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Brain Pathology (Zurich, Switzerland) Jul 2023Identification of antisynthetase syndrome (ASS) could be challenging due to inaccessibility and technical difficulty of the serology test for the less common non-Jo-1... (Review)
Review
Identification of antisynthetase syndrome (ASS) could be challenging due to inaccessibility and technical difficulty of the serology test for the less common non-Jo-1 antibodies. This study aimed to describe ASS antibody-specific myopathology and evaluate the diagnostic utility of myofiber HLA-DR expression. We reviewed 212 ASS muscle biopsies and compared myopathologic features among subtypes. Additionally, we compared their HLA-DR staining pattern with 602 non-ASS myositis and 140 genetically confirmed myopathies known to have an inflammatory component. We used t-test and Fisher's exact for comparisons and used sensitivity, specificity, positive and negative predictive values to assess the utility of HLA-DR expression for ASS diagnosis. RNAseq performed from a subset of myositis cases and histologically normal muscle biopsies was used to evaluate interferon (IFN)-signaling pathway-related genes. Anti-OJ ASS showed prominent myopathology with higher scores in muscle fiber (4.6 ± 2.0 vs. 2.8 ± 1.8, p = 0.001) and inflammatory domains (6.8 ± 3.2 vs. 4.5 ± 2.9, p = 0.006) than non-OJ ASS. HLA-DR expression and IFN-γ-related genes upregulation were prominent in ASS and inclusion body myositis (IBM). When dermatomyositis and IBM were excluded, HLA-DR expression was 95.4% specific and 61.2% sensitive for ASS with a positive predictive value of 85.9% and a negative predictive value of 84.2%; perifascicular HLA-DR pattern is common in anti-Jo-1 ASS than non-Jo-1 ASS (63.1% vs. 5.1%, p < 0.0001). In the appropriate clinicopathological context, myofiber HLA-DR expression help support ASS diagnosis. The presence of HLA-DR expression suggests involvement of IFN-γ in the pathogenesis of ASS, though the detailed mechanisms have yet to be elucidated.
Topics: Humans; Dermatomyositis; Myositis; Myositis, Inclusion Body; HLA-DR Antigens; Muscle Fibers, Skeletal; Autoantibodies
PubMed: 36882048
DOI: 10.1111/bpa.13155 -
Current Rheumatology Reports Dec 2023This article serves as a comprehensive review, focusing on digital approaches utilized in the diagnosis, monitoring, and treatment of patients with idiopathic... (Review)
Review
PURPOSE OF REVIEW
This article serves as a comprehensive review, focusing on digital approaches utilized in the diagnosis, monitoring, and treatment of patients with idiopathic inflammatory myopathies (IIM). The authors critically assess the literature published in the last three years, evaluating the advancements and progress achieved in this specific domain.
RECENT FINDINGS
Remarkable strides have been made in the realm of digital diagnostic support, particularly in image analysis and clinical prediction models, showing promise in aiding the diagnosis of IIM. The field of remote patient monitoring has also witnessed significant advancements, revolutionizing the care process by offering more convenient, data-driven, and continuous monitoring for IIM patients. Various digital tools, such as wearables, video- and voice consultations, and electronic patient-reported outcomes, have been extensively explored and implemented to enhance patient care. Survey studies consistently reveal a high acceptance of telehealth services among patients. Additionally, internet-based studies have facilitated the efficient and rapid recruitment of IIM patients for research purposes. Moreover, the integration of sensors and exoskeletons has shown great potential in significantly improving the functionality and quality of life for individuals with muscle weakness caused by IIM. The integration of digital health solutions in the care of IIM patients is steadily gaining attention and exploration. Although the existing evidence is limited, it does indicate that patients can be adequately and safely supported through digital means throughout their entire healthcare journey. The growing interest in digital health technologies holds the promise of improving the overall management and outcomes for individuals with idiopathic inflammatory myopathies.
