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Frontiers in Immunology 2024Idiopathic Inflammatory Myopathies are rare conditions with several heterogeneous disease subtypes. They can range from limited muscle or skin involvement to severe,...
Idiopathic Inflammatory Myopathies are rare conditions with several heterogeneous disease subtypes. They can range from limited muscle or skin involvement to severe, systemic, life-threatening disease. Although the etiology is unknown, some evidence suggests a role for external agents, particularly drugs. Herein, we present a case of a 71-year-old woman with chronic myeloid leukemia who developed imatinib-induced dermatomyositis . The presentation was predominantly muscular, characterized by proximal muscle weakness and myalgia of the lower limbs, with positive anti-Mi2a antibodies. Spontaneous recovery was observed after drug discontinuation, without the need for immunosuppressive therapy. This is the first confirmed description of an imatinib-induced dermatomyositis It reflects the importance of a high awareness from rheumatologists and hematologists to accurately anticipate and identify similar situations.
Topics: Humans; Female; Aged; Dermatomyositis; Imatinib Mesylate; Antineoplastic Agents; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Dermatitis
PubMed: 38745660
DOI: 10.3389/fimmu.2024.1398453 -
JCI Insight May 2024Juvenile dermatomyositis (JDM) is one of several childhood-onset autoimmune disorders characterized by a type I IFN response and autoantibodies. Treatment options are...
Juvenile dermatomyositis (JDM) is one of several childhood-onset autoimmune disorders characterized by a type I IFN response and autoantibodies. Treatment options are limited due to an incomplete understanding of how the disease emerges from dysregulated cell states across the immune system. We therefore investigated the blood of patients with JDM at different stages of disease activity using single-cell transcriptomics paired with surface protein expression. By immunophenotyping peripheral blood mononuclear cells, we observed skewing of the B cell compartment toward an immature naive state as a hallmark of JDM at diagnosis. Furthermore, we find that these changes in B cells are paralleled by T cell signatures suggestive of Th2-mediated inflammation that persist despite disease quiescence. We applied network analysis to reveal that hyperactivation of the type I IFN response in all immune populations is coordinated with previously masked cell states including dysfunctional protein processing in CD4+ T cells and regulation of cell death programming in NK cells, CD8+ T cells, and γδ T cells. Together, these findings unveil the coordinated immune dysregulation underpinning JDM and provide insight into strategies for restoring balance in immune function.
Topics: Humans; Dermatomyositis; Single-Cell Analysis; Child; Genomics; Male; Female; Interferon Type I; B-Lymphocytes; Adolescent; Child, Preschool; Leukocytes, Mononuclear; Immunophenotyping
PubMed: 38743491
DOI: 10.1172/jci.insight.176963 -
Cureus Apr 2024Coronavirus disease 2019 (COVID-19) is a life-threatening respiratory disease characterized by severe acute infection. In some cases, COVID-19 symptoms may persist for a...
Coronavirus disease 2019 (COVID-19) is a life-threatening respiratory disease characterized by severe acute infection. In some cases, COVID-19 symptoms may persist for a long term, posing a significant social problem. Long-term COVID-19 symptoms resemble those observed in various autoimmune diseases, such as dermatomyositis and polymyositis. In this report, we present the case of a 55-year-old woman who had been experiencing persistent dyspnea on exertion since contracting COVID-19 a month ago and was subsequently diagnosed with anti-synthetase syndrome (ASS). The patient presented with fever, dyspnea, rash, mechanic's hands, and arthritis. Computed tomography imaging revealed findings indicative of interstitial pneumonia. Immunological test results were positive for anti-EJ antibody, leading to a diagnosis of ASS based on Solomon's established criteria. The patient's condition improved following treatment with prednisolone, tacrolimus, and intravenous cyclophosphamide. Pathological findings of transbronchial biopsy revealed nonspecific interstitial pneumonia with organizing pneumonia, leading to speculation that ASS had developed after COVID-19. Given the scarcity of reports on ASS development post COVID-19, we conducted a literature review and compared our present case to previous ones. This report highlights the importance of considering ASS in the differential diagnosis of patients with long-term COVID-19 symptoms.
