Protein Losing Enteropathy: Symptoms, Types, Causes and Treatment

Protein Losing Enteropathy (PLE) is a fascinating yet challenging syndrome that affects people of all ages. While rare, its consequences are significant, and understanding it requires exploring the interplay between the gut, the immune system, and sometimes the heart. In this article, we’ll break down what PLE is, explore its symptoms, types, causes, and the latest in evidence-based treatment strategies.

Symptoms of Protein Losing Enteropathy

When the body loses protein through the gastrointestinal tract, a cascade of symptoms can emerge. PLE often masquerades as more common disorders, making early recognition crucial to prevent serious complications. Let’s look at how PLE typically presents and what signs should prompt further investigation.

Symptom	Clinical Feature	Typical Presentation	Source(s)
Edema	Swelling of tissues	Peripheral, facial	2 4 5
Ascites	Fluid in abdomen	Abdominal distension	2 4 5 6
Diarrhea	Watery or chronic	Persistent, recurrent	1 3 5 10
Hypoproteinemia	Low blood proteins	Lab finding	2 4 6
Malnutrition	Weight loss, weakness	Failure to thrive	4 5 6 7
Effusions	Pleural/pericardial	Shortness of breath	4 5
Abdominal pain	Cramping or chronic	Intermittent/severe	1 3 5 10
Recurrent Infections	Immune deficiency	Repeated illnesses	1 7
Thrombotic events	Blood clots	Vascular complications	1

Table 1: Key Symptoms of Protein Losing Enteropathy

Edema and Effusions

The most common and striking symptom of PLE is edema—swelling of the lower limbs, face, or even the whole body—caused by low levels of albumin and other proteins in the blood. This protein deficit can also lead to the accumulation of fluid in the abdomen (ascites), chest (pleural effusions), or around the heart (pericardial effusions) 2 4 5 6.

Gastrointestinal Symptoms

Chronic diarrhea is a hallmark symptom, often accompanied by abdominal pain and cramping. Some patients also report persistent or recurrent diarrhea, which may be mistaken for irritable bowel syndrome or infections 1 3 5 10.

Hypoproteinemia and Malnutrition

Lab tests typically reveal hypoproteinemia—especially low serum albumin. This can progress to generalized malnutrition, with signs such as weight loss, muscle wasting, and even stunted growth in children 2 4 6 7.

Immune Dysfunction and Thrombotic Complications

Because proteins lost in PLE include important components of the immune system, patients may experience recurrent infections and, in rare cases, blood clotting problems, such as in CHAPLE syndrome (CD55 deficiency) 1 7.

When to Suspect PLE

Doctors should consider PLE in any patient with unexplained low serum albumin, edema, or effusions, especially when kidney, liver, and nutritional causes have been ruled out 2 4 6.

Types of Protein Losing Enteropathy

While PLE is a syndrome rather than a single disease, it can be classified based on its underlying pathological mechanism and associated conditions. Understanding the types helps guide both diagnosis and treatment decisions.

Type	Distinctive Feature	Common Example	Source(s)
Lymphatic (Obstructive)	Lymph flow disruption	Primary lymphangiectasia	1 3 6 7 9
Erosive	Mucosal barrier breakdown	Crohn’s, ulcerative colitis	2 5 6 7
Non-Erosive (Functional)	No visible mucosal damage	Celiac disease	2 6
Cardiac-related	Venous/lymphatic congestion	Fontan procedure	3 9 11
Genetic/Inherited	Monogenic defects	CD55 deficiency (CHAPLE)	1

Table 2: Main Types of Protein Losing Enteropathy

Lymphatic (Obstructive) PLE

This type is characterized by impaired lymphatic drainage, leading to leakage of protein-rich lymph into the intestines. It is seen in conditions like primary intestinal lymphangiectasia (often genetic), secondary lymphangiectasia due to cardiac disease (e.g., after the Fontan procedure), or congenital heart defects causing elevated venous pressure 1 3 6 7 9.

Erosive PLE

Here, the cause is a breakdown of the gut’s mucosal barrier, allowing proteins to seep into the gut. Examples include Crohn’s disease, ulcerative colitis, severe infections, and pseudomembranous colitis 2 5 6 7.

Non-Erosive (Functional) PLE

In these cases, protein loss occurs despite an intact mucosal surface, likely due to increased permeability of the gut wall. Classic examples include celiac disease, some forms of eosinophilic gastroenteritis, and certain drug reactions 2 6 10.

Cardiac-Related PLE

Some patients develop PLE due to chronically increased central venous pressure or lymphatic congestion—most famously after the Fontan procedure for congenital heart disease. The altered blood and lymph flow leads to protein leakage 3 9 11.

Genetic/Inherited PLE

Rare monogenic syndromes like CHAPLE (CD55 deficiency) cause early-onset, severe PLE with unique features such as thrombotic complications due to complement system dysregulation 1.

Causes of Protein Losing Enteropathy

The root causes of PLE are diverse, spanning primary intestinal and systemic diseases. Unraveling the mechanism in each case is vital for targeted therapy.

