* This is the Professional Version. *
Diffuse Alveolar Hemorrhage
Diffuse alveolar hemorrhage is persistent or recurrent pulmonary hemorrhage. There are numerous causes, but autoimmune disorders are most common. Most patients present with dyspnea, cough, hemoptysis, and new alveolar infiltrates on chest imaging. Diagnostic tests are directed at the suspected cause. Treatment is with immunosuppressants for patients with autoimmune causes and respiratory support if needed.
Diffuse alveolar hemorrhage is not a specific disorder, but a syndrome that suggests a differential diagnosis and a specific sequence of testing.
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 yr.
Idiopathic pulmonary hemosiderosis (IPH) is a rare disease that causes recurrent diffuse alveolar hemorrhage with no detectable underlying disorder; it occurs mainly in children < 10 yr. It is thought to be due to a defect in the alveolar capillary endothelium, possibly due to autoimmune injury. Many affected patients have celiac disease.
Symptoms and signs of IPH in children include recurrent episodes of dyspnea and cough, particularly nonproductive cough initially. Hemoptysis occurs later. Children with idiopathic pulmonary hemosiderosis may present with only failure to thrive and iron deficiency anemia. The most common symptoms in adults are exertional dyspnea and fatigue due to pulmonary hemorrhage and iron deficiency anemia.
Diagnosis of IPH involves demonstration of a combination of characteristic clinical findings, iron deficiency anemia, and hemosiderin-laden macrophages in BAL fluid, or lung biopsy specimens plus no evidence of small-vessel vasculitis (pulmonary capillaritis) or another explanatory diagnosis; it is confirmed by lung biopsy if other findings are inconclusive.
Corticosteroids may reduce the morbidity and mortality of acute episodes of alveolar bleeding and may control the disease progression of pulmonary fibrosis. Some patients may require additional immunosuppressive drugs. Patients with celiac disease and IPH should be on a gluten-free diet.
Many disorders can cause alveolar hemorrhage; they include
Pulmonary infections (eg, hantavirus infection)
Toxic exposures (eg, trimellitic anhydride, isocyanates, crack cocaine, certain pesticides)
Drug reactions (eg, propylthiouracil, diphenylhydantoin, amiodarone, methotrexate, nitrofurantoin, bleomycin, montelukast, infliximab)
Cardiac disorders (eg, mitral stenosis)
Coagulation disorders caused by diseases or anticoagulant drugs
Isolated pauci-immune pulmonary capillaritis
Idiopathic pulmonary hemosiderosis
Bone marrow or solid organ transplantation
Symptoms and signs of milder diffuse alveolar hemorrhage are dyspnea, cough, and fever; however, many patients present with acute respiratory failure, sometimes leading to death. Hemoptysis is common but may be absent in up to one third of patients. Most patients have anemia and ongoing bleeding with a decreasing Hct.
There are no specific physical examination findings.
Other manifestations depend on the underlying disorder (eg, diastolic murmur in patients with mitral stenosis).
Diagnosis is suggested by dyspnea, cough, and hemoptysis accompanied by chest x-ray findings of diffuse bilateral alveolar infiltrates if one suspects diffuse alveolar hemorrhage; bronchoscopy with bronchoalveolar lavage (BAL) is strongly recommended to confirm the diagnosis, particularly when manifestations are atypical or an airway source of hemorrhage has not been excluded. Specimens show blood with numerous erythrocytes and siderophages; lavage fluid typically remains hemorrhagic or becomes increasingly hemorrhagic after sequential sampling.
Further testing for the cause should be done. Urinalysis is indicated to exclude glomerulonephritis; serum BUN and creatinine also should be measured.
Other routine tests include
Serologic tests are done to look for underlying disorders. Perinuclear-ANCA (p-ANCA) titers are elevated in some cases of isolated pauci-immune pulmonary capillaritis.
Other tests depend on clinical context. When patients are stable, pulmonary function tests may be done to document lung function. They may show increased diffusing capacity for carbon monoxide (DLco) due to increased uptake of carbon monoxide by intra-alveolar Hb; however, this finding, which is consistent with hemorrhage, does not assist with establishing a diagnosis. Echocardiography may be indicated to exclude mitral stenosis. Lung or kidney biopsy is frequently needed when a cause remains unclear or the progression of disease is too rapid to await the results of serologic testing.
Patients can require mechanical ventilation and even die as a result of hemorrhage-associated respiratory failure. Recurrent alveolar hemorrhage causes pulmonary hemosiderosis and fibrosis, both of which develop when ferritin aggregates within alveoli and exerts toxic effects. COPD occurs in some patients with recurrent diffuse alveolar hemorrhage secondary to microscopic polyarteritis.
Treatment involves correcting the cause. Corticosteroids and possibly cyclophosphamide are used to treat vasculitides, connective tissue disorders, and Goodpasture syndrome. Effectiveness of rituximab in diffuse alveolar hemorrhage has not been studied. Plasma exchange may be used to treat Goodpasture syndrome. 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, intubation with bronchial tamponade, protective strategies for the less involved lung, and mechanical ventilation.
Although diffuse alveolar hemorrhage can have various causes (eg, infection, toxins, drugs, hematologic or cardiac disorders), autoimmune disorders are the most common causes.
Symptoms, signs, and chest-x-ray findings are not specific.
Confirm diffuse alveolar hemorrhage by doing BAL to show persistent hemorrhage with sequential lavage samples.
Test for the cause by doing routine laboratory tests, autoantibody testing, and sometimes other tests.
Treat the cause (eg, with corticosteroids, cyclophosphamide, plasma exchange, and/or immunosuppressants for autoimmune causes).
* This is the Professional Version. *