-
Circulation Research Jun 2024Autoimmunity significantly contributes to the pathogenesis of myocarditis, underscored by its increased frequency in autoimmune diseases such as systemic lupus... (Review)
Review
Autoimmunity significantly contributes to the pathogenesis of myocarditis, underscored by its increased frequency in autoimmune diseases such as systemic lupus erythematosus and polymyositis. Even in cases of myocarditis caused by viral infections, dysregulated immune responses contribute to pathogenesis. However, whether triggered by existing autoimmune conditions or viral infections, the precise antigens and immunologic pathways driving myocarditis remain incompletely understood. The emergence of myocarditis associated with immune checkpoint inhibitor therapy, commonly used for treating cancer, has afforded an opportunity to understand autoimmune mechanisms in myocarditis, with autoreactive T cells specific for cardiac myosin playing a pivotal role. Despite their self-antigen recognition, cardiac myosin-specific T cells can be present in healthy individuals due to bypassing the thymic selection stage. In recent studies, novel modalities in suppressing the activity of pathogenic T cells including cardiac myosin-specific T cells have proven effective in treating autoimmune myocarditis. This review offers an overview of the current understanding of heart antigens, autoantibodies, and immune cells as the autoimmune mechanisms underlying various forms of myocarditis, along with the latest updates on clinical management and prospects for future research.
Topics: Myocarditis; Humans; Autoimmune Diseases; Animals; Autoantibodies; Autoimmunity; T-Lymphocytes; Autoantigens; Cardiac Myosins
PubMed: 38843292
DOI: 10.1161/CIRCRESAHA.124.323816 -
Cureus May 2024Overlapping autoimmune disorders are used to describe the coexistence of more than one autoimmune disease in the same patient. Mixed connective tissue disease (MCTD) and...
Overlapping autoimmune disorders are used to describe the coexistence of more than one autoimmune disease in the same patient. Mixed connective tissue disease (MCTD) and anti-synthetase syndrome (ASS) are autoimmune diseases that manifest with pulmonary involvement, presenting as persistent dyspnea. The coexistence of both conditions in the same patient is extremely rare. We herein report a case of a 44-year-old female who was diagnosed with MCTD with features of ASS (anti-Jo-1 antibody) in the setting of rheumatoid arthritis (anti-cyclic citrullinated peptide (anti-CCP) antibody), which shows temporary breathing improvement following treatment with corticosteroid and mycophenolate mofetil. However, after the completion of mycophenolate mofetil, she was found to be anti-Jo-1 antibody negative and anti-CCP antibody positive. Our case emphasizes the need to recognize overlapping autoimmune conditions in patients with complex clinical features and presentations with the immediate application of a comprehensive diagnostic approach and tailored treatment strategies. Early diagnosis and aggressive treatment are crucial for achieving remission and preventing organ damage.
PubMed: 38841030
DOI: 10.7759/cureus.59714 -
Seminars in Arthritis and Rheumatism Aug 2024Drug-induced dermatomyositis (DIDM) is a rare and underestimated variant of dermatomyositis (DM) characterized by muscle damage and skin rash and related to certain drug... (Review)
Review
Drug-induced dermatomyositis (DIDM) is a rare and underestimated variant of dermatomyositis (DM) characterized by muscle damage and skin rash and related to certain drug exposure. The spectrum of drugs causing DIDM has evolved over time, originally implicating hydroxyurea, penicillamine, and statins as causative agents. Tumor necrosis factor α inhibitors and immune checkpoint inhibitors have also been associated with such conditions. To bridge the gap between current literature and clinical practice, and therefore guide clinicians, we conducted a comprehensive review of English literature from Pubmed, EMBASE, and MEDLINE. Our analysis included demographic data, clinical features, laboratory findings, therapeutic outcomes, and extant research pertaining to the probable pathogenesis of DIDM induced by various drugs. Furthermore, we categorized the drugs involved in DIDM cases into biologics and traditional agents for subsequent statistical analysis. Over time, there has been a gradual accumulation of reported DIDM cases. A total of 69 published DIDM cases were documented in our study, among which 33 should be attributed to biologics and the remaining 36 to traditional drugs. Interestingly, 41 of all DIDM cases had a previous history of malignancies. Additionally, DIDM cases exhibited similar cutaneous and muscular manifestations to classic DM, with the exception of cases induced by hydroxyurea, which did not entail muscle damage. Positive antinuclear antibodies and anti-TIF1-γ autoantibodies have been predominantly observed in biologics-induced cases, while positive anti-TIF1-γ antibodies were merely reported in the cases that were primarily diagnosed with malignant diseases and exposed to ICIs afterwards. Anti-TIF1-γ antibodies may potentially serve as a red flag in the identification of co-existing malignant diseases in DM patients. We also provided a comprehensive summary and exploration of potential mechanisms lying behind drug-induced dermatomyositis. In conclusion, our review consolidates the current literature on DIDM, highlighting the evolving spectrum of medications and elucidating the differences in clinical manifestations, laboratory findings, and underlying mechanisms.
