Introduction Increased intraepithelial lymphocytes (IELs) with normal small bowel villous architecture (also known as Marsh 1) is found in ∼2% of duodenal biopsies. Some of the identifiable causes of raised IELs include coeliac disease (CD), non-steroidal anti-inflammatory drugs (NSAIDs), H pylori, autoimmune disorders, immunodeficiency, gastrointestinal infections and inflammatory bowel disease (IBD). Most studies have focused on evaluating/investigating individual disease entities causing raised IELs and in particular those patients belonging to the spectrum of CD. Very few studies have taken a prospective and systematic approach in identifying the underlying causes for raised IELs.
Methods To determine the causes of raised duodenal IELs in a large series of patients using a 2-step approach. Step 1: Revisit patient history (ie, autoimmune disorders, dermatitis herpetiformis, family history, NSAID usage), coeliac serology, immunoglobulins, stool cultures, glucose hydrogen breath test, colonoscopy and H pylori testing. Step 2: In those where no cause was apparent/unclear or where coeliac disease was a possibility, patients then went on to also have HLA status performed and/or a 6-week gluten challenge with repeat coeliac serology and duodenal biopsies (n=81 patients with raised IELs on first biopsy, female=60 (74%), age range 19–83, median age=47).
Results Of the 31 cases where no cause was found, 29 did have a second biopsy on gluten challenge (see Abstract 080). The IEL count had normalised in 22 (76%), with persistent marsh 1 changes in the others. In addition, more than half with no cause found had clinical symptoms consistent with a diagnosis of irritable bowel syndrome (IBS).
Conclusion The three most common identifiable causes of raised IELs are NSAIDs, H pylori and coeliac disease. Despite being extensively investigated, more than a third of cases with raised IELs have no identifiable cause. The significance and association of duodenal IELs in IBS is not yet clear. Studies have shown conflicting data, with reported IEL levels ranging from normal to slightly elevated. Nevertheless, we have reported the largest systematic experience to date and would suggest that in the group of patients with “no cause found” they can be reassured as their IEL count is likely to normalise.
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