Protein Losing Enteropathy

Protein losing enteropathy (PLE) is excessive loss of plasma proteins into the gastrointestinal lumen, producing hypoalbuminaemia and oedema.

• Mechanisms: mucosal injury (erosive), non erosive mucosal disease with increased permeability, and lymphatic obstruction (lymphangiectasia).
• Causes:
  • Erosive: inflammatory bowel disease, gastrointestinal malignancy, ulcers, NSAID enteropathy, graft versus host disease.
  • Non erosive: celiac disease, Ménétrier disease, Whipple disease, small bowel bacterial overgrowth, eosinophilic gastroenteritis, SLE, amyloidosis, cytomegalovirus, giardiasis, Helicobacter pylori.
  • Lymphatic: primary intestinal lymphangiectasia, constrictive pericarditis, right heart failure, Fontan circulation, mesenteric lymphatic obstruction (lymphoma), CHAPLE syndrome (CD55 deficiency).
• Complications: oedema, ascites, pleural effusion, malnutrition, immunoglobulin loss and infections, thrombosis, vitamin and mineral deficiencies, growth failure.

• Peripheral oedema (pitting, may be facial), ascites, pleural effusions, weight loss, fatigue.
• Diarrhoea or steatorrhoea in many, abdominal pain, vomiting.
• Lymphopenia, recurrent infections, hypocalcaemia with tetany, thromboembolism.
• Features of the cause: cardiac disease, protein losing in Fontan, systemic lupus.

• Exclude other causes of hypoalbuminaemia: nephrotic syndrome (24 hour urinary protein), liver disease, malnutrition, heart failure.
• Faecal alpha 1 antitrypsin clearance (stool volume x stool concentration divided by serum concentration): over 27 mL/day (over 56 mL/day with diarrhoea) confirms PLE; avoid gastric acid source (use PPI).
• Technetium 99m labelled albumin scintigraphy to localise the site of loss.
• Investigate cause: upper endoscopy and colonoscopy with biopsies, capsule endoscopy, CT/MR enterography, lymphoscintigraphy, echocardiography, stool studies, celiac serology, H. pylori, SIBO breath test, cardiac catheterisation, autoimmune markers.
• Check lymphocyte count, immunoglobulins, calcium, magnesium, vitamin levels.

• Treat the underlying cause (inflammatory bowel disease immunosuppression, H. pylori eradication, treat SIBO with rifaximin 550 mg three times daily, gluten free diet, treat constrictive pericarditis or heart failure).
• Dietary: high protein diet (1.5 to 2 g/kg/day), low long chain fat, medium chain triglyceride supplementation (for lymphatic disease), fat soluble vitamin supplementation.
• Albumin infusions 20% (25 to 50 g) for severe oedema, with diuretics (furosemide 20 to 80 mg with spironolactone 50 to 100 mg), only temporary relief.
• Octreotide 50 to 100 micrograms SC three times daily or lanreotide in lymphangiectasia and refractory cases.
• Budesonide 9 mg daily or prednisolone 0.5 to 1 mg/kg for inflammatory and eosinophilic causes, heparin (unfractionated 5000 units BD SC or enoxaparin) in Fontan PLE, sildenafil, and Fontan revision or heart transplantation.
• Immunoglobulin replacement (IVIG 0.4 g/kg) for recurrent infections with low IgG.
• Thromboprophylaxis for severe hypoalbuminaemia (below 20 g/L) and bed rest.
• Parenteral nutrition for severe intractable disease.
• Surgery for localised lymphatic obstruction or resection of involved bowel.
• Monitor albumin, lymphocytes, nutritional markers.