Table 3.

Selected studies associating silica inhalants with risk of rheumatoid arthritis.

Reference	Study design	Population Sample (n) RA outcomes (n)	Silica exposure methods	RA outcome methods	Cigarette smoking and other adjustment variables	Effect size (95% confidence interval) for silica and RA risk	Comments
Klockars M, Br Med J (1987) [62]	Retrospective cohort	Central and south western Finland, male granite workers aged 15 to 72 years n=1,026 silica-exposed n=35 RA	Dust concentration measured in workplace	1987 ACR criteria	No smoking adjustment Age, residential area	Incidence of disability pensions for RA: RR 5.08 (3.31-7.79)	Prevalence of RA and prevalence of patients receiving free medications for RA were significantly higher among granite workers than the general population
Turner S, Occup Environ Med (2000) [65]	Case-control	United Kingdom, pottery, sandstone, and refractory material (aluminosilicate or silica) workers n=290 n=58 RA	Duration of physician-performed occupational history	Physician-diagnosed RA	Smoking status (ever or never) Age, sex, date, occupation, parity, pneumoconiosis	Per 10 years silica exposure and all RA: OR 0.31 (0.16-0.61)	Only study suggesting a protective effect of silica for RA risk Also investigated other cumulative silica exposures
Stolt P, Ann Rheum Dis (2005) [61]	Case-control	Sweden, men aged 18 to 70 years (EIRA Study) n=552 n=276 incident RA	Self-reported exposure to stone dust, rock drilling, or stone crushing	1987 ACR criteria	Smoking status (ever or never) Age, residential area	All RA: OR 2.2 (1.2-3.9) RF-positive RA: OR 1.9 (0.9-4.0) RF-negative RA: OR 2.1 (0.8-5.1)	Older men were at particularly increased risk of all RA
Stolt, Ann Rheum Dis (2010) [60]	Case-control	Sweden, men aged 18-70 years (EIRA Study) n=1,236 n=577 incident RA	Self-reported exposure to stone dust, rock drilling, or stone crushing	1987 ACR criteria	No smoking adjustment Age, residential area	All RA: OR 1.39 (0.98-1.96) ACPA-positive RA: OR 1.67 (1.13-2.48) ACPA-negative RA: OR 0.98 (0.57-1.66)	Rock drilling exposure showed particularly high risk of ACPA-positive RA Analyses were also stratified by smoking and shared epitope status Detected statistically significant silica-smoking interaction for ACPA-positive RA
Yahya A, Mod Rheumatol (2014) [59]	Case-control	Malaysia, males aged 18-70 years (MyEIRA Study) n=362 n=129 incident RA	Self-reported exposure to stone dust, rock drilling, or stone crushing	1987 ACR criteria	No smoking adjustment Age, sex, residential area	All RA: OR 2.0 (0.9-4.6) ACPA-positive RA: OR 2.4 (1.0-5.6) ACPA-negative RA: OR 0.9 (0.2-4.5)	Also stratified by smoking status and investigated silica-smoking interaction All subjects exposed to silica were also smokers
Blanc PD, Am J Med (2015) [57]	Retrospective cohort	Sweden, male construction workers aged 30 to 84 years n=240,983 n=713 incident RA	Job-exposure matrices	Billing code	Smoking status (ever or never) Age	All RA: RR 1.33 (1.11-1.60) Seropositive RA: RR 1.28 (1.02-1.61) Seronegative RA: RR 1.46 (1.03-2.07)	Also investigated other organic dusts and risk of autoimmune diseases
Vihlborg P, BMJ Open (2017) [58]	Retrospective cohort	Sweden, male iron foundry workers and general Swedish population n=2,187 n=18 seropositive RA	Silica dust measurements for job categories (mg/m3)	Billing code	No smoking adjustment Age, sex, year	Seropositive RA: SIR 1.70 (1.01-2.69)	Also investigated sarcoidosis
Ilar A, RMD Open (2019) [50]	Case-control	Sweden, EIRA Study and national registers n=126,534 n=11,285 RA	Job-exposure matrices	2+ visits for RA and DMARD receipt	Smoking pack-years (continuous) Age, sex, county, year, alcohol use	All RA: OR 1.3 (1.2-1.5) Seropositive RA: OR 1.4 (1.2-1.5) Seronegative RA: OR 1.2 (1.0-1.4)	OR for seropositive RA higher with number of years exposed to silica Results attenuated among women

Statistically significant results are bolded.

ACPA, anti-citrullinated protein antibody; ACR, American College of Rheumatology; DMARD, disease modifying anti-rheumatic drug; EIRA, Epidemiological Investigations of Rheumatoid Arthritis; OR, odds ratio; RA, rheumatoid arthritis; RF, rheumatoid factor; RR, relative risk; SIR, standardized incidence ratio.