In the Journals

Celiac patient symptoms correlate poorly with ongoing mucosal damage

Most patients with celiac disease who were symptomatic despite adhering to a gluten free diet did not have active disease based on analysis of follow-up biopsies in a recent study, suggesting that symptoms were poor predictors of ongoing mucosal injury.

However, investigators associated mucosal injury in these patients with the use of NSAIDs, proton pump inhibitors and selective serotonin reuptake inhibitors.

“We performed this study because relatively little is known about why some patients with celiac disease have intestinal healing and some do not,” Benjamin Lebwohl, MD, MS, director of clinical research at the Celiac Disease Center at Columbia University, told Healio Gastroenterology. “This population of patients with celiac disease all had persistent symptoms — they were actually volunteering to participate in a clinical trial for a medication that would treat symptoms by digesting gluten. Intestinal healing has potentially important prognostic implications, since failure to heal may increase the risk for lymphoma and osteoporotic fractures, as well as refractory celiac disease.”

Benjamin Lebwohl, MD, MS

Benjamin Lebwohl

To identify predictors of persistent villus atrophy, Lebwohl and colleagues performed a nested cross-sectional analysis of 1,345 symptomatic adult celiac patients (81% women; 98% white; mean age, 46 years) who had a duodenal biopsy performed upon entering the CeliAction trial.

Overall, 38% (95% CI, 35-41) had active disease with persistent villus atrophy, which included 7% (95% CI, 6-9) who had severe persistent villus atrophy.

“Among those who did not have damage, this could be because gluten exposure was still happening and enough to cause symptoms but not enough to cause damage; but it is also likely that a portion of these patients were having symptoms that were unrelated to gluten exposure or to celiac disease,” Lebwohl said. “These results suggest that symptoms are not a good predictor of ongoing damage, and so there is no reliable substitute for the follow-up biopsy to assess this.”

Further, multivariable analysis revealed no association between symptoms and villus atrophy after adjusting for covariates. However, older age was a risk factor for persistent villus atrophy (OR = 5.1; 95% CI, 2.5-10.4 for patients older than 70 years compared with patients aged 18-29 years), while longer adherence to a gluten-free diet was associated with a reduced risk for persistent villus atrophy (OR = 0.37; 95% CI, 0.24-0.55 for 4-5.9 years vs. 1-1.9 years).

In addition, the investigators found that deanimated gliadin peptide IgG serology appears to be the most reliable marker for persistent villus atrophy compared with other serologies; multivariable analysis showed it was highly predictive (OR = 6.6, 95% CI, 4.3-10.3).

Finally, they found that persistent villus atrophy was associated with use of PPIs (OR = 1.6; 95% CI, 1.1–2.3), NSAIDs (OR = 1.64, 95% CI, 1.2–2.2), and SSRIs (OR = 1.74; 95% CI, 1.2–2.5).

“While it is premature to conclude that these associations imply a causal relationship, we should investigate this relationship further, given that these medications are very commonly used,” Lebwohl said. – by Adam Leitenberger

Disclosures: Lebwohl reports no relevant financial disclosures. Please see the full study for a list of all other researchers’ relevant financial disclosures.

 

Most patients with celiac disease who were symptomatic despite adhering to a gluten free diet did not have active disease based on analysis of follow-up biopsies in a recent study, suggesting that symptoms were poor predictors of ongoing mucosal injury.

However, investigators associated mucosal injury in these patients with the use of NSAIDs, proton pump inhibitors and selective serotonin reuptake inhibitors.

“We performed this study because relatively little is known about why some patients with celiac disease have intestinal healing and some do not,” Benjamin Lebwohl, MD, MS, director of clinical research at the Celiac Disease Center at Columbia University, told Healio Gastroenterology. “This population of patients with celiac disease all had persistent symptoms — they were actually volunteering to participate in a clinical trial for a medication that would treat symptoms by digesting gluten. Intestinal healing has potentially important prognostic implications, since failure to heal may increase the risk for lymphoma and osteoporotic fractures, as well as refractory celiac disease.”

Benjamin Lebwohl, MD, MS

Benjamin Lebwohl

To identify predictors of persistent villus atrophy, Lebwohl and colleagues performed a nested cross-sectional analysis of 1,345 symptomatic adult celiac patients (81% women; 98% white; mean age, 46 years) who had a duodenal biopsy performed upon entering the CeliAction trial.

Overall, 38% (95% CI, 35-41) had active disease with persistent villus atrophy, which included 7% (95% CI, 6-9) who had severe persistent villus atrophy.

“Among those who did not have damage, this could be because gluten exposure was still happening and enough to cause symptoms but not enough to cause damage; but it is also likely that a portion of these patients were having symptoms that were unrelated to gluten exposure or to celiac disease,” Lebwohl said. “These results suggest that symptoms are not a good predictor of ongoing damage, and so there is no reliable substitute for the follow-up biopsy to assess this.”

Further, multivariable analysis revealed no association between symptoms and villus atrophy after adjusting for covariates. However, older age was a risk factor for persistent villus atrophy (OR = 5.1; 95% CI, 2.5-10.4 for patients older than 70 years compared with patients aged 18-29 years), while longer adherence to a gluten-free diet was associated with a reduced risk for persistent villus atrophy (OR = 0.37; 95% CI, 0.24-0.55 for 4-5.9 years vs. 1-1.9 years).

In addition, the investigators found that deanimated gliadin peptide IgG serology appears to be the most reliable marker for persistent villus atrophy compared with other serologies; multivariable analysis showed it was highly predictive (OR = 6.6, 95% CI, 4.3-10.3).

Finally, they found that persistent villus atrophy was associated with use of PPIs (OR = 1.6; 95% CI, 1.1–2.3), NSAIDs (OR = 1.64, 95% CI, 1.2–2.2), and SSRIs (OR = 1.74; 95% CI, 1.2–2.5).

“While it is premature to conclude that these associations imply a causal relationship, we should investigate this relationship further, given that these medications are very commonly used,” Lebwohl said. – by Adam Leitenberger

Disclosures: Lebwohl reports no relevant financial disclosures. Please see the full study for a list of all other researchers’ relevant financial disclosures.