Cause Category	Example Condition	Mechanism	Source(s)
Lymphatic obstruction	Intestinal lymphangiectasia	Lymph rupture/leakage	1 3 6 7 9
Mucosal disease	Crohn’s, infection, colitis	Mucosal erosion/ulcers	2 5 6 7
Increased pressure	Heart failure, Fontan	Venous/lymphatic stasis	3 6 9 11
Genetic defects	CD55 deficiency (CHAPLE)	Complement hyperactivation	1
Inflammatory	Eosinophilic gastroenteritis	Increased permeability	10
Autoimmune	Lupus, sarcoidosis	Immune-mediated injury	6
Malignancy	Lymphoma	Lymphatic or mucosal damage	6

Table 3: Key Causes of Protein Losing Enteropathy

Lymphatic Abnormalities

Disorders that block or impair intestinal lymphatic flow—whether congenital (primary lymphangiectasia), acquired (cardiac failure, liver disease), or post-surgical (Fontan)—lead to retrograde lymph flow and protein loss 1 3 6 7 9.

Mucosal Erosions and Inflammatory Diseases

Diseases that cause ulceration of the gut lining, such as Crohn’s disease, severe infections, or pseudomembranous colitis, result in direct protein leakage into the gut 2 5 6 7.

Increased Central Venous Pressure

Conditions that chronically increase venous pressure (e.g., after the Fontan operation, constrictive pericarditis, right heart failure) can cause lymphatic hypertension and protein loss 3 6 9 11.

Genetic and Rare Syndromes

Inherited disorders like CHAPLE syndrome (CD55 deficiency) cause PLE by disrupting the regulation of the complement cascade, resulting in both protein loss and increased thrombosis risk 1.

Inflammatory and Autoimmune Disorders

Systemic diseases like systemic lupus erythematosus, sarcoidosis, and some forms of eosinophilic gastroenteritis can cause increased gut permeability and protein loss 6 10.

Malignancy

Cancers such as lymphoma can damage either the mucosa or the lymphatics, leading to PLE 6.

Treatment of Protein Losing Enteropathy

Managing PLE is complex and always tailored to the underlying cause. A multidisciplinary approach—often involving gastroenterologists, cardiologists, nutritionists, and sometimes surgeons—is essential to improve symptoms and outcomes.

Treatment Approach	Main Strategy	Key Features	Source(s)
Treat underlying cause	Disease-specific therapy	E.g., gluten-free for celiac, surgery for obstruction	2 4 6 7 11
Nutritional support	High-protein, low-fat diet	Medium-chain triglycerides, supplements	2 3 4 7
Medical therapy	Diuretics, steroids, heparin	Budesonide, vasodilators, immune modulators	3 10 11
Interventional	Lymphatic embolization	For lymphatic leaks, esp. post-Fontan	9
Surgical	Resection, transplantation	For refractory or anatomical cases	5 8 11
Supportive care	Plasma/albumin infusions	For severe hypoproteinemia	8

Table 4: Treatment Strategies for Protein Losing Enteropathy

Addressing the Underlying Cause

The cornerstone of PLE management is treating the primary disease. This may mean:

• Starting a gluten-free diet in celiac disease
• Using anti-inflammatory or immunosuppressive drugs in eosinophilic gastroenteritis or IBD
• Managing heart failure or considering surgery in cardiac-related cases 2 4 6 7 11

Nutritional and Dietary Support

A diet high in protein and energy, often with medium-chain triglycerides (MCTs) to bypass lymphatic absorption, is recommended. Nutritional supplements and vitamins are crucial, especially if fat-soluble vitamin loss is suspected 2 3 4 7.

Medical Therapy

Depending on the situation, the following might be used:

• Diuretics: To reduce edema and ascites 3
• Corticosteroids (e.g., budesonide): For inflammatory causes such as eosinophilic gastroenteritis 10 11
• Pulmonary vasodilators (e.g., sildenafil): In cardiac-related PLE 3 11
• Heparin: Occasionally used post-Fontan to reduce thrombosis risk 3
• Immune modulators: For selected immune-mediated cases 1 10

Interventional and Surgical Procedures

• Lymphatic embolization: For refractory lymphatic leaks, especially after the Fontan procedure, with promising results but potential complications 9
• Surgical resection: For localized disease or severe cases not responsive to other treatments (e.g., pseudomembranous colitis) 5
• Cardiac transplantation: For end-stage cardiac-related PLE 11

Supportive Therapy

• Albumin or plasma infusions: Used short-term in severely malnourished patients or preoperatively to stabilize protein levels 8
• Monitoring and treating complications: Such as infections and thrombotic events 1 7

The Importance of Individualized and Multimodal Therapy

No single treatment is universally effective. Many patients require a combination of medical, dietary, and sometimes surgical approaches. Relapse is common, and long-term follow-up is essential 3 11.

Conclusion

Protein Losing Enteropathy is a complex, multifaceted syndrome demanding keen clinical observation and a tailored, multidisciplinary approach. Here are the main takeaways:

• PLE is a syndrome, not a disease, with diverse causes ranging from cardiac and genetic to inflammatory and lymphatic disorders 1 2 3 6.
• Symptoms often include edema, diarrhea, ascites, and malnutrition; immune dysfunction and thrombosis may occur in rare cases 1 4 5 7.
• PLE types are classified by underlying mechanism: lymphatic obstruction, mucosal erosion, functional (non-erosive), cardiac, or genetic 1 3 6 7 9.
• Diagnosis relies on clinical suspicion and specialized tests like fecal alpha-1 antitrypsin clearance 2 4 6.
• Treatment is individualized, focusing on the underlying cause, nutritional support, medication, and sometimes interventional or surgical procedures 2 3 4 7 9 11.
• Long-term management and multidisciplinary care are crucial for optimizing outcomes and quality of life.

By understanding the spectrum of PLE, clinicians and patients alike can better navigate its challenges—moving from suspicion to diagnosis, and from supportive care to targeted treatment.