What is the treatment for protein-losing enteropathy (PLE) in patients with various underlying conditions, such as inflammatory bowel disease or lymphangiectasia?

Treatment of Protein-Losing Enteropathy

The cornerstone of treating protein-losing enteropathy is a diet severely restricted in long-chain triglycerides (<5% of total energy intake) combined with medium-chain triglyceride supplementation (>20% of total energy intake), alongside high protein intake (≥1.2 g/kg/day) and adequate calories (≥30 kcal/kg/day), while simultaneously treating the underlying cause. 1, 2, 3

Immediate Dietary Intervention

Start dietary modification immediately—do not delay while awaiting definitive diagnosis, as this approach is safe and beneficial across all etiologies of PLE 2:

• Restrict long-chain triglycerides to <5% of total energy intake to reduce intestinal chyle production and subsequent lymphatic protein loss 1, 2, 3
• Supplement with medium-chain triglycerides (MCT) to >20% of total energy intake, as MCT bypass intestinal lymphatics and are absorbed directly into the bloodstream 1, 2, 3
• Provide high protein intake of at least 1.2 g/kg actual body weight/day to compensate for ongoing protein losses 1, 2
• Ensure adequate energy intake of at least 30 kcal/kg actual body weight/day to address malnutrition 1, 2
• Supplement fat-soluble vitamins due to fat malabsorption 4

This dietary approach is particularly critical for intestinal lymphangiectasia but benefits all PLE patients 1, 5, 3.

Identify and Treat the Underlying Cause

The specific treatment depends entirely on the etiology, which must be identified through systematic evaluation 6:

Cardiac Causes

For Fontan circulation with PLE:

• Heart transplantation is indicated for severe systemic ventricular dysfunction or refractory protein-losing enteropathy 1, 2, 7
• Consider atrial septal fenestration or Fontan conversion for PLE not amenable to medical therapy 1, 2, 7
• Pulmonary vasoactive medications may improve exercise capacity and help manage symptoms 1
• Aldosterone antagonists or subcutaneous unfractionated heparin may stabilize the proteoglycan layer of the gut 1

For constrictive pericarditis:

• Surgical pericardiectomy is the definitive treatment 1, 2, 7

Do not overlook cardiac causes in patients without obvious gastrointestinal pathology—Fontan circulation and constrictive pericarditis are major contributors to PLE 2.

Inflammatory Bowel Disease

Initiate immunosuppressive therapy targeting the underlying inflammation 1, 2, 7. The specific agents should follow standard IBD treatment algorithms, but recognize that PLE represents severe disease requiring aggressive management 6.

Infectious Causes

Initiate appropriate antimicrobial therapy based on stool cultures and serologic evaluation 1, 7, 4.

Medication-Induced Enteropathy

Discontinue the offending agent immediately (such as olmesartan, mycophenolate mofetil, or azathioprine) 1, 2, 7. Do not continue these medications if medication-induced enteropathy is suspected 2.

Celiac Disease (Including Seronegative)

Implement a gluten-free diet with dietitian support 7. For seronegative enteropathy, consider HLA testing and a trial of gluten-free diet 7.

Pharmacological Management for Refractory Cases

When dietary modification and treatment of the underlying cause are insufficient:

Budesonide is recommended for patients with hypoalbuminemia poorly responsive to other therapies 1, 2:

• Budesonide has fewer systemic effects than other oral steroids but still requires close monitoring for signs of hypercortisolism 1, 2
• Corticosteroids are particularly useful when clinical, serologic, or histologic markers of inflammatory disease are present 5

Octreotide should be considered as a well-tolerated option that has demonstrated improvement in some PLE patients, particularly those with amyloidosis or refractory cases 5, 8.

Monitoring and Follow-Up

Measure serum albumin levels regularly to evaluate treatment efficacy 1, 2, 7:

• This is the primary marker for assessing response to therapy 2

Perform repeat endoscopy with biopsies at 12 months after initiating treatment to assess histologic response 1, 2, 7:

• This is particularly important for celiac disease and other mucosal disorders 7

For cardiac causes, conduct regular cardiac evaluation with echocardiography and electrocardiogram 1, 2:

• This monitors for progression of underlying cardiac disease 2

Monitor for micronutrient deficiencies, particularly in patients on fat-restricted diets, especially infants and young children 3:

• Fat-soluble vitamin deficiencies are common and require supplementation 4, 3

Critical Pitfalls to Avoid

• Do not delay dietary modification while awaiting definitive diagnosis—the low long-chain triglyceride/high MCT diet is safe and beneficial across all etiologies 2
• Do not overlook cardiac screening with echocardiography in all PLE patients, even without obvious cardiac symptoms 2, 7
• Do not rely solely on dietary management for inflammatory or infectious causes—these require targeted therapy for the underlying condition 2
• Do not continue offending medications if medication-induced enteropathy is suspected 2

Surgical Considerations

Surgery is indicated for:

• Gastrointestinal protein loss from neoplasia 5
• Inflammatory bowel disease complications requiring surgical intervention 5
• Hypertrophic gastritis refractory to medical management 5

Most other PLEs are distributed too widely for surgical intervention 5.