ABSTRACT: Occupational exposure to various chemicals, minerals, and toxins may increase the risk of rheumatoid arthritis (RA). Relationships between silica exposure and lung, renal, and autoimmune disease have been observed. Although a relationship between silica exposure and RA has been identified, it is not well defined. The evidence indicating that cigarette smoking is an independent risk factor for RA is conclusive. Agents that may be capable of inducing experimental arthritis in animals include adjuvants from bacteria, yeast, viruses, and mineral oils. In a Swedish study, exposure to any mineral oil was associated with a 30% increased relative risk of RA. (J Musculoskel Med. 2008;25:130-136)
Autoimmunity, defined as the development of an immune system response in the form of autoantibodies and T-cell responses to self-structures, has been researched widely over the years because it is prevalent in men and women from childhood throughout their adult years. Patterns of disease occurrence in families and in animal models strongly suggest a role for genetic factors. The genes most frequently associated with autoimmunity are those that regulate immune responses and cytokine production.
Environmental factors also have been hypothesized to play a role in the development of autoimmune diseases. Studies have provided strong support for the concept that these diseases result from interactions of both genetic and environmental factors.
A growing amount of the medical literature now claims that the development of rheumatoid arthritis (RA) may be influenced by occupational exposure to various chemicals, minerals, and toxins (Table). Studies that examined the role of silica and mineral oil exposure in RA have found significant associations and increased risk. In this article,we review the existing epidemiological and experimental literature on occupational exposures and their correlation to the development of RA.
METHODS AND RESULTS
Cross-referencing the terms "occupational exposure" and "environmental exposure" with the term "rheumatoid arthritis," we searched MEDLINE (1966 - 2006) and PubMed (1966 - 2006) for articles in English that were human studies. Retrieved articles were selected based on their clinical relevance and applicability.
Silica exposure and increased health risk
Epidemiological evidence has stimulated investigation into occupational exposure to suspected pathogens and carcinogens and any resultant increased health risk.The relationship between occupational silica exposure and lung disease, primarily in occupations associated with mining, has a well-documented history; accounts of occupational exposure have accumulated much evidence indicating a direct increased health risk, specifically for lung pathology.1-3 More in-depth studies are related to exposure limits, occupations with increased risk, and additional health risks related to silica exposure.4-6
Relationships between silica exposure and renal disease and autoimmune disease also have been observed.2,7-11 A relationship between silica exposure and RA has been identified, although the relationship currently is not well defined.12
Coexisting pulmonary and rheumatologic findings
In the early 1950s, Caplan13 was one of the first to document the coexistence of pulmonary and rheumatologic findings, showing chest radiograph opacities in coal miners with known RA. Further studies investigated and confirmed the positive correlation between RA and silicosis and noted that lung fibrosis is more likely to develop in workers exposed to silica who have RA than others who have similar exposure.14
- 1. Hnizdo E, Sluis-Cremer GK, Abramowitz JA. Emphysema type in relation to silica dust exposure in South African gold miners [published correction appears in Am Rev Respir Dis. 1991;144:1223]. Am Rev Respir Dis. 1991;143:1241-1247.
- 2. Berry G, Rogers A, Yeung P. Silicosis and lung cancer: a mortality study of compensated men with silicosis in New South Wales, Australia. Occup Med (Lond). 2004;54:387-394.
- 3. Pelucchi C, Pira E, Piolatto G, et al. Occupational silica exposure and lung cancer risk: a review of epidemiological studies 1996-2005. Ann Oncol. 2006;17:1039-1050.
- 4. Stacey P. Measurements of silica in air: reliability at new and proposed occupational exposure limits. J Occup Environ Hyg. 2007;4:D1-D4.
- 5. Flynn MR, Susi P. Engineering controls for selected silica and dust exposures in the construction industry—a review. Appl Occup Environ Hyg. 2003;18:268-277.
- 6. Verma DK, Purdham JT, Roels HA. Translating evidence about occupational conditions into strategies for prevention. Occup Environ Med. 2002;59:205-213; quiz 214.
- 7. Steenland K. One agent, many diseases: exposure-response data and comparative risks of different outcomes following silica exposure. Am J Ind Med. 2005;48:16-23.
- 8. McDonald JC, McDonald AD, Hughes JM, et al. Mortality from lung and kidney disease in a cohort of North American industrial sand workers: an update. Ann Occup Hyg. 2005;49:367-373.
- 9. Mulloy KB. Silica exposure and systemic vasculitis. Environ Health Perspect. 2003;111:1933-1938.
- 10. Steenland K, Sanderson W, Calvert GM. Kidney disease and arthritis in a cohort study of workers exposed to silica. Epidemiology. 2001;12:405-412.
- 11. Parks CG, Conrad K, Cooper GS. Occupational exposure to crystalline silica and autoimmune disease. Environ Health Perspect. 1999;(107 suppl 5):793-802.
- 12. Oliver JE, Silman AJ. Risk factors for the development of rheumatoid arthritis. Scand J Rheumatol. 2006;35:169-174.
- 13. Caplan A. Certain unusual radiological appearances in the chest of coal-miners suffering from rheumatoid arthritis. Thorax. 1953;8:29-37.
- 14. Miall WE. Rheumatoid arthritis in males; an epidemiological study of a Welsh mining community. Ann Rheum Dis. 1955;14:150-158.
- 15. Sluis-Cremer GK, Hessel PA, Hnizdo E, Churchill AR. Relationship between silicosis and rheumatoid arthritis. Thorax. 1986;41:596-601.
- 16. Schroeder W, Franklin EC, McEwen C. Rheumatoid factors in patients with silicosis with round nodular fibrosis of the lung in the absence of rheumatoid arthritis with a note on the failure to induce such factors in animals. Arthritis Rheum. 1962;5:10-18.
