Trigger and Risk Factors
Risk Factors
Several known risk factors of Dermatomyositis (DM) include female sex, genetics, ultraviolet radiation, prior respiratory disease, viral and bacterial infections, medications, and pollutants and other geographic environmental factors.
Triggers of DM may lead to disease flare and immune dysregulation (Table1-1).
Genetic Contributions
Genetic contributions are supported by observed associations with major histocompatibility complex (MHC) polymorphisms and human leukocyte antigen alleles. In genetically susceptible individuals, viral, bacterial, and parasitic infections can induce autoimmunity and exacerbate existing autoimmune conditions.
Patients with some human leukocyte antigen (HLA) haplotypes have a higher risk of developing DM, including HLA-A*68 in North American Whites and HLA-DRB1*0301 in African Americans, HLA-DQA1*0104 and HLA-DRB1*07 in Han Chinese, DQA1*05 and DQB1*02 in people from the UK. Patients with DM and the DRB1*03-DQA1*05-DQB1*02 haplotype have a…
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Risk Factors
Several known risk factors of Dermatomyositis (DM) include female sex, genetics, ultraviolet radiation, prior respiratory disease, viral and bacterial infections, medications, and pollutants and other geographic environmental factors.
Triggers of DM may lead to disease flare and immune dysregulation (Table1-1).
Genetic Contributions
Genetic contributions are supported by observed associations with major histocompatibility complex (MHC) polymorphisms and human leukocyte antigen alleles. In genetically susceptible individuals, viral, bacterial, and parasitic infections can induce autoimmunity and exacerbate existing autoimmune conditions.
Patients with some human leukocyte antigen (HLA) haplotypes have a higher risk of developing DM, including HLA-A*68 in North American Whites and HLA-DRB1*0301 in African Americans, HLA-DQA1*0104 and HLA-DRB1*07 in Han Chinese, DQA1*05 and DQB1*02 in people from the UK. Patients with DM and the DRB1*03-DQA1*05-DQB1*02 haplotype have a higher likelihood of developing interstitial lung disease.
Herbal Supplements
Herbal supplements stimulate the immune system, and their use has been associated with autoimmune skin disease exacerbations and even disease onset in patients with DM.
Cutaneous features of DM including persistent erythema, increased prevalence in sun-exposed areas, and photoaggravation, which implicate UV radiation as a trigger in disease pathogenesis. UV radiation intensity is a strong predictor of DM, and is a prevalent environmental trigger of disease.
Viruses
Viruses such as Coxsackie B virus, enterovirus, and parvovirus can be triggers of DM. Possible mechanisms of virus-induced autoimmunity may include alteration of cellular proteins, breakdown of self-tolerance, unmasking of hidden epitopes, autoantibody induced B cell activation, and molecular mimicry.
Drugs That May Trigger DM
The most commonly reported drugs that trigger DM (in order of frequency) include hydroxyurea, immune checkpoint inhibitors, penicillamine, and tumor necrosis factor inhibitors. Immune checkpoint inhibitors could be a trigger of DM due to the enhanced activation of anti-tumor T cells and non-specific blockage of self-tolerance. In a subset of patients with DM who are positive for anti-SAE, hydroxychloroquine may increase risk of flares.
Pregnancy
Pregnancy can affect DM symptoms, possibly due to exposure to fetal antigens, changes in maternal hormonal status, and the reactivation of certain viruses. DM can occur during pregnancy or develop during the postpartum period.
References
- Aggarwal, R., Schessl, J., Charles-Schoeman, C. et al. Safety and tolerability of intravenous immunoglobulin in patients with active dermatomyositis: results from the randomised, placebo-controlled ProDERM study. Arthritis Res Ther 26, 27 (2024).
- ArgenX Press Release. Argenx Advances Clinical Development of Efgartigimod SC in Idiopathic Inflammatory Myopathies. November 20, 2024. https://argenx.com/content/dam/argenx-corp/newsroom/press-release-pdfs/PressRelease_argenx_ALKIVIA_Ph2_20241120.pdf.coredownload.inline.pdf
