Ulcerative Colitis

The inflammatory process of UC involves only the colonic mucosa layer. The inflammation can involve the rectum and sigmoid colon or the entire colon. UC is usually symmetrical and continuous and involves the colon from the anal verge. Some patients present with isolated proctitis that can progress to involve the proximal colon. If the disease involves the entire colon (also called universal colitis) and the inflammation is severe, indirect injury of the terminal ileum, called backwash ileitis, can occur. Otherwise, any proximal gut or small bowel involvement implies CD.

Early inflammation can produce hyperemia, edema, and friability. As the inflammatory process progresses, spontaneous hemorrhage and superficial ulcerations of the mucosa develop. These can become diffuse and coalesce, forming deep, confluent ulcerations. With chronic recurrent injury, fibrosis can develop. Pseudopolyps, the result of chronic inflammation and healing, can protrude into the colonic lumen and cause obstruction. Long-standing inflammation can cause stricture formation, which can be a harbinger of underlying adenocarcinoma in patients with UC.

Severe inflammation causes thinning and dilation of the bowel wall and denudement of the mucosal lining, compromising the protective mucosal barrier. Toxic dilation, also called megacolon, can occur and possibly lead to perforation. Small rectovaginal or perirectal fistulas are rare but can occur in UC.

These distinguishing features of CD and UC become less reliable with chronic or severe disease and after successful treatment. Healing of UC can be uneven or patchy. Use of rectal or topical medications can produce rectal sparing similar to Crohn’s colitis.

Pathology

An IBD diagnosis is not always proven with endoscopic biopsies alone; it requires careful clinicopathological correlation. An endoscopic biopsy can provide a correct diagnosis of CD in 64% and a UC diagnosis in 74% of patients (Geboes, 2008). The traditional histological, pathognomonic feature of CD, the noncaseating epithelioid granuloma, is found in only 10% to 28% of endoscopic biopsies and only half of surgical specimens. Histological features that favor CD include epithelioid granulomas, discontinuous crypt distortion, discontinuous inflammation, and focal cryptitis. Transmural mucosal inflammation, fissures, and skip lesions are also pathological features of CD (Brand, 2009; Joseph & Weber, 2012). The inflammatory process can traverse all four layers of the bowel, up to and including the serosal layer.

The typical histological feature of UC is the crypt abscess with proliferation of neutrophils in the lamina propria. A heavy and diffuse mucosal inflammatory infiltrate and severe mucin depletion are additional characteristics. Histological features that favor UC include severe distortion or atrophy of the crypts with a villous or irregular mucosal surface. These histological changes can even be seen in endoscopically normal-appearing mucosa (Geboes, 2008; Joseph & Weber, 2012).

EPIDEMIOLOGY

There is considerable geographic variation in the incidence of IBD. The incidence of IBD is increasing in the Western world, with higher rates in more developed countries in North America and Europe (Molodecky et al., 2012). The incidence of CD and UC is becoming a global disease burden (Burisch & Munkholm, 2013).

The highest annual incidence of UC in Europe is 24.3 per 100,000 person-years; in Asia and the Middle East the incidence is 6.3 per 100,000 person-years; and in North America it is 19.2 per 100,000 person-years. The highest annual incidence of CD in Europe is 12.7 per 100,000 person-years; in Asia and the Middle East the incidence is 5.0 per 100,000 person-years; and in North America it is 20.2 per 100,000 person-years. The highest prevalence values for IBD are in Europe. UC prevalence is 505 per 100,000 persons and CD prevalence is 322 per 100,000 persons. In North America the prevalence for UC is 249 per 100,000 persons and CD prevalence is 319 per 100,000 persons (Khalili et al., 2012; Molodecky et al., 2012).

Both are diseases of young people, and a diagnosis of IBD is most likely to be made in patients in their teens extending to 40 years of age. The highest incidence of IBD is in patients in their 20s (Ha, 2012). Men and women have a slight difference with female predominance in CD and male predominance in UC. Although these diseases can occur in any age group, a second peak in incidence can occur in 10% to 15% of patients in their seventh and eighth decades of life (del Val, 2011; Ha, 2012). This second peak may be attributable to confusion of diverticulitis or mesenteric ischemia with IBD or, more likely, a result of more intense evaluation of elderly patients suspected of having IBD.