PubMed: 38738103
DOI: 10.7759/cureus.58004 -
The Israel Medical Association Journal... May 2024
Topics: Female; Humans; Dermatomyositis
PubMed: 38736349
DOI: No ID Found -
EBioMedicine Jun 2024Anti-MDA5 (Melanoma differentiation-associated protein-5) positive dermatomyositis (MDA5-DM) is characterised by rapidly progressive interstitial lung disease (ILD) and... (Observational Study)
Observational Study
BACKGROUND
Anti-MDA5 (Melanoma differentiation-associated protein-5) positive dermatomyositis (MDA5-DM) is characterised by rapidly progressive interstitial lung disease (ILD) and high mortality. MDA5 is an RNA sensor and a key pattern recognition receptor for the SARS-CoV-2 virus.
METHODS
This is a retrospective observational study of a surge in MDA5 autoimmunity, as determined using a 15 muscle-specific autoantibodies (MSAs) panel, between Janurary 2018 and December 2022 in Yorkshire, UK. MDA5-positivity was correlated with clinical features and outcome, and regional SARS-CoV-2 positivity and vaccination rates. Gene expression patterns in COVID-19 were compared with autoimmune lung disease and idiopathic pulmonary fibrosis (IPF) to gain clues into the genesis of the observed MDA5-DM outbreak.
FINDINGS
Sixty new anti-MDA5+, but not other MSAs surged between 2020 and 2022, increasing from 0.4% in 2019 to 2.1% (2020), 4.8% (2021) and 1.7% (2022). Few (8/60) had a prior history of confirmed COVID-19, peak rates overlapped with regional SARS-COV-2 community positivity rates in 2021, and 58% (35/60) had received anti-SARS-CoV-2 vaccines. 25/60 cases developed ILD which rapidly progression with death in 8 cases. Among the 35/60 non-ILD cases, 14 had myositis, 17 Raynaud phenomena and 10 had dermatomyositis spectrum rashes. Transcriptomic studies showed strong IFIH1 (gene encoding for MDA5) induction in COVID-19 and autoimmune-ILD, but not IPF, and IFIH1 strongly correlated with an IL-15-centric type-1 interferon response and an activated CD8+ T cell signature that is an immunologic hallmark of progressive ILD in the setting of systemic autoimmune rheumatic diseases. The IFIH1 rs1990760TT variant blunted such response.
INTERPRETATION
A distinct pattern of MDA5-autoimmunity cases surged contemporaneously with circulation of the SARS-COV-2 virus during COVID-19. Bioinformatic insights suggest a shared immunopathology with known autoimmune lung disease mechanisms.
FUNDING
This work was supported in part by the National Institute for Health Research (NIHR) Leeds Biomedical Research Centre (BRC), and in part by the National Institutes of Health (NIH) grant R01-AI155696 and pilot awards from the UC Office of the President (UCOP)-RGPO (R00RG2628, R00RG2642 and R01RG3780) to P.G. S.S was supported in part by R01-AI141630 (to P.G) and in part through funds from the American Association of Immunologists (AAI) Intersect Fellowship Program for Computational Scientists and Immunologists.
Topics: Humans; COVID-19; Interferon-Induced Helicase, IFIH1; Lung Diseases, Interstitial; SARS-CoV-2; Male; Female; Autoimmunity; Middle Aged; Autoantibodies; Aged; Retrospective Studies; Pandemics; Dermatomyositis; Adult
PubMed: 38723554
DOI: 10.1016/j.ebiom.2024.105136 -
Frontiers in Neurology 2024Inflammatory myopathy with mitochondrial pathology (IM-Mito) is a rare condition described in a few case series, and it is not clear whether it is a specific disease or...
INTRODUCTION
Inflammatory myopathy with mitochondrial pathology (IM-Mito) is a rare condition described in a few case series, and it is not clear whether it is a specific disease or a variant of Inclusion Body Myositis (IBM). Radiological data of IM-Mito patients has only been evaluated in one study.
AIM
To analyze whole-body muscle magnetic resonance imaging (MRI) features in patients with IM-Mito compared with individuals with IBM.
METHODS
Fourteen IM-Mito and ten IBM patients were included. IM-Mito was defined by endomysial inflammatory infiltrate, presence of at least 1% of Cytochrome C Oxidase negative fibers, and absence of rimmed vacuoles in muscle biopsy; and IBM was defined by the presence of dystrophic muscular abnormalities, endomysial inflammatory infiltrate, and rimmed vacuoles. Patients underwent clinical evaluation and whole-body muscle MRI to determine the presence of edema, and fatty infiltration in various muscles.
