UC typically with diarrhea, abdominal pain, gross or occult rectal bleeding, urgency to defecate, or weight loss. The presence of anemia, thrombocytosis, or hypoalbuminemia may suggest inflammatory bowel disease, but most patients with ulcerative colitis will not have those abnormalities. C-reactive protein (CRP) level and erythrocyte sedimentation rate (ESR) are relatively insensitive for detecting ulcerative colitis. Serologic tests such as ANCA or ASCA might be helpful in the differential diagnosis, but not confirmative or pathognomonic. At the time of diagnosis, infective (enteric pathogens such as Salmonella, Shigella, Yersinia, Campylobacter, E. Coli 0157:H7, or Clostridium difficile), ischemic, irradiation causes of colitis must be excluded. Endoscopic biopsy plays a key role in confirming the diagnosis of UC.

UC patients can be categorized by the severity of their disease. The accurate assessment of disease activity and extent is essential to the appropriate selection of various treatment modalities. The assessment of UC activity is based on the combination of symptoms, clinical and laboratory examinations, and endoscopic findings. Truelove-Witts criteria, Mayo score, Baron score, modified Baron Score, Sutherland index, Powell-Tuck index (St. Marks index), and Rachmilewitz index (endoscopic clinical activity index, CAI) are the commonly used disease activity measuring instruments.

According to Truelove and Witts’ classification (Table 1.2) [12], mild disease is characterized by stools up to 4 times in a day with or without blood; a normal ESR or CRP; and with no systemic signs of toxicity. Moderate disease correlates with 4–6 bloody stools per day but with minimal signs of toxicity. Patients with severe diseases have more than six bloody stools a day or observable massive and significant bloody bowel movement and evidence of toxicity such as fever, tachycardia, anemia, or an elevated ESR or CRP. Fulminant disease may manifest as abdominal tenderness or distension, continuous bleeding, and anemia with transfusion requirement or colonic dilatation [13–16].

With the importance of clinical severity assessment, endoscopy is a mainstay in the diagnosis of UC and also represents a valuable tool for assessing disease activity and extent of disease (Table 1.3). The original endoscopic grading of UC is Baron’s index. Baron index was developed mainly based on the severity of bleeding. The ulceration was not assessed in this index [17]. Mayo endoscopic scoring system has been most widely used for the assessment of endoscopic activity for UC in both clinical practice and clinical investigational settings. Mayo score consists of a 4-point scale (0–3) of appearance of the rectal mucosa [18]. UCEIS (Ulcerative Colitis Endoscopic Index of Severity) [19], a newly developed index on a 100-point scale, began to be used in the diagnosis of UC recently. The UCEIS has been undergone independent validation with different videos and investigators, evaluating operating properties of the index (responsiveness and reliability).

The indications for endoscopy in UC are the following: initial diagnosis, follow-up in asymptomatic patients, surveillance of dysplasia and colorectal cancer, and at any time that symptoms worsen or new symptoms occur.

The diagnosis of UC can be made initially by sigmoidoscopy. Mucosal biopsies are used to confirm the diagnosis and indicate the initial therapy. Colonoscopy in UC plays an important role in assessing the extension and severity of disease as well. In addition to this, colonoscopy can be used in evaluating the response to the treatment. With regard to therapeutic applications, obstructive symptoms caused by benign fibrotic strictures can be treated adequately by endoscopic balloon dilation. Epidemiological studies have demonstrated an increased risk of colorectal cancer in patients with both UC and colonic Crohn’s disease. Surveillance endoscopy is indicated for regularly obtaining multiple biopsies to exclude possible malignancy, especially in the setting of UC [1].

Continuous inflammation without skipped area and the involvement of rectum is a typical feature of UC. Inflammation or ulceration of mucosa initiates from the superjacent area of the anal canal and is distributed in a continuous and symmetrical manner. Some exceptional cases include appendiceal orifice inflammation, proximal colon involvement only, and rectal sparing after local therapy, which will be described later in this chapter. The extent of UC can be classified as proctitis, left-sided colitis, and extensive colitis (Table 1.4) [20].

For approximately one third of patients with UC is classified as having proctitis. Proctitis is limited to the rectum, especially involves up to 15 cm from the anal verge (Fig. 1.1). Because of its limited extent of colitis, it is regarded as a milder form of UC. It is associated with fewer complications and offers a better prognosis than more extensive disease. Because of its location, ulcerative proctitis can be misdiagnosed as a hemorrhoid unless careful observation is performed.

Left-sided UC includes inflammation that begins from the rectum, involving up to the colon near the splenic flexure. When inflammation is located in the rectum and sigmoid colon, it specifically refers to proctosigmoiditis (Fig. 1.2). Typically, it presents bloody diarrhea, cramps, or tenesmus. Moderate pain on the lower left side of the abdomen may occur in active disease.

The extensive colitis is an inflammation involving more proximal area to splenic flexure. Extensive colitis may begin in the rectum and spread to the transverse or more proximal colon (Fig. 1.3). In particular, inflammation of the whole colonic mucosa from the rectum to cecum is referred to as pancolitis (Fig. 1.4). Patients with extensive colitis show more frequent complications, extraintestinal manifestations, and systemic symptoms. They are also at a higher risk of colorectal cancer and are likely to receive more immunosuppressive and surgical therapies [21]. Lesions usually get more severe towards the rectum, but sometimes it is less severe inversely. Moreover, normal mucosa is usually clearly distinguishable from inflamed mucosa in UC, but sometimes, lesions are scattered around the margin, making it difficult to diagnose.

Cecal patch is the presence of flat periappendiceal lesions, and it has been recognized mostly in patients with left-sided UC or proctitis. This cecal patch or appendiceal orifice inflammation (AOI) (Fig. 1.5) is observed with reddish and friable mucosa in the cecum, especially around the appendiceal orifice. It is more frequently observed in patients with less extensive UC and is unlikely the result of patchy improvement due to treatments. Segmental ulcerative colitis (Fig. 1.6) is a term designated for cases not involving the rectum, but involving the colon focally and segmentally. Rectal sparing also can occur after local therapies such as rectal mesalamine suppositories or enema (Fig. 1.7). These are often misdiagnosed as having Crohn’s disease of the colon. Inflammation of the proximal colon and distal area such as the rectum with grossly normal skipped areas between proximal and distal areas is also considered as one of the endoscopic features of UC. Rarely, atypical inflammatory mucosal change characteristic for UC in various colonic segments without continuity can also be observed, and they are suggested to be one of the features of UC as well (Fig. 1.8).

Sometimes, nonspecific mucosal inflammation in the terminal ileum is observed in patients with UC although, by definition, UC is restricted to the colon. Involvement of the terminal ileum in UC is termed backwash ileitis. It is characterized by the presence of active enteritis involving the terminal ileum in a contiguous pattern from the cecum (Fig. 1.9) [22].