-
Arthritis Research & Therapy Jan 2024Anti-melanoma differentiation-associated gene five antibody positive (MDA5) dermatomyositis (DM) is significantly associated with rapidly progressive interstitial lung...
BACKGROUND
Anti-melanoma differentiation-associated gene five antibody positive (MDA5) dermatomyositis (DM) is significantly associated with rapidly progressive interstitial lung disease (RP-ILD). Early detection of RP-ILD remains a major challenge. This study aims to identify and validate prognostic factors for RP-ILD in MDA5 DM patients.
METHODS
Plasma samples from 20 MDA5 DM patients and 10 healthy controls (HC) were collected for proteomic analysis using liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. The proteins of interest were validated in independent samples (20 HC, 20 MDA5 DM with RP-ILD, and 20 non-RP-ILD patients) with enzyme-linked immunosorbent assay (ELISA).
RESULTS
A total of 413 differentially expressed proteins (DEPs) were detected between the MDA5 DM patients and HC. When comparing DEPs between RP-ILD and non-RP-ILD patients, 79 proteins were changed in RP-ILD patients, implicating acute inflammatory response, coagulation, and complement cascades. Six candidate biomarkers were confirmed with ELISA. Secreted phosphoprotein 1 (SPP1), serum amyloid A1 (SAA1), and Kininogen 1 (KNG1) concentrations were significantly elevated in RP-ILD patients than those in non-RP-ILD patients and HC. In the different clinical subgroups, SPP1 was particularly elevated in the high-risk RP-ILD subgroup of MDA5 DM.
CONCLUSION
This study provides novel insights into the pathogenesis of RP-ILD development in MDA5 DM and suggests the plasma protein SPP1 could serve as a potential blood biomarker for RP-ILD early warning.
Topics: Humans; Dermatomyositis; Disease Progression; Osteopontin; Chromatography, Liquid; Proteomics; Lung Diseases, Interstitial; Interferon-Induced Helicase, IFIH1; Autoantibodies; Tandem Mass Spectrometry; Biomarkers; Prognosis; Retrospective Studies
PubMed: 38167532
DOI: 10.1186/s13075-023-03243-z -
Pediatric Rheumatology Online Journal Jan 2024Juvenile Dermatomyositis (JDM) is a rare autoimmune disorder that primarily affects muscles and skin. One of the severe complications associated with JDM is calcinosis,...
BACKGROUND
Juvenile Dermatomyositis (JDM) is a rare autoimmune disorder that primarily affects muscles and skin. One of the severe complications associated with JDM is calcinosis, and treating this condition presents significant challenges. This study aimed to evaluate the efficacy and safety of local injection of infliximab into calcinosis lesions in patients with JDM.
METHODS
In this clinical trial, five patients diagnosed with JDM and calcinosis lesions were enrolled. The primary treatment consisted of weekly infliximab injections for 16 weeks, targeting all four sides of each lesion. Lesion dimensions, including length and width, were documented and monitored weekly. Before the intervention, patients underwent radiographic imaging. After the final injection in week 16, a follow-up radiographic assessment was performed. Data were analyzed using the Generalized Estimating Equation (GEE) method.
RESULTS
The lesions' size significantly decreased in both length and width during each visit. On average, the lesion length reduced by 2.66%, and the width shrank by 3.32% per visit. Based on radiographic findings, the average length and width of lesions at the initial visit were 12.09 ± 5.05 mm (range: 6.00-25.50 mm) and 6.35 ± 3.00 mm (range: 2.00-16.00 mm), respectively. The average length and width at the last visit were 5.59 ± 7.05 mm (range: 0-23.00 mm) and 3.41 ± 4.05 mm (range: 0-13.00 mm), respectively. No specific side effects related to the treatment were reported.
CONCLUSIONS
The results suggest that the direct administration of infliximab into the calcinosis lesions of patients with JDM could be a safe and effective treatment approach.
TRIAL REGISTRATION
Name of the registry: The effect of infliximab injection into calcinosis lesions on patients with juvenile dermatomyositis (JDM), Trial registration number: IRCT20210808052107N1, Registration date: 2022-07-22, URL of trial registry record: https://en.irct.ir/trial/58329 .
Topics: Humans; Dermatomyositis; Infliximab; Skin; Injections; Calcinosis
PubMed: 38166943
DOI: 10.1186/s12969-023-00941-5 -
Clinical and Experimental Rheumatology Feb 2024Anti-MDA5+ dermatomyositis was associated with poor prognosis due to the high incidence of rapid progressive interstitial lung disease, pulmonary infection. The aim of...