Topics: Dermatomyositis; Humans; Biological Products
PubMed: 38833729
DOI: 10.1016/j.semarthrit.2024.152478 -
International Journal of Rheumatic... Jun 2024Previous studies have reported low serum 25-hydroxyvitamin D [25(OH)D] levels in dermatomyositis (DM) patients, but the exact causal relationship between them remains...
BACKGROUND
Previous studies have reported low serum 25-hydroxyvitamin D [25(OH)D] levels in dermatomyositis (DM) patients, but the exact causal relationship between them remains elusive. Our aim is to confirm the causal relationship between 25(OH)D and DM risk through a Mendelian randomization study.
METHODS
Retrieve genome-wide association study (GWAS) data on 25(OH)D (n = 441 291) and DM (n cases = 201, n controls = 172 834) from the GWAS database (https://gwas.mrcieu.ac.uk/). Select single-nucleotide polymorphisms (SNPs) strongly correlated with 25(OH)D as instrumental variables (IVs). The primary analytical approach involves the use of the inverse-variance weighted method (IVW), supplemented by MR-Egger regression and weighted median methods to enhance the reliability of the results. Heterogeneity and sensitivity analyses were conducted using Cochran's Q and leave-one-out approaches, respectively.
RESULTS
The IVW analysis confirmed a positive causal relationship between genetic variation in 25(OH)D levels and DM (OR = 2.36, 95% CI = 1.01-5.52, p = .048). Although not statistically significant (all p > .05), the other methods also suggested a protective effect of 25(OH)D on DM. Based on MR-Egger intercepts and Cochran's Q analysis, the selected SNPs showed no horizontal pleiotropy and heterogeneity. Sensitivity analysis demonstrated the robustness of the results against individual SNPs.
CONCLUSION
We provide the first evidence of a causal relationship between 25(OH)D levels and DM. Our findings support the importance of measuring serum 25(OH)D levels and considering vitamin D supplementation in clinical practice for patients with DM.
Topics: Humans; Mendelian Randomization Analysis; Vitamin D; Polymorphism, Single Nucleotide; Dermatomyositis; Genome-Wide Association Study; Risk Factors; Genetic Predisposition to Disease; Biomarkers; Risk Assessment; Vitamin D Deficiency; Case-Control Studies; Phenotype; Databases, Genetic
PubMed: 38831528
DOI: 10.1111/1756-185X.15204 -
Clinical and Experimental Rheumatology Jun 2024This research aims to investigate the prevalence, epidemiological characteristics, mortality rates, survival rates and the rate of malignancy in patients diagnosed with...
OBJECTIVES
This research aims to investigate the prevalence, epidemiological characteristics, mortality rates, survival rates and the rate of malignancy in patients diagnosed with inflammatory myopathies (IIM) in Oman.
METHODS
This is a longitudinal study, that covered a span of 16 years at eight rheumatology centres in Oman. The study included all adults and paediatric patients diagnosed with different types of idiopathic inflammatory myopathies (IIM) and who fulfil either the Bohan classification criteria or the 2017 EULAR/ACR classification criteria.
RESULTS
The study included a total of 116 patient with an average age of 38.78 (±17.61 SD) years. The most prevalent form of myositis was found to be dermatomyositis (DM) 48 (41.38%), followed by polymyositis (PM) 36 (31.03%) and juvenile myositis (JDM) 18(15.52%). However, inclusion body myositis and necrotising myopathy were relatively rare conditions. The prevalence rates for DM, PM and JDM were determined as 2.2, 2.2, and 1.14 per 100,000 population respectively. Cardiac complications were observed in 14.66% of cases. Among the individuals studied, a history of malignancy was present in around 1.72% of cases. ANA antibodies were present in 71.55% of the cases, anti-Jo 1 and anti-RNP/SM antibodies were detected in 8.62%, and Anti-Ro antibodies in 24.14%. The overall mortality rate was found to be 6.90% with a rate of 11.1% among JDM cases. The five-year survival rates for PM, DM and JDM were found to be 94.4%, 91.7% and 89.0% respectively. These rates decline over a 10-year period to 67%, 69% and 83.3% respectively.
CONCLUSIONS
The study highlights the prevalence, mortality, and survival rates of IIM in Oman. Patients with JDM had a higher mortality rate. This underscores the significance of using novel healthcare strategies to improve clinical outcomes and meet special requirements for this group of patients.
