IDIOPATHIC PULMONARY HEMOSIDEROSIS
Idiopathic pulmonary hemosiderosis (IPH) is a disease of unknown origin, usually occurring in children, equally in both genders. Repeated episodes of pulmonary hemorrhage with resultant blood-loss anemia and eventual respiratory failure characterize the illness. In children, this disorder is associated with celiac disease and elevated IgA levels. Environmental exposure to molds, particularly Stachybotrys chartarum, has been suggested as a causative factor in infants with IPH, but the relationship remains unproven.
Bland pulmonary hemorrhages without immune complexes are typical histologic ﬁndings. A structural defect in the alveolar capillaries may predispose individuals to the condition. Neutrophilic inﬁltration (i.e., alveolar capillaritis or vasculitis) is not found. Repeated hemorrhages result in hemosiderin-laden alveolar macrophages and the deposition of free iron in pulmonary tissue; the latter may result in the development of lung ﬁbrosis. Obliteration of alveolar capillaries may result in pulmonary hypertension. Hemosiderin-impregnated nodules are scattered in the parenchyma, along the lymphatics, and in the draining hilar lymph nodes. The role of immunologic injury in patients with IPH remains unclear.
The onset of IPH may be insidious or with an explosive episode of hemoptysis. In some patients, anemia, constitutional symptoms, cough, and radiographic changes precede frank hemoptysis. During acute bleeding episodes, crackles, wheezes, and rhonchi with dullness to percussion are noted over the involved lung areas. Later, dyspnea, tachypnea, hepatosplenomegaly, and clubbing of the ﬁngers may be observed.
Routine laboratory data are remarkable only in the presence of marked iron deﬁciency. There is no evidence of coagulopathy, thrombocytopenia, hepatic dysfunction, or glomerulonephritis.
Physiologic abnormalities in IPH vary depending on the freshness of the hemorrhage, degree of ﬁbrosis, and severity of vascular involvement. With acute hemorrhage, the vital capacity, ﬂow rates, and arterial Po2 may be diminished; however, the DLCO (diffusing capacity for carbon monoxide) may be inappropriately high. As ﬁbrosis ensues, a restrictive pattern with reduced DLCO emerges. Irreversible pulmonary hypertension and right ventricular failure are hallmarks of the end stage of the disease.
During acute hemorrhagic episodes, the chest radiograph exhibits patchy or diffuse alveoli-ﬁlling shadows. These opacities may clear rapidly, only to appear in the same or other locations with subsequent bouts of hemorrhage. Air bronchograms are frequently obtained. High-resolution computed tomography (HRCT) scans show diffuse ground-glass or airspaceﬁlling opacities most prominent in the middle and lower lung ﬁelds. With repeated episodes, a reticular interstitial pattern persists in the areas of prior hemorrhage. The hilar lymph nodes may become enlarged. In the later stages, right ventricular hypertrophy and enlarged pulmonary arteries are common. Perfusion lung scanning with technetium-99m (99mTc) labeled albumin particles may show foci of high radioactivity in the lungs where radioactively tagged material has extravasated into the alveoli. In addition, active intrapulmonary bleeding can be visualized by pulmonary radioscintigraphy, in which autologous erythrocytes labeled with 51Cr or 99mTc are injected intravenously with subsequent recording of the radioactivity over the lungs.
IPH is a diagnosis of exclusion that is suggested by a history of recurrent episodes of hemoptysis, presence of an iron deﬁciency anemia, and typical radiographic abnormalities in a child with normal renal function. Sequential bronchoalveolar lavage (BAL) is useful because lavage aliquots are progressively more hemorrhagic. Hemosiderin-laden macrophages may be demonstrated by Prussian blue staining. BAL is most helpful in the diagnosis of diffuse pulmonary opacities without hemoptysis. In patients who do not experience the typical episodes of hemoptysis, lung biopsy is the only unequivocal means of establishing the diagnosis and may be accomplished by transbronchial or surgical lung biopsy techniques.
The prognosis in IPH is poor. Children and adolescents more frequently experience a rapid course and have a worse prognosis. In adults, the prognosis is more favorable. Corticosteroids and other immunosuppressive drugs may be effective during an acute episode. Chronic oral corticosteroids may decrease episodes of acute alveolar hemorrhage and delay progression to chronic ﬁbrotic changes. In patients with severe respiratory failure, extracorporeal membrane oxygenation may prolong survival until immunosuppressive therapy becomes effective. In IPH patients with celiac disease, a gluten-free diet has been associated with remission of pulmonary symptoms.