Background This study aimed to investigate the clinical characteristics, outcomes, and risk factors of patients with a rare but fatal manifestation of systemic lupus erythematosus (SLE), diffusive alveolar hemorrhage (DAH), stratified by infection status in a national representative cohort.

Methods This single-center retrospective study included 124 consecutive patients with SLE-DAH in a tertiary care center between 2006 to 2021. The diagnosis of DAH was made based on a comprehensive evaluation of clinical manifestations, laboratory and radiologic findings, and bronchoalveolar lavage. Demographics, clinical features, and survival curves were compared between patients with bacterial, non-bacterial, and non-infection groups. Univariate and multivariate logistic regression analysis were performed to determine the factors independently associated with bacterial infection in SLE-DAH.

Results Fifty-eight patients with SLE-DAH developed bacterial infection after DAH occurrence, thirty-two patients developed fungal and/or viral infection, and thirty-four patients were categorized as non-infection. The bacterial infection group have a worse prognosis (OR 3.059, 95%CI 1.469–6.369, p=0.002) compared with the other two groups, with a mortality rate of 60.3% within 180 days after DAH occurrence. Factors independently associated with bacterial infections in SLE-DAH included hematuria (OR 4.523, 95%CI 1.068–19.155, p=0.040), hemoglobin drop in the first 24 hours after DAH occurred (OR 1.056, 95%CI 1.001–1.115, p=0.049), and anti-Smith antibody (OR 0.167, 95%CI 0.052–0.535, p=0.003). Glucocorticoid pulse therapy and cyclophosphamide were administered in more than 50% of patients regardless of their infectious status. According to clinical experience at our hospital and in previous studies, we recommended a comprehensive management algorithm for SLE-DAH based on infection stratification.

Conclusions Infection, especially bacterial infection, is a severe complication and prognostic factor of SLE-DAH. Comprehensive management strategies, including diagnosis, evaluation, treatment, and monitoring, based on infection stratification may fundamentally improve outcomes of patients with SLE-DAH.

Comprehensive management algorithm for SLE-DAH. SLE, systemic lupus erythematosus; DAH, diffusive alveolar hemorrhage; HgB, hemoglobin; BALF, bronchoalveolar lavage fluid; Anti-Sm: anti-Smith antibodies; CTX, cyclophosphamide.