PubMed: 38829016
DOI: 10.55563/clinexprheumatol/o78ssl -
Archives of Dermatological Research May 2024
Topics: Humans; Dermatomyositis; Retrospective Studies; Female; Male; Middle Aged; Adult; Sex Factors; Aged
PubMed: 38819470
DOI: 10.1007/s00403-024-03104-y -
Rheumatology International Jul 2024Dermatomyositis (DM) is an idiopathic inflammatory myositis (IIM) characterized by skin manifestations and muscle involvement. Spontaneous intramuscular hemorrhage (SIH)...
Dermatomyositis (DM) is an idiopathic inflammatory myositis (IIM) characterized by skin manifestations and muscle involvement. Spontaneous intramuscular hemorrhage (SIH) is a fatal complication that is very rare in the course of DM, but not well known to rheumatologists. Our aim was to determine the frequency and possible risk factors of DM-related SIH. A retrospective analysis was conducted on a cohort of DM patients who were observed in the rheumatology department of the university hospital between 1998 and January 2024. The clinical, laboratory, radiological data of the patients and the treatments they received during the follow-up were analyzed. To determine possible risk factors for the development of SIH in the course of DM, our patients with DM were analyzed together with other rare SIH cases in the literature. The study included 42 of our DM patients. 32 of the patients (76.2%) were female. The median age of the patients was 53 (24-82) years, the median age of DM diagnosis of the patients was 47 (18-75) years, and the median duration of DM of the patients was 36 (2-276) months. 7.1% of patients had dysphagia, and 16.7% had intertitial lung disease (ILD). 5 (11.9%) patients were diagnosed with malignancy. The incidence rate of SIH development in our DM cohort was 0.238/100 patient years (95% CI 0.006-1.256). We tried to identify independent risk factors for SIH development by comparing our 41 DM patients without SIH with the data of patients with 23 DM-related SIH collected from the literature by adding our 1 patient (24 pts). Male sex (OR 4.97, 95% CI 1.66-14.92, p = 0.003), ILD presence (OR 9.71, 95% CI 2.99-31.47, p < 0.001), anti-MDA5 positivity (OR 16.0, 95% CI 1.60-159.3, p = 0.006), anti-Ro52 positivity (OR 11.6, 95% CI 2.93-46.34, p < 0.001), heparin use (OR 4.42, 95% CI 2.68-7.24, p < 0.001), intravenous immunoglobulin (IVIG) use (OR 11.7, 95% CI 2.26-60.54, p < 0.001), and steroid dose (OR 1.03, 95% CI 1.00-1.05, p = 0.005) were identified as risk factors for the development of SIH in the univariate analysis. The death rate due to hemorrhage was 50%. No single risk factor was found to be associated with death. As a result, SIH may occasionally arise in patients with DM. Rheumatologists should be aware that patients with dysphagia and/or ILD, who are on heparin, getting high doses of steroids, and test positive for anti-MDA5 and/or anti-Ro52 antibodies may develop SIH in the early stages of DM.
Topics: Humans; Dermatomyositis; Female; Male; Middle Aged; Risk Factors; Retrospective Studies; Adult; Aged; Hemorrhage; Aged, 80 and over; Young Adult; Incidence; Muscular Diseases
PubMed: 38809450
DOI: 10.1007/s00296-024-05612-6 -
Modern Rheumatology May 2024To clarify clinical features of anti-Ro52 antibody (Ab)-positive polymyositis (PM)/dermatomyositis (DM).
OBJECTIVES
To clarify clinical features of anti-Ro52 antibody (Ab)-positive polymyositis (PM)/dermatomyositis (DM).
PATIENTS AND METHODS
We retrospectively examined clinical features and status of anti-Ro52 Ab in patients with PM/DM admitted at the University of Tsukuba Hospital between January 2019 and February 2023. We compared anti-Ro52 Ab-positive and -negative groups.
RESULTS
A total of 40 patients were selected and analyzed. Median age at diagnosis was 61.5 (48.8-69.3) years and 34 cases were female. Twenty-three cases were PM and 17 cases were DM (including 6 clinically amyopathic dermatomyositis: CADM). Twenty-two cases were positive for anti-Ro52 Ab, 14 for anti-ARS Ab, and 6 for anti-MDA5 Ab. Interstitial lung disease (ILD) was detected in 29 cases, 9 of which were rapidly progressive. Glucocorticoid (GC)-resistant cardiomyopathy was detected in 6 cases, malignancy in 3 cases, and Sjögren's syndrome (SS) in 4 cases. Of the 22 anti-Ro52 Ab positive cases, only 3 were single-positive and the remaining 19 cases simultaneously had other autoantibodies. Comparing the anti-Ro52 Ab-positive and -negative groups, the frequencies of anti-ARS Ab positivity (63.6% vs. 0%), ILD (95.5% vs. 44.4%), GC-resistant cardiomyopathy (27.3% vs. 0%), concomitant use of immunosuppressants (95.5% vs. 55.6%), and levels of C-reactive protein (CRP) were significantly higher in the anti-Ro52 Ab-positive group (p<0.05). The frequencies of PM/DM, positivity of anti-MDA5 Ab, malignancies, and SS were comparable between groups.