RESULTS
Muscle imaging abnormalities were asymmetric in most patients with IM-Mito and IBM. Muscles with the highest average degree of fatty infiltration in both conditions were the quadriceps and medial gastrocnemius. Most patients with IM-Mito and IBM showed imaging patterns of rectus femoris relatively spared compared to other quadriceps muscles. The flexor digitorum profundus was the most affected muscle of the upper limbs in both IBM and IM-Mito.
DISCUSSION
Although the results suggest some similarities in muscle imaging features between IM-Mito and IBM, there remains uncertainty whether these two conditions are part of the same clinical spectrum.
PubMed: 38715692
DOI: 10.3389/fneur.2024.1386293 -
EJIFCC Apr 2024Creatine kinase (CK) and aldolase are markers traditionally used in the study of muscle damage (MD). As CK determination is more specific to muscle damage, the demand...
BACKGROUND-AIM
Creatine kinase (CK) and aldolase are markers traditionally used in the study of muscle damage (MD). As CK determination is more specific to muscle damage, the demand for both determinations in routine laboratory tests would entail an extra cost.
METHODS
Retrospective observational study conducted between 2019-2020. CK and aldolase concentrations from 218 patients were studied.ROC curves were analyzed for CK and aldolase for muscle damage detection. Cut-off values were selected for both strategies. Specifity of CK and aldolase for dermatomyositis or polymyositis diagnosis in our population was studied using the McNemar's test.
RESULTS
The area under the ROC curve (AUC) for total CK was 0.716 (95%CI: 0.651-0.775), for CK in males it was 0.703 (95%CI: 0.592-0.799), and for CK in females was 0.719 (95%CI: 0.636-0.793). For aldolase, AUC was 0.505 (95%CI: 0.437-0.573). Optimized cut-off points for each determination were: 112 U/L for CK in men, with a sensitivity of 73.9% (95%CI: 51.6-89.8) and a specificity of 49.2% (95%CI: 35.9-62.5); 88 U/L for CK in women, with a sensitivity of 75.0% (95%CI: 57.8-87.9) and specificity of 50.5% (95%CI: 40.4-60.6); and 5.6 U/L for aldolase, with a sensitivity of 61.0% (95%CI: 53.2-68.8) and a specificity of 38.8% (95%CI: 26.5-52.6).Regarding the individuals diagnosed with dermatomyositis or polymyositis, 66.7% and 44.4% of them were correctly classified as pathological by CK and aldolase results, respectively. McNemar's test did not reveal significant differences.
CONCLUSION
The determination of CK offers a better diagnostic performance of MD and, in addition, does not present significant differences regarding the determination of aldolase in cases of polymyositis and dermatomyositis. Therefore, the single determination of CK would be sufficient for MD screening.
PubMed: 38706738
DOI: No ID Found -
Skin Research and Technology : Official... May 2024Dermatomyositis (DM) is a rare inflammatory disease. Our research focuses on predicting poor prognosis in DM patients and evaluating the prognostic significance of...
BACKGROUND
Dermatomyositis (DM) is a rare inflammatory disease. Our research focuses on predicting poor prognosis in DM patients and evaluating the prognostic significance of ferritin and Salivary Sugar Chain Antigen-6 (KL-6) through multivariate logistic regression analysis.
METHODS
Between February 2018 and April 2020, 80 DM patients at our hospital were categorized into MDA5 positive (n = 20) and negative (n = 60) groups. We conducted multivariate logistic regression to determine DM's poor prognosis risk factors and evaluate ferritin/KL-6's predictive value for prognosis.
RESULTS
Analysis showed no gender, age, body mass index (BMI), or lifestyle (smoking, drinking) differences, nor in dyspnea, muscle weakness, skin ulcers, and acetylcysteine treatment effects (p > 0.05). Significant differences emerged in arrhythmias, interstitial pneumonia, C-reactive protein, albumin, and lactate dehydrogenase levels (p < 0.05). Before treatment, differences were negligible (p > 0.05), but post-treatment, serum KL-6 and ferritin levels dropped. MDA5 positive patients had elevated serum KL-6 and ferritin levels than survivors (p < 0.05), with a strong correlation to DM. Combined diagnosis using serum KL-6 and ferritin for DM prognosis showed area under curves of 0.716 and 0.634, significantly outperforming single-index diagnoses with an area under curve (AUC) of 0.926 (p < 0.05).