Whites are more likely to have IBD than patients of Asian, African, and Hispanic descent. IBD is more common among patients of Jewish heritage. In Israel, IBD rates are higher among European- and American-born Jewish populations than those from Africa and Asia. The geographic variability in incidence among Jewish populations appears to mirror that of the general population. Migrants to areas of higher incidence subsequently exhibit a higher rate of IBD. Studies that have indicated a higher incidence among urban residents or among members of certain occupations are probably undermined by referral bias.

Genetic Factors

Environmental Factors

Certain environmental factors contribute to the pathogenesis of IBD. Smoking is positively associated with CD, but in UC a negative association has been observed. There is slight increased risk for IBD among users of oral contraceptives (Cornish et al., 2008; Frolkis et al., 2013; Lakatos et al., 2013; Rosenfeld & Bressler, 2012).

Diet would seem a logical focus of investigation, but numerous studies examining diet and IBD have failed to demonstrate any dietary risk factors. Western-style diet (processed and fried food) and increased sugar intake are suggestive of an increased risk of CD. Low vegetable and fiber intake has been associated with development of IBD. A high intake of animal fats, polyunsaturated fatty acids, and milk protein can have an increased incidence of UC and CD (Andersen, Olsen, Carbonnel, Tjønneland, & Vogel, 2012; Yamamoto, 2013). There is no consistent evidence that prenatal vitamin supplements, tonsillectomy, childhood vaccinations, early childhood hygiene, obesity, toothpaste use, psychosocial factors, and breastfeeding or bottle-feeding play any role in the etiology of IBD (Long et al., 2012; López-Serrano, Pérez-Calle, & Fernández-Rodríguez, 2010; Shaw, Blanchard, & Bernstein, 2011).

DIAGNOSTIC CRITERIA

There are no set diagnostic criteria for IBD. The diagnosis of CD is based on the history and clinical profile and supporting radiographic, histological, or endoscopic data. Most patients will give a history of at least 6 weeks of symptoms, thus excluding most acute infectious enterocolitides. Several conditions can act as impostors of CD, including tuberculosis, Yersinia enteritis, Entamoeba histolytica, and Chlamydia. Appendicitis, intestinal lymphoma or carcinoma, carcinoid tumor of the small bowel, celiac sprue, and diverticulitis often can be mistaken for CD.

UC can be mistaken for several conditions that produce inflammation and ulceration of the colonic mucosa and bloody diarrhea: Escherichia coli, Salmonella, Shigella, Campylobacter, E. histolytica, and cytomegalovirus. Other impostors include diverticulitis, cancer of the colon, ischemic colitis, nonsteroidal anti-inflammatory drug colopathy, radiation injury to the rectum, pseudomembranous or antibiotic-associated colitis, and solitary rectal ulcer syndrome (Hisabe, Hirai, Matsui, & Watanabe, 2013; Hundorfean, et al., 2013; Quigley & Bernstein, 2012; Sonnenberg & Genta, 2012).

HISTORY AND PHYSICAL EXAMINATION

In the teenage patient, a history of developmental delay resulting from malabsorption may be elicited. Patients will often give a history of increased borborygmi. Nocturnal abdominal pain, severe enough to interrupt a sound sleep, or nocturnal bowel movements help to distinguish IBD from functional syndromes of the bowel. Gross rectal bleeding may be seen but is unusual. Most patients complain of frequent, loose, nonbloody stools and right lower quadrant pain.

Symptoms of intermittent small intestinal obstruction or a frank perforation may suggest underlying CD. Fistulas can penetrate adjoining abdominal or perineal structures such as the urinary bladder, producing pyuria, fecaluria, or pneumaturia. Penetration of the skin or vagina may present with passage of air, stool, or mucus. Complications, including toxic megacolon and colonic perforation, associated with UC can also be seen in CD. Patients may give a history of “missed” appendectomy—that is, ileitis that was mistaken for appendicitis.

