What is Idiopathic Pulmonary Hemorrhage?
Idiopathic pulmonary hemorrhage is a rare condition that affects the airways and lungs. This condition is divided into two groups based on if it comes on suddenly (acute) or develops over a long time (chronic). Sudden idiopathic pulmonary hemorrhage often shows up as widespread bleeding in the lung’s air sacs (diffuse alveolar hemorrhage or DAH), while slower, long-term pulmonary hemorrhage usually appears as idiopathic pulmonary hemosiderosis (IPH) after repeated bleeding in the lung’s air sacs. Sometimes, these terms are used interchangeably.
The first time idiopathic pulmonary hemorrhage was described was in 1864. Back then, it was called “brown lung induration.” Later on, in 1931, a more detailed description was given after post-death examinations (autopsies) revealed a lot of hemosiderin (an element that comes from the breakdown of hemoglobin, a part of red blood cells) in the lungs of two children.
Pulmonary hemorrhage refers to bleeding in the lungs or lower respiratory tract. This can be severe and even life-threatening. In DAH, the sudden widespread bleeding isn’t limited to just one part of the lungs. In IPH, repeat bleeding in the lung’s air sacs leads to the build-up of hemosiderin. Cells in the lungs, called alveolar macrophages, absorb these hemosiderin particles usually within 36 to 72 hours, and they can stay in the lungs for up to 8 weeks.
Acute idiopathic pulmonary hemorrhage in infants (AIPHI) is a rare, quite distinct form of the condition that occurs in infants. It’s characterized by sudden bleeding in the lungs of an otherwise healthy infant without other known related medical conditions, including prematurity.
The effects of IPH can range from cases that show no symptoms to severe, life-threatening breathing failure. AIPHI often shows up suddenly with severe breathing distress. Because it’s rare and can look different in different people, IPH often trips up many doctors, leading to incorrect diagnoses. Unfortunate, a late diagnosis often leads to delayed treatment and, ultimately, poor outcomes.
What Causes Idiopathic Pulmonary Hemorrhage?
Idiopathic Pulmonary Hemorrhage (IPH), as the name suggests, is a condition for which we don’t know the exact cause. ‘Idiopathic’ comes from a word that means ‘unknown’, and ‘pulmonary hemorrhage’ means bleeding in the lungs. IPH is a diagnosis made when all other possible causes of lung bleeding have been examined and discounted. These could include conditions like vasculitis, an inflammation of the blood vessels, or bleeding disorders such as von Willebrand disease, a condition that can lead to excessive bleeding.
Medical professionals also need to ensure that the bleeding isn’t coming from somewhere else in the body, such as the gastrointestinal tract. Although IPH isn’t very well-understood, some potential triggers may include lower respiratory tract infections, celiac disease, and an allergy to cow’s milk protein, but these connections are not definite. This may be because IPH is a rare disease, so we don’t have a lot of data to examine.
Some reports have mentioned a possible connection with Down’s syndrome. Also, there once was speculation about an association with a particular type of mold, Stachybotrys chartarum, but this idea has since been refuted. As of now, no clear link has been established between IPH and environmental factors such as tobacco smoking.
Risk Factors and Frequency for Idiopathic Pulmonary Hemorrhage
IPH, or Idiopathic Pulmonary Hemosiderosis, is an uncommon condition mainly found in children, particularly those under 10 years of age. In fact, it’s estimated that this age group accounts for 80% of all IPH cases. The disease’s occurrence shows two peak periods: one for children under 5 and another for those over 11 years. Adult cases of IPH are usually diagnosed before the person turns 30. IPH is rarely found in infants, with a study in Boston revealing only 4 cases out of 154 infants with lung bleeding diagnosed with this condition.
On a global scale, IPH cases range from 0.24 to 1.23 per million people. There’s no gender preference for the disease among children. However, adult males seem to have a higher occurrence rate than adult females. It also doesn’t favor any particular ethnicity. There have been instances where multiple family members were diagnosed with IPH, but there’s no known genetic link to the disease yet.
- IPH mainly affects children, especially those under 10, accounting for 80% of all cases.
- There are two peak periods of occurrence: one for kids below 5 and another for those over 11.
- IPH rarely occurs in infants.
- Adult cases of IPH are usually diagnosed before age 30.
- On a global scale, the disease occurs in 0.24 to 1.23 people per million.
