Back to Basics: An Overview of IBD

The APP Institute | Inflammatory Bowel Disease virtual event kicked off on August 13 with a “Back to Basics” overview of inflammatory bowel disease (IBD) presented by Emily Block Williams, FNP-C, APN, and Emanuelle Bellaguarda, MD​, both from Northwestern Medicine in Chicago.

Williams began by reviewing the prevalence of IBD, explaining ​that some 4.9 million people globally had IBD in 2019​, with 405,000 new cases diagnosed that year​. “Over the next 10 years, it is projected that there will be an increase by more than half a percent in people diagnosed with inflammatory bowel disease,” she stated. “By 2030, a total of 4 million Americans will be living with IBD. It’s clear to see that inflammatory bowel disease is on the rise.”

The advanced therapies available to treat IBD are quite expensive, Williams said. It is estimated that in a given year $7.2 billion —$3.6 billion for Crohn’s disease (CD) and $2.7 billion for ulcerative colitis (UC)—in the US. The cost per person-year in the US of IBD exceed the costs per person-year attributable to diabetes mellitus. ​

There are other indirect costs that should be noted, she said, such as increased disability, reduced quality of life, and reduced productivity at work, which add to costs to the patients and to the health care system as a whole.

“We still don’t know what causes this disease,” Dr Bellaguarda said, as she reviewed the multiple theories about etiology of and risk factors for IBD, including genetic predisposition. “We have identified more than 200 genes that can trigger dysregulation of mucosal immunity,” on exposure to environmental factors such as diet and medications.

Among the many possibilities for causation are the hygiene hypothesis, she explained. “Being raised and growing up in an extremely clean environment is not the best. When patients ask what they can do to prevent IBD, the first thing I tell them is to get a dog. That’s one of the few things we have proof that helps to diversify the microbiome. We need to exposure our kids to dirt.”

Diet is of course an important factor, Dr Bellaguarda said. “The Western diet, high milk fat diet, does change the bacteria in our gut and can cause the dysbiosis that can trigger the onset of IBD.” Other factors that may contribute to the development of IBD include a variety of medications, disturbed sleep, lack of physical activity, and smoking. “Stress is the most common factor that our patients report that can trigger a flare” of IBD.

She explained that there is a possibility that IBD is a response to a nonspecific injury to the gut, which results in acute inflammation. Some patients may have just one flare in their lifetime; but in genetically predisposed patients, that initial injury may chronic inflammation. 

 “Ulcerative colitis is a superficial continuous inflammation that begins just proximal to the anal verge and moves upward,” Dr Bellaguard explained. When the rectum alone is inflamed up to 15-20 centimeters, the condition is called proctitis. In left-sided colitis inflammation extends up to about 40 cm to the splenic flexure; and inflammation throughout the colon is referred to as pancolitis. “Ulcerative colitis always ends at the cecum; it never goes into the small bowel,” she noted.

Patients with UC typically present with rectal bleeding, urgency, tenesmus, diarrhea, and some abdominal cramping and pain. A patient who has isolated proctitis may complain of constipation, Dr Bellaguarda explained, which is caused by the inflamed rectum preventing the evacuation of stool.

Endoscopically, UC is characterized by a Mayo score, in which rectal bleeding, stool frequency, physician assessment, and endoscopy appearance are individually rated from 0 (normal) to 3 (severe.) These scores are combined to identify the overall severity of disease, which can range from mild disease marked by 4 or fewer stools per day with little to no blood to fulminant disease or pancolitis, with 10 or more bloody stool daily, continuous bleeding, toxicity, abdominal pain, and the need for transfusion.

Dr Bellaguard also reviewed the Truelove-Witts Severity Index for stratifying UC into mild, moderate, severe, and fulminant disease. Patients with severe disease may require hospitalization while patients with fulminant disease need to be treated as in-patients, and, she stressed, “you need to have your surgical team on board. Even if you’re thinking about medical therapy engage your surgical team early on in case the patient starts failing first- and second-line therapy.” She also emphasized that 30% of patients will present with fulminant UC and will require a surgical intervention at their first presentation. “It’s not uncommon to see these patients and timely intervention is very important to prevent toxic megacolon.”

Unlike UC, which is limited to the colon, Crohn’s disease can involve the entire alimentary system, Dr Bellaguarda explained, from the mouth to the anus. “Most commonly, however, Crohn’s disease presents at the end of the small bowel in the terminal ileum going into the cecum in about 70% of the cases.”

CD also can present with strictures and fistulas and with extraintestinal manifestations as well, she stated, such as joint pain, eye issues such as uveitis, and skin issues as well. The endoscopic appearance of CD tends to show deeper ulcerations than those typically found with UC. Because the ulcers are deeper, the disease can progress through the bowel wall, Dr Bellaguard continued, which can lead to internal fistulas between sections of the gut or to the perianal area.

Symptoms of CD include diarrhea, abdominal pain, loss of appetite and weight, fever, rectal bleeding, and among the pediatric patients, growth delay. The most common symptom is fatigue, Dr Bellaguarda said.

Although, as she explained earlier the causes of CD and UC are not fully understood, research has identified certain inflammatory pathways and enabled the development of recent advanced therapies that can interrupt those pathways, including the tumor necrosis factor inhibitors (TNFi), anti-integrins, interleukin-12/23 and -23 inhibitors, Janus kinase inhibitors, and sphingosine 1 phosphate receptor modulators.

Williams reviewed the factors that increase disease progression have drawn greater attention in recent years. For UC, she explained, the key factors that put a patient at higher risk of disease progression include:

• Diagnosis at or before the age of 40
• Extensive colitis​
• Deep ulcers​
• Corticosteroid dependency​
• History of hospitalization​
• High C-reactive protein and ESR​ or fecal calprotectin
• Clostridium difficile infection​
• Cytomegalovirus infection

She noted that a growing body of evidence shows that early intervention, including treatment with advanced therapies, leads to better outcomes. “Our current STRIDE 2 guidelines have a long-term goal of achieving mucosal healing, because we know that untreated inflammation over time can increase the risk of colon cancer.”

There is some overlapping of risk factors for disease progression in Crohn’s disease and UC, Williams stated, such as younger age at diagnosis. Other risk factors include:

• Initial extensive bowel involvement​
• Ileal/ileocolonic involvement​
• Perianal/severe rectal disease​
• Penetrating or stenosing disease phenotype​

“In these patients with more risk factors and a higher disease burden, it’s important to employ advanced agents early,” she emphasized. These patients with risk factors require closer monitoring, Williams said.

“Why do these things matter?” Emily asked. “They help to guide treatment and lead to better outcomes.”