What is inflammatory bowel disease (IBD)? Actually IBD isn’t just one disease—it is the umbrella term used to describe autoimmune conditions that cause inflammation in the gastrointestinal (GI) tract. The most common forms of IBD are Crohn’s disease and ulcerative colitis, two very different chronic illnesses that need lifelong treatment. While IBDs affect just 1% of the population, they can have a devastating impact on quality of life if not brought under control, says Brooks D. Cash, MD, chief of the Division of Gastroenterology, Hepatology and Nutrition at University of Texas Health Science Center at Houston.
Understanding Crohn’s Disease
Crohn’s disease can affect any portion of the GI tract, from the mouth to the rectum. What’s more, it’s a transmural disease, meaning that it causes inflammation across all the layers of the wall of the GI tract, including muscles and nerves, not just the inner lining (mucosa). Because of this, it’s possible to develop fistulas—abnormal tubelike connections—from the gut to the skin or to another organ, such as the bladder, uterus or vagina. Fistulas can lead to abscesses (localized infections) within the body or can drain into other organs or body cavities or even through the skin. The inflammation in Crohn’s disease may not be contiguous and can skip areas, especially in the colon, Example: The sigmoid colon can be inflamed with deep ulcers…then the descending colon may be normal…and then there might be inflammation in the transverse colon. In about 40% to 50% of people with Crohn’s disease, the small intestine is affected, especially the last section called the terminal ileum.
Understanding Ulcerative Colitis
In contrast to Crohn’s disease, ulcerative colitis (UC) affects only the mucosa, or interior surface, of the colon (the large intestine). UC almost always starts in the rectum, which is the last part of the colon. How much of the colon will become involved with UC varies from person to person. There are data to suggest that early recognition and treatment can limit the degree of UC within the colon. UC may be limited to the rectum or to the left side of the colon (the rectosigmoid area) or can extend up into more proximal areas of the colon. Patients with UC involving the entire colon have pancolitis. Unlike Crohn’s disease, UC is expressed in a continuous fashion, meaning that there are no intervening normal areas between affected sections of colon, and UC affects only the colon.
Another inflammatory bowel disease is microscopic colitis, in which the inflammation is only microscopic, so there are no ulcerations or inflammatory changes that can be seen with a colonoscopy. Microscopic colitis most often affects older women and has been linked to other autoimmune conditions such as thyroid disease and celiac disease as well as some medications. The inflammation of microscopic colitis interferes with water absorption from the colon and typically presents with diarrhea. It is diagnosed through examination of small biopsy samples obtained during colonoscopy. It does not appear to be related to Crohn’s disease or UC and does increase the risk for other forms of IBD.
Recognizing Inflammatory Bowel Disease Symptoms
Crohn’s and UC share symptoms including abdominal pain and diarrhea, but there are some differences. In the early stage, Crohn’s disease can mimic irritable bowel syndrome (IBS), a non-inflammatory condition affecting between 5% to 10% of the population. Some people may not see a doctor until pain from dangerous complications—an abscess, fistula or stricture (an obstruction in the bowel)—becomes impossible to ignore. Because UC almost always starts in the lower parts of the colon, bloody bowel movements or diarrhea are among the most common presenting symptoms of UC.
Timing is another clue. IBD presents most often younger in life, primarily from mid-to-late teens (it can begin even earlier) up to age 30, but we also have seen a slight increase of cases after age 60.
Causes of Inflammatory Bowel Disease
There are still no hard-and-fast answers for why some people develop an IBD and others don’t. Autoimmune conditions such as Crohn’s and UC tend to run in families…and our immune systems are in part determined by our genetics. But IBDs aren’t just genetic disorders. There likely are environmental triggers that may trigger the development of IBD. One theory: Exposure to pathogens, whether bacterial or viral, in combination with a susceptible immune system, can trigger an IBD.
