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Diffuse alveolar hemorrhage: Diagnosing it and finding the cause

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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.


 

References

Diffuse alveolar hemorrhage can complicate a large number of clinical conditions. It may present in different ways and may be life-threatening, and it poses an important challenge for the clinician.1

Diffuse alveolar hemorrhage is an uncommon condition in which blood floods the alveoli, usually at multiple sites. It is also known as intrapulmonary hemorrhage, diffuse pulmonary hemorrhage, pulmonary alveolar hemorrhage, pulmonary capillary hemorrhage, alveolar bleeding, or microvascular pulmonary hemorrhage.

In this article we review the causes, clinical features, diagnostic criteria, treatment, and prognosis of diffuse alveolar hemorrhage.

CAUSES OF DIFFUSE ALVEOLAR HEMORRHAGE

A number of diseases can cause diffuse alveolar hemorrhage (Table 1). Although no prospective study has yet identified which cause is the most common, in a series of 34 cases,2 Wegener granulomatosis accounted for 11 cases, Goodpasture syndrome four cases, idiopathic pulmonary hemosiderosis four, collagen vascular disease four, and microscopic polyangiitis three. In a series of 29 cases of diffuse alveolar hemorrhage associated with capillaritis,3 the most common cause was isolated pauci-immune pulmonary capillaritis (8 cases).
Table 2 summarizes the frequency of diffuse alveolar hemorrhage in some conditions in which it can occur, as well as some of the diagnostic features that should prompt consideration of the specific cause.

THREE CHARACTERISTIC PATTERNS

In general, diffuse alveolar hemorrhage can occur in three characteristic patterns, which reflect the nature of the underlying vascular injury1:

Diffuse alveolar hemorrhage associated with vasculitis or capillaritis. As described by Spencer4 50 years ago, pulmonary capillaritis is the most frequent underlying histologic lesion described in diffuse alveolar hemorrhage. Neutrophils infiltrate the interalveolar and peri-bronchiolar septal vessels (pulmonary interstitium),5 leading to anatomic disruption of the capillaries (ie, impairment of the alveolocapillary barrier) and to extravasation of red blood cells into the alveoli and interstitium. Neutrophil apoptosis and fragmentation, with subsequent release of the intracellular proteolytic enzymes and reactive oxygen species, beget more inflammation, intra-alveolar neutrophilic nuclear dust, fibrin and inflammatory exudate, and fibrinoid necrosis of the interstitium.6,7

‘Bland’ pulmonary hemorrhage (ie, without capillaritis or vasculitis). In this pattern, red blood cells leak into the alveoli without any evidence of inflammation or destruction of the alveolar capillaries, venules, and arterioles. The epithelial lesions are usually microscopic and are scattered geographically.

Diffuse alveolar hemorrhage associated with another process or condition (eg, diffuse alveolar damage, lymphangioleiomyomatosis, drug-induced lung injury, metastatic tumor to the lungs, mitral stenosis). Diffuse alveolar damage is the main underlying lesion of the acute respiratory distress syndrome and is characterized by formation of an intra-alveolar hyaline membrane, by interstitial edema with minimal inflammation, and, at times, by “secondary” diffuse alveolar hemorrhage. In this third category of diffuse alveolar hemorrhage, the underlying process causes alveolar hemorrhage by processes other than pulmonary vascular inflammation or direct extravasation of red cells.

THE CLINICAL PRESENTATION

The clinical presentation of diffuse alveolar hemorrhage may reflect either alveolar bleeding alone or features of the underlying cause (eg, hematuria in Wegener granulomatosis, arthritis in systemic lupus erythematosus). Hence, its recognition requires a high degree of suspicion.

Some patients present with severe acute respiratory distress requiring mechanical ventilation. However, dyspnea, cough, and fever are the common initial symptoms and are most often acute or subacute (ie, present for less than a week). The fever is usually due to the underlying cause, such as lupus.

Hemoptysis may be absent at the time of presentation in up to a third of patients because the total alveolar volume is large and can absorb large amounts of blood, without extending more proximally into the airways. Apparent hemoptysis, if present, must be differentiated from hematemesis or pseudohemoptysis (alveolar flooding with fluid that resembles blood, as in Serratia marcescens pneumonia, in which the reddish hue of the infecting organism can create the impression of alveolar bleeding).

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