- Among children, the disease doesn’t prefer any gender, but in adults, it’s more prevalent in males.
- There’s no known ethnic preference for IPH.
- While family clustering cases have been reported, there’s no known genetic basis for the disease.
Signs and Symptoms of Idiopathic Pulmonary Hemorrhage
Idiopathic pulmonary hemorrhage is a medical condition that can present differently depending on whether it’s acute or chronic. The acute form often starts suddenly with severe breathlessness and coughing up of blood. If not treated quickly, this can be life-threatening. On the other hand, the chronic form has a slower onset with varying symptoms such as coughing up blood, iron deficiency anemia, cough, and breathlessness due to recurring episodes of acute pulmonary hemorrhage. The most common symptoms are anemia and breathlessness. In severe cases, this condition can lead to oxygen deprivation in the body, mainly affecting infants.
- Severe breathlessness and coughing up blood
- Anemia due to iron deficiency
- Cough
- Breathlessness
Notably, it’s rare in children to see the classical triad of symptoms, including coughing up blood, iron-deficiency anemia, and scattered shadows on chest scans. Some children might also show symptoms like weight loss and failure to grow and develop normally.
Interestingly, in some infants who develop sudden pulmonary hemorrhage, they may not show signs of respiratory distress, and chest scans may show normal results. This situation is sometimes referred to as ‘probable AIPHI.’ In certain cases of this condition, iron deficiency anemia may be the first sign, appearing several months before other symptoms. These patients often require repeated blood transfusions, even with iron supplements.
Furthermore, there are other less common and non-specific symptoms such as recurrent chest infections, fever, chest pain, and rapid breathing.
- Recurrent chest infections
- Fever
- Chest pain
- Rapid breathing
Physical examination findings might differ based on if it’s an acute or chronic case. In the acute phase, the physical examination could appear normal or show signs of respiratory distress like rapid breathing. In the chronic phase, patients may show paleness, failure to grow, weight loss, or an enlarged liver and spleen. However, in some cases, the examination could be entirely normal. If lung scarring has taken place, there may be finger and toe clubbing signs of long-term oxygen deprivation.
Testing for Idiopathic Pulmonary Hemorrhage
Acute IPH, a lung bleeding condition, is a complex condition to diagnose. It often takes time and other possible causes of lung and systemic bleeds must be ruled out first. Unfortunately, due to its rarity and the potential for unusual symptoms, like anemia without clear respiratory symptoms, misdiagnosis or delayed diagnosis is frequent.
The correct diagnosis can sometimes take up to a decade to be identified. However, doctors tend to suspect IPH in patients who have repeated chest infections, persistent anemia that doesn’t improve with iron supplements, and unusual patches in the lungs on chest x-rays, provided other causes of anemia have been ruled out.
For infants, it’s essential to also disregard any congenital heart disease, prematurity, congenital and acquired lung diseases, and inherited or developed coagulation disorders. It’s also crucial to make sure that any gastrointestinal bleeding is not the cause of the observed symptoms.
Simple blood tests may show changes like reduced hemoglobin counts and hematocrit, an increased number of white blood cells, or an elevated rate at which red blood cells settle at the bottom of a test tube of blood. Chest X-ray findings could also show patchy or focal shadowing or ‘air bronchograms’ – air-filled bronchi seen on the image.
A more sophisticated imaging method, such as a high-resolution CT scan, can provide more specific details. It could show changes like ground-glass opacities, consolidations, in addition to tiny nodules and lines in the lungs, often related to varying degrees of scarring. Such scans are valuable in confirming the X-ray findings and understanding how extensive the disease is.
Lung functional tests could also show a restrictive pattern, meaning the volume of the lungs could be reduced.
An examination of lung tissues under a microscope, known as a lung biopsy, is the definitive diagnostic method for IPH. In the biopsy, we can visualize iron-laden cells. However, it’s a complicated procedure and often not feasible in children.
An alternate and more practical method is the analysis of broncho-alveolar lavage (BAL) fluid. This fluid is retrieved from the lungs and analyzed for increasing red blood cell count, which would occur in cases of lung bleeding, or for infectious agents. This procedure has a success rate of about 92%.
Gastric fluid analysis can also be used, particularly in children. However, this method isn’t as reliable, although its sensitivity can be improved by repeated sampling and testing.
