What is Protein-Losing Enteropathy?
Protein-losing enteropathy (PLE) is a health issue where too many proteins are lost through the digestive system. This can happen due to various causes. It is often suspected in patients who have lower levels of protein in their blood and when other potential causes of low protein levels have been ruled out.
What Causes Protein-Losing Enteropathy?
There are three main categories of health issues that can lead to an excessive amount of protein being lost in your stool:
1. Diseases that cause erosion or ulcers in the digestive system
This group includes problems that cause swelling and sores in the digestive tract, like ulcerative colitis and Crohn’s disease, different types of abdominal cancers, sores in the stomach or start of the small intestine, an infection caused by a bacteria named “Clostridium difficile”, a medical condition called carcinoid syndrome that affects hormones, and a serious complication of transplant surgery known as “graft vs. host disease.”
2. Diseases that don’t necessarily cause visible sores or ulcers in the digestive system
Diseases in this category include celiac disease (an autoimmune disorder triggered by gluten), Menetrier’s disease (a rare stomach disorder), amyloidosis (a rare disorder where abnormal proteins build up in organs), burns to the skin, an inflammation of the digestive tract called eosinophilic gastroenteritis, too much bacteria in the gut, intestinal parasitic infections, Whipple’s disease (a rare bacterial infection), collagenous colitis (a form of microscopic colitis), complications related to AIDS, mixed connective tissue diseases, lupus, and rheumatoid arthritis.
3. Problems that increase pressure in the tissue surrounding intestines or block lymph (a fluid that contains white blood cells)
Possible causes here might include a rare disorder that causes the lymph vessels in the small intestine to improperly form or become blocked, conditions affecting the right side of the heart, constrictive pericarditis (a rare type of heart disease), some congenital heart diseases, a surgical procedure called the Fontan procedure, cirrhosis with related high blood pressure in the liver, blockage of veins carrying blood from the liver, tuberculosis or sarcoidosis affecting the tissue connecting the intestines to the abdominal wall, retroperitoneal fibrosis (a rare disorder that leads to inflammation and hardening of tissues behind the intestines), lymphoma (a type of cancer), or a blockage in the main lymphatic duct.
Risk Factors and Frequency for Protein-Losing Enteropathy
Protein-losing enteropathy is a condition whose frequency of occurrence and prevalence remain unknown. It can impact anyone, regardless of their age, race, or gender and doesn’t show preference towards any group in particular.
Signs and Symptoms of Protein-Losing Enteropathy
Protein-losing enteropathy is a condition where you lose protein from your intestines into your stools. This can be due to various causes, both related to your gut and related to other organs like the heart. The symptoms differ depending on the cause but generally, when the body loses lots of protein, it leads to swelling all over the body. This happens because the loss of protein lowers pressure inside your blood vessels, causing fluids to leak out into the surrounding tissues. This is most commonly seen as swelling in the feet and legs.
You might also experience a bloated abdomen from excess fluid build-up or fluid in your lungs causing difficulty with breathing. If your gut is the primary cause of the protein loss, you might have symptoms related to your digestive system like diarrhea, bloating, or abdominal pain.
Loss of protein can also mean your body loses antibodies and immune cells leading to an increased risk of infections. People with this condition are more prone to infections and may also fall prey to infections that don’t usually affect healthy individuals.
In individuals where the heart disease leads to protein loss, symptoms related heart failure like pitting edema (swelling that leaves a dent when pressed), fluid in the lungs, shortness of breath, and elevated neck vein pressure might be seen.
Signs and symptoms of protein-losing enteropathy include:
- Swelling all over the body, especially in the feet and legs
- Bloated abdomen from fluid build-up
- Difficulty with breathing due to fluid in the lungs
- Diarrhea, bloating, or abdominal pain if gut-related
- Increased risk of infections due to loss of antibodies and immune cells
- Heart failure symptoms like pitting edema, fluid in lungs, shortness of breath, and high neck vein pressure in case of heart disease-related protein loss
Testing for Protein-Losing Enteropathy
If your doctor suspects you have a medical condition called protein-losing enteropathy (PLE), it’s typically because you have a low protein level in your blood. They would first eliminate other common causes, like serious malnourishment (not getting enough nutrients from food), nephrotic syndrome (a type of kidney damage), or chronic liver diseases. Protein-losing enteropathy causes a decrease in different types of proteins, known as albumin and globulins, in your blood. However, if your test results show only a low level of albumin but normal globulins, your doctor might consider other causes.
To confirm protein-losing enteropathy, your doctor will most commonly suggest a test called Alpha 1 antitrypsin (A1AT) intestinal clearance. Essentially, this is a test where you collect stool samples over a day, and the A1AT protein levels in both your stool and blood are measured. The A1AT protein is quite large and doesn’t break down much in your gut, so it leaves the body in your stool in a digestible form. The formula for this test is quite simple: the volume of stool is multiplied by the A1AT in the stool and divided by the A1AT in the blood serum. Normally, your body should clear less than 13ml of A1AT in a day. Clearing more than 27 ml/day suggests you may have PLE.
Your doctor should be aware that different conditions can affect this clearance test. For example, if you have diarrhea, this can increase A1AT clearance, so a higher threshold of more than 56ml/24 hr should be used under those conditions. Furthermore, increased stomach acidity can also break down more A1AT, so ideally, this test should be taken while you’re on antacids (drugs to reduce stomach acidity), especially if your doctor suspects that over secretion in your stomach is driving protein loss. Moreover, if you have blood in your stools (a sign of gastrointestinal bleeding), this can also increase A1AT clearance.
If the A1AT test is inconclusive, your doctor can suggest other tests like 51Cr-labeled albumin clearance and technetium 99 labeled serum albumin scintigraphy, which are very sensitive but are often not readily available, more complicated, and costly. Hence, they are not regularly used.
