What is Protein Losing Enteropathy?

Medically Reviewed by Dany Paul Baby, MD on April 21, 2022
7 min read

Protein-losing enteropathy (PLE) is a condition where your body loses needed proteins because they’ve leaked into your gastrointestinal tract — also known as your intestines or bowels. 

PLE is usually the result of a separate chronic — i.e., long-term — condition and is more of a symptom than an independent disease. It can be a difficult condition to diagnose and treat, but there is hope. 

Ultimately, the way that your medical team handles this condition will depend on the underlying cause.  

When you have protein-losing enteropathy, you’re specifically losing more proteins through your intestines than your body is producing. This leaves you in a state called hypoproteinemia.

Over 60 different conditions are known to lead to protein-losing enteropathy. 

In general, there are three broad categories of diseases that can result in PLE. The first of these include erosive and ulcerative gastrointestinal disorders. 

Examples include:

The second category includes gastrointestinal disorders that aren’t erosive or ulcerative. Examples include: 

The final category includes conditions that increase pressure on your interstitial fluid — found between your cells — or interfere with your lymph system. 

Examples of these conditions include: 

The exact reasons why each of these conditions leads to PLE are still unclear — but new research is shedding light on some underlying connections. In all cases, the main way that these proteins seem to get into your intestine is through lymph fluids.  

In the case of congenital heart disease — for example — research indicates that this condition leads to increased pressure within your heart that ends up congesting your liver. This causes your liver to create too much lymphatic fluid, which is rich in a protein called albumin. This then leaks into your intestines where they connect to your stomach. 

In conditions that affect your GI tract, the reason for the loss of proteins is that your body is worse at reabsorbing and recycling them. The same intestinal membrane problems that make reabsorption difficult also lead to even more proteins leaking out. It’s a two-fold loss of amino acids — the building blocks that your body uses for fresh proteins. 

These example mechanisms aren’t the only ways for underlying conditions to cause protein leakage, which is part of why the condition is so difficult to manage. More research is needed to understand the connections between PLE and all of its potential causes.  

Since proteins present in your lymph fluid are the main ones lost to PLE, it’s important for you to understand what your lymph system is — and how it relates to your other organs. 

Your lymph system is a crucial part of your immune system and is composed of: 

  • Organs — like your tonsils and spleen, some of which make lymph fluid
  • Lymph nodes — which make white blood cells
  • Lymph vessels — which connect all of your organs to your blood vessels

Lymph nodes are small hubs for your lymph system and are located around your body in areas like your: 

  • Armpit
  • Groin
  • Neck
  • In the center of your chest

Lymph fluid is composed of white blood cells that attack bacteria and an intestinal fluid — called chyle — that contains proteins and fats. 

It’s normal for your lymph system to interact with all parts of your body — including your intestines, but in cases of PLE, your underlying condition has affected your lymph system in some way. It can no longer interact with your organs the way that it’s supposed to. 

The prevalence of protein-losing enteropathy is unknown in both the U.S. and on a global scale. A single study, though, estimated a PLE rate of about 3.8% in European patients that had undergone a Fontan operation — a type of heart surgery. 

Many of the diseases that lead to the condition can affect people of any age, gender, or race. Some are inherited, but others can develop without any known family history. 

If you’ve already been diagnosed with one of the many chronic diseases associated with this condition, then you’re at an increased risk of developing PLE. Keep in mind, though, that it’s only a rare side effect for most of these diseases. 

PLE can be especially pronounced in people who are unaware that they have one of these other diseases. This is because they haven’t started undergoing any treatments for their underlying condition or their PLE. 

There are two stages to obtaining a full diagnosis with protein-losing enteropathy. The first step is to determine whether or not you have PLE or a condition with similar symptoms. Alternative possibilities that your doctor will have to rule out include: 

  • Chronic liver disease
  • Kidney conditions — including nephrotic syndrome
  • Protein-calorie malnutrition
  • Malabsorption syndromes
  • Heart failure

Your doctor can measure total protein levels, as well as levels of the specific protein — albumin — with a blood test. Albumin is made by your liver, and large amounts of it can be lost due to PLE. 

