Celiac Symptoms Common Despite Dietary Adherence

Nearly half of patients with celiac disease experienced clinically relevant events even while highly adherent to a gluten-free diet (GFD), according to a retrospective follow-up study in Italy.

These events were rarely caused by poor adherence to the diet (4%) or complications (2%), reported Annalisa Schiepatti, MD, of the University of Pavia in Italy, and colleagues.

The leading causes of those clinical events during follow-up among the 189 patients studied stemmed from functional gastrointestinal (GI) disorders (30%), gastroesophageal reflux disease (18%), and micronutrient deficiencies (10%), the authors wrote in Digestive Diseases and Sciences.

“Based on our results, the high prevalence of functional gastrointestinal disorders, gastroesophageal reflux disease, and micronutrient deficiencies while on a GFD suggest a possible role for dietary quality rebalancing, as crucial intervention, in addition to maintaining a strict lifelong GFD adherence,” they noted.

No significant relationship was seen between GFD adherence at follow-up biopsy and the occurrence of events.

The 30% rate of functional GI problems “may sound high, but depending on what criteria are used, rates as high as this can be seen in the general population,” Eamonn Quigley, MD, of Houston Methodist Hospital in Texas, told MedPage Today. “One issue that arises in all such papers is how certain they are that patients are strictly adherent to their gluten-free diet and that their celiac disease is in complete remission.”

“Our own work suggested that low-grade inflammation may account for some of these symptoms in both inflammatory bowel disease and celiac disease,” said Quigley, who was not involved in the study.

Despite being on a GFD, as many as 30% of celiac disease patients may not achieve complete resolution of symptoms and histological lesions.

For this study, Schiepatti and colleagues examined medical records data from a referral center in Italy with 189 celiac disease patients who followed a long-term GFD after having a duodenal biopsy from 2000 to 2021. Diet adherence was evaluated up to 2008.

Contrary to prior reports, most patients in this study had good GFD adherence (90.9%), after excluding 13 patients with missing data. Overall, 50.3% had ongoing symptoms at follow-up, including 37% who had persistent symptoms at diagnosis despite following a GFD and 24.6% who developed new symptoms.

Among the patients, 88 had clinical events, for an overall incidence of 83.5 per 1,000 person-years (95% CI 70.9-97.6). Clinically relevant events were defined as signs or symptoms that occurred during follow-up and required diagnostic tests, treatment, emergency room access, or even hospitalization.

The mean age at diagnosis was 36 years, and 70% of patients were women. Average follow-up time was 112 months. Those who had at least one clinical event were over two times more likely to have a classical pattern of celiac disease at diagnosis and a persistence of villus atrophy on duodenal biopsy at follow-up.

After an average of 16 months since diagnosis, 15.4% still had “a certain degree” of villus atrophy on duodenal biopsy. Among them, most had initial but incomplete histological improvement despite good GFD adherence (18 of 29). Less common was poor GFD adherence (n=9) or complicated celiac disease (n=2).

Eleven with villus atrophy had persistent symptoms on their follow-up biopsy.

Predictors of clinically relevant events included age 45 or older at diagnosis (HR 1.68, 95% CI 1.05-2.69) and presenting with a classical pattern of celiac disease (HR 1.63, 95% CI 1.04-2.54).

Event-free rates were 65% at 5 years and 51% at 10 years. Among 157 events, 92 required outpatient medical treatment, 63 required diagnostic investigations, and 13 required emergency room care or admission. Common symptoms leading up to the clinical events included 19% with gastroesophageal reflux disease, 15% with diarrhea, and 13% with dyspepsia. Notably, 63 diagnostic tests were performed, mostly involving upper GI endoscopic biopsy (44%), colonoscopy (21%), or abdominal ultrasound (11%).

Among those ages 45 and up at diagnosis, 46% with classical celiac disease and 62% with non-classical or silent celiac disease remained event-free at 5 years, which dropped to 25% and 47%, respectively, at 10 years. Event-free rates were better for those under age 45, with 60% of those with classical celiac disease and 80% with non-classical or silent celiac disease remaining event-free at 5 years and 51% and 60%, respectively, at 10 years.

After an average follow-up of 146 months after diagnosis, five patients had died — all of whom experienced at least one clinical event during follow-up.

The authors acknowledged limitations to the study, including its single-centered design and limited sample size. No standardized method of categorizing heterogeneous symptoms was used.