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Hemosiderosis

  • Author: Galia D Napchan, MD; Chief Editor: Michael R Bye, MD  more...
 
Updated: Jan 14, 2015
 

Background

Pulmonary hemosiderosis (PH) is characterized by repeated episodes of intra-alveolar bleeding that lead to abnormal accumulation of iron as hemosiderin in alveolar macrophages and subsequent development of pulmonary fibrosis and severe anemia. See the image below.

Image of a kidney viewed under a microscope. The b Image of a kidney viewed under a microscope. The brown areas contain hemosiderin.

Pulmonary hemosiderosis can occur as a primary disease of the lungs or can be secondary to cardiovascular or systemic disease. In children, primary pulmonary hemosiderosis is more common than secondary types.

Three variants of primary pulmonary hemosiderosis are recognized: (1) pulmonary hemosiderosis associated with antibody to the basement membrane of the lung and kidney (ie, Goodpasture syndrome), (2) pulmonary hemosiderosis associated with hypersensitivity to proteins in cow's milk (ie, Heiner syndrome), and (3) idiopathic pulmonary hemosiderosis (IPH).

The diagnosis of isolated pulmonary hemosiderosis or idopathic pulmonary hemosiderosis is a diagnosis of exclusion, requiring thorough review and elimination of other causes of primary and secondary pulmonary hemosiderosis.

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Pathophysiology

In 1975, Thomas and Irwin divided pulmonary hemosiderosis into 3 categories: one category in which anti–glomerular basement membrane (anti-GBM) is present, a second category in which immune complexes are found, and a third category in which neither can be demonstrated.

Following this classification, the pathophysiology of pulmonary hemosiderosis[1] can be divided into 3 groups.

Group 1 pulmonary hemosiderosis is defined by pulmonary hemorrhage associated with circulating anti-GBM antibodies. This condition defines Goodpasture syndrome. This syndrome is characterized by linear immunofluorescence deposition of immunoglobulin and complement along the basement membrane of the lung tissue and the kidney glomeruli and is associated with vascular damage and diffuse defragmentation of the basement membrane on electron microscopy.

Group 2 pulmonary hemosiderosis is defined as pulmonary hemorrhage and immune complex disease. This combination has been reported as a rare manifestation of systemic lupus erythematosus (SLE) and other connective tissue disorders, including cryoglobulinemia, Henoch-Schönlein purpura, mixed connective tissue disease, and Wegener granulomatosis.

Studies of patients with pulmonary hemosiderosis associated with hypersensitivity to cow's milk (ie, Heiner syndrome) have demonstrated circulating immune complexes; alveolar deposits of immunoglobulin G (IgG), immunoglobulin A (IgA), and C3; peripheral blood eosinophilia; and delayed hypersensitivity to proteins from cow's milk.

Group 3 pulmonary hemosiderosis is defined as pulmonary hemorrhage without demonstrable immunologic association. This category includes idopathic pulmonary hemosiderosis, bleeding disorders, cardiovascular diseases, widespread infection, and toxic inhalation. Idiopathic pulmonary hemosiderosis is morphologically characterized by intra-alveolar hemorrhage and subsequent abnormal accumulation of iron in the form of hemosiderin inside pulmonary macrophages. Recurrent episodes of hemorrhage lead to thickening of the alveolar basement membrane and interstitial fibrosis. Transmission electron microscopy of lung biopsies has shown that the major damage in this disorder involves capillary endothelium and its basement membrane, but no electro-dense deposits have been identified.

In the early 1990s, the incidence of acute idiopathic pulmonary hemosiderosis in young infants increased in several midwestern US cities, especially in the Cleveland area. Epidemiological research led to the discovery of heavy growth of the toxigenic fungus Stachybotrys atra in almost all of the case homes, suggesting that exposure to that mold can cause idiopathic pulmonary hemosiderosis in infants. Subsequent data question this association.

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Epidemiology

Frequency

United States

Idiopathic pulmonary hemosiderosis is an uncommon yet well-recognized disorder. Exact figures regarding prevalence are lacking. Familial recurrence has been reported but is rare.

International

Idiopathic pulmonary hemosiderosis is a rare disorder, with a reported yearly incidence of 0.24 (Sweden) and 1.23 (Japan) cases per million children.

Mortality/Morbidity

No national database monitors children with pulmonary hemosiderosis. Patients with idiopathic pulmonary hemosiderosis have a mean survival rate of 2.5-5 years after diagnosis. Death can occur acutely from massive hemorrhage or after progressive pulmonary insufficiency and right heart failure.

Sex

In patients younger than 10 years, reports of idiopathic pulmonary hemosiderosis show equal distribution between males and females in the United States, Sweden, and Greece; however, in Japan the female-to-male ratio was 2.25:1. In patients older than 10 years, the male-to-female ratio is 2:1.

Age

Idiopathic pulmonary hemosiderosis may occur in people of any age, from the neonatal period to late adulthood, but it is most common in children aged 1-7 years. Goodpasture syndrome usually occurs in young adult males and is rare in infants. Heiner syndrome is usually diagnosed in children aged 6 months to 2 years.

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Contributor Information and Disclosures
Author

Galia D Napchan, MD Pediatric Pulmonologist, Joe DiMaggio Children's Hospital

Galia D Napchan, MD is a member of the following medical societies: American Academy of Pediatrics

Disclosure: Nothing to disclose.

Coauthor(s)

Isaac Talmaciu, MD Clinical Assistant Professor, Department of Pediatrics, Florida Atlantic University School of Medicine

Isaac Talmaciu, MD is a member of the following medical societies: American Academy of Pediatrics, American Thoracic Society

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Charles Callahan, DO Professor, Chief, Department of Pediatrics and Pediatric Pulmonology, Tripler Army Medical Center

Charles Callahan, DO is a member of the following medical societies: American Academy of Pediatrics, American College of Chest Physicians, American College of Osteopathic Pediatricians, American Thoracic Society, Association of Military Surgeons of the US, Christian Medical and Dental Associations

Disclosure: Nothing to disclose.

Chief Editor

Michael R Bye, MD Professor of Clinical Pediatrics, State University of New York at Buffalo School of Medicine; Attending Physician, Pediatric Pulmonary Division, Women's and Children's Hospital of Buffalo

Michael R Bye, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Chest Physicians, American Thoracic Society

Disclosure: Nothing to disclose.

Additional Contributors

Thomas Scanlin, MD Chief, Division of Pulmonary Medicine and Cystic Fibrosis Center, Department of Pediatrics, Rutgers Robert Wood Johnson Medical School

Thomas Scanlin, MD is a member of the following medical societies: American Association for the Advancement of Science, Society for Pediatric Research, American Society for Biochemistry and Molecular Biology, American Thoracic Society, Society for Pediatric Research

Disclosure: Nothing to disclose.

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Image of a kidney viewed under a microscope. The brown areas contain hemosiderin.
 
 
 
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