If your blood test shows low protein levels then your doctor will follow up with a stool test. This test is specifically designed to look for levels of the protein Alpha 1 antitrypsin (A1AT) in your stool. 

A1AT makes a good baseline for measuring amounts of lost protein because it’s excreted — intact — from your GI tract on a daily basis. Quantities are consistent among most humans, and the protein is relatively easy to detect. This means that if you have high levels of A1AT in your stool, then it’s likely that you’re losing greater amounts of other proteins too. 

There are other tests that can confirm your diagnosis of PLE if your A1AT tests are inconclusive, but these are more expensive and not available at all hospitals. One example is a test that monitors the way you clear radioactively labeled albumin from your body.

Once your doctor has confirmed that you have PLE, the second step is to undergo more tests to find out what underlying disease is causing this complication. Possible additional examinations include: 

  •  Imaging analysis — like X-rays, CT scans, and MRIs
  • A colonoscopy
  • Other endoscopy and enteroscopy techniques — all of which involve the use of tiny cameras on tubes
  • Wireless capsule endoscopy — a newer technique where you swallow a pill-sized camera capable of transmitting a wireless visual feed

There’s a good chance that the exact symptoms of your protein-losing enteropathy will depend on your underlying condition. 

However, the most common symptom found in all cases of PLE is swelling in your hands and lower legs — a condition known as peripheral edema. Your low protein levels lead to increased pressure in your capillaries — your smallest blood vessels. This forces fluid to seep into surrounding tissues, creating a swollen feeling. 

Other generalized symptoms include trouble digesting food and problems gaining weight. 

Symptoms that are more common in people with gastrointestinal causes for their PLE include:

  • Diarrhea
  • Bloating
  • Abdominal pain
  • Frequent infections — from the autoimmune triggers associated with some gastrointestinal conditions
  • Opportunistic infections — also from the autoimmune associations

If your PLE is caused by a heart condition then you could also have symptoms of heart failure, such as: 

  • Pitting edema — a type of swelling near your skin
  • Pleural effusions — fluid build-up around your lungs 
  • Shortness of breath 
  • Elevated pressure in your jugular 

Some of the main treatments for protein-losing enteropathy involve getting protein back into your body. This can be done by: 

  • Modifying your diet so you eat more foods that are low in fat and high in protein
  • Adding dietary supplements to your routine
  • Infusing protein intravenously — done under medical supervision 

You can also modify your habits to help the swelling in your hands and legs. This could involve raising your arms and legs above your heart — when you’re able to — and wearing compression stockings that gently squeeze your legs. 

Other treatments will focus on managing or curing your underlying condition — so they’ll vary widely for different cases of PLE. 

Some examples include: 

  • Surgery to remove growths from your intestine — or a portion of the organ
  • Embolization surgery to plug holes in your duodenum — used when the cause involves lymph fluid entering your intestines in this area
  • Medications to treat infections
  • Radiological intervention to fix abnormal lymph vessels

Your doctor will need to determine the best treatment plan for you based on your symptoms and diagnosis. Your long-term protein-losing enteropathy prognosis will ultimately depend on the causal disease. Some conditions have better outcomes than others. 

Protein-losing enteropathy is a rare condition in general — so there aren’t very many cases of this complication in children. When it does occur, though, the nutritional problems caused by PLE are particularly dangerous for people whose bodies are still developing.

Proteins are used in almost all of the activities that your body performs — so growing children need plenty of them. If your child goes too long with undiagnosed PLE, then their symptoms could start to resemble those of malnourished children. 

Possible symptoms include: 

  • Being short for their age
  • Being thin for their age
  • Having less energy than their peers
  • Having a weakened immune system
  • Increased anxiety and mood swings

Protein-related malnutrition isn’t good at any age. If these low protein levels are present when your child is actively trying to grow, their bodies are less likely to reach their full developmental potential. 

You should see a doctor as soon as you notice any symptoms that resemble PLE or malnutrition in your child. The sooner they get treatment, the better off they’ll be.