While there is a predilection for IBD in Caucasians, they present in people of all races. There are also data showing that geography is a factor. Example: The incidence of IBDs is higher in northern regions of the US than in southern ones…and some studies have found IBD to be more prevalent in urban areas than rural ones.
Treating Inflammatory Bowel Disease
Treatment is essential to improve quality of life and decrease complications. There have been tremendous advancements in therapeutics over the past three decades. Before the development of the currently available classes of IBD therapies, we had to rely on broadly acting medications like steroids such as prednisone and immunomodulators, including azathioprine and 6-mercaptopurine (6-MP), all of which have potential side effects and long-term risks. Prolonged exposure to steroids has been associated with adverse effects such as mood disorders and insomnia, weight gain, skin and hair changes, impaired glucose control, cataracts and osteoporosis, whereas immunomodulators have been associated with pancreatitis and bone marrow problems in some patients.
Another older class of medications called 5-aminosalicylic acid (5-ASA) drugs still are very appropriate for people who have mild UC, but they don’t work well for Crohn’s disease or severe UC.
The first major advance in IBD treatment was the introduction of the biologic infliximab (Remicade) approved in 1998. This drug—known as a TNF-alpha blocker—shuts down tumor necrosis factor alpha, one of the body’s molecules that incites inflammation.
Three other major classes of biologic therapies have been tested and FDA-approved and are the mainstays of therapy…
- Remicade and other TNF-alpha blockers including adalimumab (Humira) and certolizumab pegol (Cimzia).
- Integrin blockers that stop specific white blood cells that can enter the GI tract and cause inflammation, including vedolizumab (Entyvio).
- Interleukin blockers that target the proteins interleukin-12 and interleukin-23, which have been linked to inflammation in the GI tract, such as ustekinumab (Stelara) and risankizumab (Skyrizi).
It’s often a matter of finding the biologic that is most effective and best tolerated by a patient. If a patient continues to have flare-ups while taking one drug, the doctor may increase the dose. If he/she is already at the maximum dose, the doctor likely will move to a different biologic therapy or class.
Why Remission Matters
Thirty years ago, remission was considered to be the absence of symptoms. While symptom relief is crucial to patients, the real keys to IBD remission are achieving endoscopic remission, meaning that an endoscopy shows no evidence of inflammation…and histologic remission, when there’s no evidence of inflammation when a tissue sample is examined under a microscope. While it makes sense that most patients who are in endoscopic and histologic remission are also in clinical remission (meaning they have few, if any, symptoms), it is not uncommon for patients to be in clinical remission but still have smoldering inflammation present in the GI tract. We know through multiple studies that if there’s still inflammation, even in the absence of symptoms, eventual recurrences or relapses are more likely. Also, chronic, low-grade inflammation in the colon can lead to abnormal cell growth, called dysplasia, in the mucosa. These changes are considered early-stage malignancy and increase risk for colon cancer in patients with IBD.
Because of the association between IBD and colorectal cancer, people with IBD typically will have surveillance endoscopies and colonoscopies according to a schedule outlined by their doctors, in some cases as frequently as every one to three years. Often, tissue samples from targeted areas of the GI tract will be taken, even if it looks normal on endoscopy, to check for signs of dysplasia or cancer.
When the dysplasia is considered high grade—or significantly abnormal—the medical team may recommend colectomy, removal of the colon. This is a drastic, life-changing surgery, so the goal is to find the right drug or combination of drugs before someone ever gets to that point.
Important: Even in remission, people need to remain on their therapy because IBDs are chronic diseases without a cure. That means treatment must be continued to remain effective. In fact, interrupting IBD therapy can hamper the drug’s effectiveness because the body can form antibodies that neutralize the medication. If that happens, the patient may need to try a different medication that may not be as effective or well tolerated.
On the horizon: There are always new therapies being developed in the biologic or immune-modifying realm that promise to perform even better than what we currently have available. Though still in the development stages, some of these therapies likely will be approved during the next few years and offer even more options to patients with IBD.
