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Seminars in Respiratory and Critical... Jun 2024Antisynthetase syndrome (ASyS) is now a widely recognized entity within the spectrum of idiopathic inflammatory myopathies. Initially described in patients with a triad... (Review)
Review
Antisynthetase syndrome (ASyS) is now a widely recognized entity within the spectrum of idiopathic inflammatory myopathies. Initially described in patients with a triad of myositis, arthritis, and interstitial lung disease (ILD), its presentation can be diverse. Additional common symptoms experienced by patients with ASyS include Raynaud's phenomenon, mechanic's hand, and fever. Although there is a significant overlap with polymyositis and dermatomyositis, the key distinction lies in the presence of antisynthetase antibodies (ASAs). Up to 10 ASAs have been identified to correlate with a presentation of ASyS, each having manifestations that may slightly differ from others. Despite the proposal of three classification criteria to aid diagnosis, the heterogeneous nature of patient presentations poses challenges. ILD confers a significant burden in patients with ASyS, sometimes manifesting in isolation. Notably, ILD is also often the initial presentation of ASyS, requiring pulmonologists to remain vigilant for an accurate diagnosis. This article will comprehensively review the various aspects of ASyS, including disease presentation, diagnosis, management, and clinical course, with a primary focus on its pulmonary manifestations.
Topics: Humans; Myositis; Lung Diseases, Interstitial; Autoantibodies; Diagnosis, Differential
PubMed: 38710221
DOI: 10.1055/s-0044-1785536 -
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 -
Journal of the American Academy of... May 2024
PubMed: 38704031
DOI: 10.1016/j.jaad.2024.03.052 -
Rheumatology (Oxford, England) May 2024This study aimed to establish a screening model for differentiating anti-synthetase syndrome (ASS) from other antinuclear antibody (ANA)-associated rheumatic diseases...
OBJECTIVE
This study aimed to establish a screening model for differentiating anti-synthetase syndrome (ASS) from other antinuclear antibody (ANA)-associated rheumatic diseases (AARD) using a combination of cytoplasmic and non-cytoplasmic ANA (ncANA) patterns.
METHODS
This retrospective observational study included patients with AARDs such as systemic lupus erythematosus (SLE), systemic sclerosis (SSc), Sjögren's syndrome (SS), mixed connective tissue disease (MCTD), and polymyositis/dermatomyositis (PM/DM) who underwent ANA screening between April 2012 and December 2021. Variables included age, sex, ANA patterns (Cytoplasmic and ncANA), and titers. Logistic regression analysis of Cytoplasmic and ncANA patterns was performed to differentiate ASS from other AARDs.
RESULT
The 981 diagnosed cases of AARDs consisted of SS (n = 451), SSc (n = 264), SLE (n = 201), PM/DM (n = 104), MCTD (n = 52), and ASS, including PM/DM (n = 64). Of these, 155 patients had ≥2 overlapping diseases; however, there was no overlap between AARDs and ASS. ASS is more likely to occur when the cytoplasmic titer is positive and the ncANA <320. Receiver operating characteristic (ROC) analysis of the Cytoplasmic and ncANA range revealed an area under the ROC curve (AUC) of 0.885 (95% CI: 0.844 to 0.927).
CONCLUSION
It is important to detect cytoplasmic patterns as an ANA screening test for ASS diagnosis, even if the titer is low. Additionally, combining the cytoplasmic and ncANA patterns yields more accurate ASS screening results.
PubMed: 38696756
DOI: 10.1093/rheumatology/keae245 -
Journal of Autoimmunity Jun 2024The link between type I IFN and adaptive immunity, especially T-cell immunity, in JDM still remained largely unclear. This study aimed to understand the effect of...
The link between type I IFN and adaptive immunity, especially T-cell immunity, in JDM still remained largely unclear. This study aimed to understand the effect of elevated type I IFN signaling on CD8 T cell-associated muscle damage in juvenile dermatomyositis (JDM). This study used flow cytometry (FC) and RT‒PCR were used to examine the circulating cell ratio and type I IFN response. And scRNA-seq was used to examine peripheral immunity in 6 active JDM patients, 3 stable JDM patients, 3 juvenile IMNM patients and 3 age-matched healthy children. In vivo validation experiments were conducted using a mouse model induced by STING agonists and an experimental autoimmune myositis model (EAM). In vitro experiments were conducted using isolated CD8 T-cells from JDM patients and mice. We found that active JDM patients showed an extensive type I IFN response and a decreased CD8 T-cell ratio in the periphery (P < 0.05), which was correlated with muscle involvement (P < 0.05). Both new active JDM patients and all active JDM patients showed decreased CD8 TCM cell ratios compared with age and gender matched stable JDM patients (P < 0.05). Compared with new pediatirc systemic lupus erythematosus (SLE) patients, new active JDM patients displayed decreased CD8 T-cell and CD8 TCM cell ratios (P < 0.05). Active JDM patient skeletal muscle biopsies displayed an elevated type I IFN response, upregulated MHC-I expression and CD8 T-cell infiltration, which was validated in EAM mice. sc-RNAseq demonstrated that type I IFN signalling is the kinetic factor of abnormal differentiation and enhances the cytotoxicity of peripheral CD8 T cells in active JDM patients, which was confirmed by in vivo and in vitro validation experiments. In summary, the elevated type I IFN signalling affected the differentiation and function of CD8 T cells in active JDM patients. Skeletal muscle-infiltrating CD8 T cells might migrate from the periphery under the drive of type I IFN and increased MHC I signals. Therapies targeting autoantigen-specific CD8 T cells may represent a potential new treatment direction.