CONCLUSION
Serum KL-6 and ferritin show marked abnormalities in DM, useful as indicators for evaluating polymyositis and DM conditions. However, the study's small sample size is a drawback. Expanding the sample size is essential to monitor serum KL-6 and ferritin changes in DM patients under treatment more closely, aiming to improve clinical assessment and facilitate detailed research.
Topics: Adult; Aged; Female; Humans; Male; Middle Aged; Biomarkers; Dermatomyositis; Ferritins; Interferon-Induced Helicase, IFIH1; Logistic Models; Mucin-1; Multivariate Analysis; Predictive Value of Tests; Prognosis; Risk Factors
PubMed: 38682785
DOI: 10.1111/srt.13701 -
RMD Open Apr 2024Risk prediction for patients with polymyositis/dermatomyositis-associated interstitial lung disease (PM/DM-ILD) is challenging due to heterogeneity in the disease...
OBJECTIVES
Risk prediction for patients with polymyositis/dermatomyositis-associated interstitial lung disease (PM/DM-ILD) is challenging due to heterogeneity in the disease course. We aimed to develop a mortality risk prediction model for PM/DM-ILD.
METHODS
This prognostic study analysed patients with PM/DM-ILD admitted to Nanjing Drum Hospital from 2016 to 2021. The primary outcome was mortality within 1 year. We used a least absolute shrinkage and selection operator (LASSO) logistic regression model to identify predictive laboratory indicators. These indicators were used to create a laboratory risk score, and we developed a mortality risk prediction model by incorporating clinical factors. The evaluation of model performance encompassed discrimination, calibration, clinical utility and practical application for risk prediction and prognosis.
RESULTS
Overall, 418 patients with PM/DM-ILD were enrolled and randomly divided into development (n=282) and validation (n=136) cohorts. LASSO logistic regression identified four optimal features in the development cohort, forming a laboratory risk score: C reactive protein, lactate dehydrogenase, CD3+CD4+ T cell counts and PO2/FiO2. The final prediction model integrated age, arthralgia, anti-melanoma differentiation-associated gene 5 antibody status, high-resolution CT pattern and the laboratory risk score. The prediction model exhibited robust discrimination (area under the receiver operating characteristic: 0.869, 95% CI 0.811 to 0.910), excellent calibration and valuable clinical utility. Patients were categorised into three risk groups with distinct mortality rates. The internal validation, sensitivity analyses and comparative assessments against previous models further confirmed the robustness of the prediction model.
CONCLUSIONS
We developed and validated an evidence-based mortality risk prediction model with simple, readily accessible clinical variables in patients with PM/DM-ILD, which may inform clinical decision-making.
Topics: Humans; Lung Diseases, Interstitial; Male; Female; Middle Aged; Dermatomyositis; Risk Assessment; Prognosis; Aged; Adult; Risk Factors; Logistic Models; Polymyositis; ROC Curve
PubMed: 38663883
DOI: 10.1136/rmdopen-2023-003850 -
Frontiers in Immunology 2024Juvenile dermatomyositis (JDM) is the most common inflammatory myopathy affecting children, being marked by chronic inflammation which mostly impacts on both skin and... (Review)
Review
Juvenile dermatomyositis (JDM) is the most common inflammatory myopathy affecting children, being marked by chronic inflammation which mostly impacts on both skin and skeletal muscles; diagnostic criteria of JDM include an unforeseeable mixture of clinical features, while treatment modalities commonly require corticosteroids or immunosuppressant agents. Although the pathogenesis of JDM is not completely understood, several infectious triggers have been linked to its priming via anecdotal reports related to children. Pediatric cases of recent-onset JDM have been temporally associated to an infectious disease by the power of increased titers of circulating antibodies to a putative infectious agent, including parasites, and/or detectable viral RNA or bacterial DNA. With this narrative review we offer an update about JDM association with a host of infections, namely parvovirus B19, Epstein-Barr virus, Coxsackie virus, human immune deficiency virus, severe acute respiratory syndrome coronavirus 2, and , as resulting from the medical literature. Few are the evidence-proved results addressing JDM as an unambiguous post-infectious disorder and available data specifically related to children are poor, highlighting the need of further research into the exploration between environmental cut-out factors and JDM.
Topics: Humans; Dermatomyositis; Child; COVID-19; SARS-CoV-2
PubMed: 38660309
DOI: 10.3389/fimmu.2024.1377952