Chapter 68: Alveolar Hemorrhage Syndromes

Introduction

Diffuse alveolar hemorrhage (DAH) is a potentially catastrophic complication of myriad immune and nonimmune disorders.^1–3 Clinical features are broad, but hemoptysis, infiltrates on chest radiographs, hypoxemia, and progressive respiratory insufficiency are common to diverse etiologies.² Nonimmune causes of alveolar hemorrhage include endobronchial tumors, arteriovenous malformations or aneurysms, ulcerative tracheobronchitis, hemorrhagic pneumonia, bronchiectasis, congestive heart failure, uremia, thrombocytopenia or coagulopathy, pulmonary venoocclusive disease, infections, and massive pulmonary embolism.^4,5 These nonimmune causes need to be excluded in patients with severe alveolar hemorrhage. Depending upon the clinical scenario, coagulation profiles and ancillary tests (e.g., echocardiogram, chest computed tomographic [CT] pulmonary angiography, fiberoptic bronchoscopy) may be required to establish a specific diagnosis. In addition, other causes of diffuse parenchymal infiltrates (but without severe alveolar hemorrhage) share features in common with DAH syndromes (e.g., cryptogenic organizing pneumonia, hypersensitivity pneumonia, pulmonary alveolar proteinosis, and diverse interstitial or alveolar lung disorders). A discussion of these disorders is beyond the scope of this chapter, which focuses primarily on immune-mediated causes of DAH.

Autoimmune Causes of Alveolar Hemorrhage: Differential Diagnosis

Autoimmune DAH results from diffuse injury to the pulmonary microvasculature (termed capillaritis or endotheliitis) (Table 68-1).^6,7 Systemic necrotizing vasculitides^8,9 (principally microscopic polyangiitis [MPA]^10,11 and Wegener’s granulomatosis ¹² account for most cases of autoimmune DAH.* Other causes of autoimmune DAH include antiglomerular basement membrane (anti-GBM) antibody disease,^13–15 connective tissue disease (CTD) (principally systemic lupus erythematosus [SLE]),¹⁶ exogenous agents or drugs.¹⁷ In many of these disorders, rapidly progressive glomerulonephritis (RPGN) is present concomitantly.^18,19 In most patients with autoimmune DAH and glomerulonephritis (GN), anti-GBM antibody and immune complexes are lacking.¹⁹ The term pauci-immune glomerulonephritis has been used to refer to this group of patients, who encompass a heterogeneous group of disorders.^20,21 (discussed in detail below).

Idiopathic pulmonary hemosiderosis (IPH), a rare cause of recurrent DAH with no renal or extrapulmonary component, occurs primarily in children^22–24 and remains a diagnosis of exclusion.

Differentiation of these diverse syndromes can usually be accomplished by serological studies and by kidney biopsy. In such cases, lung biopsy is not required. GN can be demonstrated in the great majority of patients with DAH complicating granulomatosis with polyangiitis (GPA)¹² or MPA.^7,10,11 By ...