Once protein-losing enteropathy is confirmed, with high A1AT clearance, your doctor will need to do more tests to find the root cause and decide on the best treatment strategy. Your doctor will take into account your medical history and conduct a physical examination. Additional basic laboratory tests like a complete blood count, liver function tests, and kidney function tests are commonly performed.
If your symptoms suggest a gastrointestinal cause of protein loss, your doctor might go for tests for celiac disease (a disease where your intestine is sensitive to gluten), tests for chronic intestinal infections, or imaging studies of your abdomen and pelvis. In some cases, your doctor might also suggest endoscopies, which involve inserting a thin tube with a light and a camera into your body through your mouth or rectum to visualize your gastrointestinal tract. If autoimmune conditions like lupus or rheumatoid arthritis are suspected, your doctor will ask for an autoimmune workup (tests to identify autoimmune diseases). Furthermore, if your doctor thinks that your heart might cause PLE, they would request an echocardiogram (an ultrasound of your heart) and tests that help determine if you have heart failure.
One specific cause of Protein-losing enteropathy is a surgical procedure known as a Fontan procedure on patients with congenital (from birth) heart disease, so your doctor will keep this possibility in mind.
Treatment Options for Protein-Losing Enteropathy
Treating the condition causing protein-losing enteropathy, or PLE, is the main focus of the treatment. Besides targeting the underlying condition, changing your diet can also significantly help manage PLE. A diet that’s high in protein and medium chain triglycerides (which are types of fats more easily absorbed by the body), and low in other fats is recommended. Patients may also need to replace any micronutrients, electrolytes, and vitamins they lack due to their condition.
For instance, if heart failure is what’s causing PLE, then taking medications for heart failure can help. Diuretics, or water pills, can help if symptoms like too much fluid in the body are present. In more extreme cases, getting a surgery called a pericardiectomy can provide relief for a condition known as constrictive pericarditis which is a heart issue where the sac around your heart restricts its ability to function properly.
If inflammation in the bowels is the cause, such as in inflammatory bowel disease or certain conditions like lupus or rheumatoid arthritis, drugs that weaken the immune system’s response (immunosuppressive medications) can help. Parasitic infections that can cause PLE are treated separately. In some cases, surgical removal of parts of the affected digestive tract might be necessary for Menetrier’s disease (a rare, chronic disorder that affects the stomach lining) and refractory inflammatory bowel disease, a condition that does not respond to standard treatments.
Medications like octreotide and budesonide have been found to be beneficial in certain conditions causing PLE, such as primary intestinal lymphangiectasia (a disorder causing the lymph vessels in the small intestine to leak), Menetrier’s disease, and eosinophilic gastroenteritis (an allergic inflammatory reaction in the digestive tract). In some cases of PLE tied to the Fontan procedure (a surgery to repair certain types of heart defects), corticosteroids may help.
Regular check-ups are essential once treatment begins. During these check-ups, the doctor will check levels of essential vitamins and micronutrients, protein levels in the blood, and Alpha-1 Antitrypsin (A1AT) clearance – a test that helps determine how well the liver is functioning.
What else can Protein-Losing Enteropathy be?
When identifying the cause of Protein Losing Enteropathy (PLE) – condition where too much protein is lost from the body – doctors keep in mind various conditions that can reduce protein levels in the body. These conditions can vary depending on what’s primarily causing the PLE. Common conditions include:
- Chronic liver diseases, which reduce protein due to reduced production
- kidney conditions that cause a lot of protein to be lost in urine, like Nephrotic Syndrome
- severe malnutrition that is both protein and calorie based
- conditions that prevent proper absorption of nutrients
- heart failure
- skin burns
What to expect with Protein-Losing Enteropathy
The outlook for protein-losing enteropathy, often called PLE, can change depending on why it’s happening in the first place. “Protein-losing enteropathy” is a fancy way of saying that your body is losing too much protein due to conditions in your intestines. If the original cause of this condition can be successfully treated, then PLE can potentially be completely cured.
Possible Complications When Diagnosed with Protein-Losing Enteropathy
The complications experienced largely depend on the underlying medical condition causing protein-losing enteropathy. For instance, people with Inflammatory Bowel Disease (IBD) may also have to deal with colon cancer, anemia, primary sclerosing cholangitis, among other issues. If the protein-losing enteropathy originates from a disease causing ulcers, these patients can experience an ulcer rupture leading to peritonitis, a dangerous infection in the abdomen. For those afflicted by Clostridium difficile colitis, a bacterial infection of the colon, a serious complication called toxic megacolon could develop.
Patients can also have deficiencies in certain micronutrients and vitamins, particularly those that are fat-soluble, due to poor nutrient absorption. Further, as a result of a decrease in immunoglobulins and lymphocytes, vital components of the immune system, patients may become more susceptible to recurring and opportunistic infections.
Potential Complications:
- Development of colon cancer
- Anemia
- Primary sclerosing cholangitis
- Perforation of an ulcer, leading to peritonitis
- Toxic megacolon in patients with Clostridium difficile colitis
- Deficiency of micronutrients and fat-soluble vitamins
- Increased risk of recurrent or opportunistic infections due to decline in immunoglobulins and lymphocytes
Preventing Protein-Losing Enteropathy
Protein-losing enteropathy, or PLE, is a health issue where the body loses too many proteins through the digestive system. This can result in low protein levels in the blood. The most common symptom of this condition is swelling in the arms and legs, also known as edema. PLE can be caused by various illnesses. Depending on the root cause of the PLE, different specialists may need to be consulted. The outlook of the condition depends on what is causing the PLE in the first place.
