Alveolar Hemorrhage Syndrome
Diffuse alveolar hemorrhage is not a specific disorder, but a syndrome that has a specific differential diagnosis and a specific sequence of testing. Some disorders that cause diffuse alveolar hemorrhage are associated with glomerulonephritis; then the disorder is defined as a pulmonary-renal syndrome.
Diffuse alveolar hemorrhage results from widespread damage to the pulmonary small vessels, leading to blood collecting within the alveoli. If enough alveoli are affected, gas exchange is disrupted. The specific pathophysiology and manifestations vary depending on cause. For example, isolated pauci-immune pulmonary capillaritis is a small-vessel vasculitis limited to the lungs; its only manifestation is alveolar hemorrhage affecting people aged 18 to 35 years.
Diffuse alveolar hemorrhage may occur in a variety of immune and nonimmune disorders. Hemoptysis, alveolar infiltrates on chest radiograph, anemia, dyspnea, and occasionally fever are characteristic. Rapid clearing of diffuse lung infiltrates within 2 days is a clue to the diagnosis of diffuse alveolar hemorrhage. Pulmonary hemorrhage can be associated with an increased single-breath diffusing capacity for carbon monoxide (DlCO).
Causes of diffuse immune alveolar hemorrhage have been classified as anti-basement membrane antibody disease (Goodpasture syndrome), vasculitis and collagen vascular disease (systemic lupus erythematosus, granulomatosis with polyangiitis, systemic necrotizing vasculitis, and others), and pulmonary capillaritis associated with idiopathic rapidly progressive glomerulonephritis.
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.
Symptoms and signs
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.
Treatment involves correcting the cause.
Corticosteroids and possibly cyclophosphamide are used to treat vasculitides, connective tissue disorders, and Goodpasture syndrome. Rituximab has been studied in ANCA-associated vasculitis and has been shown to be noninferior to cyclophosphamide for induction treatment and superior to azathioprine for remission treatment.
Several studies have reported successful use of recombinant activated human factor VII in treating severe unresponsive alveolar hemorrhage, but such therapy is controversial because of possible thrombotic complications.
Other possible management measures include supplemental oxygen, bronchodilators, reversal of any coagulopathy, and intubation with protective strategies as for acute respiratory distress syndrome (ARDS) and mechanical ventilation.