OBJECTIVES
Anti-MDA5+ dermatomyositis was associated with poor prognosis due to the high incidence of rapid progressive interstitial lung disease, pulmonary infection. The aim of this study is to investigate the abundance and clinical relevance of exhaustion markers on peripheral CD8 T cells from patients with idiopathic inflammatory myopathy (IIM).
METHODS
Twenty-nine healthy controls (HCs) and 71 patients with IIM were enrolled, including 42 with anti-MDA5+ and 18 with anti-MDA5- dermatomyositis (DM) and 11 with anti-synthetase syndrome (ASS). Flow cytometry was applied to detect PD-1, TIM-3 and LAG-3 in CD8 T cells. The clinical associations of the CD8 T cell exhaustion phenotype in patients with anti-MDA5+ DM were analysed.
RESULTS
CD8 T cells from patients with anti-MDA5+ DM showed significantly increased LAG-3, TIM-3 and PD-1 compared to those from patients with anti-MDA5- IIM (18 with anti-MDA5- DM and 11 with ASS) or HCs (adjusted p all < 0.05). CD8 T cells with distinct exhaustion levels were all significantly increased in anti-MDA5+ DM patients compared with HCs (p all < 0.05). Patients with high level of PD-1+ TIM-3+LAG-3+ CD8+ T cells had a significant higher incidence of pulmonary fungal infections but lower counts of CD4+ and CD8+ T cells. ROC analysis revealed that the frequency of PD-1+TIM-3+LAG-3+CD8+ T cell significantly predicted pulmonary fungal infections (area under the curve: 0.828).
CONCLUSIONS
CD8 T cells from patients with anti-MDA5+ DM show significant exhausted phenotype, and increased exhausted CD8 T cells were associated with high risk of pulmonary fungal infection.
Topics: Humans; Dermatomyositis; Hepatitis A Virus Cellular Receptor 2; Interferon-Induced Helicase, IFIH1; Programmed Cell Death 1 Receptor; Autoantibodies; CD8-Positive T-Lymphocytes; T-Lymphocytes; Retrospective Studies; Prognosis
PubMed: 38153165
DOI: 10.55563/clinexprheumatol/e51d3m -
Clinical and Experimental Rheumatology Feb 2024To determine the efficacy and safety of nintedanib in patients with anti-melanoma differentiation-associated gene 5 antibody positive dermatomyositis-associated...
OBJECTIVES
To determine the efficacy and safety of nintedanib in patients with anti-melanoma differentiation-associated gene 5 antibody positive dermatomyositis-associated interstitial lung disease (anti-MDA5+ DM-ILD).
METHODS
The study was a retrospective cohort design that evaluated patients with anti-MDA5+ DM who either received or did not receive nintedanib. Clinical symptoms, laboratory tests, and survival were compared in the two groups using a propensity score-matched analysis. The primary endpoint was mortality, while adverse events were recorded descriptively.
RESULTS
After propensity score matching, 14 patients who received nintedanib (nintedanib+ group) and matched 56 patients who did not receive nintedanib (nintedanib- group) were enrolled. Compared with the nintedanib- group, the nintedanib+ group had a lower incidence of heliotrope and arthritis, higher lymphocyte counts, lower serum ferritin levels, and greater 12-month survival (all p<0.005). Although lung function, HRCT score, and lung VAS were not statistically different between the two groups, the longitudinal study showed significant improvement in HRCT scores (p=0.028) and pulmonary VAS (p=0.019) in the nintedanib+ group. Adverse events occurred in 28.6% of patients, with the most common adverse event with nintedanib being diarrhoea.
CONCLUSIONS
Nintedanib may be effective for improving clinical symptoms, laboratory parameters, lung lesions, and survival in anti-MDA5+ DM. Diarrhoea was the most common adverse event associated with nintedanib, although the drug was well tolerated by most patients.
Topics: Humans; Prognosis; Dermatomyositis; Retrospective Studies; Disease Progression; Longitudinal Studies; Interferon-Induced Helicase, IFIH1; Autoantibodies; Lung Diseases, Interstitial; Diarrhea; Indoles
PubMed: 38153137
DOI: 10.55563/clinexprheumatol/c0i032 -
Clinical and Experimental Rheumatology Feb 2024
Topics: Humans; Dermatomyositis; Psoriasis; Heterocyclic Compounds, 3-Ring
PubMed: 38153132
DOI: 10.55563/clinexprheumatol/ki4jbt -
Clinical and Experimental Rheumatology Feb 2024This study aimed to describe the clinical features of patients with anti-melanoma differentiation-associated gene 5 (anti-MDA5) antibody-positive dermatomyositis (DM)...
