-
Journal of Investigative Medicine High... 2024Dermatomyositis (DM) presents with inflammatory myopathy and distinct skin manifestations, often linked to specific autoantibodies. Anti-transcriptional intermediary...
Dermatomyositis (DM) presents with inflammatory myopathy and distinct skin manifestations, often linked to specific autoantibodies. Anti-transcriptional intermediary factor-1 gamma (TIF-1γ) antibodies (Abs) are typically linked to DM in older patients and malignancy in 15% to 40% of cases. We highlight a case of a 24-year-old female who presented with weakness of proximal muscles, periorbital edema, heliotrope rash, erosions on oral mucosa, and painful scaly rash on the lower extremities. Transcriptional intermediary factor-1 gamma Abs were positive, confirming inflammatory myopathy. Treatment with steroid pulse therapy and immunoglobulin led to improvement. Evaluation for malignancy yielded unremarkable results. This case underscores the importance of recognizing and managing DM with TIF-1γ Ab positive, even in atypical demographics, and highlights the need for comprehensive malignancy evaluation.
Topics: Humans; Female; Dermatomyositis; Autoantibodies; Young Adult; Transcription Factors
PubMed: 38904327
DOI: 10.1177/23247096241263065 -
Frontiers in Immunology 2024A diagnosis of dermatomyositis requires recognition of distinct patterns of skin disease in combination with, and sometimes without, muscle weakness. Often, a striking...
A diagnosis of dermatomyositis requires recognition of distinct patterns of skin disease in combination with, and sometimes without, muscle weakness. Often, a striking contrast between involved and uninvolved areas is observed. Familiar patterns include eyelid and midfacial eruptions, Gottron papules/sign, and upper back (shawl sign), central chest (V/open collar sign), and lateral thigh (holster sign) involvement. More recently, new specific antibody/phenotype-associated patterns have been reported. We describe a case series of two distinct patterns of skin involvement in six adult patients with both classical and amyopathic dermatomyositis. Three had paraneoplastic disease. All had intermediate to richly pigmented skin; five were of Afro-Caribbean and one was of Asian-Caribbean descent. Four were men, and two were women. Ages ranged from 41 to 89 years. All patients had concomitant hallmark signs (facial, hand, and/or trunk signs). Three were amyopathic. The first pattern involved a sharply demarcated, horizontally oriented hyperpigmented patch/thin plaque across the shoulders and upper chest, extending up the anterior neck. The second was the combination of the classical upper back shawl distribution with distinct mid-back sparing and diffuse involvement of the lower back. Named patterns help with the recognition of skin rashes in dermatomyositis. Based on the current lexicon describing items of apparel, we liken the first pattern to a "fur stole and turtleneck" sign and the latter to a "halter-back" or "reflected-shawl" sign. Biopsies revealed hyperkeratosis and interface dermatitis, often with epidermal atrophy, compatible with dermatomyositis. These patterns perhaps represent the coalescence of already well-described signs, photo-exacerbation, koebnerization, mechanical stretch, and other currently unclear factors contributing to patterning in dermatomyositis. Pattern distribution recognition is particularly valuable in individuals with richly pigmented skin who may lack typical violaceous erythema. The distinct demarcation led to the initial misdiagnosis of allergic contact dermatitis or other exogenous dermatitis in most of our patients. Further work involves evaluation of antibody phenotype and internal involvement associations. Limitations include lack of specific antibody panels and longitudinal follow-up data.
Topics: Humans; Dermatomyositis; Male; Female; Adult; Middle Aged; Aged; Aged, 80 and over; Skin; Autoantibodies
PubMed: 38903505
DOI: 10.3389/fimmu.2024.1400575 -
Respiratory Research Jun 2024To assess the effectiveness of HRCT-based radiomics in predicting rapidly progressive interstitial lung disease (RP-ILD) and mortality in anti-MDA5 positive...
OBJECTIVES
To assess the effectiveness of HRCT-based radiomics in predicting rapidly progressive interstitial lung disease (RP-ILD) and mortality in anti-MDA5 positive dermatomyositis-related interstitial lung disease (anti-MDA5 + DM-ILD).
METHODS
From August 2014 to March 2022, 160 patients from Institution 1 were retrospectively and consecutively enrolled and were randomly divided into the training dataset (n = 119) and internal validation dataset (n = 41), while 29 patients from Institution 2 were retrospectively and consecutively enrolled as external validation dataset. We generated four Risk-scores based on radiomics features extracted from four areas of HRCT. A nomogram was established by integrating the selected clinico-radiologic variables and the Risk-score of the most discriminative radiomics model. The RP-ILD prediction performance of the models was evaluated by using the area under the receiver operating characteristic curves, calibration curves, and decision curves. Survival analysis was conducted with Kaplan-Meier curves, Mantel-Haenszel test, and Cox regression.