- 17. Jones RN, Turner-Warwick M, Ziskind M, Weill H. High prevalence of antinuclear antibodies in sandblasters’ silicosis. Am Rev Respir Dis. 1976;113:393-395.
- 18. Turner S, Cherry N. Rheumatoid arthritis in workers exposed to silica in the pottery industry. Occup Environ Med. 2000;57:443-447.
- 19. Calvert GM, Rice FL, Boiano JM, et al. Occupational silica exposure and risk of various diseases: an analysis using death certificates from 27 states of the United States. Occup Environ Med. 2003;60:122-129.
- 20. Stolt P, Kuällberg H, Lundberg I, et al. Silica exposure is associated with increased risk of developing rheumatoid arthritis: results from the Swedish EIRA study. Ann Rheum Dis. 2005;64:582-586.
- 21. Klockars M, Koskela RS, Jaärvinen E, et al. Silica exposure and rheumatoid arthritis: a follow up study of granite workers 1940-81. Br Med J (Clin Res Ed). 1987;294:997-1000.
- 22. Karlson EW, Lee IM, Cook NR, et al. A retrospective cohort study of cigarette smoking and risk of rheumatoid arthritis in female health professionals. Arthritis Rheum. 1999;42:910-917.
- 23. Costenbader KH, Feskanich D, Mandl LA, Karlson EW. Smoking intensity, duration, and cessation, and the risk of rheumatoid arthritis in women. Am J Med. 2006;119:503.e1-9.
- 24. Klareskog L, Padyukov L, Lorentzen J, Alfredsson L. Mechanisms of disease: genetic susceptibility and environmental triggers in the development of rheumatoid arthritis. Nat Clin Pract Rheumatol. 2006;2:425-433.
- 25. Klareskog L, Stolt P, Lundberg K, et al. A new model for an etiology of rheumatoid arthritis: smoking may trigger HLA-DR (shared epitope)-restricted immune reactions to autoantigens modified by citrullination. Arthritis Rheum. 2006;54:38-46.
- 26. Ding M, Chen F, Shi X, et al. Diseases caused by silica: mechanisms of injury and disease development. Int Immunopharmacol. 2002;2:173-182.
- 27. Vanheé D, Gosset P, Boitelle A, et al. Cytokines and cytokine network in silicosis and coal workers’ pneumoconiosis. Eur Respir J. 1995;8:834-842.
- 28. Castranova V. Signaling pathways controlling the production of inflammatory mediators in response to crystalline silica exposure: role of reactive oxygen/nitrogen species. Free Radic Biol Med. 2004;37:916-925.
- 29. Zeidler PC, Castranova V. Role of nitric oxide in pathological responses of the lung to exposure to environmental/occupational agents. Redox Rep. 2004;9:7-18.
- 30. Vallyathan V, Shi X. The role of oxygen free radicals in occupational and environmental lung diseases. Environ Health Perspect. 1997;105(suppl 1):165-177.
- 31. Green MJ, Gough AK, Devlin J, et al. Serum MMP-3 and MMP-1 and progression of joint damage in early rheumatoid arthritis. Rheumatology (Oxford). 2003;42:83-88.
- 32. Audibert F, Chedid L. Adjuvant disease induced by mycobacteria, determinants of arthritogenicity. Agents Actions. 1976;6:75-85.
- 33. Chang YH, Pearson CM, Abe C. Adjuvant polyarthritis, IV: induction by a synthetic adjuvant: immunologic, histopathologic, and other studies. Arthritis Rheum. 1980;23:62-71.
- 34. Kohashi O, Tanaka A, Kotani S, et al. Arthritis-inducing ability of a synthetic adjuvant, N-acetylmuramyl peptides, and bacterial disaccharide peptides related to different oil vehicles and their composition. Infect Immun. 1980;29:70-75.
- 35. Kleinau S, Erlandsson H, Holmdahl R, Klareskog L. Adjuvant oils induce arthritis in the DA rat, I: characterization of the disease and evidence for an immunological involvement. J Autoimmun. 1991;4:871-880.
- 36. Holmdahl R, Lorentzen JC, Lu S, et al. Arthritis induced in rats with nonimmunogenic adjuvants as models for rheumatoid arthritis. Immunol Rev. 2001;184:184-202.
- 37. Ianaro A, Cicala C, Calignano A, et al. Antivery late antigen-1 monoclonal antibody modulates the development of secondary lesion and T-cell response in experimental arthritis. Lab Invest. 2000;80:73-80.
- 38. Jacobson PB, Morgan SJ, Wilcox DM, et al. A new spin on an old model: in vivo evaluation of disease progression by magnetic resonance imaging with respect to standard inflammatory parameters and histopathology in the adjuvant arthritic rat. Arthritis Rheum. 1999;42:2060- 2073.
- 39. Halloran MM, Szekanecz Z, Barquin N, et al. Cellular adhesion molecules in rat adjuvant arthritis. Arthritis Rheum. 1996;39:810-819.
- 40. Tak PP, Gerlag DM, Aupperle KR, et al. Inhibitor of nuclear factor kappaB kinase beta is a key regulator of synovial inflammation. Arthritis Rheum. 2001;44:1897-1907.
- 41. Kuroda Y, Akaogi J, Nacionales DC, et al. Distinctive patterns of autoimmune response induced by different types of mineral oil. Toxicol Sci. 2004;78:222-228.
- 42. Lundberg I, Alfredsson L, Plato N, et al. Occupation, occupational exposure to chemicals and rheumatological disease: a register based cohort study. Scand J Rheumatol. 1994;23:305-310.
- 43. Olsson AR, Skogh T, Wingren G. Occupational determinants for rheumatoid arthritis. Scand J Work Environ Health. 2000;26:243-249.