Study Looks at Possible Link Between Skin Exposure to Silica and Autoimmune Disorders

Kathryn Creek once dismissed the hypothesis that skin exposure to beryllium can lead to chronic beryllium disease as the ravings of a "crazy scientist." But after learning more about the possible link between the two, she now believes the hypothesis "really made a lot of sense."

Inspired by the work of that scientist who she affectionately joked seemed crazy at the time Sally Tinkle, formerly of NIOSH Creek is now testing a similar hypothesis: that skin exposure to fine and ultrafine silica particulate can lead to autoimmune disorders such as systemic lupus erythemotosus (commonly known as lupus) and rheumatoid arthritis.

While the link between occupational exposure to silica and autoimmune disorders has been well-established, Creek explained, most studies have focused on inhalation exposure. (Silicosis, a chronic lung disease caused by inhalation exposure of silica dust, is not considered a disorder of the immune system.) But Creek, a project leader at the Los Alamos National Laboratory in Los Alamos, N.M., wonders if, in some cases, "we have not been looking at the right exposure pathway."

"Have we failed to recognize a route of entry by ultrafine particulate to the largest organ in the body, the skin?" Creek queries in the abstract to her presentation at the Second International Symposium on Nanotechnology and Occupational Health, which was held Oct. 3-6 in Minneapolis.

Creek's investigation of the possible link between skin exposure to silica and autoimmune disorders has been spurred by evidence of high rates of such disorders which typically are predominant among women in male-dominated occupations such as sand molding; foundry work; hard rock, slate, granite, uranium and coal mining; sandblasting; and masonry.

Considering her estimate that 85 percent of scleroderma and lupus patients in the general population are female, she concludes that the high rates of lupus in male-dominated trades such as hard rock mining are "remarkable."

Such questions, and Tinkle's research that points to the possibility that chronic beryllium disease may be initiated by ultrafine particulate skin exposure, have led to her hypothesis: That "skin exposure to fine and ultrafine silica probably crystalline silica can result in a susceptible or predisposed individual developing an autoimmune disorder such as SLE, rheumatoid arthritis or scleroderma."

For the hypothesis, she defines ultrafine particles as those having an aerodynamic or physical overall size of 100 nanometers or less, and fine particles as those having an aerodynamic or physical overall size between 1 microgram and 100 nanometers.

Skin is a 'Very Immunoligically Active Organ'

Autoimmune disorders which also include connective tissue disease and multiple sclerosis are immunological disorders or diseases that trigger the body to produce antibodies, which in turn attack the body's own cells and tissues, according to Creek.

Creek, who is working with Michael McCawley of the University of West Virginia in her study, explained that the skin is a "very immunologically active organ" and that is the largest organ of the body.

"It has more immune-type cells than the lung and, if foreign particles invade, Langerhans' cells grab the particles and move to the nearest lymph nodes, where the immune system can learn to recognize the invader," she said. "These immune cells then can travel through the body, telling other parts of the body what they have learned about the invaders."

Drawing a possible parallel to beryllium, Creek pointed to the research of Tinkle and others that suggests that beryllium particles can penetrate the skin to the dermis layer. (Tinkle's hypothesis is that skin exposure to beryllium works in conjunction with inhalation exposure to trigger beryllium sensitization.)

"We know that there are a large number of immune cells in the skin," Creek explained. "We know that skin exposure to beryllium [from inadvertent cutaneous injection] can result in the particulate traveling up to the lymph nodes. Therefore, this pathway seems more likely than the inhalation route."

Have a Program in Place to Prevent Skin Exposure

Could the skin likewise be a primary exposure route for silica particulate?

Creek noted that the study of the link between skin exposure to silica and autoimmune diseases is ongoing and that the two researchers have not come to any conclusions yet.

However, Creek offered these recommendations to employers and safety managers:

  • Keep particulate off the skin. "We don't know that skin is an impervious barrier to particulate," Creek said. "In fact, it may very well be that it isn't a barrier to fine and ultrafine particles, especially to un-intact skin." Have a program in place to monitor surface cleanliness, to prevent migration of particulate to non-work areas and to provide skin protection to employees that directly handle the materials or have a risk of skin exposure.
  • Plan for cuts and abrasions to the skin. Make sure wounds are cleaned well and monitor them.
  • Be cautious about using animal-testing and short human trials as an "end-all" to your understanding of the risks. Immune diseases of which autoimmune diseases are a subset are difficult to understand, often have a long latency period (as does chronic beryllium disease) and often have multiple, vague symptoms that make them difficult to diagnose. It is quite possible that the animals selected for testing do not have the genetic markers for the disease.
  • Review all literature, paying special attention to immune diseases associated with the chemicals being used.
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