A new population-based epidemiologic study, presented in The Journal of Rheumatology, reveals statistically significant associations of occupational mercury exposure, work in a dental laboratory or office, and agricultural work involving the mixing of pesticides with risks for developing systemic lupus erythematosus (SLE).1

Infectious agents and chemical or other compounds with immunomodulating potential have been suspected of stimulating the initiation and progression of SLE, but the role of these nongenetic stimuli has remained poorly understood. The new findings have important implications for an increased understanding of SLE.

While it is well known that genetic susceptibility plays an important role in the etiology of SLE, some previous research has suggested that additional factors may be involved.2,3 "The results of this trial point out that there is something in addition to genetics that results in SLE," lead investigator Glinda S. Cooper, PhD, tenure track investigator at the Epidemiology Branch of the National Institute of Environmental Health Sciences, told CIAOMed. "If we only focus on genetics, we won't understand the full story."

Animal studies have revealed mercury-induced autoimmunity,4-6 but no prior investigation has examined the association between mercury exposure in humans and SLE, nor have exposures to solvents and pesticides been examined extensively in occupational or population-based epidemiologic studies. The current study investigated the association between occupational exposures (ie, mercury, solvents, pesticides), specific jobs (ie, teaching, health care, cosmetology), and work schedules (ie, rotating shifts, night jobs) and the risk for developing SLE.

The associations were shown to be fairly strong, but prevalence of exposures was low with estimates based on a small number of cases and controls. "At this point, there is no immediate impact on clinical practice other than for those who have an interest in the etiology of lupus and possible occupational associations," Dr. Cooper emphasized. "These findings are way too premature."

The study sample (N = 265) was comprised of recently diagnosed SLE patients from the Carolina Lupus Study; all participants fulfilled the American College of Rheumatology classification criteria for SLE. The mean age at diagnosis was 39 years and median time from diagnosis to enrollment was 13 months. The study sample included 90% female and 60% African American participants. Population-based controls (N = 355) were frequency matched to the cases by age, sex, and state (North and South Carolina).

For data collection, the investigators used a 60-minute in-person interview based on a questionnaire. The potential occupational exposure to mercury was calculated with a dichotomous rating scheme (ie, yes, no). Solvent exposure was assessed via 5 rating categories: "likely-high," "possible-high," "possible-moderate," "indirect," and "none." Agricultural workers' pesticide exposure data was rated by exposure categories of "none," "applied but did not mix," and "mixed pesticides." For analysis of shift work, reports of night or rotating shifts that included night shifts, were considered positive. Analyses were limited to experiences occurring before age at diagnosis for SLE cases with a corresponding age used for controls. Logistic regression was implemented to examine associations between work history and risk for developing SLE. Results were adjusted for age, state, race, and education level.

No evidence was found of associations between occupational exposure to solvents, applying pesticides, or cosmetology work and heightened SLE risk. However, investigators observed statistically significant associations between agricultural work that involved mixing pesticides (OR 7.4, 95% CI 1.4, 40.0) and self-reported mercury exposure and SLE (OR 3.6, 95% CI 1.3, 10.0) (P <.05).

"These data need to be replicated," Dr. Cooper emphasized. "If I were to do another study, it would probably focus on exposures to the specific kinds of pesticides being used by farmers in rural areas. [Also], the animal literature on mercury is so strong, other sources of mercury should be investigated, possibly including diet."

Working in dental occupations (OR 7.1, 95% CI 2.2, 23.4) was shown to be associated with elevated SLE risk, as were health care jobs involving patient contact, with the strongest association occurring among those in health care occupations who had worked for 5 years or longer (OR 2.0, 95% CI 1.0, 4.0).

"The higher risk for health care workers raises questions," Dr. Cooper pointed out. For example: Is something else going on? Is this population more likely to seek medical care and thus be diagnosed?"

Shift work was marginally associated with SLE (OR 1.6, 95% CI 0.99, 2.7). Estimated effects of shift work differed slightly by race, with a stronger effect among African American patients (OR 2.3, 95% CI 1.0, 5.2), but no additional association with health care work. Among white participants, there was no association of shift work with higher SLE risk, however, health care work was associated with an elevated risk (OR 2.5, 95% CI 1.1, 5.6).

Negative findings of exposures previously suspected of an association with SLE were also notable in the present study. Although past research has indicated a higher-than- expected rate of autoimmune disease mortality among school teachers, no association between teaching or child care jobs and greater risk of SLE was found by the current investigators.

"The findings for teachers and child care workers may indicate that we don't need to go any further with SLE," Dr. Cooper noted. "The stronger associations at this point appear to be with multiple sclerosis."

Dr. Cooper and the study authors recommended that future research elicit greater detail pertaining to specific tasks and activities within the context of specific hypotheses (eg, health care workers' potential contact with blood-borne pathogens) or specific types of chemical exposures that may influence the risk of developing SLE, as well as potential mechanisms that may be relevant with respect to night shifts or shift rotations.

The investigation was supported by the Division of Intramural Research of the National Institute of Environmental Health Sciences and the National Center for Minority Health and Health Disparities of the National Institutes of Health.

References:

  1. Cooper GS, Parks CG, Treadwell EL, St. Clair EW, Gilkeson GS, Dooley MA. Occupational risk factors for the development of systemic lupus erythematosus. J Rheumatol. 2004;31:1928-1933.
  2. Jarvinen P, Kaprio J, Makitalo R, Koskenvuo M, Aho K. Systemic lupus erythematosus and related systemic diseases in a nationwide twin cohort: an increased prevalence of disease in MZ twins and concordance of disease features. J Intern Med. 1992;231:67-72.
  3. Deapen D, Escalante A, Weinrib L, et al. A revised estimate of twin concordance in systemic lupus erythematosus. Arthritis Rheum. 1992;35:311-318.
  4. Pollard KM, Pearson DL, Hultman P, Deane TN, Lindh U, Kono DH. Xenobiotic acceleration of idiopathic systemic autoimmunity in lupus-prone bxsb mice. Environ Health Perspect. 2001;109:27-33.
  5. Bagenstose LM, Salgame P, Monestier M.
    Murine mercury-induced autoimmunity: a model of chemically related autoimmunity in humans. Immunol Res. 1999;20:67-78.
  6. Via CS, Nguyen P, Niculescu F, Papadimitriou J, Hoover D, Silbergeld EK. Low-dose exposure to inorganic mercury accelerates disease and mortality in acquired murine lupus. Environ Health Perspect. 2003;111:1273-1277.