Recent years have seen a proliferation of effective targeted treatments for ulcerative colitis (UC). But before considering a management plan, the initial steps for a patient who presents with possible UC are clinical and endoscopic evaluation and assessment of severity, which will help determine the course of treatment to be followed.
Clinical Concerns
The disease is characterized by relapsing and remitting episodes of mucosal inflammation that cause symptoms of diarrhea, bleeding, urgency, and pain on the left side of the abdomen. The most common ages of onset are 15 to 30 years.
Infection must initially be ruled out, particularly with Clostridium difficile, which increasingly has been recognized as a potentially severe complication of inflammatory bowel disease (IBD). Estimates of the infection in patients with new-onset or recurrent disease range from 5% to 47% and reported that mortality among hospitalized IBD patients was four times greater than in patients without the concomitant infection.
Other types of infection that could have similar presentations as UC include those caused by Escherichia coli, Salmonella, and Campylobacter.
In up to one-third of patients, extraintestinal manifestations also can occur, with peripheral arthritis being the most common, but there can also be canker sores in the mouth and skin changes.
The patient's history clearly is important. Certain triggers of disease have been identified, including recent smoking cessation and the use of nonsteroidal anti-inflammatory drugs. However, the strongest risk factor is a family history, according to Ashwin N. Ananthakrishnan, MD, of the Crohn's and Colitis Center, Massachusetts General Hospital in Boston.
"A patient with a family history of ulcerative colitis has a two- to five-fold increased risk," Ananthakrishnan told 鶹ý.
UC differs from the other form of IBD, Crohn's disease, in several ways. "Crohn's is more a pain-predominant process," said Siddharth Singh, MD, of the University of California San Diego. "Patients with Crohn's disease experience abdominal pain and may also have diarrhea, rectal bleeding, and weight loss, whereas ulcerative colitis is a more diarrhea-predominant process," Singh explained. However, the definitive diagnosis requires endoscopy.
In UC, the inflammation is rather superficial, starting at the rectum and continuing to different degrees through the colon, whereas the inflammation in Crohn's disease is much more patchy and deep, and can affect any part of the intestine. Approximately 70% of patients with Crohn's disease have some involvement of the small intestine, and only about 20% to 30% have involvement of the colon alone, according to Singh.
Assessing Severity and Prognosis
Once the diagnosis has been confirmed, the key factor is to determine the severity of disease and the risk of complications, according to Singh. This includes how active the disease is, whether inflammatory markers such as C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) are elevated, how much bleeding is present, and how many bowel movements the patient reports. Other factors that should be considered include the presence of anemia, whether nutritional status is adequate, and the overall burden of inflammation.
The American College of Gastroenterology (ACG) has recently issued a on UC in adults, which includes a proposed UC activity index that classifies patients into mild or moderate-severe disease.
In mild disease, there are fewer than four stools per day, blood in the stool is intermittent, and urgency is mild and occasional. Hemoglobin levels are normal, ESR is below 30 mm/h, and CRP is elevated. An additional marker, fecal calprotectin, is present at levels of 150 to 200 μg/g, and the Mayo endoscopy subscore is 1.
In addition, the Ulcerative Colitis Endoscopic Index of Severity (UCEIS) is 2 to 4. The UCEIS reflects the endoscopic vascular pattern, visible blood on the mucosal surface, and erosions or visible ulcers in the mucosa. The inclusion of this index and the Mayo subscore in the proposed ACG activity index reflects the current attitude toward treatment: "With increasing recognition of endoscopic mucosal response and remission as treatment targets and their prognostic significance for future relapses, need for hospitalization and surgery, it is essential to include endoscopic severity assessment in the diagnosis and management of UC," the ACG guideline states.
The disease is considered moderate-to-severe with more than six stools per day, frequent blood in the stool, and urgency is described as "often." Hemoglobin is below 75% of normal, ESR is above 30 mm/h, CRP is elevated, and fecal calprotectin is above 150 to 200 μg/g. The Mayo subscore is 2 to 3, and the UCEIS ranges from 5 to 8.
UC also can evolve, initially from limited disease to more extensive. "Patients who are likely to have a more severe disease course are younger and have severe endoscopic inflammation and require steroids at the time of diagnosis," said Ananthakrishnan.
Once the diagnosis is made and severity assessed, decisions on treatment can begin and long-term complications considered.
Disclosures
Ananthakrishnan disclosed relevant relationships with Pfizer, Takeda, and Gilead, as well as support from the NIH and the Crohn's and Colitis Foundation.
Singh disclosed support from the NIH, the American College of Gastroenterology, and the Crohn's and Colitis Foundation.