Smoking Increases Inflammatory Joint Signs in Relatives of RA Patients

While these participants were at increased risk of RA based on positive family history, they were likely further away from developing classifiable RA than the participants in previous studies.

In a high-risk cohort of first-degree relatives (FDRs) of patients with rheumatoid arthritis (RA), researchers demonstrated that both age and history of cigarette smoking were associated with the development of signs of inflammatory joints. The research was published in Arthritis & Rheumatology.

“No prospective studies have evaluated the effect of the shared epitope and non-HLA genetic loci on the risk of inflammatory joint signs,” wrote Jeffrey A Sparks, MD, MMSc, of Brigham and Women’s Hospital and Harvard Medical School in Boston, Massachusetts and colleagues. “Moreover, limited data exist on environmental and serologic risk factors for preclinical RA progression in unaffected FDRs.”

To determine whether known environmental, genetic, and serologic risk factors of RA were associated with inflammatory joint signs, the researchers analyzed 966 unaffected, non-Hispanic white first degree relatives of those with RA from Studies of the Etiology of RA (SERA), a multicenter, prospective FDR cohort study.

Participants’ mean ± SD age was 47.2 ± 15.5 years, 70.8% were female, their mean ± SD BMI was 27.4 ± 6.1 kg/m2, and 43.9% had either smoked in the past or had been current smokers.

During physical examination at baseline, 222 participants (23.0%) had at least 1 swollen or tender joint at RA-specific sites. Eighty participants (8.3%) had ≥1 swollen joint and 195 (20.2%) had ≥1 tender joint at baseline when compared to non-smokers  (odds ratio [OR] 1.89 [95% confidence interval (95% CI) 1.26–2.82]).

A cigarette smoking history of >10 pack-years was further found to be associated with increased odds of having inflammatory joint signs at baseline evaluation. This association persisted at followup evaluation 2 years later (OR 2.66 [95% CI 1.01–7.03]).

When performing subanalysis according to age, researchers found that FDRs < 50 years of age who had a smoking history of >10 pack-years had the greatest degree of increase risk of having inflammatory joint signs when compared to nonsmokers of the same age group (OR 4.39 [95% CI 2.22–8.66].

“We demonstrated that age and cigarette smoking were associated with inflammatory joint signs in a high-risk cohort of RA first degree relatives in SERA,” the authors wrote. “Cumulative cigarette smoking was associated with inflammatory joint signs both at baseline and at 2 years of follow-up.”

The researchers noted that smoking at younger ages increased the risk of inflammatory joint signs >4-fold.

Most previous studies that have evaluated transitions between preclinical RA phases focused on the transition from joint pain or inflammatory arthritis to classifiable RA. “Our study is the first to prospectively evaluate genetic, environmental, and serologic risk factors among unaffected FDRs,” the authors noted. “This group is at increased risk of RA based on positive family history, but many were asymptomatic and seronegative, so are likely further away from developing classifiable RA than the subjects in the previous studies.”

Summary & Clinical Applicability

In this study of unaffected first-degree relatives (FDRs) of patients with RA, researchers found that smoking and age were associated with inflammatory joint signs. They did not find any association with other RA risk factors such as genetic risk scores (GRS), excess BMI, sex, parity, education, and RA-related autoantibodies.

The researchers concluded that cigarette smoking may play a role in the phases of preclinical RA pathogenesis, and that larger studies with longer follow-up are necessary to examine the transitions between preclinical RA phases.

Limitations & Disclosures

  • It is possible that inflammatory joint signs identified were not due to inflammation or synovitis, especially in the metacarpophalangeal joints or wrists
  • Plain radiography, magnetic resonance imaging, and ultrasonography may have improved the classification of inflammatory joint signs, but were not available. More accurate assessments of joint inflammation in at-risk participants may be possible in future studies with advanced imaging or synovial biopsy.

No conflicts of interest were disclosed by study authors.

Related Articles


Sparks JA, Chang S, Deane KD, et al. Associations of smoking and age with inflammatory joint signs among unaffected first-degree relatives of rheumatoid arthritis patients: results from studies of the etiology of rheumatoid arthritis. Arthritis Rheumatol. 2016;68(8):1828-38. doi:10.1002/art.39630.

follow @RheumAdvisor