Clinical Characteristics, Comorbidities, and Sex-related Differences Among Smoking and Non-smoking Patients with Rheumatoid Arthritis: A Matched Case-control Study.

BACKGROUND

Smoking may increase levels of pro-inflammatory cytokines, which is an important contributor to rheumatoid arthritis (RA) pathogenesis.

OBJECTIVES

The aim of this study was to describe the characteristics of RA patients who were smokers compared with non-smokers.

METHODS

A total of 849 RA patients who were smokers out of a large RA cohort of 10,364 patients (8.2%) were compared to 924 age-, sex-, and body mass index-matched RA patients who were non-smokers. Patients were subjected to full history-taking and clinical examination. Laboratory tests such as rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) were measured. The disease activity score 28 (DAS28) and the health assessment questionnaire (HAQ) score were assessed.

RESULTS

The mean age among smokers was 46.4 ± 11.3 years, the male-female ratio was 3:1, and the mean disease duration was 6.4 ± 6.2 years. There was a significantly higher frequency of diabetes mellitus, hypertension, and metabolic syndrome in smokers compared to non-smokers (13.7%, 17.1%, and 9.2% vs. 8.4%, 12.9%, and 3.5%; P < 0.0001, P = 0.01, P < 0.0001, respectively), while hypothyroidism was more common in non-smokers (P = 0.03). Rheumatoid nodules (P = 0.03), oral ulcers (P = 0.002), keratoconjunctivitis sicca (P = 0.043), and neurological manifestations (P = 0.002) were significantly more common in smokers, but the DAS28 was lower (4.2 ± 1.5 vs. 4.8 ± 2.5; P < 0.0001). RA-related changes were significantly more common in female smokers than in males. On regression analysis, none of the differences found in the comparison between smokers and non-smokers remained significant.

CONCLUSIONS

Smoking in RA patients was found to be associated with a higher frequency of traditional comorbidities, rheumatoid nodules, oral ulcers, sicca complex, and neurological manifestations, but a lower disease activity. There is an obvious sex-driven pattern, with clinical alterations occurring more frequently in female smokers. Higher RF, anti-CCP, and double seropositivity are more observable in males and positive antinuclear antibody in females.