CONCLUSION
Anti-Ro52 Ab were frequently positive in PM/DM and anti-Ro52 Ab-positive patients showed significantly higher rates of anti-ARS Ab positivity and ILD, GC-resistant cardiomyopathy, concomitant use of immunosuppressants, and higher levels of CRP. Anti-Ro52 Ab may be useful as a severity marker in PM/DM.
PubMed: 38804908
DOI: 10.1093/mr/roae052 -
Rinsho Shinkeigaku = Clinical Neurology Jun 2024A 23-year-old man was admitted to our hospital with a one-year history of muscle weakness and atrophy. He had noticed contractures of the fingers of both hands from the...
A 23-year-old man was admitted to our hospital with a one-year history of muscle weakness and atrophy. He had noticed contractures of the fingers of both hands from the age of 18. Examination revealed a skin rash including heliotrope rash and Gottron's sign, joint contractures in the extremities, dysphagia, extensive muscle weakness and marked muscle atrophy. The serum creatine kinase level was 272 IU/l and muscle biopsy showed typical perifascicular atrophy but little lymphocyte invasion. There was no interstitial pneumonia or malignancy, but muscle tendons showed elevated CT values suggesting calcification or fibrosis. Anti-nuclear matrix protein 2 (NXP-2) antibody-positive dermatomyositis was diagnosed on the basis of the serum antibody level. Methylprednisolone pulse therapy ameliorated the skin rash and bulbar palsy, but muscle weakness, atrophy and joint contractures were resistant to the treatment. There have been no previous reports of young adults with anti-NXP-2 antibody-positive dermatomyositis in whom joint contracture became evident as early as 4 years beforehand, which is a important feature for differential diagnosis of dermatomyositis.
Topics: Humans; Dermatomyositis; Male; Young Adult; Autoantibodies; Contracture; Biomarkers; Pulse Therapy, Drug; Methylprednisolone; Diagnosis, Differential; RNA-Binding Proteins; Nuclear Proteins; Adult; Adenosine Triphosphatases; DNA-Binding Proteins; Transcription Factors
PubMed: 38797685
DOI: 10.5692/clinicalneurol.cn-001970 -
Rheumatology (Oxford, England) May 2024Idiopathic inflammatory myopathies (IIM) can present with acute IIM-related lung injury and respiratory failure, leading to a high mortality risk in intensive care units...
OBJECTIVES
Idiopathic inflammatory myopathies (IIM) can present with acute IIM-related lung injury and respiratory failure, leading to a high mortality risk in intensive care units (ICU). Extracorporeal membrane oxygenation (ECMO) in acute respiratory distress syndrome can be lifesaving. We aimed to report a case series of IIM patients that received ECMO.
METHODS
Patients with IIM from tertiary care centers in Belgium, Canada, Denmark, United States, and Sweden who underwent ECMO were reviewed to describe clinical characteristics, disease outcomes and hospitalization course. Clinical characteristics at admission and during ICU stay including ECMO complications and mortality causes were summarized.
RESULTS
The study included 22 patients (50% female, mean±SD age at admission 47 ± 12 years) with anti-MDA5 positive dermatomyositis (68%), anti-synthetase syndrome (14%), polymyositis (9%), overlap myositis (5%) and non-MDA5 dermatomyositis (5%). Patients had low comorbidity scores and 46% had received immunosuppression before their ICU admission. Eight (36%) patients died in the ICU, six (27%) were bridged to recovery and eight (36%) were bridged to transplant. When comparing patients bridged to recovery and those who died in the ICU, those who died were older (p= 0.03) and had higher median Charlson comorbidity index scores (p= 0.05). Both groups had similar frequencies of ECMO-related complications (33% vs 50%, p= 0.94).
CONCLUSION
In the patients exposed to ECMO in this case series, 14 were successfully bridged to recovery or transplant, while 8 died in the ICU. Large studies are needed to collect data on clinical outcomes in patients with IIM-ILD exposed to ECMO to identify the best candidates for the intervention.
PubMed: 38796679
DOI: 10.1093/rheumatology/keae311