Diffuse alveolar hemorrhage syndrome is persistent or recurrent pulmonary hemorrhage. There are numerous causes, but autoimmune disorders are the most common. Most patients present with dyspnea, cough, hemoptysis, and new alveolar infiltrates. 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 syndrome is not a specific entity but is a syndrome that suggests a differential diagnosis and a specific sequence of testing.

Pathophysiology

Diffuse alveolar hemorrhage syndrome results from widespread damage of the pulmonary small vessels, leading to blood collection within the alveoli, thereby disrupting O₂ and CO₂ exchange. The specific pathophysiology and manifestations vary depending on cause. For example, isolated pauci-immune pulmonary capillaritis is a small-vessel vasculitis limited to the lung; its only manifestation is alveolar hemorrhage affecting people aged 18 to 35 yr. Idiopathic pulmonary hemosiderosis is diffuse alveolar hemorrhage syndrome with no detectable underlying disorder; it occurs mainly in children < 10 yr and is thought to be due to a defect in the alveolar capillary endothelium, possibly due to autoimmune injury.

Etiology

Many disorders can cause alveolar hemorrhage; they include

• Autoimmune disorders (eg, systemic vasculitides, Goodpasture's syndrome, antiphospholipid antibody syndrome)
• Pulmonary infections (eg, invasive aspergillosis, 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

Symptoms and signs of milder diffuse alveolar hemorrhage syndrome 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. Children with idiopathic pulmonary hemosiderosis may have failure to thrive.

There are no specific physical examination findings.

Other manifestations depend on the underlying disorder (eg, diastolic murmur in patients with mitral stenosis).

Diagnosis

• Chest x-ray
• Sometimes bronchoscopy
• Serologic and other tests to diagnose the cause

Diagnosis is suggested by dyspnea, cough, and hemoptysis accompanied by chest x-ray findings of diffuse bilateral alveolar infiltrates. Bronchoscopy with bronchoalveolar lavage (BAL) may be done to confirm the diagnosis 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 even after sequential sampling.

Evaluation of the cause

Further testing for the cause should be done. Urinalysis is indicated to exclude glomerulonephritis; serum BUN and creatinine also should be done. Other routine tests include CBC, coagulation studies, platelet counts, and serologic tests (antinuclear antibody, anti–double-stranded DNA [anti-dsDNA], antiglomerular basement membrane [anti-GBM] antibodies, antineutrophil cytoplasmic antibodies [ANCA], antiphospholipid antibody) to look for underlying disorders; perinuclear-ANCA (p-ANCA) titers are elevated in some cases of isolated pauci-immune pulmonary capillaritis. Diagnosis of idiopathic pulmonary hemosiderosis involves demonstration of iron deficiency anemia and hemosiderin-laden macrophages in BAL fluid or lung biopsy specimens when there is no evidence of small-vessel vasculitis (pulmonary capillaritis) or of other diagnoses.

Alveolar Hemorrhage

Other tests depend on clinical context. 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. BAL is done when diffuse alveolar hemorrhage is suspected. 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.

Prognosis

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

• Corticosteroids
• Sometimes cyclophosphamide or plasmapheresis
• Supportive measures

Treatment involves correcting the cause. Corticosteroids and possibly cyclophosphamide are used to treat vasculitides, connective tissue disorders, and Goodpasture's syndrome. Plasmapheresis may be used to treat the Goodpasture's syndrome. Corticosteroids are also used to treat idiopathic pulmonary hemosiderosis; immunosuppressants are added for nonresponders. Several studies have reported successful use of recombinant activated human factor VII in treating alveolar hemorrhage.

Other possible management measures include supplemental O₂, bronchodilators, reversal of any coagulopathy, intubation with bronchial tamponade, protective strategies for the less involved lung, and mechanical ventilation.

Last full review/revision July 2009 by Marvin I. Schwarz, MD