Management of Patients with Intact Villi on Biopsy

Diagnostic Considerations

The clinical management of patients with intact villi on duodenal biopsy should focus on evaluating for seronegative enteropathies and other conditions that may present with increased intraepithelial lymphocytes (IELs) without villous atrophy, as recommended by the American Gastroenterological Association 1, 2
Confirming proper orientation and quality of biopsy specimens with an experienced gastrointestinal pathologist is crucial to ensure accurate assessment of villous architecture, according to the American Gastroenterological Association 2
Reviewing all available serologic testing for celiac disease, including IgA tissue transglutaminase (tTG) antibodies, total IgA levels, IgA endomysial antibodies (EMA), and IgA/IgG deamidated gliadin peptide (DGP) antibodies, is essential for diagnosis, as suggested by the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition 1, 3, 4

Early or developing celiac disease may present with intact villi and increased IELs, and a trial of gluten-free diet for 6 months may be recommended, as proposed by the American College of Gastroenterology 3
Seronegative celiac disease, which is characterized by negative serology but responds to gluten-free diet, should be considered in the differential diagnosis, according to the American Gastroenterological Association 2, 6
Non-celiac causes of increased IELs, such as autoimmune disorders, inflammatory bowel disease, medication-related, infections, post-infectious diarrhea, food protein intolerances, and small intestinal bacterial overgrowth, should be investigated, as recommended by the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition 7

For suspected celiac disease, a gluten-free diet trial for 6 months may be recommended, and clinical response and repeat serology should be monitored, as suggested by the American College of Gastroenterology 1, 3
HLA-DQ2/DQ8 typing is useful in ruling out celiac disease, especially in patients who are self-treated on a gluten-free diet without prior proper testing, according to the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition 4, 5

For patients with suspected early celiac disease or seronegative celiac disease on gluten-free diet, repeat duodenal biopsy in 12-24 months to assess for histological changes is recommended, as proposed by the American Gastroenterological Association 9
For patients with persistent symptoms despite negative workup, consider repeat biopsy with samples from the jejunum, and video capsule endoscopy may provide additional diagnostic information, according to the American College of Gastroenterology 1