Diffuse alveolar hemorrhage: Diagnosing it and finding the cause
ABSTRACTDiffuse alveolar hemorrhage is an acute, life-threatening event, and repeated episodes can lead to organizing pneumonia, collagen deposition in small airways, and, ultimately, fibrosis. Among the many conditions it can accompany are Wegener granulomatosis, microscopic polyangiitis, Goodpasture syndrome, connective tissue disorders, antiphospholipid antibody syndrome, infectious or toxic exposures, and neoplastic conditions. Its many causes and presentations pose an important challenge to the clinician.
KEY POINTS
- Most patients present with dyspnea, cough, hemoptysis, and new alveolar infiltrates. Early bronchoscopy with bronchoalveolar lavage is generally required to confirm the diagnosis; blood in the lavage specimens (with numerous erythrocytes and siderophages) establishes the diagnosis.
- Therapy targets both the autoimmune destruction of the alveolar capillary membrane and the underlying condition. Corticosteroids and immunosuppressive agents remain the gold standard.
- In patients with diffuse alveolar hemorrhage and renal impairment (pulmonary-renal syndrome), kidney biopsy can be considered to identify the cause and to direct therapy.
DIAGNOSTIC EVALUATION
Generally speaking, dyspnea, cough, hemoptysis, and new alveolar infiltrates in conjunction with bloody bronchoalveolar lavage specimens (with numerous erythrocytes and siderophages) establish the diagnosis of diffuse alveolar hemorrhage. Surgical biopsy from the lung or another organ involved by an underlying condition is often necessary.
Physical examination
The physical findings are nonspecific and may reflect the underlying systemic vasculitis or collagen vascular disorder (eg, with accompanying rash, purpura, eye lesions, hepatosplenomegaly, or clubbing).
Imaging studies
Radiography may show new or old or both new and old patchy or diffuse alveolar opacities. Recurrent episodes of hemorrhage may lead to reticular interstitial opacities due to pulmonary fibrosis, usually with minimal (if any) honeycombing. Kerley B lines suggest mitral valve disease or pulmonary veno-occlusive disease as the cause of the hemorrhage.
Computed tomography may show areas of consolidation interspersed with areas of ground-glass attenuation and preserved, normal areas.
Currently, nuclear imaging such as gallium or tagged red blood cell studies have little role in evaluating diffuse alveolar hemorrhage. Other nuclear studies, geared to reveal breakdown of the microcirculatory integrity and extravasation of red blood cells out of the vessels, have also not been proven useful.
Evaluating pulmonary function
Diffuse alveolar hemorrhage may cause impairment of oxygen transfer and hypoxemia. In addition, it can cause several other abnormalities of pulmonary function.
Increased diffusing capacity. Because blood in the lungs can absorb inhaled carbon monoxide, the diffusing capacity for carbon monoxide (DLCO) may be distinctively increased. Serial increases in the DLCO may indicate progressive alveolar hemorrhage. However, the clinical instability of patients experiencing active alveolar bleeding precludes performing the DLCO measurement maneuvers, rendering the DLCO test relatively impractical.
Restrictive changes. Because recurrent episodes of diffuse alveolar hemorrhage can lead to interstitial fibrosis, restrictive changes—ie, decreased total lung capacity, decreased forced vital capacity (FVC), and preserved ratio of the forced expiratory volume in 1 second (FEV1) to the FVC—may characterize diffuse alveolar hemorrhage.
Obstructive changes (less common). Less commonly, patients with diffuse alveolar hemorrhage may have spirometric changes indicating airflow obstruction—ie, decreased FEV1 and decreased ratio of FEV1 to FVC—possibly because neutrophilic infiltration from blood extravasation into the alveolar sacs causes release of reactive oxygen species and proteolytic enzymes, which in turn may cause small airway and parenchymal damage such as bronchiolitis and emphysema. A pattern of obstructive lung disease associated with recurrent diffuse alveolar hemorrhage should prompt consideration of an underlying condition that can cause airflow obstruction, such as sarcoidosis, microscopic polyangiitis, or Wegener granulomatosis, or, less commonly, lymphangioleiomyomatosis, histiocytosis X, pulmonary capillaritis, or sometimes idiopathic pulmonary hemosiderosis.
As an example of an unusual circumstance, we have described elsewhere a case of a woman with idiopathic pulmonary hemosiderosis with multiple episodes of diffuse alveolar hemorrhage and resultant emphysema.8 Radiographic images showed several very large cysts, one of which herniated through the incision site of an open lung biopsy.
Decreased exhaled nitric oxide. Though currently unavailable in most clinical pulmonary function laboratories, evaluation of exhaled gas or condensate may have value in diagnosing diffuse alveolar hemorrhage.9 Specifically, because increased intra-alveolar hemoglobin binds nitric oxide, as it does carbon monoxide, levels of exhaled nitric oxide may be decreased in diffuse alveolar hemorrhage. In contrast to the difficulty of measuring DLCO in patients with active alveolar bleeding or hemoptysis, analysis of exhaled gas is clinically feasible, making this a promising diagnostic test.
Laboratory evaluation
Hematologic assessment in patients with diffuse alveolar hemorrhage generally reveals:
- Acute or chronic anemia
- Leukocytosis
- Elevated erythrocyte sedimentation rate
- Elevated C-reactive protein level (particularly in patients whose alveolar hemorrhage is due to systemic disease or vasculitis, or both).
Renal abnormalities such as elevated blood urea nitrogen and serum creatinine or abnormal findings on urinalysis (with hematuria, proteinuria, and red blood cell casts indicating glomerulonephritis) can also occur, as diffuse alveolar hemorrhage may complicate several pulmonary-renal syndromes such as Goodpasture syndrome and Wegener granulomatosis.