Topics: Humans; Quality of Life; Myositis; Surveys and Questionnaires
PubMed: 37962833
DOI: 10.1007/s11926-023-01119-4 -
Brain and Nerve = Shinkei Kenkyu No... May 2024Immune-mediated necrotizing myopathy (IMNM) is a form of autoimmune myositis characterized by the presence of necrotic and regenerating process as a major finding in the... (Review)
Review
Immune-mediated necrotizing myopathy (IMNM) is a form of autoimmune myositis characterized by the presence of necrotic and regenerating process as a major finding in the muscle. Anti-SRP and anti-HMGCR have been identified as IMNM-specific autoantibodies. Patients with this disease often present with severe muscle weakness and markedly elevated serum creatine kinase (CK) levels. Differentiation from muscular dystrophy is challenging in certain cases. When patients meet the condition "subacute onset", "hyperCKemia over 1000 IU/L", and "clinical diagnosis of muscular dystrophy lacking molecular diagnosis", the possibility of IMNM should be considered. Autoantibody measurement, including of anti-SRP and HMGCR antibodies, is recommended. Treatment with corticosteroid in combination with immunosuppressants, intravenous immunoglobulin, and rituximab can be performed.
Topics: Humans; Necrosis; Autoantibodies; Autoimmune Diseases; Myositis; Hydroxymethylglutaryl CoA Reductases; Immunoglobulins, Intravenous; Muscle, Skeletal; Signal Recognition Particle
PubMed: 38741508
DOI: 10.11477/mf.1416202655 -
Advances in Clinical Chemistry 2024Idiopathic inflammatory myopathies (IIM), generally referred to as myositis is a heterogeneous group of diseases characterized by muscle inflammation and/or skin... (Review)
Review
Idiopathic inflammatory myopathies (IIM), generally referred to as myositis is a heterogeneous group of diseases characterized by muscle inflammation and/or skin involvement, diverse extramuscular manifestations with variable risk for malignancy and response to treatment. Contemporary clinico-serologic categorization identifies 5 main clinical groups which can be further stratified based on age, specific clinical manifestations and/or risk for cancer. The serological biomarkers for this classification are generally known as myositis-specific (MSAs) and myositis-associated antibodies. Based on the use of these antibodies, IIM patients are classified into anti-synthetase syndrome, dermatomyositis, immune-mediated necrotizing myopathy, inclusion body myositis, and overlap myositis. The current classification criteria for IIM requires clinical findings, laboratory measurements, and histological findings of the muscles. However, the use MSAs and myositis-associated autoantibodies as an adjunct for disease evaluation is thought to provide a cost-effective personalized approach that may not only guide diagnosis but aid in stratification and/or prognosis of patients. This review provides a comprehensive overview of contemporary autoantibodies that are specific or associated myositis. In addition, it highlights possible pathways for the detection and interpretation of these antibodies with limitations for routine clinical use.
Topics: Humans; Autoantibodies; Myositis; Biomarkers
PubMed: 38762242
DOI: 10.1016/bs.acc.2024.04.001 -
Clinical and Experimental Rheumatology Feb 2024Inclusion body myositis (IBM) is a progressive, debilitating muscle disease commonly encountered in patients over the age of 50. IBM typically presents with asymmetric,... (Review)
Review
Inclusion body myositis (IBM) is a progressive, debilitating muscle disease commonly encountered in patients over the age of 50. IBM typically presents with asymmetric, painless, progressive weakness and atrophy of deep finger flexors and/or quadriceps muscle. Many patients with IBM develop dysphagia. However, atypical presentations of IBM with isolated dysphagia, asymptomatic hyper-CKemia, foot drop, proximal weakness, axial weakness, and facial diplegia have been reported. Other acquired and some inherited disorders may present similar to IBM, and this list gets more expansive when considering atypical presentations. In general, disease progression of IBM leads to loss of hand function and impaired ambulation, and most IBM patients become wheelchair dependent within 13-15 years of disease onset. Hence, IBM impacts negatively patients' quality of life and reduces longevity compared to the general population. Acknowledging the complete clinical spectrum of IBM presentation and excluding mimics would shorten the time to diagnosis, lead to prompt initiation of supportive management and avoid unproven therapy. Ongoing advanced phase studies in IBM provide hope that a therapy may soon be available. Therefore, an added potential benefit of early diagnosis would be prompt initiation of disease-modifying therapy once available.
