title: Systemic lupus erythematosus complicated by diffuse alveolar haemorrhage: risk factors, therapy and survival.
abstract: OBJECTIVE
  While diffuse alveolar haemorrhage (DAH) is recognised as a life-threatening complication of systemic lupus erythematosus (SLE), little is known about its risk factors and response to treatment. We describe 22 cases of DAH in a US lupus cohort of approximately 1000 patients, and compare them to 66 controls from the same outpatient cohort.
  
  
  METHODS
  We captured variables pertaining to diagnoses of SLE and secondary antiphospholipid syndrome (APS), and analysed them by univariate testing. Those variables with p values <0.05 were then further considered in a multivariate model. Kaplan-Meier curves were constructed for each group, and survival was analysed by Log-rank test.
  
  
  RESULTS
  Of the 22 patients with DAH, 59% were diagnosed with DAH within 5 years of lupus diagnosis. By univariate testing, several manifestations of SLE and APS were more common in patients with DAH, including history of thrombocytopenia, cardiac valve disease, low C3, leucopenia, neuropsychiatric features, haemolysis, arterial thrombosis, lupus anticoagulant, secondary APS and low C4. On multivariate analysis, history of thrombocytopenia and low C3 were maintained as independent risk factors. Importantly, only two patients had platelet counts <50 000/µL at the time of the DAH episode, arguing that DAH was not simply a haemorrhagic complication of thrombocytopenia. All patients were treated with increased immunosuppression, including various combinations of corticosteroids, plasmapheresis, cyclophosphamide, rituximab and mycophenolate mofetil. Notably, all patients in the cohort survived their initial episode of DAH. While the patients with DAH did well in the short-term, their long-term survival was significantly worse than controls. Several of the deaths were attributable to thrombotic complications after recovering from DAH.
  
  
  CONCLUSIONS
  To the best of our knowledge, this is the largest case-control study of lupus DAH to date. History of thrombocytopenia was strongly predictive of DAH (OR ∼40). A number of APS manifestations correlated with DAH by univariate analysis, and deserve further consideration in larger studies.
authors.affiliation: Division of Rheumatology, Department of Internal Medicine , University of Michigan , Ann Arbor, Michigan , USA.
authors.forename: Nayef M
authors.initials: NM
authors.lastname: Kazzaz
authors.affiliation: Division of Rheumatology, Department of Internal Medicine , University of Michigan , Ann Arbor, Michigan , USA.
authors.forename: Patrick
authors.initials: P
authors.lastname: Coit
authors.affiliation: Division of Rheumatology, Department of Internal Medicine , University of Michigan , Ann Arbor, Michigan , USA.
authors.forename: Emily E
authors.initials: EE
authors.lastname: Lewis
authors.affiliation: Division of Rheumatology, Department of Internal Medicine , University of Michigan , Ann Arbor, Michigan , USA.
authors.forename: W Joseph
authors.initials: WJ
authors.lastname: McCune
authors.affiliation: Division of Rheumatology, Department of Internal Medicine , University of Michigan , Ann Arbor, Michigan , USA.
authors.forename: Amr H
authors.initials: AH
authors.lastname: Sawalha
authors.affiliation: Division of Rheumatology, Department of Internal Medicine , University of Michigan , Ann Arbor, Michigan , USA.
authors.forename: Jason S
authors.initials: JS
authors.lastname: Knight
keywords: Antiphospholipid Syndrome; Diffuse alveolar hemorrhage; Thrombocytopenia