Authors: Nermeen A Awad , Lujain B Baghlaf , Rasha A Alsulami , Samah Alotaibi , Sarah K Alshehabi , Wed S Bin Madhi

Abstract

Background: Smoking may modify systemic lupus erythematosus (SLE) activity, damage, and phenotype. This review aims to summarize associations between smoking exposure and SLE outcomes.
Methods: Systematic review of primary studies assessing smoking in SLE and reporting clinical or biomarker outcomes. Five eligible studies (2002–2021) were included (total N=1,079). Participants were predominantly female (87–96.2%); where reported, most were Caucasian (73.7–92%) with mean/median age 37–49 years and disease duration ~9–13.5 years. Smoking exposure definitions varied substantially, limiting direct quantitative pooling and precluding meta-analysis across studies. 
Results: Ever-smoking prevalence ranged ~37–51%. In one observational study, current smokers had higher disease activity than never smokers (mean total SLEDAI 15.63±1.63 vs 9.03±0.99; p=0.0024) and a dose–response by packs/day (p=0.001). In a retrospective cohort, never exposure to active or second-hand smoke reduced risk of damage accrual (SDI>0: RR 0.78, 95% CI 0.62–0.97; p=0.0228). Heavy smoking (>20 pack-years) was associated with discoid rash (OR 2.22), photosensitivity (OR 2.19) and neurological disorder (OR 3.16), but inversely associated with renal disorder (OR 0.40), non-erosive arthritis (OR 0.45) and haematological disorder (OR 0.40). Current smoking increased cutaneous damage (any OR 2.73; scarring OR 4.70; active rash OR 6.18). IL-17A levels were similar in SLE and controls, did not correlate with SLEDAI-2K or SDI, and inversely correlated with years of smoking (Rs≈−0.43; p≈0.001). Another study reported no significant differences in cumulative damage scores across smoking categories.

Conclusion: Evidence from five heterogeneous studies links smoking with higher SLE activity and cutaneous damage and suggests phenotype-specific associations. Standardized exposure measures and prospective designs are needed. 

Keywords: Systemic lupus erythematosus, smoking, autoimmune diseases, risk factors, disease activity.