Association Between Antiphospholipid Antibodies and Diffuse Alveolar Hemorrhage Risk in Systemic Lupus Erythematosus: A Systematic Review and Meta-Analysis

Objectives: To assess the association of antiphospholipid antibodies (aPL) and diffuse alveolar hemorrhage (DAH) in patients with systemic lupus erythematosus (SLE) by performing a systematic review and meta-analysis.

Methods: Multiple databases were systematically searched from inception to February 2024. Studies were eligible if they included patients with SLE (population), reported aPL status (exposure), and DAH (outcome). We pooled the estimates as odds ratio (OR) using fixed-effect models. We examined the association between aPL and DAH, as well as associations based on aPL subtypes or concomitant antiphospholipid syndrome (APS).

Results: Out of 454 screened studies, nine were included in meta-analysis, encompassing 7,746 patients with SLE, of whom 2016 (26.0%) were aPL positive and 163 (2.1%) had DAH. Patients with SLE and positive aPL (any) were more likely to develop DAH than aPL-negative patients (OR = 1.76, 95% CI 1.24-2.49; I2= 0%). Patients with SLE and positive lupus anticoagulant (LA; OR = 1.76, 95% CI 1.06-2.93, I2= 35%) or positive anticardiolipin IgG (OR = 1.62, 95% CI 1.13-2.34, I2=0%) had a higher likelihood of developing DAH compared with patients that were negative for these aPL. An APS diagnosis was associated with a 2.5-fold increased likelihood of DAH compared with subjects without APS (OR = 2.46, 95% CI 1.23-4.92, I2=0%). Positivity of anti-β2 glycoprotein I IgG was not significantly associated with DAH among patients with SLE (OR = 0.78, 95% CI 0.45-1.36, I2=0%).

Conclusions: In patients with SLE, aPL positivity increases the risk of DAH compared with aPL-negative patients, particularly in those positive for LA and anticardiolipin IgG.