Hemosiderosis
Encyclopedia
Idiopathic pulmonary haemosiderosis (or idiopathic pulmonary hemosiderosis; IPH) is a lung
disease
of unknown cause that is characterized by alveolar
capillary
bleeding and accumulation of haemosiderin in the lungs. It is rare, with an incidence
between 0.24 and 1.23 cases per million people.
in 1864 in patients after their death. Wilhelm Ceelen later correlated his findings to the clinical symptom
s of two children who died of IPH in 1931. The first living patient was diagnosed by Jan Waldenström
in 1944. It has been given several names, including:
, which in itself causes additional lung damage. Meanwhile, there is insufficient iron for inclusion into the haemoglobin molecules inside red blood cell
s which carry oxygen
to body tissues for cellular respiration
.
Idiopathic pulmonary haemosiderosis can occur either as a primary lung disorder or as the sequela to other pulmonary, cardiovascular or immune system disorder.
, diffuse parenchymal infiltrates on chest radiographs, and iron deficiency anaemia
. It is diagnosed at an average age of 4.5 plus or minus 3.5 years, and it is twice as common in females. The clinical course of IPH is exceedingly variable, and most of the patients continue to have episodes of pulmonary haemorrhage
despite therapy. Death may occur suddenly from acute pulmonary haemorrhage or after progressive pulmonary insufficiency resulting in chronic respiratory failure
.
s are the mainstay of treatment of IPH, though they are controversial and lack clear evidence in their favour. They are thought to decrease the frequency of haemorrhage, while other studies suggest that they do not have any effect on the course or prognosis of this disease. In either case, steroid therapy has significant side effects. Small trials have investigated the use of other medications, but none has emerged as a clear standard of care. This includes immune modulators such as hydroxychloroquine
, azathioprine
, and cyclophosphamide
. 6-mercaptopurine as a long-term therapy may prevent pulmonary haemorrhage. A 2007 scientific letter. reports preliminary success in preventing pulmonary haemorrhage with the anti-oxidant N-acetylcysteine.
Lung
The lung is the essential respiration organ in many air-breathing animals, including most tetrapods, a few fish and a few snails. In mammals and the more complex life forms, the two lungs are located near the backbone on either side of the heart...
disease
Disease
A disease is an abnormal condition affecting the body of an organism. It is often construed to be a medical condition associated with specific symptoms and signs. It may be caused by external factors, such as infectious disease, or it may be caused by internal dysfunctions, such as autoimmune...
of unknown cause that is characterized by alveolar
Pulmonary alveolus
An alveolus is an anatomical structure that has the form of a hollow cavity. Found in the lung parenchyma, the pulmonary alveoli are the dead ends of the respiratory tree, which outcrop from either alveolar sacs or alveolar ducts, which are both sites of gas exchange with the blood as well...
capillary
Capillary
Capillaries are the smallest of a body's blood vessels and are parts of the microcirculation. They are only 1 cell thick. These microvessels, measuring 5-10 μm in diameter, connect arterioles and venules, and enable the exchange of water, oxygen, carbon dioxide, and many other nutrient and waste...
bleeding and accumulation of haemosiderin in the lungs. It is rare, with an incidence
Incidence (epidemiology)
Incidence is a measure of the risk of developing some new condition within a specified period of time. Although sometimes loosely expressed simply as the number of new cases during some time period, it is better expressed as a proportion or a rate with a denominator.Incidence proportion is the...
between 0.24 and 1.23 cases per million people.
History
The condition was first described as "brown lung induration" by Rudolf VirchowRudolf Virchow
Rudolph Carl Virchow was a German doctor, anthropologist, pathologist, prehistorian, biologist and politician, known for his advancement of public health...
in 1864 in patients after their death. Wilhelm Ceelen later correlated his findings to the clinical symptom
Symptom
A symptom is a departure from normal function or feeling which is noticed by a patient, indicating the presence of disease or abnormality...
s of two children who died of IPH in 1931. The first living patient was diagnosed by Jan Waldenström
Jan G. Waldenström
Jan Gösta Waldenström was a Swedish doctor of internal medicine, who first described the disease which bears his name, Waldenström's macroglobulinemia....
in 1944. It has been given several names, including:
- Haemosiderin accumulation
- Pulmonary haemosiderosis
- Brown induration of lung
- Essential brown induration of lung
- Ceelen-Gellerstedt syndrome (after physicians Wilhelm Ceelen and Nils Gellerstedt)
Pathophysiology
Being idiopathic, IPH by definition has an unknown cause. It is thought to be an immune-mediated disease. The lung bleeding causes accumulation of ironIron
Iron is a chemical element with the symbol Fe and atomic number 26. It is a metal in the first transition series. It is the most common element forming the planet Earth as a whole, forming much of Earth's outer and inner core. It is the fourth most common element in the Earth's crust...
