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Silica exposure among male current smokers is associated with a high risk of developing ACPA-positive rheumatoid arthritis
  1. Patrik Stolt1,
  2. Abqariyah Yahya1,2,
  3. Camilla Bengtsson1,
  4. Henrik Källberg1,
  5. Johan Rönnelid3,4,
  6. Ingvar Lundberg5,
  7. Lars Klareskog4,
  8. Lars Alfredsson1,
  9. the EIRA Study Group
  1. 1Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
  2. 2Institute for Medical Research, Jalan Pahang, Kuala Lumpur, Malaysia
  3. 3Unit of Clinical Immunology, Uppsala University, Uppsala, Sweden
  4. 4Rheumatology Unit, Department of Medicine, Karolinska Institutet at Karolinska Hospital, Solna, Stockholm, Sweden
  5. 5Department of Occupational and Environmental Medicine, Uppsala University Hospital, Uppsala, Sweden
  1. Correspondence to Dr Patrik Stolt, Institute of Environmental Medicine, Karolinska Institutet, Box 210, S-171 77 Stockholm, Sweden; patrikstolt{at}


Objective To study the association between silica exposure, separately as well as combined with smoking, and the risk of developing rheumatoid arthritis (RA) with or without the presence of antibodies against citrullinated peptide antigens (ACPA).

Methods This Swedish population based case–control study analysed 577 incident RA cases and 659 randomly selected controls, all men aged 18–70 years, included during May 1996 to May 2006. Self-reported silica exposure, defined as exposure to stone dust, rock drilling or stone crushing and cigarette smoking was registered. ACPA status among cases was analysed.

Results Silica-exposed subjects were found to have a moderately increased risk of ACPA-positive RA (odds ratio (OR) adjusted for age and residency=1.67 (95% CI 1.13 to 2.48), but not of ACPA-negative RA (OR=0.98 (95% CI 0.57 to 1.66)), compared with subjects unexposed to silica. Subjects exposed to rock drilling were found to have a somewhat more markedly increased risk of ACPA-positive RA (OR=2.34 (95% CI 1.17 to 4.68)). A high risk of developing ACPA-positive RA was observed among silica-exposed current smokers (OR=7.36 (95% CI 3.31 to 16.38)), exceeding the risk expected from the separate effects of silica exposure and current smoking, indicating an interaction between these exposures (attributable proportion due to interaction=0.60 (95% CI 0.26 to 0.95)).

Conclusion Silica exposure combined with smoking among men is associated with an increased risk of developing ACPA-positive RA. These results suggest that different inhalation exposures may interact in the aetiology of ACPA-positive RA.

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  • EIRA Study Group Göran Lindahl, Danderyd Hospital; Berit Sverdrup, Eskilstuna Hospital; Helena Hellström, Falu lasarett; Tomas Weitoft, Gävle Hospital; Bengt Lindell, Kalmar Hospital; Birgitta Nordmark, Johan Bratt and Ingiäld Hafström, Karolinska University Hospital; Ido Leden, Kristianstad Hospital; Björn Löfström, Katrineholm Hospital; Ann Bengtsson and Thomas Skogh, Linköping hospital; Elisabeth Lindqvist, Lund University Hospital; Lennart Jacobsson, Malmö University Hospital; Kjell Huddénius, Rheumatology Clinic in Stockholm City; Christin Lindström, Sophiahemmet; Annika Teleman, Spenshult Hospital; Eva Baecklund and Ann Knight, Uppsala University Hospital; Olle Svernell, Västervik Hospital.

  • Competing interests None.

  • Funding The study was supported by grants from the Swedish Medical Research Council, from the Swedish Council for Working life and Social Research, from King Gustaf V’s 80-year foundation, from the Swedish Rheumatism Association, from Stockholm County Council, from the insurance company AFA and from NIH (P60 AR047782).

  • Ethics approval This study was conducted with the approval of the regional committee on ethics at Karolinska Institutet, Stockholm, Sweden.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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