Etiology

Most cases of DAH are associated with an underlying immunologic, rheumatologic, or vasculitic disorder but other diagnoses may manifest as recurrent or chronic pulmonary bleeding (Table 400-1).

Table 400-1 CLASSIFICATION OF DIFFUSE ALVEOLAR HEMORRHAGE SYNDROMES

From Susarla SC, Fan LL: Diffuse alveolar hemorrhage syndromes in children, Curr Opin Pediatr 19:314–320, 2007.

Pulmonary hemosiderosis has historically been classified as primary or secondary. Primary pulmonary hemosiderosis (PPH) is described as encompassing the diagnoses of IPH, Goodpasture syndrome (Chapter 511), and Heiner syndrome (cow’s milk hyperreactivity); Goodpasture syndrome (or anti–basement membrane antibody disease) appears to be the most common among these entities as a cause of pulmonary hemorrhage.

Secondary pulmonary hemosiderosis refers to the remaining, diverse group of potential etiologies. Among these are cardiac causes of pulmonary hemosiderosis, such as congestive heart failure, pulmonary hypertension, and mitral valve stenosis. Vasculitic and collagen vascular diseases such as systemic lupus erythematosus (SLE; Chapter 152), rheumatoid arthritis (Chapter 148), Wegener granulomatosis (Chapter 161.4), and Henoch-Schönlein purpura (HSP; Chapter 161.1) are another important group to consider in the differential diagnosis. Coagulopathies are encountered and may be either inherited or acquired. Prematurity is also a recognized risk factor for hemorrhage. Pulmonary hemosiderosis has been well described in association with celiac disease. Postinfectious processes such as hemolytic-uremic syndrome (Chapter 478.4) and immunodeficiency syndromes, including chronic granulomatous disease (CGD; Chapter 124) have also been implicated. Numerous medications, environmental exposures, chemicals, and food allergens have been reported as potential causes.