RESULTS
Over a median follow-up time of 31.6 months (interquartile range: 12.9-49.1 months), 24 patients lost to follow-up and 46 patients lost their lives (27.9%, 46/165). The Risk-score based on bilateral lungs performed best, attaining AUCs of 0.869 and 0.905 in the internal and external validation datasets. The nomogram outperformed clinico-radiologic model and Risk-score with AUCs of 0.882 and 0.916 in the internal and external validation datasets. Patients were classified into low- and high-risk groups with 50:50 based on nomogram. High-risk group patients demonstrated a significantly higher risk of mortality than low-risk group patients in institution 1 (HR = 4.117) and institution 2 cohorts (HR = 7.515).
CONCLUSION
For anti-MDA5 + DM-ILD, the nomogram, mainly based on radiomics, can predict RP-ILD and is an independent predictor of mortality.
Topics: Humans; Male; Female; Retrospective Studies; Lung Diseases, Interstitial; Middle Aged; Dermatomyositis; Interferon-Induced Helicase, IFIH1; Tomography, X-Ray Computed; Adult; Predictive Value of Tests; Aged; Nomograms; Autoantibodies; Disease Progression; Risk Assessment; Follow-Up Studies; Radiomics
PubMed: 38902680
DOI: 10.1186/s12931-024-02843-w -
Annals of the Rheumatic Diseases Jun 2024Autoantibodies targeting intracellular proteins are common in various autoimmune diseases. In the context of myositis, the pathologic significance of these...
OBJECTIVES
Autoantibodies targeting intracellular proteins are common in various autoimmune diseases. In the context of myositis, the pathologic significance of these autoantibodies has been questioned due to the assumption that autoantibodies cannot enter living muscle cells. This study aims to investigate the validity of this assumption.
METHODS
Confocal immunofluorescence microscopy was employed to localise antibodies and other proteins of interest in myositis muscle biopsies. Bulk RNA sequencing was used to examine the transcriptomic profiles of 669 samples, including those from patients with myositis, disease controls and healthy controls. Additionally, antibodies from myositis patients were introduced into cultured myoblasts through electroporation, and their transcriptomic profiles were analysed using RNA sequencing.
RESULTS
In patients with myositis autoantibodies, antibodies accumulated inside myofibres in the same subcellular compartment as the autoantigen. Bulk RNA sequencing revealed that muscle biopsies from patients with autoantibodies targeting transcriptional regulators exhibited transcriptomic patterns consistent with dysfunction of the autoantigen. For instance, in muscle biopsies from patients with anti-PM/Scl autoantibodies recognising components of the nuclear RNA exosome complex, an accumulation of divergent transcripts and long non-coding RNAs was observed; these RNA forms are typically degraded by the nuclear RNA exosome complex. Introducing patient antibodies into cultured muscle cells recapitulated the transcriptomic effects observed in human disease. Further supporting evidence suggested that myositis autoantibodies recognising other autoantigens may also disrupt the function of their targets.
CONCLUSIONS
This study demonstrates that, in myositis, autoantibodies are internalised into living cells, causing biological effects consistent with the disrupted function of their autoantigen.
PubMed: 38902010
DOI: 10.1136/ard-2024-225773 -
Advances in Skin & Wound Care Jul 2024Clinically amyopathic dermatomyositis (CADM) is a rare subtype of dermatomyositis that presents with cutaneous features and no muscle involvement. This case report... (Review)
Review
Clinically amyopathic dermatomyositis (CADM) is a rare subtype of dermatomyositis that presents with cutaneous features and no muscle involvement. This case report describes a 26-year-old woman with recurrent and multiple digital ulcerations coinciding with the start of winter each year. There was no evidence of myopathy, and antibody testing yielded negative results. A diagnosis of CADM was ultimately made based on clinicopathologic correlation. The patient's ulcers demonstrated excellent response to a combination therapy of hydroxychloroquine and potent topical and systemic steroids. Herein, the authors discuss the pathologic and immunologic characteristics of CADM.
Topics: Humans; Dermatomyositis; Female; Adult; Skin Ulcer; Fingers; Hydroxychloroquine; Treatment Outcome
PubMed: 38899820
DOI: 10.1097/ASW.0000000000000147 -
Skin Research and Technology : Official... Jun 2024Dermatomyositis (DM) manifests as an autoimmune and inflammatory condition, clinically characterized by subacute progressive proximal muscle weakness, rashes or both...
