Environmental triggers of dermatomyositis: a narrative review

Bax, Christina E.; Maddukuri, Spandana; Ravishankar, Adarsh; Pappas‐Taffer, Lisa; Werth, Victoria P.

doi:10.21037/atm-20-3719

Cited by 27 publications

(25 citation statements)

References 120 publications

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“…Viral antigens might play a triggering role in the onset of DM. This hypothesis is in accordance with numerous clinical observations suggesting a possible link between myopathies and infectious triggering agents [ 35 ]. With regard to the type I IFN signaling pathway, it consists of an important group of cytokines that are produced by innate immune cells, acting on adaptive immune cells.…”

Section: Discussionsupporting

confidence: 92%

Ten genes are considered as potential biomarkers for the diagnosis of dermatomyositis

Xiao

Lin

2021

PLoS ONE

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Objective This study aimed to identify the biomarkers and mechanisms for dermatomyositis (DM) progression at the transcriptome level through a combination of microarray and bioinformatic analyses. Method Microarray datasets for skeletal muscle of DM and healthy control (HC) were downloaded from the Gene Expression Omnibus (GEO) database, and differentially expressed genes (DEGs) were identified by using GEO2R. Enrichment analyses were performed to understand the functions and enriched pathways of DEGs. A protein–protein interaction network was constructed to identify hub genes. The top 10 hub genes were validated by other GEO datasets. The diagnostic accuracy of the top 10 hub genes for DM was evaluated using the area under the curve of the receiver operating characteristic curve. Result A total of 63 DEGs were identified between 10 DM samples and 9 HC samples. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis indicated that DEGs are mostly enriched in response to virus, defense response to virus, and type I interferon signaling pathway. 10 hub genes and 3 gene cluster modules were identified by Cytoscape. The identified hub genes were verified by GSE1551 and GSE11971 datasets and proven to be potential biomarkers for the diagnosis of DM. Conclusion Our work identified 10 valuable genes as potential biomarkers for the diagnosis of DM and explored the potential underlying molecular mechanism of the disease.

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Section: Discussionsupporting

confidence: 92%

Ten genes are considered as potential biomarkers for the diagnosis of dermatomyositis

Xiao

Lin

2021

PLoS ONE

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“…In general, viral infections are a well-known trigger of dermatomyositis [ 30 ]. Furthermore, seasonal clustering of MDA5-positive dermatomyositis with lower incidence in European summer months is known [ 31 ].…”

Section: Discussionmentioning

confidence: 99%

New-onset dermatomyositis following SARS-CoV-2 infection and vaccination: a case-based review

et al. 2022

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Dermatomyositis is a rare, type I interferon-driven autoimmune disease, which can affect muscle, skin and internal organs (especially the pulmonary system). In 2021, we have noted an increase in new-onset dermatomyositis compared to the years before the SARS-CoV-2 pandemic in our center. We present four cases of new-onset NXP2 and/or MDA5 positive dermatomyositis shortly after SARS-CoV-2 infection or vaccination. Three cases occurred within days after vaccination with Comirnaty and one case after SARS-CoV-2 infection. All patients required intensive immunosuppressive treatment. MDA5 antibodies could be detected in three patients and NXP2 antibodies were found in two patients (one patient was positive for both antibodies). In this case-based systematic review, we further analyze and discuss the literature on SARS-CoV-2 and associated dermatomyositis. In the literature, sixteen reports (with a total of seventeen patients) of new-onset dermatomyositis in association with a SARS-CoV-2 infection or vaccination were identified. Ten cases occurred after infection and seven after vaccination. All vaccination-associated cases were seen in mRNA vaccines. The reported antibodies included for instance MDA5, NXP2, Mi-2 and TIF1γ. The reviewed literature and our cases suggest that SARS-CoV-2 infection and vaccination may be considered as a potential trigger of interferon-pathway. Consequently, this might serve as a stimulus for the production of dermatomyositis-specific autoantibodies like MDA5 and NXP2 which are closely related to viral defense or viral RNA interaction supporting the concept of infection and vaccination associated dermatomyositis.

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“…We also speculate that viral infection may be a trigger, with viral-induced myocarditis leading to the development of anti-MDA5 (+) CADM. It has long been suspected that viruses may be involved in the development of PM/DM (e.g., Parvo virus, Coxsackie virus) (27)(28)(29). The type1 IFN pathway, which has antiviral effects, is activated in PM/DM (30).…”

Section: Discussionmentioning

confidence: 99%

ECG Changes Through Immunosuppressive Therapy Indicate Cardiac Abnormality in Anti-MDA5 Antibody-Positive Clinically Amyopathic Dermatomyositis

et al. 2022

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Anti-melanoma differentiation-associated gene 5 (MDA5) antibody, a dermatomyositis (DM)-specific antibody, is strongly associated with interstitial lung disease (ILD). Patients with idiopathic inflammatory myopathy (IIM) who are anti-MDA5 antibody positive [anti-MDA5 (+)] often experience chest symptoms during the active disease phase. These symptoms are primarily explained by respiratory failure; nevertheless, cardiac involvement can also be symptomatic. Thus, the aim of this study was to investigate cardiac involvement in anti-MDA5 (+) DM. A total of 63 patients with IIM who underwent electrocardiography (ECG) and ultrasound cardiography (UCG) during the active disease phase from 2016 to 2021 [anti-MDA5 (+) group, n = 21; anti-MDA5-negative (-) group, n = 42] were enrolled in the study, and their clinical charts were retrospectively reviewed. The ECG and UCG findings were compared between the anti-MDA5 (+) and anti-MDA5 (-) groups. All anti-MDA5 (+) patients had DM with ILD. The anti-MDA5 (+) group showed more frequent skin ulcerations and lower levels of leukocytes, muscle enzymes, and electrolytes (Na, K, Cl, and Ca) than the anti-MDA5 (-) group. According to the ECG findings obtained during the active disease phase, the T wave amplitudes were significantly lower for the anti-MDA5 (+) group than for the anti-MDA5 (-) group (I, II, and V4–6 lead; p < 0.01; aVF and V3, p < 0.05). However, the lower amplitudes were restored during the remission phase. Except for the E wave, A wave and Sep e’, the UCG results showed no significant differences between the groups. Four patients with anti-MDA5 (+) DM had many leads with lower T wave and cardiac abnormalities (heart failure, diastolic dysfunction, myocarditis) on and after admission. Though anti-MDA5 (+) patients clinically improved after immunosuppressive therapy, some of their ECG findings did not fully recover in remission phase. In conclusion, anti-MDA5 (+) DM appears to show cardiac involvement (electrical activity and function) during the active phase. Further studies are necessary to clarify the actual cardiac condition and mechanism of these findings in patients with anti-MDA5 (+) DM.

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Environmental triggers of dermatomyositis: a narrative review

Cited by 27 publications

References 120 publications

Ten genes are considered as potential biomarkers for the diagnosis of dermatomyositis

Ten genes are considered as potential biomarkers for the diagnosis of dermatomyositis

New-onset dermatomyositis following SARS-CoV-2 infection and vaccination: a case-based review

ECG Changes Through Immunosuppressive Therapy Indicate Cardiac Abnormality in Anti-MDA5 Antibody-Positive Clinically Amyopathic Dermatomyositis

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