Topics: Humans; CD8-Positive T-Lymphocytes; Interferon Type I; Animals; Muscle, Skeletal; Mice; Signal Transduction; Autoantigens; Female; Dermatomyositis; Male; Child; Disease Models, Animal; Adolescent; Child, Preschool
PubMed: 38692172
DOI: 10.1016/j.jaut.2024.103232 -
JAMA Dermatology Jun 2024
Topics: Humans; Dermatomyositis; Lung Diseases, Interstitial; Methotrexate; Female; Middle Aged; Male; Adult; Dermatologic Agents; Risk Factors; Aged
PubMed: 38691354
DOI: 10.1001/jamadermatol.2024.0785 -
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 -
Current Rheumatology Reviews Apr 2024Mixed Connective Tissue Disease (MCTD) is a rare condition in children, characterized by a high titer of anti-ribonucleoprotein-U1 (anti-U1 RNP) antibodies, often...
BACKGROUND
Mixed Connective Tissue Disease (MCTD) is a rare condition in children, characterized by a high titer of anti-ribonucleoprotein-U1 (anti-U1 RNP) antibodies, often presenting with overlapping features of two or more rheumatologic disorders, including juvenile idiopathic arthritis (JIA), systemic lupus erythematous (SLE), systemic sclerosis (SSc), and juvenile dermatomyositis/polymyositis (JDM/PM).
CASE PRESENTATION
We report the case of an 8-year-old girl with a history of fever, hair loss, lower extremities edema, weakness, oral aphthous ulcers, and a high titer of anti-U1 RNP antibodies, which is consistent with the diagnosis of MCTD. The patient received immunomodulator drugs, and her disease went into remission.
CONCLUSION
Diagnosing MCTD in pediatric patients can be challenging. It should be considered especially in cases with recurrent muscular weakness or pain, lupus-like manifestations, and edema. Moreover, serum anti-U1 RNP testing can be a helpful diagnostic tool.
PubMed: 38676474
DOI: 10.2174/0115733971272403231221103006 -
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 -
International Journal of Rheumatic... Apr 2024To determine the direct health service costs and resource utilization associated with diagnosing and characterizing idiopathic inflammatory myopathies (IIMs), and to...
AIM
To determine the direct health service costs and resource utilization associated with diagnosing and characterizing idiopathic inflammatory myopathies (IIMs), and to assess for limitations and diagnostic delay in current practice.
METHODS
A retrospective, single-center cohort analysis of all patients diagnosed with IIMs between January 2012 and December 2021 in a large tertiary public hospital was conducted. Demographics, resource utilization and costs associated with diagnosing IIM and characterizing disease manifestations were identified using the hospital's electronic medical record and Health Intelligence Unit, and the Medicare Benefits Schedule.
RESULTS
Thirty-eight IIM patients were identified. IIM subtypes included dermatomyositis (34.2%), inclusion body myositis (18.4%), immune-mediated necrotizing myopathy (18.4%), polymyositis (15.8%), and anti-synthetase syndrome (13.2%). The median time from symptom onset to diagnosis was 212 days (IQR: 118-722), while the median time from hospital presentation to diagnosis was 30 days (8-120). Seventy-six percent of patients required emergent hospitalization during their diagnosis, with a median length of stay of 8 days (4-15). The average total cost of diagnosing IIM was $15 618 AUD (STD: 11331) per patient. Fifty percent of patients underwent both MRI and EMG to identify affected muscles, 10% underwent both pan-CT and PET-CT for malignancy detection, and 5% underwent both open surgical and percutaneous muscle biopsies. Autoimmune serology was unnecessarily repeated in 37% of patients.
CONCLUSION
The diagnosis of IIMs requires substantial and costly resource use; however, our study has identified potential limitations in current practice and highlighted the need for streamlined diagnostic algorithms to improve patient outcomes and reduce healthcare-related economic burden.
Topics: Humans; Retrospective Studies; Myositis; Male; Female; Middle Aged; Tertiary Care Centers; Hospitals, Public; Hospital Costs; Aged; Adult; Health Resources; Health Care Costs; Delayed Diagnosis; Predictive Value of Tests; Time Factors; Australia
PubMed: 38661316
DOI: 10.1111/1756-185X.15153