BACKGROUND
Dermatomyositis (DM) manifests as an autoimmune and inflammatory condition, clinically characterized by subacute progressive proximal muscle weakness, rashes or both along with extramuscular manifestations. Literature indicates that DM shares common risk factors with atherosclerosis (AS), and they often co-occur, yet the etiology and pathogenesis remain to be fully elucidated. This investigation aims to utilize bioinformatics methods to clarify the crucial genes and pathways that influence the pathophysiology of both DM and AS.
METHOD
Microarray datasets for DM (GSE128470, GSE1551, GSE143323) and AS (GSE100927, GSE28829, GSE43292) were retrieved from the Gene Expression Omnibus (GEO) database. The weighted gene co-expression network analysis (WGCNA) was used to reveal their co-expressed modules. Differentially expression genes (DEGs) were identified using the "limma" package in R software, and the functions of common DEGs were determined by functional enrichment analysis. A protein-protein interaction (PPI) network was established using the STRING database, with central genes evaluated by the cytoHubba plugin, and validated through external datasets. Immune infiltration analysis of the hub genes was conducted using the CIBERSORT method, along with Gene Set Enrichment Analysis (GSEA). Finally, the NetworkAnalyst platform was employed to examine the transcription factors (TFs) responsible for regulating pivotal crosstalk genes.
RESULTS
Utilizing WGCNA analysis, a total of 271 overlapping genes were pinpointed. Subsequent DEG analysis revealed 34 genes that are commonly found in both DM and AS, including 31 upregulated genes and 3 downregulated genes. The Degree Centrality algorithm was applied separately to the WGCNA and DEG collections to select the 15 genes with the highest connectivity, and crossing the two gene sets yielded 3 hub genes (PTPRC, TYROBP, CXCR4). Validation with external datasets showed their diagnostic value for DM and AS. Analysis of immune infiltration indicates that lymphocytes and macrophages are significantly associated with the pathogenesis of DM and AS. Moreover, GSEA analysis suggested that the shared genes are enriched in various receptor interactions and multiple cytokines and receptor signaling pathways. We coupled the 3 hub genes with their respective predicted genes, identifying a potential key TF, CBFB, which interacts with all 3 hub genes.
CONCLUSION
This research utilized comprehensive bioinformatics techniques to explore the shared pathogenesis of DM and AS. The three key genes, including PTPRC, TYROBP, and CXCR4, are related to the pathogenesis of DM and AS. The central genes and their correlations with immune cells may serve as potential diagnostic and therapeutic targets.
Topics: Humans; Computational Biology; Dermatomyositis; Atherosclerosis; Biomarkers; Protein Interaction Maps; Gene Expression Profiling; Databases, Genetic; Gene Regulatory Networks
PubMed: 38899746
DOI: 10.1111/srt.13808 -
Journal of Nippon Medical School =... Jun 2024Mixed connective tissue disease (MCTD) is characterized by mixed features of systemic lupus erythematosus, systemic sclerosis, and polymyositis/dermatomyositis and is...
Mixed connective tissue disease (MCTD) is characterized by mixed features of systemic lupus erythematosus, systemic sclerosis, and polymyositis/dermatomyositis and is rare in children. Here, we report a case of MCTD in a 10-year-old girl who presented at our hospital with arthralgia, Raynaud's phenomenon, and fatigue. Blood tests were positive for anti-U1-ribonucleoprotein (RNP) antibodies and for rheumatoid factors (RFs) IgG-RF and anti-galactose-deficient IgG. Levels of myogenic enzymes and hypergammaglobulinemia were elevated. Macrophages were prominent in bone marrow, with scattered phagocytic macrophages. MCTD was diagnosed based on the patient's symptoms and laboratory findings. Methylprednisolone pulse therapy combined with oral tacrolimus was administered, which led to resolution of symptoms. Three months after pulse therapy, arthralgia worsened and methotrexate was administered. Arthralgia improved but did not resolve. Magnetic resonance imaging performed to investigate the hip pain revealed a mature ovarian teratoma, which was surgically removed. Because the pain persisted and interfered with her daily life, she was treated with tocilizumab for joint pain relief, which decreased the pain level. Tocilizumab is a candidate for additional treatment of juvenile idiopathic arthritis-like arthritis associated with childhood-onset MCTD.
PubMed: 38897945
DOI: 10.1272/jnms.JNMS.2025_92-303 -
Respiratory Medicine Case Reports 2024Nemaline rod myopathy (NRM) is a rare muscle disorder defined by muscle weakness, respiratory insufficiency, and dysphagia. Respiratory muscle involvement can lead to...
BACKGROUND
Nemaline rod myopathy (NRM) is a rare muscle disorder defined by muscle weakness, respiratory insufficiency, and dysphagia. Respiratory muscle involvement can lead to acute hypercapnic respiratory failure, posing significant challenges in management.