Ulcerative Colitis

UC patients most often present with bloody stools accompanied by mucus and diarrhea. If only the rectum is inflamed, patients may complain of constipation with a sense of urgency and passage of bloody mucus. The passage of gross blood is the cardinal feature of UC. Disease limited to the distal or left colon is usually not accompanied by constitutional symptoms, whereas universal or more severe disease can produce symptoms of malaise, nausea, and diffuse abdominal pain. UC has a strong tendency toward recurrence, and patients may give a previous history of hospitalization for severe disease or toxic megacolon. A history of recent discontinuation of tobacco may also be elicited.

Extraintestinal manifestations occur in both UC and CD. The most common extraintestinal manifestations are musculoskeletal and mucocutaneous, including axial and peripheral arthritis, acute ocular inflammation, erythema nodosum, and pyoderma gangrenosum. The most significant musculoskeletal manifestation is ankylosing spondylitis, which can occur in 1% to 5% of patients. The arthritis affects the larger joints. Some manifestations may precede the bowel symptoms, and diagnosing IBD may be difficult. Other manifestations (e.g., ankylosing spondylitis) are not related to the severity of the disease, and treatment is challenging. Common extraintestinal manifestations of CD are anemia, amyloidosis, aphthous stomatitis, cholangitis, cholelithiasis, episcleritis, erythema nodosum, inflammatory arthropathies, nephrolithiasis, osteoporosis, and uveitis. Arthritis, oral ulcerations, primary sclerosing cholangitis, pericholangitis, and pyoderma gangrenosum are common extraintestinal manifestations of UC. Hypercoagulability (deep vein thrombosis, cerebrovascular accident, pulmonary embolus) is an extra intestinal manifestation that can be present in both (Veloso, 2011).

DIAGNOSTIC STUDIES

An IBD diagnosis is formulated from a combination of histological, radiological, endoscopic, and/or biochemical surveillance, as a single gold standard is not available (Panes et al., 2013).

Laboratory Tests

IBD can produce many abnormalities in routine screening laboratory tests. Anemia, leukocytosis, and elevated platelet counts may be noted on the complete blood count. Patients with UC are more likely to have a microcytic anemia, whereas those with CD of the small bowel usually have macrocytic anemia from malabsorption of cobalamin (vitamin B₁₂) or folic acid. The erythrocyte sedimentation rate and the C-reactive protein level, both nonspecific indicators of inflammation, can be elevated in both forms of IBD. Abnormal liver function tests, including levels of alkaline phosphatase and transaminases, may be seen in IBD because of reactive hepatitis or primary sclerosing cholangitis.

Low serum protein and albumin levels can be seen in IBD and can indicate chronicity and severity. Electrolyte abnormalities, including hypokalemia, hypomagnesemia, and hypocalcemia, can be documented in many IBD patients, especially those taking steroids.

Serologic blood tests to help distinguish between UC and CD are available. The presence of perinuclear antineutrophil cytoplasmic antibodies (p-ANCA) suggests UC, with 70% of UC patients having high titer antibodies to p-ANCA and 20% of CD patients having low titers. The presence of high titers of anti-Saccharomyces cervisiae antibodies (ASCA) and anti–outer membrane protein C (OmpC) suggests CD (Vasseur et al., 2012; Zhang et al., 2012). Low titers of these can be seen in UC patients (Strober & Gottesman, 2009). Pancreatic autoantibodies (PAB) have been discovered to be specific for CD and goblet cell autoantibodies (GAB) have specificity for UC, but sensitivity is low for both tests (Prideaux, De Cruz, Ng, & Kamm, 2012; Tesija Kuna, 2013). However, 10% of patients with IBD may not be categorized by these assays.

Radiography

Once a diagnosis of IBD is suspected, contrast radiography is a useful tool in making the diagnosis of IBD but not in determining clinical activity.

Endoscopy