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 9–26). Pulmonary hemorrhage can be associated with an increased single-breath diffusing capacity for carbon monoxide (DLCO).
Diffuse alveolar hemorrhage. CT scan of the lungs with bilateral ground glass opacities resulting from diffuse alveolar hemorrhage in a patient with ANCA-associated vasculitis caused by microscopic polyangiitis.
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. Combinations of immunosuppressive drugs (initially methylprednisolone, 30 mg/kg intravenously over 20 minutes every other day for three doses, followed by daily oral prednisone, 1 mg/kg/day, with cyclophosphamide, 2 mg/kg orally per day) and plasmapheresis have yielded excellent results.
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.
et al. Prognostic factors in anti-glomerular basement membrane disease: a multicenter study of 119 patients. Front Immunol. 2019 Jul 18;10:1665.
et al. Diffuse alveolar hemorrhage in autoimmune diseases. Curr Rheumatol Rep. 2017 May;19(5):27.
et al. Antiglomerular basement membrane disease. Semin Respir Crit Care Med. 2018 Aug;39(4):494–503.
et al. Alveolar hemorrhage in vasculitis (primary and secondary). Semin Respir Crit Care Med. 2018 Aug;39(4):482–93.
et al. Anti-glomerular basement membrane disease: an update on subgroups, pathogenesis and therapies. Nephrol Dial Transplant. 2019 Nov 1;34(11):1826–32.