OBJECTIVES
This study aimed to describe the clinical features of patients with anti-melanoma differentiation-associated gene 5 (anti-MDA5) antibody-positive dermatomyositis (DM) who had macrophage activation syndrome (MAS).
METHODS
We retrospectively examined 44 patients with anti-MDA5-positive DM and compared the clinical features between patients with MAS (n = 11) and those without (n=33). Patients without MAS were selected randomly in the same year as those with MAS at a ratio of 3:1. Among patients with MAS, we compared the features between non-survivors and survivors. We used Fisher's exact test, Student's t test, the Mann-Whitney U test and the log-rank test for statistical analysis.
RESULTS
Patients complicated with MAS had a significantly higher incidence of infection, heliotrope sign, Gottron's papule, V-neck sign, and higher serum levels of ferritin, aspartate aminotransferase (AST), lactic dehydrogenase (LDH), and creatine kinase (CK) than those without MAS (p<0.05). Among the 11 patients with MAS, 4 (36.4%) died after intensive treatment. Deceased patients were older, given more combination therapy with tofacitinib (TOF) and had a higher incidence of rapid progressive interstitial lung disease, infection, heart failure and renal impairment than those who survived (p<0.05).
CONCLUSIONS
Among anti-MDA5-positive DM, Infection, DM typical rashes, and higher serum levels of ferritin, AST, LDH, and CK were more common in patients complicated with MAS. The mortality of patients with MAS was high, particularly among patients who were older, given more combination therapy with TOF, and had RP-ILD, infection, heart failure and renal impairment.
Topics: Humans; Prognosis; Dermatomyositis; Retrospective Studies; Macrophage Activation Syndrome; Interferon-Induced Helicase, IFIH1; Autoantibodies; Lung Diseases, Interstitial; Ferritins; Heart Failure
PubMed: 38147318
DOI: 10.55563/clinexprheumatol/2537nv -
Clinical and Experimental Rheumatology Feb 2024To investigate the clinical characteristics of subcutaneous emphysema (SE) and mediastinal emphysema (ME) occurring in patients with anti-melanoma...
The clinical characteristics of subcutaneous and mediastinal emphysema in anti-melanoma differentiation-associated 5 positive dermatomyositis associated with interstitial lung disease.
OBJECTIVES
To investigate the clinical characteristics of subcutaneous emphysema (SE) and mediastinal emphysema (ME) occurring in patients with anti-melanoma differentiation-associated gene 5 antibody-positive dermatomyositis associated with interstitial lung disease (anti-MDA5-positive DM-ILD).
METHODS
In this retrospective study, a total of 117 anti-MDA5-positive DM-ILD patients were admitted to our hospital. All patients underwent an assessment of autoantibodies, serum ferritin levels, and lung high-resolution CT scans.
RESULTS
In patients with anti-MDA5-positive DM-ILD, the incidence of SE/ME was found to be 11.1%, which was significantly higher compared to patients with anti-synthetase syndrome (p<0.01). The mortality rate among anti-MDA5-positive DM-ILD patients with SE/ME was significantly higher than those without SE/ME (p=0.0022). There was no statistically significant difference in the occurrence of SE/ME between patients with positive anti-Ro-52 antibodies and those with negative anti-Ro-52 antibodies (p=0.18). Patients with higher serum ferritin levels (1000 ng/ml ≤serum ferritin ≤1500 ng/ml) had a higher likelihood of developing SE/ME compared to patients with lower serum ferritin levels (serum ferritin <500 ng/ml) (p<0.01). Among 13 anti-MDA5-positive DM-ILD patients with SE/ME, six (46.2%) developed SE/ME within 1 month of being diagnosed and 53.8% of patients underwent positive pressure ventilation prior to the onset of SE/ME.
CONCLUSIONS
We found that SE/ME is not uncommon in anti-MDA5-positive DM-ILD and is an important factor associated with poor patient prognosis. The occurrence of SE/ME is correlated with high levels of serum ferritin and is not related to anti-Ro-52 antibodies. Rheumatologists should pay close attention to SE/ME caused by positive pressure ventilation in anti-MDA5-positive DM-ILD patients.
