Pulmonary Hemosiderosis

Etiology

The varied etiologies of pulmonary hemosiderosis are classified on the basis of the presence or absence of pulmonary capillaritis , a pathologic process that is characterized by inflammation and cellular disruption of the alveolar interstitium and capillary bed. Although the finding of pulmonary capillaritis is nonspecific with regard to underlying diagnosis, its presence appears to be an important negative prognostic factor in DAH and may indicate an underlying systemic vasculitic process or collagen vascular disease.

Disorders associated with pulmonary capillaritis may include systemic lupus erythematosus (SLE; see Chapter 183 ), drug-induced capillaritis, granulomatosis with polyangiitis (previously Wegener granulomatosis), Goodpasture syndrome, and Henoch-Schönlein purpura (see Chapter 192 ). The finding of DAH in patients with granulomatosis with polyangiitis and microscopic polyangiitis (MPA; see Chapter 192 ) is frequently associated with pathologic evidence of pulmonary capillaritis. In patients with Goodpasture syndrome or SLE, DAH has been reported both with and without the associated finding of capillaritis. A number of systemic autoimmune and inflammatory disorders may predispose a host to DAH with pulmonary capillaritis. Similarly, a variety of drugs have been associated with the finding of pulmonary capillaritis but mechanisms of cellular derangement are as yet unidentified.

These disorders are distinguished from those without pulmonary capillaritis. Those disorders in which the pathologic finding of capillary network disruption is absent are further divided into cardiac (pulmonary hypertension, mitral stenosis) and noncardiac (immunodeficiency, Heiner syndrome, coagulopathies, IPH) etiologies. Table 435.1 provides a summary and classification of the diagnoses that may manifest as recurrent or chronic pulmonary bleeding.

Epidemiology

Disorders that present as DAH are highly variable in their severity, as well as in their associated symptomatology and identifiable abnormalities in laboratory testing; the diagnosis may be significantly delayed, making frequency estimates unreliable. Similarly, the prevalence of IPH is largely unknown. Of the children and young adults diagnosed with IPH in the past, it has been postulated that the etiology of the hemorrhage might have been discovered if they had been studied with the newer and more advanced diagnostics available today; specific serologic testing has vastly improved our ability to appreciate immune mediated disease. Estimates of prevalence obtained from Swedish and Japanese retrospective case analyses vary from 0.24 to 1.23 cases per million. Children and adolescents account for 30% of cases. The ratio of affected males:females is 1 : 1 in the childhood diagnosis group, and men are only slightly more affected in the group diagnosed as young adults.

Pathology

In pulmonary capillaritis, key histologic features include (1) fibrin thrombi, which occlude capillaries, (2) fibrin clots adherent to interalveolar septae, (3) fibrinoid necrosis of capillary walls, and (4) interstitial erythrocytes and hemosiderin. Illustrative but nonspecific pathologic findings, such as vascular smooth muscle hypertrophy (pulmonary hypertension), edema (mitral stenosis), or thrombosis (vascular thrombosis with infarction), may be found in those disorders that cause DAH without pulmonary capillaritis. The finding of blood in the airways or alveoli is representative of a recent hemorrhage. With repeated episodes of pulmonary hemorrhage, lung tissue appears brown secondary to this presence of hemosiderin. Hemosiderin-laden macrophages (HLMs) are seen with recovering, recurrent, or chronic pulmonary hemorrhage and are identifiable both in bronchoalveolar lavage fluid and in pathologic specimens of lung tissue. It takes 48-72 hr for the alveolar macrophages to convert iron from erythrocytes into hemosiderin. In a murine model, HLMs appear 3 days after a single episode of pulmonary hemorrhage and peak at 7-10 days. HLMs may be detectable for weeks to months after a hemorrhagic event. Other nonspecific pathologic findings include thickening of alveolar septa, goblet cell hyperplasia, and hypertrophy of type II pneumocytes. Fibrosis may be seen with chronic disease.