TREATMENT OF DIFFUSE ALVEOLAR HEMORRHAGE
Therapy for diffuse alveolar hemorrhage consists of treating both the autoimmune destruction of the alveolar capillary membrane and the underlying condition. Corticosteroids and immunosuppressive agents remain the gold standard for most patients. Recombinant-activated human factor VII seems to be a promising new therapy, although further evaluation is needed.
Immunosuppressive agents are the mainstay of therapy for diffuse alveolar hemorrhage, especially if associated with systemic or pulmonary vasculitis, Goodpasture syndrome, and connective tissue disorders. Most experts recommend intravenous methylprednisolone (Solu-Medrol) (up to 500 mg every 6 hours, although lower doses seem to have similar efficacy) for 4 or 5 days, followed by a gradual taper to maintenance doses of oral steroids.
In patients with pulmonary-renal syndrome, therapy should be started as soon as possible to prevent irreversible renal failure.
Besides corticosteroids, other immunosuppressive drugs such as cyclophosphamide (Cytoxan), azathioprine (Imuran), mycophenolate mofetil (CellCept), and etanercept (Enbrel) may be used in diffuse alveolar hemorrhage, especially when the condition is severe, when first-line therapy with corticosteroids has proven ineffective (generally not advised, unless the condition is mild) or when specific underlying causes are present (eg, Wegener granulomatosis, Goodpasture syndrome, systemic lupus erythematosus). Intravenous cyclophosphamide (2 mg/kg/day, adjusted to renal function) is generally the preferred adjunctive immunosuppressive drug and may be continued for several weeks or until adverse effects occur, such as blood marrow suppression, infection, or hematuria. Thereafter, most clinicians switch to consolidative or maintenance therapy with methotrexate or another agent.
Plasmapheresis is indicated for diffuse alveolar hemorrhage associated with Good-pasture syndrome or with other vasculitic processes in which the titers of pathogenetic immunoglobulins and immune complexes are very high: for example, ANCA-associated vasculitis with overwhelming endothelial injury and a hypercoagulable state. However, the merits of plasmapharesis in diffuse alveolar hemorrhage associated with conditions other than Goodpasture syndrome has not been evaluated in prospective studies.
It remains unclear whether intravenous immunoglobulin therapy adds to the treatment of diffuse alveolar hemorrhage due to vasculitis or other connective tissue disease.
Several case reports have reported successful use of recombinant activated human factor VII in treating alveolar hemorrhage due to allogeneic hematopoietic stem cell transplantation, ANCA-associated vasculitis, systemic lupus erythematosus, or antiphospholipid syndrome. If borne out by larger experience, recombinant activated human factor VII may gain more widespread use in diffuse alveolar hemorrhage.
Other possible management measures include supplemental oxygen, bronchodilators, reversal of any coagulopathy, intubation with bronchial tamponade, protective strategies for the less involved lung, and mechanical ventilation.
The prognosis for diffuse alveolar hemorrhage depends on the underlying cause (Table 3).
Recurrent episodes may lead to various degrees of interstitial fibrosis, especially in patients with underlying Wegener granulo-matosis, mitral stenosis, long-standing and severe mitral regurgitation, and idiopathic pulmonary hemosiderosis. Obstructive lung disease may also complicate microscopic polyangiitis and idiopathic pulmonary hemosiderosis.
Acknowledgment: We acknowledge and appreciate the assistance of Dr. Carol Farver, who provided the pathologic specimens.