Topics: Humans; Myositis, Inclusion Body; Deglutition Disorders; Quality of Life; Muscle Weakness; Myositis
PubMed: 38436356
DOI: 10.55563/clinexprheumatol/fhrx3q -
Rheumatology International Jul 2023Idiopathic inflammatory myopathies (IIM) are rare disorders characterised by the presence of skeletal muscle inflammation, with interstitial lung disease (ILD) being the... (Review)
Review
Idiopathic inflammatory myopathies (IIM) are rare disorders characterised by the presence of skeletal muscle inflammation, with interstitial lung disease (ILD) being the most frequent pulmonary manifestation. The spectrum of clinical presentations of myositis related ILD (M-ILD) encompasses a chronic process to a rapidly progressive ILD (RP-ILD); which is associated with a high mortality rate. The most effective treatments remain controversial and poses a unique challenge to both rheumatologists and respiratory physicians to manage. Given the rare heterogenous nature of M-ILD, there is a paucity of data to guide treatment. The cornerstone of existing treatments encompasses combinations of immunosuppressive therapies, as well as non-pharmacological therapies. In this review, we aim to summarize the current pharmacological therapies (including its dosing regimens and side effects profiles) and non-pharmacological therapies. Based on the existing literature to date, we propose a treatment algorithm for both chronic M-ILD and RP-ILD.
Topics: Humans; Myositis; Lung Diseases, Interstitial; Lung; Inflammation; Treatment Outcome; Autoantibodies; Retrospective Studies
PubMed: 37126103
DOI: 10.1007/s00296-023-05336-z -
Cells Sep 2023Dermatomyositis (DM), antisynthetase syndrome (AS), immune-mediated necrotizing myopathy (IMNM), and inclusion body myositis (IBM) are four major types of idiopathic...
Dermatomyositis (DM), antisynthetase syndrome (AS), immune-mediated necrotizing myopathy (IMNM), and inclusion body myositis (IBM) are four major types of idiopathic inflammatory myopathy (IIM). Muscle biopsies from each type of IIM have unique transcriptomic profiles. MicroRNAs (miRNAs) target messenger RNAs (mRNAs), thereby regulating their expression and modulating transcriptomic profiles. In this study, 18 DM, 12 IMNM, 6 AS, 6 IBM, and 6 histologically normal muscle biopsies underwent miRNA profiling using the NanoString nCounter system. Eleven miRNAs were exclusively differentially expressed in DM compared to controls, seven miRNAs were only differentially expressed in AS, and nine miRNAs were specifically upregulated in IBM. No differentially expressed miRNAs were identified in IMNM. We also analyzed miRNA-mRNA associations to identify putative targets of differentially expressed miRNAs. In DM and AS, these were predominantly related to inflammation and cell cycle progression. Moreover, our analysis showed an association between miR-30a-3p, miR-30e-3p, and miR-199b-5p downregulation in DM and the upregulation of target genes induced by type I interferon. In conclusion, we show that muscle biopsies from DM, AS, and IBM patients have unique miRNA signatures and that these miRNAs might play a role in regulating the expression of genes known to be involved in IIM pathogenesis.
Topics: Humans; Myositis; MicroRNAs; Myositis, Inclusion Body; Autoimmune Diseases; RNA, Messenger
PubMed: 37681930
DOI: 10.3390/cells12172198 -
Seminars in Arthritis and Rheumatism Aug 2023Polyarthritis is commonly reported in idiopathic inflammatory myositis patients, but few studies have focused on the overlap of myositis with rheumatoid arthritis which... (Review)
Review
OBJECTIVES
Polyarthritis is commonly reported in idiopathic inflammatory myositis patients, but few studies have focused on the overlap of myositis with rheumatoid arthritis which is a difficult diagnosis in the absence of well-defined diagnostic criteria. The primary objective of this scoping review was to map the field of research to explore the potential diagnoses in patients presenting with both myositis and polyarthritis.
