Introduction
Idiopathic pulmonary hemorrhage (IPH) is a rare lung disease primarily affecting children who are under the age of 10. Patients affected by this disease often experience bleeding in the lungs which can result in repeated episodes of breathlessness and coughing accompanied by blood. The recurrent episodes of diffuse alveolar hemorrhage can often lead to multiple respiratory problems and permanent lung damage.
What Is Idiopathic Pulmonary Hemosiderosis?
Idiopathic pulmonary hemosiderosis (IPH) is a disorder characterized by recurrent episodes of bleeding into the lungs that can lead to anemia and lung disease. The term idiopathic means that the cause is not yet known, pulmonary means lung involvement, and hemosiderosis refers to hemosiderin (the storage form of iron in the body) deposition. Even though the body can remove excess blood from the lungs, the iron that is left behind cannot be removed. This iron can lead to permanent damage to the lungs.
What Are the Causes of Idiopathic Pulmonary Hemosiderosis?
The definitive cause of idiopathic pulmonary hemosiderosis is unknown and is thought to be an autoimmune disease. The autoimmune hypothesis states that cells that are responsible to provide immunity end up causing bleeding in the lungs and irreversible scarring over time. Although the definitive mechanism is unknown, scientists suggest that bioactive proteins like histamine, vascular endothelial growth factor (VEGF), or eosinophil cationic protein (ECP) could be the offending agents. When a yet-to-be-discovered antigen triggers the immune cells, inappropriate activation of these cells takes place leading to lung bleeding.
The other possible causes that are thought to be associated with idiopathic pulmonary hemosiderosis are as follows:
-
Toxic insecticides.
-
Fungal toxin exposure.
-
Premature birth.
-
Rheumatoid arthritis (a chronic inflammatory bone condition affecting multiple bones and joints).
-
Thyrotoxicosis (a medical condition that occurs when excess thyroid hormones are released into the blood).
-
Autoimmune hemolytic anemia (an uncommon autoimmune disorder that causes the destruction of red blood cells).
-
Celiac disease (an immune disorder resulting in small intestine damage).
-
Genetics (this disease has been reported in children and siblings of idiopathic pulmonary hemosiderosis patients).
-
Environmental components like secondhand smoking and mold exposure.
-
Patients with Down syndrome are considered to be at high risk of developing idiopathic pulmonary hemosiderosis.
What Are the Symptoms of Idiopathic Pulmonary Hemosiderosis?
The symptoms of idiopathic pulmonary hemosiderosis are normally present in two phases, acute and chronic. The acute phase often presents with episodes of intra-alveolar bleeding and other symptoms like chronic cough, dyspnea, etc. The chronic phase involves the slow resolution of symptoms with or without treatment. The symptoms of idiopathic pulmonary hemosiderosis are as follows:
-
Dyspnea (shortness of breath).
-
Hemoptysis (coughing up blood).
-
Chronic coughs.
-
Fever.
-
Anemia (low red blood cells).
-
Chest pain.
-
Hepatosplenomegaly (enlarged spleen and liver).
-
Failure to thrive or deficient growth in children.
-
Pallor (pale skin).
-
Allergy.
-
Pulmonary infiltrates.
-
Asphyxiation (oxygen deprivation leading to suffocation).
-
Cardiomegaly (increase in the size of the heart).
-
Respiratory failure.
-
Heart murmurs (unusual or extra sound heard during a heartbeat).
-
Crackles (discontinuous and adventitious lung sounds heard during inspiration and sometimes during exhalation).
How to Diagnose Idiopathic Pulmonary Hemosiderosis?
As idiopathic pulmonary hemosiderosis is a rare disease, it is mostly diagnosed by ruling out the other possible causes of scarring or bleeding in the lungs. Often a multidisciplinary team involving pulmonologists, rheumatologists, critical care doctors, thoracic surgeons, and respiratory therapists is involved. The various tests that may help in diagnosing idiopathic pulmonary hemosiderosis are as follows:
-
Sputum Testing: Sputum testing with Prussian blue and hematoxylin-eosin stains. Stains for bacteria, mycobacteria, and fungi are also done.
-
Blood Tests: Blood tests to check blood cell counts, antibody levels, and iron studies are performed.
-
Prothrombin Time: Activated partial thromboplastin time (aPTT) and prothrombin time (PT) to evaluate bleeding disorders.
-
Urinalysis: Urinalysis for proteinuria and hematuria to rule out secondary pulmonary hemosiderosis.
-
Imaging Studies: Imaging tests like plain film chest radiographs and CT (computed tomography) scans.
-
Bronchoalveolar Lavage (BAL): It is also termed bronchioalveolar washing, where little amounts of sterile saline are instilled into the lungs and collected later for evaluation.
-
Bronchoscopy: This method is one of the typical diagnostic criteria for idiopathic pulmonary hemosiderosis. This procedure involves passing a bronchoscope (a thin tube) through the nose or mouth down into the throat and lungs. It helps in viewing the airways and taking samples of the fluids present in the lungs to diagnose lung disorders.
-
Lung Biopsy: Lung biopsy involves removing tissue from the lungs and observing it under a microscope for signs of some diseases.
What Are the Treatment Options for Idiopathic Pulmonary Hemosiderosis?
The main aim of idiopathic pulmonary hemosiderosis treatment is to suppress the immune response and reduce damage by preventing multiple bleeding episodes. There is no definitive treatment for idiopathic pulmonary hemosiderosis. However, the commonly accepted treatment measures are as follows:
-
Steroids: Steroids help in controlling the bleeding into the lungs and the scarring that occurs afterward.
-
Immunosuppressants: Immunosuppressants are medications that assist in preventing lung bleeding by subduing the immune system. The commonly used drugs are Cyclophosphamide, Hydroxychloroquine, 6-Mercaptopurine or Azathioprine, Mycophenolate mofetil, or Rituximab.
-
Stem Cell Transplant: This is an experimental treatment option. Stem cell transplant therapy involves using the body’s stem cells in modulating the immune system and thereby preventing bleeding.
-
Blood Transfusions: Idiopathic pulmonary hemosiderosis involves huge blood loss in patients. Hence replacing the lost blood due to lung bleeding helps to relieve the symptoms of anemia in patients.
-
Extracorporeal Membrane Oxygenation (ECMO): In extracorporeal membrane oxygenation, blood is pumped outside the body to a heart-lung machine that helps in removing carbon dioxide and sending oxygen-containing blood back into the body. ECMO is often used as a temporary life support system during end-stage lung disease or acute severe bleeding until a lung transplant can be successfully accomplished for appropriate patients.
-
Lung Transplant: A lung transplant is a final treatment option for severe cases of idiopathic pulmonary hemosiderosis. There are chances of IPH recurrence even in the transplanted lung, however, very few lung transplant cases have been reported.
Conclusion
Even though idiopathic pulmonary hemosiderosis is a relatively rare disease it poses a diagnostic dilemma as it is either misdiagnosed or missed entirely. Since it is a rare disease, there is very limited research that is going on. Further studies on idiopathic pulmonary hemosiderosis including case reviews would be beneficial in diagnosing and formulating efficient treatment plans for patients in the future. In the current scenario, patients with IPH should be approached by an interprofessional team of specialists including pulmonologists, primary care providers, and hospitalists. Early recognition and prompt treatment of the disease would help in improving the symptoms and enable the patients to lead better lives.