Topics: Humans; Prognosis; Dermatomyositis; Retrospective Studies; Mediastinal Emphysema; Interferon-Induced Helicase, IFIH1; Lung Diseases, Interstitial; Autoantibodies; Ferritins
PubMed: 38147317
DOI: 10.55563/clinexprheumatol/84kd56 -
Journal of Neuromuscular Diseases 2024Idiopathic inflammatory myopathies (IIMs) are a heterogeneous group characterized by muscle weakness and skin symptoms and are categorized into six subtypes:... (Review)
Review
PURPOSE OF REVIEW
Idiopathic inflammatory myopathies (IIMs) are a heterogeneous group characterized by muscle weakness and skin symptoms and are categorized into six subtypes: dermatomyositis (DM), polymyositis (PM), anti-synthetase syndrome (ASS), immune-mediated myopathy (IMNM), inclusion body myopathy (IBM), and overlap myositis. Myositis-specific autoantibodies were detected for the diagnosis and classification of IIM. This review highlights the pathogenic contributions of the complement system, microangiopathy, and inflammation in IIM.
RECENT FINDINGS
Deposition of complement around capillaries and/or the sarcolemma was observed in muscle biopsy specimens from patients with DM, ASS, and IMNM, suggesting the pathomechanism of complement-dependent muscle and endothelial cell injury. A recent study using human muscle microvascular endothelial cells showed that Jo-1 antibodies from ASS induce complement-dependent cellular cytotoxicity in vitro. Based on both clinical and pathological observations, antibody- and complement-mediated microangiopathy may contribute to the development of DM and anti-Jo-1 ASS. Juvenile DM is characterized by the loss of capillaries, perivascular inflammation, and small-vessel angiopathies, which may be related to microinfarction and perifascicular atrophy. Several serum biomarkers that reflect the IFN1 signature and microangiopathy are elevated in patients with DM. The pathological observation of myxovirus resistance protein A (MxA), which suggests a type 1 interferon (IFN1) signature in DM, supports the diagnosis and further understanding of the pathomechanism of IIM. A recent report showed that an increase in triggering receptor expressed on myeloid cells (TREM-1) around perimysial blood vessels and muscles in patients with IIM plays a role in triggering inflammation and promoting the migration of inflammatory cells by secreting proinflammatory cytokines, such as tumor necrosis factor α.
SUMMARY
The deposition of complement in muscles and capillaries is a characteristic feature of DM, ASS, and IMNM. Microangiopathy plays a pathogenic role in DM, possibly resulting in perifascicular atrophy. Further understanding of the detailed pathomechanism regarding complement, microangiopathy, and inflammation may lead to novel therapeutic approaches for IIM.
Topics: Humans; Capillaries; Endothelial Cells; Myositis; Muscle, Skeletal; Muscular Diseases; Inflammation; Atrophy
PubMed: 38143369
DOI: 10.3233/JND-230168 -
Life (Basel, Switzerland) Dec 2023Polymyositis is a rare condition with an unknown etiology occurring more frequently in adult women. There is a lack of evidence on the coexistence of PM and CMV...
Polymyositis is a rare condition with an unknown etiology occurring more frequently in adult women. There is a lack of evidence on the coexistence of PM and CMV infection in a patient with hypothyroidism due to Hashimoto's Thyroiditis. However, the growing occurrence of both CMV infection and the simultaneous occurrence of autoimmune diseases points out a relationship, while the association direction remains unclear. Case outline: A 32-year-old woman recently treated for HT hypothyroidism was admitted to the hospital two weeks after being treated for common flu by the family doctor, complaining about a worsening condition with muscle pain, weakness, frequent falls, and fatigue. The first tests showed a normalized thyroid function, with elevated values of troponin and serum creatinine kinase (CK). The immunological tests revealed the presence of a high titer of CMV IgG antibodies and raised levels of CMV DNA. Pelvis MRI images demonstrated markedly elevated signals on the STIR sequences in the pelvis, thighs, and calves, indicating active and severe multifocal myositis. The diagnosis of PM was confirmed with the muscle biopsy on day 7 of hospitalization. The patient showed significant improvements within two weeks after the medical therapy and physiotherapy.
PubMed: 38137932
DOI: 10.3390/life13122331 -
Anais Brasileiros de Dermatologia 2024
Topics: Humans; Female; Breast Neoplasms; Dermatomyositis; Pemphigoid, Bullous; Autoantibodies
PubMed: 38135558
DOI: 10.1016/j.abd.2023.01.007