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Ann Rheum Dis. 2001 Oct; 60(10): 934–939.
PMCID: PMC1753392

Comorbidity and lifestyle, reproductive factors, and environmental exposures associated with rheumatoid arthritis


OBJECTIVE—To evaluate the influence of lifestyle, reproduction, and some external factors on the development of rheumatoid arthritis (RA) and to describe its comorbidity.
METHODS—Cases were identified retrospectively from 1980 to 1995 at the University Hospital in Linköping, Sweden. The study comprised 422 cases and 859 randomly selected population referents. Data on possible aetiological factors and comorbidity were collected by postal questionnaire.
RESULTS—The response rates were 67% among cases and 59% among referents. A decrease in the occurrence of atopic allergy was seen in the cases (odds ratio (OR) 0.6, 95% confidence interval (CI) 0.4 to 1.0). There was a positive association between RA and insulin treatment (OR 10.2, 95% CI 1.7 to 60.8) in women, and women with a short fertile period had an increased risk of RA (OR 2.5, 95% CI 1.1 to 5.4). Current and previous smoking were associated with increased risks for RA in both sexes, and in men a dose-response relationship was found with number of tobacco pack years (p for trend <0.005). The risk for RA decreased with increasing level of education in both men and women. Increased risks were seen in men born into households with private wells (OR 2.8, 95% CI 1.5 to 5.2), residentially exposed to mould (OR 4.6, 95% CI 1.1 to 20.2), or exposed to farm animals (OR 3.3, 95% CI 0.7 to 16.6). In women there were positive associations between RA and reporting a previous joint injury (OR 2.5, 95% CI 1.0 to 6.6) and prolonged exposure to hair dyes (OR 1.9, 95% CI 0.8 to 4.5).
CONCLUSIONS—RA, a disease with features of T helper 1 (Th1) dominated immune response, was inversely associated with atopic allergy, a Th2 dominated condition, while there were indications of a strong positive association with Th1 related diabetes mellitus. The results support a causal relationship between smoking and RA. The level of education was inversely associated with RA, while there was a positive association between RA and certain residential factors in men and a short fertile period in women.

