Australian Scleroderma Cohort Study reveals risk from silica exposure

Wednesday, 16 Sep 2020

A history of occupational exposure to respirable crystiline silica (RSC) in men is skewing the strong female predominance typically observed among patients with systemic sclerosis (SSc).

The first Australian study to investigate the association between RSC exposure and SSc has found a history of silica exposure in 33% of men in the Australian Scleroderma Cohort Study.

While only 13.8% of the entire cohort of 1,670 people were male, 57.9% of those who reported silica exposure were men. The overall frequency of silica exposure in the female-predominant cohort was 7.5%.

The study found people in the silica-exposed group were significantly more likely than the non-exposed group to have diffuse-SSc (40.5% v 24.7%), anti-Scl 70 antibody positivity (27.6% vs 14.0%), digital ulceration (58.4% vs 44.3%), tendon friction rubs (14.6% vs 8.1%), joint contractures (55.7% vs 37.4%), cardiac involvement (3.2% vs 0.3%), a higher peak modified Rodnan skin score [15.7 vs 10.9) and worse physical function (SSc HAQ scores 2.3 vs 1.9).

ILD was more common in the silica-exposed group but the difference did not reach statistical significance.

A sub-group analysis of male patients exposed to silica confirmed that anti-Scl 70 antibody positivity (37.5% vs 21.6%), joint contractures (70.4% vs 48.4%), cardiac involvement (5.5% vs 0.6%,) and a higher peak modified Rodnan skin score [19.4 vs 14.1) were significantly more common than in men who were not exposed.

“In multivariable regression analysis, silica exposure was associated with male sex [odds ratio (OR) 14.9, 95% CI: 14.9, 25.7, P < 0.001], joint contractures (OR 1.8, 95% CI: 1.0, 3.3, P ¼ 0.05) and worse sHAQ score (OR 1.4, 95% CI: 1.1, 1.7, P ¼ 0.01) and negatively associated with older age (years) at onset of SSc skin involvement (OR 0.98, 95% CI: 0.96, 1.0, P ¼ 0.02),” the study found.

“In the multivariable survival model, silica exposure does not have a significant impact on survival when covariants include disease subtype and PAH,” it said.

The authors, from the Australian Scleroderma Interest Group, said their findings “set the scene for informing occupational policies aimed at disease prevention in countries like Australia where SSc is not considered an occupational disease.”

“Despite the emerging epidemic in Australia of rapidly progressive silicosis, an incurable yet preventable lung disease secondary to the occupational exposure to crystalline silica generated during the cutting of ‘artificial stone’ benchtops, there is limited appreciation of the fact that silica exposure is associated with other health consequences such as connective tissue diseases, predominantly SSc.”

Forgotten association

Senior investigator Associate Professor Mandana Nikpou, from the University of Melbourne told the limbic the association between silica exposure and systemic sclerosis had been largely forgotten.

“The first reports go quite a long way back and we have been treating the disease for decades since that time and seldom have we sought a detailed occupational history from our patients and seldom have we ever really thought that there might be an occupational element to this autoimmune disease.”

She said rheumatologists often get asked by patients why they have developed conditions such as RA, lupus or scleroderma.

“And the standard response is that we don’t really know. We suspect it is a multi-factorial process in genetically susceptible individuals who then come across other factors such as environmental exposures.”

She said the study suggested there was certainly an occupational element to SSc.

“Based on those self-reported exposures, a whopping third of our male patients with SSc were reporting occupational exposure to silica mostly in manufacturing and building industries.”

She said she now suspected the figure was probably an underestimate.

“It is conceivable that if a significant proportion of the cases can be attributable to silica then maybe there are other environmental toxins that people are coming across in the course of their occupation that could also account for a substantial percentage of cases of SSc.”

She said the data collected in the initial questionnaires didn’t really drill down deeply enough into the duration and types of occupational exposures so further research was required.

“We don’t really understand the mechanisms behind the development of autoimmune disease like SSc as a result of silica exposure. It is possible that this autoimmunity comes about from inhaling the dust but the other possibility is that maybe the exposure is through other interfaces. It may not all be inhalation, it may be cutaneous exposure as well.”

“This has major implications for public health policy and in terms of occupational health and safety because if a significant proportion of cases of SSc that we see is occupational, then that is something that could potentially be prevented.”

She said patients with known occupational exposure to silica required close follow-up to check for any issues with their lungs or the early features of autoimmune disease e.g. with blood tests for autoantibodies.

“Once SSc has developed, it really is about treating the disease on its merits, as you would any other case of SSc.”

She said it was conjecture but possible that there was also an occupational component to SSc in women through exposure to other as yet unknown chemicals and materials.

“I would say that until now we have underestimated how much SSc has an occupational element and maybe there is still a lot more about potential occupational exposures that put people at risk that we still need to identify.”

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