CASE PRESENTATION
Our patient is a 73-year-old male with a history of polymyositis, who presented with acute hypercapnic respiratory failure secondary to a suspected polymyositis flare. Despite initial management, the patient experienced complications, including dysphagia, thrombocytopenia, and altered mental status. Neurological consultations revealed conflicting opinions regarding the primary diagnosis, suggesting inclusion body myositis. The patient's condition continued to deteriorate, prompting discussions about prognosis and palliative care options. This case highlights the challenges in managing respiratory failure in patients with late-onset nemaline myopathy and the importance of multidisciplinary care in addressing complex medical needs.
CONCLUSION
This case emphasises the complexity of managing respiratory failure in patients with late-onset nemaline myopathy and the significance of adopting a multidisciplinary approach. Timely interventions, including respiratory support, dysphagia management, and palliative care discussions, are vital in optimizing patient care and quality of life. Further research is warranted to elucidate optimal management strategies and improve outcomes in this patient population.
PubMed: 38881774
DOI: 10.1016/j.rmcr.2024.102069 -
Zeitschrift Fur Rheumatologie Jun 2024Idiopathic inflammatory myopathies (IIM) are rare diseases (incidence 1:100,000) with a wide range of clinical symptoms and manifestations. Typical indicators of IIM...
Idiopathic inflammatory myopathies (IIM) are rare diseases (incidence 1:100,000) with a wide range of clinical symptoms and manifestations. Typical indicators of IIM are proximally emphasized muscle weakness and myalgias, which are usually accompanied by elevated creatine kinase levels and muscle atrophy. The autoantibody diagnostics separate IIM into different entities, which are each associated with a typical risk of organ manifestations and the occurrence of tumors. The IIM represents an interdisciplinary challenge and the diagnostics and treatment require the involvement of several disciplines including rheumatology, neurology, neuropathology, dermatology and pneumology. An accurate diagnosis and careful tumor screening are essential because of the association between certain subgroups of IIM and the occurrence of malignant tumors.
PubMed: 38864855
DOI: 10.1007/s00393-024-01523-w -
Journal of Inflammation Research 2024There are no studies examining the role of the neutrophil-to-lymphocyte ratio (NLR), the C-reactive protein-to-albumin ratio (CAR), the systemic inflammatory index...
The Clinical Value of the Neutrophil-to-Lymphocyte Ratio, the C-Reactive Protein-to-Albumin Ratio, the Systemic Inflammatory Index, and the Systemic Inflammatory Response Index in Patients with the Anti-Synthetase Syndrome.
OBJECTIVE
There are no studies examining the role of the neutrophil-to-lymphocyte ratio (NLR), the C-reactive protein-to-albumin ratio (CAR), the systemic inflammatory index (SII), and the systemic inflammatory response index (SIRI) in anti-synthetase syndrome (ASS). We aim to compare NLR, CAR, SII, and SIRI in ASS and dermatomyositis/polymyositis (DM/PM), as well as to examine potential correlations between NLR, CAR, SII, and SIRI and clinical features and laboratory parameters in ASS.
METHODS
Retrospective collection of data from 111 patients with ASS and 175 patients with DM/PM. A Spearman rank correlation analysis was utilized to analyze the correlation between NLR, CAR, SII, and SIRI and inflammatory indexes. Receiver operating characteristic (ROC) curves were used to assess the diagnostic value. Univariate logistic regression analysis was performed to assess risk factors for interstitial lung disease (ILD).
RESULTS
Compared with DM/PM, NLR, CAR, SII, and SIRI were significantly greater in ASS patients (p < 0.05). NLR, CAR, SII, and SIRI were correlated with albumin, lactic dehydrogenase (LDH), C-reactive protein (CRP), ferritin, white blood cell (WBC), platelets, and myositis disease activity assessment visual analog scales (MYOACT) score (p < 0.05). The ROC curves analysis showed that NLR, SII, and SIRI were all highly predictive of the occurrence of ASS. Comparisons based on clinical characteristics showed elevated levels of NLR, CAR, SII, and SIRI in ASS patients with ILD, fever, and infection (p < 0.05). Univariate logistic regression analysis revealed that NLR, CAR, and SII were significant risk factors for ASS-ILD (p < 0.05).
CONCLUSION
The levels of NLR, CAR, SII, and SIRI were higher in ASS than in DM/PM and correlated with disease activity and specific clinical features. NLR, CAR, SII, and SIRI may be an aid in differentiating ASS from DM/PM and maybe promising biomarkers for ASS.
PubMed: 38855168
DOI: 10.2147/JIR.S460610