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Selected References

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  • Weyand CM, Goronzy JJ. The molecular basis of rheumatoid arthritis. J Mol Med (Berl) 1997 Nov-Dec;75(11-12):772–785. [PubMed]
  • Wilder RL. Adrenal and gonadal steroid hormone deficiency in the pathogenesis of rheumatoid arthritis. J Rheumatol Suppl. 1996 Mar;44:10–12. [PubMed]
  • Miossec P, van den Berg W. Th1/Th2 cytokine balance in arthritis. Arthritis Rheum. 1997 Dec;40(12):2105–2115. [PubMed]
  • Muraille E, Leo O. Revisiting the Th1/Th2 paradigm. Scand J Immunol. 1998 Jan;47(1):1–9. [PubMed]
  • Silman AJ, Ollier WE, Bubel MA. Autoimmune thyroid disease and thyroid autoantibodies in rheumatoid arthritis patients and their families. Br J Rheumatol. 1989 Feb;28(1):18–21. [PubMed]
  • Verhoef CM, van Roon JA, Vianen ME, Bruijnzeel-Koomen CA, Lafeber FP, Bijlsma JW. Mutual antagonism of rheumatoid arthritis and hay fever; a role for type 1/type 2 T cell balance. Ann Rheum Dis. 1998 May;57(5):275–280. [PMC free article] [PubMed]
  • Allanore Y, Hilliquin P, Coste J, Renoux M, Menkès CJ. Decreased prevalence of atopy in rheumatoid arthritis. Lancet. 1998 Feb 14;351(9101):497–497. [PubMed]
  • O'Driscoll BR, Milburn HJ, Kemeny DM, Cochrane GM, Panayi GS. Atopy and rheumatoid arthritis. Clin Allergy. 1985 Nov;15(6):547–553. [PubMed]
  • Hochberg MC. Changes in the incidence and prevalence of rheumatoid arthritis in England and Wales, 1970-1982. Semin Arthritis Rheum. 1990 Apr;19(5):294–302. [PubMed]
  • Brennan P, Ollier B, Worthington J, Hajeer A, Silman A. Are both genetic and reproductive associations with rheumatoid arthritis linked to prolactin? Lancet. 1996 Jul 13;348(9020):106–109. [PubMed]
  • Holmdahl R. Female preponderance for development of arthritis in rats is influenced by both sex chromosomes and sex steroids. Scand J Immunol. 1995 Jul;42(1):104–109. [PubMed]
  • Symmons DP, Bankhead CR, Harrison BJ, Brennan P, Barrett EM, Scott DG, Silman AJ. Blood transfusion, smoking, and obesity as risk factors for the development of rheumatoid arthritis: results from a primary care-based incident case-control study in Norfolk, England. Arthritis Rheum. 1997 Nov;40(11):1955–1961. [PubMed]
  • Uhlig T, Hagen KB, Kvien TK. Current tobacco smoking, formal education, and the risk of rheumatoid arthritis. J Rheumatol. 1999 Jan;26(1):47–54. [PubMed]
  • Karlson EW, Lee IM, Cook NR, Manson JE, Buring JE, Hennekens CH. A retrospective cohort study of cigarette smoking and risk of rheumatoid arthritis in female health professionals. Arthritis Rheum. 1999 May;42(5):910–917. [PubMed]
  • Voigt LF, Koepsell TD, Nelson JL, Dugowson CE, Daling JR. Smoking, obesity, alcohol consumption, and the risk of rheumatoid arthritis. Epidemiology. 1994 Sep;5(5):525–532. [PubMed]
  • Krause A, Kamradt T, Burmester GR. Potential infectious agents in the induction of arthritides. Curr Opin Rheumatol. 1996 May;8(3):203–209. [PubMed]
  • Lundberg I, Alfredsson L, Plato N, Sverdrup B, Klareskog L, Kleinau S. Occupation, occupational exposure to chemicals and rheumatological disease. A register based cohort study. Scand J Rheumatol. 1994;23(6):305–310. [PubMed]
  • Moens HB, Corstjens A, Boon C. Rheumatoid arthritis is not associated with prior tonsillectomy or appendectomy. Clin Rheumatol. 1994 Sep;13(3):483–486. [PubMed]
  • Darwish MJ, Armenian HK. A case-control study of rheumatoid arthritis in Lebanon. Int J Epidemiol. 1987 Sep;16(3):420–424. [PubMed]
  • Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS, Healey LA, Kaplan SR, Liang MH, Luthra HS, et al. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum. 1988 Mar;31(3):315–324. [PubMed]
  • Olsson AR, Skogh T, Wingren G. Occupational determinants for rheumatoid arthritis. Scand J Work Environ Health. 2000 Jun;26(3):243–249. [PubMed]
  • Wolfe F. The effect of smoking on clinical, laboratory, and radiographic status in rheumatoid arthritis. J Rheumatol. 2000 Mar;27(3):630–637. [PubMed]
  • Saag KG, Cerhan JR, Kolluri S, Ohashi K, Hunninghake GW, Schwartz DA. Cigarette smoking and rheumatoid arthritis severity. Ann Rheum Dis. 1997 Aug;56(8):463–469. [PMC free article] [PubMed]
  • Jónsson T, Thorsteinsson J, Valdimarsson H. Does smoking stimulate rheumatoid factor production in non-rheumatic individuals? APMIS. 1998 Oct;106(10):970–974. [PubMed]
  • Vliet Vlieland TP, Buitenhuis NA, van Zeben D, Vandenbroucke JP, Breedveld FC, Hazes JM. Sociodemographic factors and the outcome of rheumatoid arthritis in young women. Ann Rheum Dis. 1994 Dec;53(12):803–806. [PMC free article] [PubMed]
  • Heliövaara M, Aho K, Knekt P, Impivaara O, Reunanen A, Aromaa A. Coffee consumption, rheumatoid factor, and the risk of rheumatoid arthritis. Ann Rheum Dis. 2000 Aug;59(8):631–635. [PMC free article] [PubMed]
  • Lafaille JJ. The role of helper T cell subsets in autoimmune diseases. Cytokine Growth Factor Rev. 1998 Jun;9(2):139–151. [PubMed]
  • De Carli M, D'Elios MM, Zancuoghi G, Romagnani S, Del Prete G. Human Th1 and Th2 cells: functional properties, regulation of development and role in autoimmunity. Autoimmunity. 1994;18(4):301–308. [PubMed]
  • Zhang D, Nikkari S, Vainionpä R, Luukkainen R, Yli-Kerttula U, Toivanen P. Detection of rubella, mumps, and measles virus genomic RNA in cells from synovial fluid and peripheral blood in early rheumatoid arthritis. J Rheumatol. 1997 Jul;24(7):1260–1265. [PubMed]
  • Miligi L, Seniori Costantini A, Crosignani P, Fontana A, Masala G, Nanni O, Ramazzotti V, Rodella S, Stagnaro E, Tumino R, et al. Occupational, environmental, and life-style factors associated with the risk of hematolymphopoietic malignancies in women. Am J Ind Med. 1999 Jul;36(1):60–69. [PubMed]
  • Georgescu L, Paget SA. Lymphoma in patients with rheumatoid arthritis: what is the evidence of a link with methotrexate? Drug Saf. 1999 Jun;20(6):475–487. [PubMed]
  • Correa A, Jackson L, Mohan A, Perry H, Helzlsouer K. Use of hair dyes, hematopoietic neoplasms, and lymphomas: a literature review. II. Lymphomas and multiple myeloma. Cancer Invest. 2000;18(5):467–479. [PubMed]
  • Brun JG, Nilssen S, Kvåle G. Breast feeding, other reproductive factors and rheumatoid arthritis. A prospective study. Br J Rheumatol. 1995 Jun;34(6):542–546. [PubMed]
  • Koepsell TD, Dugowson CE, Nelson JL, Voigt LF, Daling JR. Non-contraceptive hormones and the risk of rheumatoid arthritis in menopausal women. Int J Epidemiol. 1994 Dec;23(6):1248–1255. [PubMed]
  • Robins J, Greenland S, Breslow NE. A general estimator for the variance of the Mantel-Haenszel odds ratio. Am J Epidemiol. 1986 Nov;124(5):719–723. [PubMed]

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