or subacute onset, severe weakness, and elevated creatine kinase levels, poses diagnostic and... (Review)
Review
PURPOSE OF REVIEW
Immune-mediated necrotizing myopathy (IMNM), characterized by acute or subacute onset, severe weakness, and elevated creatine kinase levels, poses diagnostic and therapeutic challenges. This article provides a succinct overview of IMNM, including clinical features, diagnostic strategies, and treatment approaches.
RECENT FINDINGS
Recent insights highlight the different clinical presentations and therapeutic options of IMNM stratified by autoantibody positivity and type. Additionally, recent findings call into question the reported link between statin use and IMNM. This review synthesizes current knowledge on IMNM, emphasizing its distinct clinical features and challenging management. The evolving understanding of IMNM underscores the need for a comprehensive diagnostic approach that utilizes a growing range of modalities. Early and aggressive immunomodulatory therapy remains pivotal. Ongoing research aims to refine diagnostic tools and therapeutic interventions for this challenging muscle disorder, underscoring the importance of advancing our understanding to enhance patient outcomes.
Topics: Humans; Muscle, Skeletal; Necrosis; Myositis; Autoimmune Diseases; Muscular Diseases; Autoantibodies
PubMed: 38589696
DOI: 10.1007/s11910-024-01337-y -
Brain and Nerve = Shinkei Kenkyu No... May 2024Sporadic inclusion body myositis (sIBM) is an intractable and progressive skeletal muscle disease of unknown etiology. Muscle biopsy typically reveals endomysial... (Review)
Review
Sporadic inclusion body myositis (sIBM) is an intractable and progressive skeletal muscle disease of unknown etiology. Muscle biopsy typically reveals endomysial inflammation, invasion of mononuclear cells into non-necrotic fibers, and rimmed vacuoles, suggesting that inflammation and degeneration co-exist in the pathomechanism. According to a nationwide survey conducted by a research team of the Ministry of Health, Labor, and Welfare, the number of patients is increasing in Japan as well. The clinical progression shows a slow and chronic deterioration. sIBM is usually diagnosed five years after onset. Muscle weakness and atrophy in the quadriceps, wrist flexors, and finger flexors are typical neurological findings of sIBM. Dysphagia and asymmetric weakness are often found. Serum creatine kinase is usually below 2,000 IU/L. sIBM is generally refractory to current therapy, such as steroids or immunosuppressants. Understanding the pathomechanism of sIBM is crucial for developing effective therapeutic strategies.
Topics: Myositis, Inclusion Body; Humans; Disease Progression
PubMed: 38741510
DOI: 10.11477/mf.1416202657 -
Annals of the Rheumatic Diseases Jun 2024With improved understanding of disease pathogenesis and availability of outcome measures, there has been a remarkable increase in the number of therapeutic clinical...
With improved understanding of disease pathogenesis and availability of outcome measures, there has been a remarkable increase in the number of therapeutic clinical trials in idiopathic inflammatory myopathies (myositis) over the last three years reaching as many as five trials per site. These trials share similar design and inclusion/exclusion criteria resulting in a competitive clinical trial landscape in myositis. While these are exciting times for the myositis field, we have a number of concerns about the design and conduct of the myositis trials. These include competitive landscape, lengthy placebo arms, underrepresentation of minority groups among participants, use of patient reported outcome measures with limited/no data on validity in myositis, antiquated disease classification criteria, and unclear performance of the ACR/EULAR Myositis Response Criteria in skin-predominant patients despite inclusion of these patients in trials. In this viewpoint, we further discuss these concerns and offer potential solutions such as including patient perspectives in the trial design and adoption of innovative frameworks.
Topics: Humans; Clinical Trials as Topic; Myositis; Patient Reported Outcome Measures; Research Design
PubMed: 38216318
DOI: 10.1136/ard-2023-224652