APP Institute IBD Opens With “Back to Basics”

Understanding the immunology and phenotypes of inflammatory bowel disease (IBD) can help to guide therapeutic management and help stratify risk, explained David Rubin, MD, and Marita Kametas, MSN, APN, as they opened the first APP Institute Inflammatory Bowel Disease on July 26.

Dr Rubin is the Joseph B Kirsner Professor In Medicine, chief of Gastroenterology, Hepatology and Nutrition, and director of the Inflammatory Bowel Disease Center at the University of Chicago School of Medicine. Marita Kametas is a certified ostomy specialist and certified medical surgical nurse and the manager of the Advanced Practice Service for the section of gastroenterology at the University of Chicago School of Medicine.

In this “Back to Basics: An Overview of IBD,” Dr Rubin reviewed the epidemiology and prevalence of ulcerative colitis (UC) and Crohn’s disease (CD) as well as the “perfect storm” that includes the microbiome, genetics, environment, and immune response that results in IBD.

Of the 3.1 million Americans with IBD, about half are diagnosed with CD and half with UC, he noted. Typically patients are diagnosed between the ages of 15 and 30, although some patients are diagnosed at very young ages and a growing proportion of patients with IBD are 50 years of age or more. Although people of Eastern European Jewish descent are at a higher risk of developing IBD, Dr Rubin said, “The usual patient we see who has IBD has no family history, isn’t Jewish, and essentially feels like they were struck by lightning when they developed this problem.”

The genetics of IBD is complex, with 242 susceptibility genetic loci identified, Ms Kametas stated. Although, as Dr Rubin pointed out, most patients do not have a family history of IBD, an important risk factor is having a first-degree family member with UC or CD. “This can be an important prognostic factor for our patients.”

The effect of the environment on development of IBD is incompletely understood, Dr Rubin noted. Obesity, a Westernized diet with significant amounts of meat and fat, smoking, urban living, lack of physical activity, vitamin D deficiency, and antibiotic use in childhood d may contribute to the development of IBD. He pointed out that having had an appendectomy for true appendicitis can be somewhat protective against IBD.

The microbiome of the gut “is a complex ecosystem that actually satisfies the definition of an organ unto itself,” with more than one trillion organisms, Dr Rubin explained. “It remains a bit of a chicken-or-egg about whether the microbiome is driving the IBD, or if the dysregulated immune system is affecting the microbiome.”

Infection may be one contributor to the initial dysregulation of the immune system that triggers IBD, Dr Rubin continued. “It’s not uncommon for us to hear that a patient had food poisoning or C difficile, or a viral infection, and then didn’t recover fully.”

Acute colitis, such as that caused by infection, “can look like just ulcerative colitis,” he cautioned, but there are some features common to acute colitis such as edema, cryptitis in the lamina propria, straight crypts, more surface damage, and preservation of mucin. In UC, there will be less surface damage, decreased mucin, no edema, and crypt branching. “All it takes is about 3 weeks for crypt branching to begin,” he said. He further pointed out that both infection causing an acute colitis and chronic colitis can exist simultaneously.

Ms Kametas reviewed the differences between disease activity and disease severity. Activity consists of the current inflammatory burden and symptom burden, and the objective and subjective assessments of disease. Severity focuses on historical disease behavior, including need for surgery, extent of bowel involvement, and complications.

“When I first see a patient, I trace the story of how we got to today,” she said, beginning with the age at diagnosis; disease location; disease behavior, such as perianal disease; extraintestinal manifestations; previous treatments; concomitant conditions; past surgeries; any history of nutritional deficiencies; and historical disease behavior compared to recent. “I will ask them about how they’re doing today, and if it’s a good day, how does that compare to most days? Are today’s symptoms representative?”

Assessment of risk for disease progression and complications among patients is a critical step, Dr Rubin explained. For example, patients with Crohn’s disease who were diagnosed prior to age 30, who have extensive bowel involvement, with deep ulcerations, prior resections, and/or stricturing disease or perianal disease are at significantly higher risk of poor outcomes, such as additional surgeries and hospitalizations.

Among patients with UC, diagnosis at or before age 40, elevated C-reactive protein and erythrocyte sedimentation rate, steroid dependency, and/or a history of hospitalizations are indications of higher risk of colectomy and complications, he said. Understanding the degree of risk helps the clinician in choosing therapies and designing a treatment plan with appropriate intervals of monitoring.

Dr Rubin emphasized the need to look beyond the lumen at extraintestinal manifestations. “Patients may not volunteer, so ask whether they’re having joint pain. What locations? In small or large joints? In the spine or peripheral joints?” Similarly, caregivers should explore other indications of EIMs, such as changes in skin, nails, or hair. Patients with IBD may be at increased risk for fatty liver even when they are not overweight, and for primary sclerosing cholangitis, as well as uveitis, growth delays in children, and other conditions.

“Quiet lumen, noisy EIM” can describe how some EIMs may present independent of flares, Ms Kametas said. “This highlights the need for a multidisciplinary approach.” She explained that some EIMs, such as aphthous ulcers, may be predictive of flares of bowel disease.

Dr Rubin noted that the presence and types of EIMs can guide therapy choices. “Some therapies will work with both conditions, such as an IL-23 which can treat the bowel and the skin,” he explained, which can facilitate patient convenience and adherence and make treatment more likely to be approved under insurance.

Early diagnosis is important, both presenters stressed, to stratify risk, implement early targeted therapy, and halt disease progression. “Early diagnosis is the key to disease modification; the downstream risks of complications are much higher without it,” Dr Rubin stated.

They agreed that there are specific benchmarks in a treat-to-target approach for IBD care. “The first benchmark is the patient feels better,” Ms Kametas said. “Then the second is when labs start to normalize.”

Dr Rubin added, “The ultimate goals are sustained functional remission and disease modification. We want our patients functionally well, able to do everything they want to do in life,”