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Running the numbers in celiac disease

August 11, 2023

A new scoring system could help determine who needs a follow-up biopsy

By Amy Ratner, director of scientific affairs

Increasingly, numerical scores measure how we’re doing in everything from the Wordle word game to how many steps we take every day to how many minutes we spend on social media.

Now, a group of international researchers has come up with a five-point scoring system for those with celiac disease to determine the risk of having persistent intestinal damage.

The score is based on how old you were at diagnosis, the kind of symptoms you had when diagnosed, how well you have responded to the gluten-free diet and how well you keep to the gluten-free diet.

Those diagnosed at 45 years of age or older who had classic symptoms at diagnosis, have had a poor response to the gluten-free diet and/or don’t adequately follow the gluten-free diet, would have the highest score, a five, and would be most likely to have persistent damage to the intestine.

Persistent intestinal damage linked to complications

This persistent intestinal damage predicts increased development of complications and mortality in adult patients, the study, published in the journal Gut, also found.

The scoring system, which is based on information from diagnosis and follow-up, could be used as a “personalized and cost-effective approach to determining the need for a follow-up biopsy,” according to study authors from institutions in the United States, the United Kingdom and Italy.

A number of researchers have been looking for a method of predicting whether someone’s intestine is healing on a gluten-free diet without resorting to an endoscopy and biopsy, which are invasive and carry some risks. But scientists have not yet discovered a biomarker, a kind of red flag raised by the body, that can be readily measured to indicate when there is damage in the intestine.

Until a biomarker is found, a biopsy is the only way intestinal damage or healing can be determined. While follow-up biopsy in all patients is not routine, guidelines suggest that the procedure be done when patients do not recover on a gluten-free diet.

Meanwhile, up to 40 percent of those with persistent intestinal damage due to celiac disease do not have ongoing symptoms, the study says.

“Our score allows clinicians to identify these patients are higher risk even in the absence of ongoing symptoms,” the authors wrote.

While some persistent intestinal damage is caused by serious complications related to celiac disease, in most cases it can be traced to how well someone is following the gluten-free diet, according to the study.

How the scoring is done

The scoring system works like miniature golf, where the higher the number means the worse you are doing.

Diagnosis at 45 years or older, classical presentation of celiac disease, and lack of response to the gluten-free diet all receive one point in the score tally. Poorly following the gluten-free diet receives two points. The score is calculated by adding these points. Classical celiac disease presents as diarrhea, weight loss and fatty stools. Examples of classic celiac disease include patients with diarrhea and weight loss or weight loss and anemia.

Someone with a score of one or less is unlikely to have persistent intestinal damage and would not need a follow-up biopsy, while those with a score of three to five would be considered high risk and a follow-up biopsy should be done. A score of two would indicate intermediate risk and should be evaluated on a case by case basis.

The study provides evidence that the risks of celiac disease are based on more than intestinal damage, but are also related to age and clinical presentation, for example, weight loss, said Dan Leffler, MD, a gastroenterologist at Beth Israel Deaconess Medical Center, medical director of clinical science at Takeda Pharmaceutical Company and a study author.

How the study was done

Study participants included 694 adult patients diagnosed at celiac centers at the University of Pavia, Italy, Royal Hallamshire Hospital, Sheffield, UK and Beth Israel Deaconess, Boston, from 2000 to 2020. All had follow-up biopsies. Of these, about 23 percent were found to have persistent intestinal damage. Among those with persistent damage, 21 percent had complications of celiac disease. Biopsy results and data about follow-up, including development of complications and mortality, were collected and reviewed.  

Clinical response to the gluten-free diet was defined as improvement or end to symptoms and abnormalities in celiac disease blood tests and nutritional deficiencies that had been found at diagnosis. Persistent intestinal damage, also called persistent villous atrophy, was defined as measuring above a certain level on follow-up biopsy despite a gluten-free diet. An interview with a dietitian and response to questionnaires about the diet were used to determine how well study participants were following the gluten-free diet.

Complications of celiac disease were defined as malignant and pre-malignant abdominal conditions, including refractory celiac disease type 1 and 2, ulcerative jejuno-ileitis, abdominal lymphomas and small bowel carcinomas.

Nearly 84 percent of study participants were following the gluten-free diet. About 34 percent had ongoing symptoms.  

Persistent intestinal damage common

Persistent intestinal damage is “a common clinical scenario,” the study says.

Complication-free survival and overall survival were significantly lower in those with persistent intestinal damage compared to those who had intestinal recovery from the damage of celiac disease.

Results that show persistent intestinal damage is associated with increased complications and mortality “fill in an important gap in the natural history of celiac disease,” the study says. The findings complete a picture of the sequence of events in which persistent inflammation and tissue damage lead to poor long-term health. This also occurs in other chronic diseases, including inflammatory bowel disease, the study notes.

A second group of adult study participants with celiac disease who had follow-up biopsies mainly from 2020 to 2022 were enrolled and their results were used to test how well use of scores to predict risk of persistent damage worked. Results regarding persistent intestinal damage in this group were similar to those found in the first group, about 20 percent.

Ongoing damage related to poor adherence to gluten-free diet

Overall, about 80 percent of ongoing damage was attributed to poorly following the gluten-free diet, while 20 percent was due to malignant complications, the study found.

About half of the cases of complications were due to refractory celiac disease type 1, which the study says has “the best prognosis among the complications of celiac disease.” This type of refractory celiac disease is marked by a lack of response to a strict gluten-free diet after six to 12 months, with symptoms, intestinal damage and an abnormal population of white blood cells in the gut. Type 1 is the less severe form of the condition. The authors also note that refractory type 1 may be related to gluten being consumed unintentionally.

Poor gluten-free diet adherence was the most significant predictor of intestinal damage in all study analyses, the authors wrote. “This is not surprising and confirms that poor gluten-free diet adherence is a risk for poor outcomes in celiac disease,” the study says. “This underlines the importance of strictly following a gluten-free diet for patients with celiac disease.”

While the scoring system would lead to more frequent biopsies in those whose tally is high, Leffler said it is reasonable to follow older patients more frequently. “This is not different from what is done for a lot of inflammatory gastrointestinal diseases, such as ulcerative colitis where dysplasia screening is more frequent with age,” he added.

As for what patients who have biopsies that reveal intestinal damage despite following a gluten-free diet should do, Leffler said it’s a good question. In the absence of treatments outside the gluten-free diet, it’s “really an individualized discussion between the patient and their clinical team,” he said.

You can read more about the study here.


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