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Risk factors for mortality in patients with systemic lupus erythematosus (SLE) who develop diffuse alveolar hemorrhage (DAH) included older age and longer disease duration, Chinese researchers reported.

In a meta-analysis, significant correlations were seen for older age at the time of DAH diagnosis, with a standardized mean difference of 0.35 (95% CI 0.08-0.61, P=0.01), according to Lidan Zhao, MD, and colleagues from the Peking Union Medical College in Beijing.

Duration of SLE also showed a significant correlation with mortality, with a standardized mean difference of 0.28 (95% CI 0.01-0.55, P=0.042), the researchers reported online in .

DAH is a rare but potentially lethal complication of SLE, with mortality rates up to 85.7% having been reported. It is believed to result from pulmonary capillaritis, and can develop in up to 6% of patients hospitalized with SLE. "The deposition of immune complexes and the activation of complement within the lungs are central to the development of parenchymal disease in SLE," they explained.

The condition is associated with hemoptysis, shortness of breath, hypoxemia, and sharp declines in hemoglobin levels, with imaging findings of diffuse ground-glass opacities or hilar-centered consolidation. Patients also may have bronchoalveolar lavage findings of hemosiderin-laden macrophages.

Previous studies have sought to identify factors that are associated with mortality, but have had conflicting results. For example, contradictory findings have been reported for the influence of disease activity, the presence of lupus nephritis, and the effects of cyclophosphamide treatment.

In an attempt to clarify these prognostic concerns, Zhao and colleagues conducted a systematic review and meta-analysis that included eight cohort and case-control studies, all of which were retrospective in design. A total of 251 patients with 262 episodes of DAH were included.

The eight studies ranged in number of patients from eight to 94, and had mortality rates ranging from 29.2% to 61.9%. The methodologic quality of the studies was "relatively high," although some heterogeneity was observed.

Factors other than age and disease duration that were associated with mortality were:

• Infection, OR 2.77 (95% CI 1.55-4.95, P=0.001)
• Plasmapheresis, OR 1.96 (95% CI 1.04-3.70, P=0.038)
• Mechanical ventilation, OR 6.11 (95% CI 3.37-11.39, P<0.0001)

Factors that were not found to be predictive of mortality included sex, the presence of lupus nephritis, declines in hemoglobin, levels of complement, SLE disease activity scores, and treatment with cyclophosphamide or intravenous immunoglobulin.

With regard to the lack of mortality association seen with lupus nephritis, which has traditionally been viewed as a poor prognostic factor in SLE, the authors suggested "that DAH itself can lead to high mortality, far exceeding what lupus nephritis can contribute; thus, the 'add-on' of lupus nephritis makes no difference." Alternatively, the small number of cases may have introduced bias to the analysis. "More studies and a larger sample size concerning this issue may help identify the role of lupus nephritis in the outcome of SLE-DAH," they wrote.

They also emphasized the importance of concurrent infection, which is the most common cause of death among patients with SLE and can relate to both the disease itself and the powerful immunosuppressive drugs used to treat it. "Blood filled in the alveolar spaces in a patient with DAH is a favorable medium for bacterial growth, which increases the risk of infection," they noted. The presence of infection also complicates treatment, and throughout the course of DAH, preventive measures and rapid detection are of great importance, they said.

Cyclophosphamide is commonly used in severe SLE and in up to half of patients with DAH. In , the use of this immunosuppressant was associated with worse outcomes, with a mortality rate of 70%, but a showed beneficial effects and an increased likelihood of survival after adjusting for factors such as disease activity and mechanical ventilation. Advances in the care of critically ill patients may have contributed to the differences observed in these studies.

The factors associated with SLE-DAH mortality identified in this meta-analysis -- older age, longer disease duration, infection, and the use of plasmapheresis and mechanical ventilation -- should be given increased attention in prognostic and treatment decisions, the authors concluded.

A limitation of the analysis was the retrospective design of the included studies.

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