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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 imaging, hypoxemia, and progressive respiratory insufficiency are commonly seen in many other diverse etiologies.3 Other causes of diffuse parenchymal infiltrates (e.g., cryptogenic organizing pneumonia, hypersensitivity pneumonia, pulmonary alveolar proteinosis, other interstitial or alveolar lung disorders) must be excluded. Additionally, nonimmune causes of pulmonary alveolar hemorrhage include endobronchial tumors, arteriovenous malformations or aneurysms, ulcerative tracheobronchitis, hemorrhagic pneumonia, bronchiectasis, congestive heart failure, uremia, thrombocytopenia or coagulopathy, pulmonary veno-occlusive disease, massive pulmonary embolism, and infections.4,5 Depending upon the clinical scenario, coagulation profiles and ancillary tests (e.g., echocardiogram, chest computed tomographic [CT] pulmonary angiography, bronchoscopy) may be required to establish a specific diagnosis. A discussion of these disorders is beyond the scope of this chapter, which focuses primarily on immune-mediated causes of DAH. We begin with an overview of the many syndromes causing alveolar hemorrhage before discussing each individually.

AUTOIMMUNE CAUSES OF ALVEOLAR HEMORRHAGE: DIFFERENTIAL DIAGNOSIS

Autoimmune DAH results from diffuse injury to the pulmonary microvasculature (termed capillaritis or endotheliitis) (Table 68-1).2,6 Systemic necrotizing vasculitides1,7–10 (principally, microscopic polyangiitis [MPA]11–15 and granulomatosis with polyangiitis [GPA, formerly Wegener granulomatosis])6,16 account for most cases of autoimmune DAH. Both GPA and MPA are often linked to antineutrophil cytoplasmic antibodies (ANCA)13,16 and are encompassed in the term ANCA-associated vasculitis (AAV).17 Eosinophilic granulomatosis with polyangiitis (EGPA) (formerly Churg-Strauss Syndrome) is included as an AAV, even though EGPA is only rarely associated with DAH.17–20 Other causes of autoimmune DAH include anti–glomerular basement membrane (anti-GBM) antibody disease,21–25 connective tissue disease (CTD, principally systemic lupus erythematosus [SLE]),26–30 and exogenous agents or drugs.31–34 In many of these disorders, rapidly progressive glomerulonephritis (RPGN) is concomitantly present.35,36 In most patients with autoimmune DAH and glomerulonephritis (GN), anti-GBM antibody and immune complexes are lacking.36 The term pauci-immune glomerulonephritis has been used to refer to this group of patients, who encompass a heterogenous group of disorders.36–38 Interestingly, rare patients with “pauci-immune capillaritis” have DAH but no extrapulmonary involvement.39 Idiopathic pulmonary hemosiderosis, a rare cause of recurrent DAH with no renal or extrapulmonary component, occurs primarily in children40–42 and remains a diagnosis of exclusion.

TABLE 68-1Etiology of Autoimmune Diffuse Alveolar Hemorrhage

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