Cigarette smoking and disease activity, organ damage, and cutaneous manifestations in systemic lupus erythematosus: a systematic review
Nermeen A Awad, Lujain B Baghlaf, Rasha A Alsulami, Samah Alotaibi, Sarah K Alshehabi, Wed S Bin Madhi<p><strong><span class="TextRun" lang="EN-GB" xml:lang="EN-GB" data-contrast="auto"><span class="NormalTextRun">Background</span><span class="NormalTextRun">: </span></span></strong><span class="TextRun" lang="EN-GB" xml:lang="EN-GB" data-contrast="auto"><span class="NormalTextRun">Smoking may </span><span class="NormalTextRun">modify</span><span class="NormalTextRun"> systemic lupus erythematosus (SLE) activity</span><span class="NormalTextRun">, </span><span class="NormalTextRun">damage</span><span class="NormalTextRun">, </span><span class="NormalTextRun">and phenotype</span><span class="NormalTextRun">. </span><span class="NormalTextRun">This review aims to summarize associations between smoking exposure and SLE outcomes.<br /><strong>Methods:</strong> 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.<span class="EOP" data-ccp-props="{"201341983":0,"335551550":3,"335551620":3,"335559740":480}"> <br /><strong>Results: </strong>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.</span></span></span></p> <p><span class="TextRun" lang="EN-GB" xml:lang="EN-GB" data-contrast="auto"><span class="NormalTextRun"><span class="EOP" data-ccp-props="{"201341983":0,"335551550":3,"335551620":3,"335559740":480}"><strong>Conclusion</strong>: 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. </span><br /></span></span></p> <p> </p> <p> </p>