The only treatment for celiac disease is strict adherence to a gluten-free diet and, in an ideal world, compliance with this treatment would reverse all symptoms and physical attributes of the disease (i.e. damage to the small intestine). Unfortunately, that is not always the case; many patients continue to experience a wide range of symptoms and, in some cases, persistent intestinal damage in the form of villous atrophy (flattened villi). Researchers at Columbia University sought to more closely analyze these cases.

Srihari Mahadev, MD, a gastroenterologist working with researchers at the Celiac Disease Center at Columbia University, provided a summary of the study recently published in Alimentary Pharmacology and Therapeutics: “Celiac disease causes inflammation in the small intestine, which usually reverses on a gluten-free diet. But for a significant proportion of patients, the injury to the intestine does not heal even after some time avoiding gluten. We studied celiac patients with persistent symptoms despite a gluten-free diet, to find out how frequently small bowel damage was found on follow-up endoscopy with biopsy. The majority of those we studied had normal biopsies, with about 40% having persistent injury, suggesting that there are many different causes for persistent symptoms in celiac patients aside from active celiac disease. We also looked at medication use, and found that patients taking certain acid-lowering medications (PPIs), anti-inflammatories (NSAIDs) and antidepressants (SSRIs) were slightly less likely to heal their small intestine. The impact of medication use was very small, and as our results are preliminary, we need more studies before we can draw conclusions about their impact on intestinal healing in celiac disease.”

All subjects whose cases were analyzed for this study had signed up to participate in a clinical trial. To participate in the trial, patients had to have been diagnosed with celiac disease by a physician, been on a gluten-free diet for at least one year, and had persistent, self-reported, moderate to severe gastroenterological symptoms. Those who continued to report symptoms during a particular window of the trial underwent duodenal biopsy; it is this subset of 1,345 patients who served as the cohort for the present study.

Male patients were found to be somewhat more likely to experience persistent villous atrophy, as were older patients. Longer time on a gluten-free diet seemed to have a protective effect, with those who had followed the diet for less than two years experiencing more atrophy than those who were on the diet four years or longer. No notable positive or negative correlations were identified with any specific symptoms, though the original sample may have been predisposed to symptom reporting due to wanting to participate in the clinical trial. Some serological tests were predictive of persistent villous atrophy (i.e. elevated DGP IgG and TTG IgA).

Most interesting was the relationship between the use of certain classes of medications with the presence of persistent villous atrophy. Acid reducing medication (PPIs), non-steroidal anti-inflammatories (NSAIDs), and certain types of mood medication (SSRIs) all seemed to be associated with persistent villous atrophy. These are all widely used medications; further study regarding their relationship to delayed mucosal healing is warranted.

Medication Use Associated with Persistent Villous Atrophy