What is the next step in managing a patient with increased lamina propria and epithelial lymphocytes in a duodenal biopsy, but a negative celiac panel?

Management of Increased Duodenal Intraepithelial Lymphocytes with Negative Celiac Panel

The next step in managing a patient with increased lamina propria and epithelial lymphocytes in a duodenal biopsy but negative celiac panel should be HLA-DQ2/DQ8 testing and investigation of other potential causes of lymphocytic duodenosis. 1

Diagnostic Algorithm for Lymphocytic Duodenosis with Negative Celiac Serology

Step 1: Confirm Histological and Serological Findings

• Verify that intraepithelial lymphocytes (IELs) are ≥25/100 enterocytes 1, 2
• Confirm negative celiac serology (IgA-tTG, IgA-EMA, IgG-DGP)
• Ensure patient was on a gluten-containing diet during testing

Step 2: HLA Testing

• Order HLA-DQ2/DQ8 testing 1
  • If negative: Effectively rules out celiac disease
  • If positive: Supports possible celiac disease but requires further investigation

Step 3: Investigate Alternative Etiologies

Systematically evaluate for other causes of lymphocytic duodenosis:

1. Infections:

   • Test for H. pylori (most common non-celiac cause) 1
   • Consider giardiasis, cryptosporidiosis, viral infections

2. Medications:

   • Review for NSAIDs, olmesartan, mycophenolate mofetil 1

3. Other conditions:

   • Autoimmune disorders (thyroiditis, type 1 diabetes)
   • Small intestinal bacterial overgrowth
   • Non-celiac gluten sensitivity
   • Food protein intolerances (milk, soy, eggs)

Step 4: Consider Gluten Challenge and Repeat Biopsy

• If high clinical suspicion despite negative serology:
  • Ensure adequate gluten intake (at least 4 weeks) 1
  • Repeat duodenal biopsy with multiple samples (≥6) including duodenal bulb 1, 3

Important Considerations

Pitfalls to Avoid

• Don't dismiss lymphocytic duodenosis: 16% of cases with lymphocytic duodenosis but normal villous architecture may still have celiac disease 1
• Don't rely solely on distal duodenal biopsies: Celiac changes can sometimes be present only in the duodenal bulb 3
• Don't overlook IgA deficiency: Check total IgA levels if not already done, as IgA deficiency can cause false-negative celiac serology 1

Clinical Pearls

• Normal IEL count in duodenum is <25/100 enterocytes, significantly lower than the outdated standard of 40/100 derived from jejunal biopsies 2
• The pattern of lymphocytic infiltration can provide clues: celiac disease typically shows increased epithelial lymphocytes with rich plasma cell population in lamina propria 4
• Persistent epithelial activation may be present even in treated celiac disease, as evidenced by reduced CCR9 expression on intraepithelial lymphocytes 5

By following this systematic approach, you can determine whether the patient has seronegative celiac disease or another condition causing lymphocytic duodenosis, leading to appropriate treatment and improved outcomes.