9-28: Alveolar Hemorrhage Syndromes

Diffuse alveolar hemorrhage may occur in a variety of immune and nonimmune disorders. Alveolar infiltrates on chest radiograph, dyspnea, anemia, hemoptysis and, occasionally, fever are characteristic. Rapid clearing of diffuse lung infiltrates within 2 days is a clue to the diagnosis of diffuse alveolar hemorrhage (eFigure 9–25). Pulmonary hemorrhage can be associated with an increased single-breath diffusing capacity for carbon monoxide (DL_CO), although this test is infrequently obtained. Sequential BAL on bronchoscopy is the preferred method for diagnosis. Diffuse alveolar hemorrhage is confirmed when lavage aliquots are progressively more hemorrhagic.

Causes of diffuse immune alveolar hemorrhage include anti-basement membrane antibody disease (Goodpasture syndrome), granulomatosis with polyangiitis, systemic necrotizing vasculitis, pulmonary capillaritis associated with idiopathic rapidly progressive glomerulonephritis, systemic lupus erythematosus, and other vasculitic and collagen vascular diseases. Nonimmune causes of diffuse hemorrhage include coagulopathy, mitral stenosis, necrotizing pulmonary infection, drugs (penicillamine), toxins (trimellitic anhydride), and idiopathic pulmonary hemosiderosis.

Goodpasture syndrome is idiopathic recurrent alveolar hemorrhage and rapidly progressive glomerulonephritis. The disease is mediated by anti-glomerular basement membrane antibodies. Goodpasture syndrome occurs mainly in men who are in their 30s and 40s. Hemoptysis is the usual presenting symptom, but pulmonary hemorrhage may be occult. Dyspnea, cough, hypoxemia, and diffuse bilateral alveolar infiltrates are typical features. Iron deficiency anemia and microscopic hematuria are usually present. The diagnosis is based on characteristic linear IgG deposits detected by immunofluorescence in glomeruli or alveoli and on the presence of anti-glomerular basement membrane antibody in serum. The combination of plasmapheresis plus immunosuppressive therapy is recommended, rather than immunosuppressive therapy alone. Immunosuppression with the combination of corticosteroids and cyclophosphamide is recommended.

Idiopathic pulmonary hemosiderosis is a disease of children or young adults characterized by recurrent pulmonary hemorrhage; in contrast to Goodpasture syndrome, renal involvement and anti-glomerular basement membrane antibodies are absent, but iron deficiency is typical. It is frequently associated with celiac disease. Treatment of acute episodes of hemorrhage with corticosteroids may be useful. Recurrent episodes of pulmonary hemorrhage may result in interstitial fibrosis and pulmonary failure.