Inflammatory Bowel Disease

Inflammatory bowel disease (IBD), comprised of ulcerative colitis and Crohn’s disease, is characterized by chronic inflammation of the gastrointestinal tract and elevated pro-inflammatory markers. Inflammatory bowel disease mainly affects the gastrointestinal tract but is also known to have extraintestinal complications due to persistent long-standing systemic inflammation. About 3 million Americans have IBD, with about 70,000 new cases being diagnosed per year. The prevalence of IBD has increased globally with the number of individuals affected by IBD across the globe increasing from 3.7 million in 1990 to 6.8 million in 2017.

Ulcerative colitis is characterized by relapsing and remitting episodes of inflammation limited to the mucosal (innermost) layer of the colon. It almost always involves the rectum, and the extent often involves more proximal portions of the colon in a continuous fashion. Crohn’s disease, on the other hand, is characterized by transmural (affects all layers of the intestine) inflammation and by ‘skip areas’ (areas of normal-appearing intestine interrupted by areas of inflammation) and can affect any part of the gastrointestinal tract from the mouth to anus (but more commonly affects the terminal ileum and proximal colon), as opposed to ulcerative colitis which is limited to the colon. As a result of its transmural nature, Crohn’s disease may lead to areas of narrowing (strictures) and development of sinus tracts, leading to fistula formation.

With regards to its epidemiology, it tends to affect younger individuals with the age of onset for IBD being between 15 and 30 years, with a smaller second peak in incidence between 50 and 80 years of age (also known as older-onset IBD). Studies have also demonstrated a slight female predominance and increased prevalence in Jewish and Caucasian populations.

So what causes IBD? IBD is thought to result due to an interplay of genetics, innate and adaptive immune responses, gut microbiota, environmental and behavioral factors. Some of the lifestyle factors that have been associated with increased risk of IBD include smoking, lack of physical activity, low vitamin D, infection of the gastrointestinal tract (gastroenteritis) and sleep deprivation. Certain medications such as antibiotics and NSAIDs (non-steroidal anti-inflammatory drugs) have also been associated with increased risk of IBD.

Diagnosing IBD usually starts with a good history and physical exam. Patients with IBD typically present with chronic diarrhea (>4 weeks), frequently with blood in stool, abdominal pain and urgency. Other associated symptoms may include fever, fatigue, and weight loss along with extraintestinal manifestations in a few patients such as oral ulcers, skin rash, eye pain or redness and new joint pains.

Diagnostic modalities for IBD includes laboratory testing, cross-sectional imaging and endoscopy with biopsies. Laboratory work-up includes testing for markers of systemic inflammation such as serum C-reactive protein (CRP) and stool studies for markers of intestinal inflammation such as fecal calprotectin and stool lactoferrin to differentiate between intestinal inflammation and functional gastrointestinal disease. It is important to rule out infectious gastroenteritis and colitis through stool studies for enteric pathogens including Clostridium difficile. Ileocolonoscopy with intubation of the terminal ileum is performed for confirmation of diagnosis of IBD. During ileocolonoscopy, the terminal ileum in intubated and mucosal biopsies are performed, particularly if the mucosa appears inflamed, to rule out Crohn’s disease (which frequently involves the ileum). Then, endoscopic evaluation of the colon is undertaken for inflammation (erythema, congestion, edema, erosions, ulcerations, stenosis etc.), and biopsies are performed separately from the right colon, the left colon and the rectum to define the endoscopic and histologic extent of the disease. Several clinical and endoscopic indices exist for description of disease activity and severity. With regards to cross-sectional imaging, small bowel imaging - via magnetic resonance enterography (MRE) or computed tomography enterography (CTE) - is needed for Crohn’s disease to evaluate the proximal and mid small bowel since it is inaccessible via ileocolonoscopy.

It is noteworthy that years of longstanding inflammation seen in IBD patients results in a higher incidence of Colorectal Cancer (CRC) than that of the general population. Due to this, patients diagnosed with IBD with significant colonic involvement (involving greater than one-third of the colon) need frequent endoscopic evaluation with colonoscopy at least once every three years, after eight years of diagnosis of IBD for surveillance of colorectal neoplasia.

Finally, while medical management of IBD is beyond the scope of this brief overview, the treatment goal for patients with IBD is to achieve clinical and endoscopic remission, with histologic remission (mucosal healing) in ulcerative colitis and transmural healing in Crohn’s disease being “ideal” targets. Management of IBD requires a multidisciplinary approach with involvement of a gastroenterologist, colorectal surgeon (especially for moderate to severe disease), radiologist, pharmacist, nutritionist and a dedicated IBD-nurse navigator. Medical management with immunomodulators, biological agents and other advanced therapies directed at decreasing inflammation currently form the mainstay of IBD therapy. Based on disease activity and severity, several therapeutic options exist for mild to moderate or moderate to severe IBD, including: 5-aminosalicylates (oral and topical), steroids (oral and topical), anti-tumor necrosis alpha agents, vedolizumab, ustekinumab, tofacitinib, and several new therapeutic agents being approved by the FDA or currently in clinical trials. Patients with aggressive disease with persistent or recurrent symptoms and endoscopic inflammation non-responsive to medical therapy may need further intervention with surgical resection.

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