Silica dust, heavy metal, solvents may contribute to myositis with lung involvement
Key takeaways:
- Silica exposure was linked to overlap myositis and myositis with lung disease symptoms, while smoking further increased risk.
- Myositis with lung disease symptoms was also associated with moderate-to-high heavy metals, solvents exposure.
Exposures to silica dust, solvents or heavy metals increase the likelihood of developing various forms of myositis, especially more severe forms involving the lungs, according to data published in Arthritis Care & Research.
The study originated with a questionnaire from the myositis registry MYOVISION, which asked about potential environmental risk factors in addition to other clinical characteristics, Lisa G. Rider, MD, head of the Environmental Autoimmunity Group at the National Institute of Environmental Health Sciences (NIEHS), told Healio.
“We worked with Christine Parks, PhD, MSPH, epidemiologist in the Chronic Disease Epidemiology Group of the NIEHS epidemiology branch, to collect and perform a systematic review and analysis of occupational and hobby exposure data,” Rider said. “We examined whether they were contributing to myositis phenotypes, or subgroups of myositis, as very few prior studies have addressed these exposures in patients with myositis.
“An earlier MYOVISION study showed exposure to UV radiation and sun from jobs and hobbies were associated with the dermatomyositis phenotype, and in the current study we evaluated myositis phenotypes and respiratory exposures to dust or fumes,” she added.
The questionnaires were completed mostly by mail, with patients reporting specific jobs and hobbies prior to receiving a diagnosis of idiopathic inflammatory myositis (IIM). Based on their responses, three expert reviewers ranked the potential intensity of patients’ exposure to silica dust, heavy metals or solvents, as well as the certainty of their assessment. The researchers used logistic regression models to calculate the odds of exposures associated with various IIM phenotypes.
The phenotypes under analysis included three “classic” IIM subgroups — defined as dermatomyositis, polymyositis and inclusion body myositis — as well as overlap myositis, in which there is also a second autoimmune diagnosis, such as scleroderma. A severe phenotype, antisynthetase syndrome, was analyzed by proxy and defined as IIM-associated lung disease symptoms plus fever and/or arthritis, or LD+ for short.
According to the researchers, high exposure to silica — defined as dust from sand, rock, clay tile or brick — more than doubled the odds of developing dermatomyositis (OR = 2.02; 95% CI, 1.18-3.46) vs. inclusion body myositis. Silica exposure was also linked to increased odds of developing overlap myositis (OR = 2.07; 95% CI, 1.19-3.61) and LD+, the proxy for antisynthetase syndrome (OR = 1.75; 95% CI, 1.1-2.78).
This association for LD+ was mostly seen among smokers. Compared with non-smokers with no or low silica exposure, patients who reported smoking with high or moderate levels of silica exposure were at greater risk for LD+ (OR = 2.53; 95% CI, 1.31-4.9).
As for heavy metals, moderate to high exposure carried increased odds of antisynthetase syndrome (OR = 1.49; 95% CI, 1-2.14) and overlap myositis (OR = 1.59; 95% CI, 0.99-2.55), compared with no exposure. Among patients with dermatomyositis or polymyositis, high-intensity solvent exposure was associated with LD+ (OR = 1.61; 95% CI, 1.01-2.57).
“The findings of this study suggest that exposure to certain chemicals through occupation or hobbies — shown to be a risk factor for systemic, autoimmune rheumatic diseases — may also be associated with specific clinical subgroups of disease, particularly those associated with lung disease,” Rider said. “In addition to the interaction with smoking, we saw some evidence that risk may increase as one is exposed to more of these factors.”
According to Parks, future avenues for research include comparing cases with population controls to learn about the risk for developing myositis associated with these exposures. In addition, more studies with rigorous exposure assessment in clinically well-defined myositis populations are needed, she said.
“Ideally, studies could also include biomarkers of some exposures, such as metals, known to accumulate in the body,” Parks told Healio. “But retrospective assessment of biomarkers in cases after diagnosis may be influenced by having the disease, and many exposures lack biomarkers for past exposures and so require questionnaires, especially to identify exposures that may contribute to disease susceptibility rather than acting to trigger symptom onset.
“Studying whether these exposures also contribute to clinical phenotypes, such as lung disease or multiple autoimmune diagnoses, in other systemic autoimmune diseases may help identify patients at risk for more severe outcomes,” Parks added.
For more information:
Lisa G. Rider, MD, can be reached at riderl@mail.nih.gov.
Christine Parks, PhD, MSPH, can be reached at parks1@niehs.nih.gov.
Perspective
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Occupational exposure to silica dust significantly increases the risk for systemic sclerosis and has been linked to other connective tissue diseases, including rheumatoid arthritis, systemic lupus erythematosus, small-vessel vasculitis, sarcoidosis and, in this article, idiopathic inflammatory myositis.
Research, including a nationwide study from Denmark, confirms an increased risk for SSc, RA, SLE and vasculitis, particularly in men. Although the relative risk is lower for SLE and vasculitis compared with SSc and RA, evidence suggests a causative link.
Case-control studies from the Americas and Europe further support the connection between silica exposure and SLE, though not all studies confirm an increased risk for biopsy-confirmed lupus nephritis. Crystalline silica exposure is also associated with anti-neutrophil cytoplasmic antibody-related diseases, with most studies reporting a relative risk greater than 2.
Historical research has long recognized this association of silica and scleroderma, dating back more than a century to Scottish physician Byrom Bramwell, MD, FRCP, FRSE. In the 1960s, rheumatologist Gerald Rodnan, MD, further confirmed silica exposure as a key factor in SSc, particularly among coal miners and foundry workers. Raynaud’s phenomenon was frequently observed in these cases.
In cases of silica-associated systemic sclerosis (Si-SSc), diffuse SSc is more common, with high prevalence of interstitial lung disease (81%) and poorer overall survival. Si-SSc is also linked to digital ulcers, myocardial dysfunction and anti-Scl-70 positivity, all indicating a worse prognosis.
Silica particles are believed to trigger immune responses by activating alveolar macrophages, leading to inflammation, cytokine production and autoimmunity. This process stimulates fibroblasts to produce excess collagen, resulting in fibrosis and silicotic nodules.
Heavy metals have been implicated in autoimmune diseases such as SLE, RA and multiple sclerosis. At high doses, heavy metals can induce epigenetic changes, oxidative stress and a proinflammatory immune response, potentially exacerbating autoimmune conditions including idiopathic inflammatory myositis.
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