How is protein losing enteropathy (PLE) evaluated and managed?

Evaluation and Management of Protein Losing Enteropathy (PLE)

Protein losing enteropathy requires a systematic diagnostic approach focused on identifying the underlying cause, with treatment directed at the specific etiology while supporting nutritional status through dietary modifications and protein supplementation.

Diagnostic Evaluation

Initial Assessment

• PLE should be suspected in patients with unexplained hypoproteinemia after excluding other causes such as malnutrition, proteinuria, and impaired protein synthesis due to liver disease 1
• Diagnosis is confirmed by measuring fecal alpha-1 antitrypsin clearance, which is the most common diagnostic test for PLE 1

Diagnostic Testing Algorithm

1. Laboratory evaluation:

   • Serum protein and albumin levels
   • Immunoglobulin levels (particularly IgG)
   • Complete blood count
   • Liver function tests
   • Urinalysis to exclude proteinuria 2

2. Confirmation of protein loss:

   • Fecal alpha-1 antitrypsin clearance (gold standard) 1
   • Alternative: Tc-99m-labeled human serum albumin scintigraphy to detect and localize protein leakage 3

3. Identification of underlying cause:

   • Endoscopy with biopsies of the small intestine and colon 4
   • Video capsule endoscopy and device-assisted enteroscopy for small bowel evaluation 5
   • Cardiac screening (echocardiogram) to assess for cardiac causes 2
   • Stool cultures and serologic evaluation for infectious causes 2
   • Radiographic imaging (CT, MRI) as indicated 1

Etiological Classification

Primary Causes of PLE

1. Erosive gastrointestinal disorders:

   • Inflammatory bowel disease (Crohn's disease)
   • Infections (giardiasis, tuberculosis, Whipple's disease) 4

2. Non-erosive gastrointestinal disorders:

   • Intestinal lymphangiectasia
   • Eosinophilic gastroenteritis
   • Celiac disease (including seronegative enteropathy)
   • Common variable immunodeficiency (CVID) 4

3. Disorders with increased central venous pressure or lymphatic obstruction:

   • Congenital heart disease
   • Constrictive pericarditis
   • Fontan procedure complications 4

Management Strategies

Targeted Treatment Based on Etiology

• For identified causes, treat the underlying condition:
  • Infectious causes: Appropriate antimicrobial therapy (e.g., metronidazole for giardiasis) 4
  • Inflammatory conditions: Immunosuppressive therapy (e.g., steroids, azathioprine, infliximab) 4
  • Cardiac causes: Heart transplantation may be beneficial for severe single ventricle dysfunction or protein-losing enteropathy 4

Nutritional Management

• Dietary modifications:
  • High-protein diet with supplementation of fat-soluble vitamins 2
  • For lymphangiectasia: Low-fat diet with medium-chain triglycerides (MCT) to bypass intestinal lymphatics 6

Monitoring and Follow-up

• Regular assessment of serum protein and albumin levels 2
• Monitoring for micronutrient deficiencies, particularly in patients on fat-restricted diets 6
• Repeat endoscopy with biopsies may be necessary to assess response to therapy, typically after 12 months of treatment 4

Special Considerations

Seronegative Enteropathy

• In cases of seronegative enteropathy with villous atrophy:
  • Evaluate for celiac disease with HLA testing (DQ2, DQ8) 4
  • Consider trial of gluten-free diet with follow-up endoscopy to assess response 4
  • If no improvement, consider other causes of enteropathy 4

Idiopathic PLE

• For stable patients with unidentified etiology of seronegative enteropathy:
  • Consider repeating endoscopy after a period without intervention, as some cases (72%) show spontaneous resolution of villous atrophy 4
  • For persistent symptoms without identified cause, budesonide may be beneficial 4

Cardiac-Related PLE

• In patients with Fontan circulation:
  • Creation of atrial septal fenestration or Fontan conversion may be considered 4
  • Heart transplantation may be necessary for severe cases, though protein-losing enteropathy does not always resolve post-transplant 4

Common Pitfalls to Avoid

• Initiating gluten-free diet before completing diagnostic testing for celiac disease, which can affect accuracy of both serologic and histologic results 4
• Failing to obtain adequate number of duodenal biopsies (4-6 specimens recommended) 4
• Overlooking medication history, particularly angiotensin II receptor blockers like olmesartan which can cause enteropathy 4
• Neglecting to monitor for micronutrient deficiencies in patients on fat-restricted diets 6