Patients who have ulcerative colitis and Crohn’s disease often report symptoms without showing endoscopic evidence of the disease, and their providers struggle to make sense of the disparity. In a new study, investigators used fecal calprotectin levels to assess symptoms most associated with disease activity.

“A patient will say they’re having lots and lots of symptoms, but we don’t find inflammation during a colonoscopy, which means we need to investigate other causes,” said Kerri Glassner, DO, an assistant professor of clinical medicine at Houston Methodist Hospital and Weill Cornell Medical College, in New York City, who was not involved in the study.

To tease out the relationship between inflammation and specific IBD symptoms, researchers at the University of Manitoba, in Winnipeg, and the University of Toronto assessed the prevalence of symptoms and elevated fecal calprotectin (FCP) levels in the Manitoba Living with IBD Study. They measured symptom prevalence in 156 patients from self-reports on the Inflammatory Bowel Disease Inventory.

Beginning in 2015, study participants completed an online survey every other week for two years, reporting whether and to what extent they were experiencing any of a list of 22 symptoms. They mailed in stool samples for FCP tests at the start of the study, after 26 and 52 weeks, and after any self-reported symptom flares.

The team grouped results by the participants’ sex, and whether they had CD or UC. About two-thirds of participants had CD. Within those groups, the researchers compared the prevalence of self-reported symptoms and flares with the presence of elevated FCP.

Reporting their findings at Canadian Digestive Diseases Week 2023, the investigators found that several symptoms stood out for their associations with high FCP levels—most notably, bowel movement urgency, which strongly predicted inflammation in both UC and CD (J Can Assoc Gastroenterol 2023;6:40; abstract A74).

Urgency strongly predicted disease activity. Patients who reported mild to severe urgency were six times more likely to have active disease than those who did not.

Fatigue was the most common symptom among all participants, affecting large portions of patients with both active and inactive disease. However, the absence of fatigue predicted the absence of inflammation. Those without fatigue were highly unlikely to have reported a flare or to have active disease, as defined by their reported symptoms in the online survey. On the high end, in male participants with UC who did not report experiencing fatigue, there was about a 94% chance that their disease was inactive and a 75% chance that their FCP levels were normal.

Other symptoms predicted inflammation for subgroups of study participants. In men with UC, those who reported loose or liquid bowel movements were much more likely to have elevated FCP levels: more than three times as likely in men and nearly twice as likely in women. Women with UC who reported blood in stool were about twice as likely to have elevated FCP levels.

The knowledge that some specific symptoms correlate with objective markers of IBD can inform treatment plans, according to Charles Bernstein, MD, the study’s senior investigator and the director of the Inflammatory Bowel Disease Clinical and Research Centre at the University of Manitoba. “It is important to inquire about an array of symptoms, not just frequency and whether or not there is blood,” he said, “and also … to explore whether or not there is active inflammation before therapy decisions can be reliably made.”

The researchers did not separate data between patients with specific subgroups of IBD, such as isolated small bowel CD and colonic CD, and they still do not know much about how symptoms correlate with FCP levels in patients with these subtypes of IBD. Dr. Bernstein told Gastroenterology & Endoscopy News that he plans to explore the relationship between symptoms and inflammation within more specific disease phenotypes.

Dr. Glassner suggested that future studies should also include imaging and endoscopy as objective measures of disease to obtain information about patients with ileal CD, for example, which doesn’t reliably correlate with high FCP levels.

—Jen Monnier