Risk factors for mortality of diffuse alveolar hemorrhage in systemic lupus erythematosus: a systematic review and meta-analysis

Abstract

Background Diffuse alveolar hemorrhage (DAH) is a rare but life-threatening complication of systemic lupus erythematosus (SLE). The current knowledge of the prognostic factors for SLE-associated DAH is controversial. This meta-analysis was undertaken to investigate the relevant risk factors for mortality in SLE-associated DAH. Methods Studies were searched from PubMed, EMBASE, and Web of Science databases published up to May 27, 2020, and were selected or removed according to the inclusion and exclusion criteria. Two reviewers extracted data independently from the enrolled studies, and the odds ratios (OR) or the standardized mean difference (SMD) was utilized to identify and describe the prognostic factors for mortality. Results Eight studies encompassing 251 patients with SLE-associated DAH were included in the meta-analysis. No significant publication bias was shown. Age at the diagnosis of DAH (SMD = 0.35, 95% confidence interval (CI) (0.08, 0.61), P = 0.01, I2 = 0.0%) was found to be an independent risk factor of mortality. Longer lupus disease duration (SMD = 0.28, 95% CI (0.01, 0.55), P = 0.042, I2 = 0.0%), concurrent infection (OR = 2.77, 95% CI (1.55, 4.95), P = 0.001, I2 = 37.5%), plasmapheresis treatment (OR = 1.96, 95% CI (1.04, 3.70), P = 0.038, I2 = 14.6%), and mechanical ventilation (OR = 6.11, 95% CI (3.27, 11.39), P < 0.0001, I2 = 23.3%) were also related to poor survival, whereas no noticeable relationships were revealed between survival and concurrent lupus nephritis (OR = 5.45, 95% CI (0.52, 56.95), P = 0.16, I2 = 58.4%) or treatment of cyclophosphamide (CTX) (OR = 0.74, 95% CI (0.16, 3.41), P = 0.70, I2 = 75.5%). Conclusions Older age at the diagnosis of DAH, longer disease duration of SLE, concurrent infection, plasmapheresis treatment, and mechanical ventilation were found related to increased mortality in patients with SLE-associated DAH according to our meta-analysis. However, due to limited studies with heterogeneity, these results should be interpreted cautiously. Notably, severe diseases rendered the requirement of plasmapheresis treatment and mechanical ventilation are themselves associated with poor outcome. Randomized trials of therapeutics are needed to determine the most efficacious strategies for SLE-associated DAH for better management of this life-threatening complication.

A case report of pediatric systemic lupus erythematosus with diffuse alveolar hemorrhage following COVID-19 infection: Causation, association, or chance?

“…Regardless of whether it is caused by SLE, DAH is a life-threatening condition that necessitates early treatment and a thorough investigation to identify the underlying cause. [ 21 ] In a recently published systematic review, Jiang et al [ 29 ] concluded that older age at DAH diagnosis, increased SLE disease duration, requirement for plasmapheresis or mechanical ventilation, and concurrent infection are risk factors associated with poor survival in SLE-related DAH. However, due to its rarity in the pediatric age group, most of the risk factors and the therapeutic interventions for that age group are extrapolated from reports on adults.…”

Respiratory Manifestations in Systemic Lupus Erythematosus

“…CYC can be added in severe forms but data on its efficacy are contrasting with an increased mortality in the study of Zamora et al [37], when compared to the beneficial effect in the study of Sun et al [40]. However, a recent meta-analysis did not confirm an association with CYC and survival [41]. Other immunosuppressants have been used, such as cyclosporine, azathioprine, tacrolimus, mycophenolate mofetil (MMF), without any conclusive evidence.…”

“…Plasmapheresis is generally used in patients with refractory and more severe disease, with contrasting results in literature [41]. Adverse events can occur in up to 10% of cases, are more frequent in the first procedure and are generally mild or moderate, including access site or device problems, hypotension and syncope, tingling, urticaria, nausea/vomiting, chills, fever, arrhythmia [47].…”

“…Prognosis is poor, with a mortality rate of up to 70-92%, (average 50%); however, a trend in the reduction of mortality was observed in the recent years, likely due to a better knowledge of the disorder, a more rapid diagnosis and a precocious introduction of novel, targeted therapies [8]. Older age, longer lupus disease duration, acute massive hemoptysis, requirement of mechanical ventilation and plasmapheresis treatment, thrombocytopenia (not universally accepted) and infections are associated with an increased risk of mortality [8,10,41]. However, severe diseases rendered the requirement of plasmapheresis treatment and mechanical ventilation are themselves associated with poor outcome.…”

“…The presence of other comorbidities must also be considered. Among survivors, 70-90% can eventually develop pulmonary fibrosis therefore a strict follow-up is mandatory [10,41]. Randomized trials of therapeutics are needed to determine the most efficacious strategies for SLE-associated DAH for better management of this life-threatening complication.…”