, which in itself causes additional lung damage. Meanwhile, there is insufficient iron for inclusion into the haemoglobin molecules inside red blood cell
Red blood cell
Red blood cells are the most common type of blood cell and the vertebrate organism's principal means of delivering oxygen to the body tissues via the blood flow through the circulatory system...
s which carry oxygen
Oxygen
Oxygen is the element with atomic number 8 and represented by the symbol O. Its name derives from the Greek roots ὀξύς and -γενής , because at the time of naming, it was mistakenly thought that all acids required oxygen in their composition...
to body tissues for cellular respiration
Cellular respiration
Cellular respiration is the set of the metabolic reactions and processes that take place in the cells of organisms to convert biochemical energy from nutrients into adenosine triphosphate , and then release waste products. The reactions involved in respiration are catabolic reactions that involve...
.
Idiopathic pulmonary haemosiderosis can occur either as a primary lung disorder or as the sequela to other pulmonary, cardiovascular or immune system disorder.
- PH1 involves PH with circulating anti-GMB antibodiesAnti-glomerular basement membrane antibodyAnti-glomerular basement membrane antibody is an antibody which is found in Goodpasture's syndrome but not found in microscopic polyangiitis....
. - PH2 involves PH with immune complex disease such as systemic lupus erythematosusSystemic lupus erythematosusSystemic lupus erythematosus , often abbreviated to SLE or lupus, is a systemic autoimmune disease that can affect any part of the body. As occurs in other autoimmune diseases, the immune system attacks the body's cells and tissue, resulting in inflammation and tissue damage...
, SLE. - PH3 involves no demonstrable immune system involvement.
Related or similar conditions
There are many pulmonary problems that may seem to mimic haemosiderosis but do not necessarily include the deposits of iron into the lung. The deposition of iron in the lungs, occurring in the form of haemosiderin, is the defining characteristic of this illness. These other conditions may occur separately or together with haemosiderosis.- Pulmonary FibrosisPulmonary fibrosisPulmonary fibrosis is the formation or development of excess fibrous connective tissue in the lungs. It is also described as "scarring of the lung".-Symptoms:Symptoms of pulmonary fibrosis are mainly:...
- Adult Respiratory Distress Syndrome (ARDS)
- Immune Complex Disease
- intra-alveolar bleeding
Diagnosis
Clinically, IPH manifests as a triad of haemoptysisHemoptysis
Hemoptysis or haemoptysis is the expectoration of blood or of blood-stained sputum from the bronchi, larynx, trachea, or lungs Hemoptysis or haemoptysis is the expectoration (coughing up) of blood or of blood-stained sputum from the bronchi, larynx, trachea, or lungs Hemoptysis or haemoptysis ...
, diffuse parenchymal infiltrates on chest radiographs, and iron deficiency anaemia
Iron deficiency anemia
Iron-deficiency anemia is a common anemia that occurs when iron loss occurs, and/or the dietary intake or absorption of iron is insufficient...
. It is diagnosed at an average age of 4.5 plus or minus 3.5 years, and it is twice as common in females. The clinical course of IPH is exceedingly variable, and most of the patients continue to have episodes of pulmonary haemorrhage
Pulmonary hemorrhage
Pulmonary hemorrhage is an acute bleeding from the lung, especially in the upper respiratory tract and the endotracheal tube. When evident clinically, the condition is usually massive, associated with bleeding in other sites as well as more than one third of the lungs...
despite therapy. Death may occur suddenly from acute pulmonary haemorrhage or after progressive pulmonary insufficiency resulting in chronic respiratory failure
Respiratory failure
The term respiratory failure, in medicine, is used to describe inadequate gas exchange by the respiratory system, with the result that arterial oxygen and/or carbon dioxide levels cannot be maintained within their normal ranges. A drop in blood oxygenation is known as hypoxemia; a rise in arterial...
.
Treatment
CorticosteroidCorticosteroid
Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex. Corticosteroids are involved in a wide range of physiologic systems such as stress response, immune response and regulation of inflammation, carbohydrate metabolism, protein catabolism, blood electrolyte...
s are the mainstay of treatment of IPH, though they are controversial and lack clear evidence in their favour. They are thought to decrease the frequency of haemorrhage, while other studies suggest that they do not have any effect on the course or prognosis of this disease. In either case, steroid therapy has significant side effects. Small trials have investigated the use of other medications, but none has emerged as a clear standard of care. This includes immune modulators such as hydroxychloroquine
Hydroxychloroquine
Hydroxychloroquine is an antimalarial drug, sold under the trade names Plaquenil,Axemal, Dolquine, and Quensyl, also used to reduce inflammation in the treatment of rheumatoid arthritis and lupus...
, azathioprine
Azathioprine
Azathioprine is a purine analogue immunosuppressive drug. It is used to prevent organ rejection following organ transplantation and to treat a vast array of autoimmune diseases, including rheumatoid arthritis, pemphigus, inflammatory bowel disease , multiple sclerosis, autoimmune hepatitis, atopic...
, and cyclophosphamide
Cyclophosphamide
Cyclophosphamide , also known as cytophosphane, is a nitrogen mustard alkylating agent, from the oxazophorines group....
. 6-mercaptopurine as a long-term therapy may prevent pulmonary haemorrhage. A 2007 scientific letter. reports preliminary success in preventing pulmonary haemorrhage with the anti-oxidant N-acetylcysteine.