Treatment Options for Idiopathic Pulmonary Hemorrhage
Idiopathic pulmonary hemosiderosis (IPH) is a condition that does not have a single, universally recognized best treatment. However, high-dose steroid medications are often used to help manage the symptoms of IPH, and have shown good results. It’s important to know that this disease often comes back, even after treatment.
For more severe cases, or when steroids cannot be taken or are not well-tolerated, doctors may use immune-suppressing medications like hydroxychloroquine, azathioprine, cyclophosphamide, and 6-mercaptopurine. These drugs can be used alongside steroids or on their own.
In babies, steroids have been given at doses of 2 mg for each kilogram of body weight per day. The treatment lasts for between 80 and 210 days and has shown to be effective. In older children and adults, case reports suggest a dose of less than 1 mg per kilogram of body weight per day. The steroid treatment is continued until the alveolar infiltrates, or excess fluid and cells in the small air sacs of the lungs, have cleared up. After this, the dose is gradually decreased.
In some cases, using a combination of azathioprine and steroids has led to better outcomes. There are also other treatment options that may be effective, but their effectiveness is not yet well-known. These include intravenous immunoglobulin (IVIG), a type of therapy that uses a mixture of antibodies; plasmapheresis, a process that filters the blood and removes harmful substances; liposteroids, a type of steroid; and dietary changes. For example, people with both celiac disease and IPH may see an improvement in their symptoms with a gluten-free diet.
What else can Idiopathic Pulmonary Hemorrhage be?
: When doctors are trying to diagnose IPH (Idiopathic Pulmonary Hemosiderosis), they also need to consider other conditions that could have similar symptoms. These conditions include:
- Various types of vasculitis like microscopic polyangiitis, Wegener’s granulomatosis, Churg Strauss syndrome, etc.
- Other conditions like Goodpasture’s syndrome, antiphospholipid syndrome, and lung transplant rejection.
- Non-vasculitic conditions like coagulopathies (disorders affecting blood clotting, such as von Willebrand disease), pulmonary embolism, lung cancers, lung injury, etc.
- Restrictive lung diseases, other autoimmune diseases, recurrent respiratory infections, and more.
In essence, the accurate diagnosis of IPH can be challenging due to the wide range of alternative conditions that need to be ruled out.
What to expect with Idiopathic Pulmonary Hemorrhage
The outcome for patients with IPH, or Idiopathic Pulmonary Hemosiderosis, depends on several factors. These can include how quickly the disease is diagnosed, how soon treatment is started, and whether the person has other health conditions. Prompt diagnosis and early treatment generally lead to a better outcome.
On average, patients with IPH live for about 2.5 years. But there’s hopeful news, too. In one study, 86% of patients lived beyond 5 years. The death rate is 50% for this disease, however, a study showed that none of the 4 infants with a variation of IPH (AIPHI) died. It’s important to note that this disease can be harder to manage and the outcomes can be worse in children and teenagers compared to adults.
The most common cause of death in patients with IPH is acute respiratory failure. This could be due to severe lung bleeding, or complications from chronic respiratory failure and a heart condition called cor pulmonale that can happen as a result of severe lung scarring. Long-term use of a type of medication called steroids can reduce illness and the chance of death in patients with IPH.
Possible Complications When Diagnosed with Idiopathic Pulmonary Hemorrhage
The condition can cause an immediate complication called hypoxic respiratory failure. This is when there is not enough oxygen in your blood to reach your tissues and cells. It’s a serious condition and can even cause death, and is particularly risky for children. In the long-term, complications can include anemia, which is a condition where your red blood cells don’t carry enough oxygen to serve your body’s needs. Pulmonary fibrosis is another possible complication. This is a lung disease that occurs when lung tissue becomes damaged and scarred, making it difficult for you to breathe. Other lung diseases that restrict your breathing can also occur. Lastly, using corticosteroids for long periods can have side effects which can lead to complications.
Possible Complications:
- Hypoxic respiratory failure
- Anemia
- Pulmonary fibrosis
- Other restrictive pulmonary lung diseases
- Side effects of long-term corticosteroid use
Preventing Idiopathic Pulmonary Hemorrhage
Just like with other diseases that affect the lungs and breathing, it’s recommended that patients or the people taking care of them visit the hospital as soon as they notice any symptoms. Since the cause of the disease is unknown, there are no specific steps one can take to prevent it. Also, this disease cannot be spread from person to person.