METHODS
Two electronic databases (MEDLINE/PubMed® and Web of Science®) were systematically searched using the terms (myositis OR 'inflammatory idiopathic myopathies') AND (polyarthritis OR 'rheumatoid arthritis') without any publication date limit.
RESULTS
Among individual records, 280 reports met inclusion criteria after full-text review. There was heterogeneity in the definition of overlap myositis as well as the characteristics of rheumatoid arthritis. In many studies, key data were lacking; rheumatoid factor status was reported in 56.8% (n=151), anti-citrullinated proteins antibodies status in 18.8% (n=50), and presence or absence of bone erosions in 45.1% (n=120) of the studies. Thirteen different diagnoses were found to associate myositis with polyarthritis: antisynthetase syndrome (29.6%, n=83), overlap myositis with rheumatoid arthritis (16.1%, n=45), drug-induced myositis (20.0%, n=56), rheumatoid myositis (7.5%, n=21), inclusion body myositis (1.8%, n=5), overlap with connective tissue disease (20.0%, n=56), and others (5.0%, n=14).
CONCLUSION
The spectrum of joint and muscle inflammatory diseases encompasses many diagnoses including primitive and secondary myositis associated with RA or arthritis mimicking RA. This review highlights the need for a consensual definition of OM with RA to better individualise this entity from the numerous differential diagnoses.
Topics: Humans; Arthritis, Rheumatoid; Autoantibodies; Muscles; Myositis; Myositis, Inclusion Body
PubMed: 37210805
DOI: 10.1016/j.semarthrit.2023.152227 -
Rheumatic Diseases Clinics of North... May 2024Myositis induced by immune checkpoint inhibitors (ICIs) is an infrequent, potentially fatal, immune-related adverse event. It has higher incidence in patients who... (Review)
Review
Myositis induced by immune checkpoint inhibitors (ICIs) is an infrequent, potentially fatal, immune-related adverse event. It has higher incidence in patients who receive combination ICI therapy compared to monotherapy. Patients can present with clinical manifestation symptoms of myositis alone or in combination with myocarditis and/or myasthenia gravis, which significantly worsens the course and prognosis. Diagnosis can generally be made on the basis of clinical presentation, elevation of muscle enzymes, and electromyographic changes, but some patients may require a muscle biopsy. The first line of therapy is high-dose corticosteroids, followed by immunosuppression, plasmapheresis, or intravenous immunoglobulin in patients with severe disease.
Topics: Humans; Immune Checkpoint Inhibitors; Myositis; Immunoglobulins, Intravenous
PubMed: 38670726
DOI: 10.1016/j.rdc.2024.02.003 -
Brain and Nerve = Shinkei Kenkyu No... Jul 2023Antisynthetase syndrome-associated myositis is a major form of autoimmune myositis defined by the presence of anti-aminoacyl tRNA synthetase autoantibodies. It involves...
Antisynthetase syndrome-associated myositis is a major form of autoimmune myositis defined by the presence of anti-aminoacyl tRNA synthetase autoantibodies. It involves the skeletal muscle as well as the lungs, joints, and skin. Severity of each symptom varies by autoantibody subtype; anti-OJ is associated with severe muscle involvement. Pathological changes from the perimysium to the adjacent perifascicular area, including perifascicular necrosis, is a distinctive feature. The skeletal muscle provides an immunological micro-milieu for specific plasma cells. Therapies against plasma cells or factors defining B cell/plasma cell niche may be a more effective mechanism-specific treatment.
Topics: Humans; Myositis; Muscle, Skeletal; Autoimmune Diseases; Amino Acyl-tRNA Synthetases; Autoantibodies
PubMed: 37431077
DOI: 10.11477/mf.1416202432