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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 -
Orphanet Journal of Rare Diseases Apr 2024Rapid progressive interstitial lung disease (RP-ILD) is the leading cause of anti-melanoma differentiation associated protein 5 antibody positive dermatomyositis...
Elevated serum B-cell activator factor levels predict rapid progressive interstitial lung disease in anti-melanoma differentiation associated protein 5 antibody positive dermatomyositis.
BACKGROUND
Rapid progressive interstitial lung disease (RP-ILD) is the leading cause of anti-melanoma differentiation associated protein 5 antibody positive dermatomyositis (anti-MDA5DM) related death. Elevated serum B-cell activating factor (BAFF) levels have been implicated in connective tissue diseases associated ILD. Here, we evaluate whether BAFF could be a prognostic biomarker for predicting RP-ILD in anti-MDA5DM patients.
METHODS
Serums were collected from 39 patients with anti-MDA5DM (20 with RP-ILD and 19 with non-RP-ILD), 20 antisynthase syndrome (ASS) patients and 20 healthy controls (HC). BAFF concentration was measured by an enzyme-linked immunosorbent assay.
RESULTS
Serum BAFF level was higher in anti-MDA5DM patients than those in ASS patients and HC (3882.32 ± 1880.09 vs. 2540.89 ± 1403.04 and 2486.28 ± 767.97 pg/mL, p = 0.0056 and 0.0038, respectively). Within anti-MDA5DM groups, RP-ILD patients exhibited higher BAFF concentration than non-RP-ILD group (4549.78 ± 1839.97 vs. 3297.28 ± 1794.69 pg/mL, p = 0.04). The BAFF concentration was positively correlated with levels of C-reactive protein (CRP), dehydrogenase (LDH) and cytokeratin (CK) in anti-MDA5DM patients (r = 0.350, p = 0.035; r = 0.393, p = 0.016; r = 0.518, p = 0.001; respectively). The best cut-off value of BAFF concentration was 2971.5 pg/mL by ROC curve (AUC area = 0.690, p = 0.045) and BAFF > 2971.5 pg/mL was an independent risk factor for RP-ILD using multivariate analysis (OR = 9.389, 95% CI = 1.609-54.769; p = 0.013).
CONCLUSIONS
Serum BAFF could be a useful prognostic biomarker for early detecting RP-ILD risk in anti-MDA5DM patients.
Topics: Humans; Dermatomyositis; Interferon-Induced Helicase, IFIH1; Autoantibodies; Lung Diseases, Interstitial; Biomarkers; Prognosis; Retrospective Studies; Disease Progression
PubMed: 38637830
DOI: 10.1186/s13023-024-03153-6 -
Basic and Clinical Neuroscience 2023Muscle biopsy is commonly used to diagnose inflammatory myopathies. We evaluated the ability of muscle ultrasound, a non-invasive and simple tool, to distinguish between...
INTRODUCTION
Muscle biopsy is commonly used to diagnose inflammatory myopathies. We evaluated the ability of muscle ultrasound, a non-invasive and simple tool, to distinguish between healthy subjects and patients with inflammatory myopathy.
METHODS
This study was conducted on 17 patients recently diagnosed with biopsy inflammatory myopathies (12 dermatomyositis, 5 polymyositis) compared with 17 age- and gender-matched healthy control adults. All patients underwent clinical assessments, including manual muscle testing, hand-held dynamometry, and muscle ultrasound evaluations, including thickness and echo intensity in predefined muscle groups.
RESULTS
The disease duration was seven months (interquartile range: 3 to 11 months). Except for the biceps and gastrocnemius, patients' muscles had significantly higher echo intensity and lower thickness than the control group. The echo intensity sum-score manifested the highest area under the curve compared to the sum-scores of other variables (echo intensity vs manual muscle testing: Area under curves-difference=0.18, P<0.01; echo intensity vs dynamometry: Area under curves-difference=0.14, P=0.02; echo intensity vs thickness: Area under curves-differences-difference=0.25, P<0.01).
CONCLUSION
The echo intensity of muscles differed significantly between healthy individuals and patients with inflammatory myopathies and may serve as a useful diagnostic biomarker.
PubMed: 38628832
DOI: 10.32598/bcn.2021.3567.1 -
International Journal of Surgery Case... May 2024Intestinal duplication is an uncommon congenital malformation affecting the alimentary tract. This article presents a case of enteric duplication cyst (EDC) in an adult,...
INTRODUCTION AND IMPORTANCE
Intestinal duplication is an uncommon congenital malformation affecting the alimentary tract. This article presents a case of enteric duplication cyst (EDC) in an adult, accompanied by a review of the available literature.
CASE PRESENTATION
A 34-year-old woman with polymyositis underwent a routine CT scan as part of her medical assessment revealing an 8 cm mass near the caecum and terminal ileum. Diagnostic procedures confirmed a cystic spherical mass. The patient underwent ileo-cecal resection, with primary anastomosis and an uneventful recovery.
CLINICAL DISCUSSION
Studies indicate that the frequency of polymyositis coexisting with a neoplasm range from 6 % to 40 %. Therefore, a body CT scan is recommended for patients with myopathy as in our patient. Intestinal duplications are predominantly found in children but can also occur in adults, often discovered incidentally or due to complications. Diagnostic imaging techniques, such as ultrasonography and CT scan, are crucial in identifying duplication location and characteristics. In this case, colonoscopy indicated ileocecal valve compression, and histological examination confirmed an enteric duplication cyst with ectopic gastric mucosa.
CONCLUSION
Enteric duplication cysts are rare, and the existing literature on the topic somewhat limited. Early diagnosis and surgical intervention are essential to stave off potential complications and reduce morbidity. Clinician awareness of enteric duplication cysts enables timely management, enhancing patient outcomes. Further research is needed to improve understanding and optimize patient care.
PubMed: 38615468
DOI: 10.1016/j.ijscr.2024.109606 -
Reumatologia Clinica Apr 2024The use of specific antibodies in inflammatory myopathies has improved the characterization of this disease, identifying different clinical phenotypes. Patients with...
The use of specific antibodies in inflammatory myopathies has improved the characterization of this disease, identifying different clinical phenotypes. Patients with dermatomyositis (DM) and anti-MDA5 antibodies display typical skin symptoms, lesser muscular involvement, and a prevalence of interstitial lung disease (ILD) of up to 91%. Beyond ILD, spontaneous pneumomediastinum (SN) has been identified as a rare but potentially fatal pulmonary manifestation. Two cases of this complication in patients with anti-MDA5 DM are reported.
Topics: Female; Humans; Male; Middle Aged; Autoantibodies; Dermatomyositis; Interferon-Induced Helicase, IFIH1; Mediastinal Emphysema
PubMed: 38614887
DOI: 10.1016/j.reumae.2024.04.002