Ulcerative Colitis

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Continuing Education Activity

Ulcerative colitis is an idiopathic inflammatory condition of the colon which results in diffuse friability and superficial erosions on the colonic wall and associated bleeding. It is the most common form of inflammatory bowel disease worldwide. Characteristically, it involves inflammation restricted to the mucosa and submucosa of the colon. Typically, the disease starts in the rectum and extends proximally in a continuous manner. In the United States, the disease accounts for a quarter-million provider visits annually. This activity reviews the evaluation and management of ulcerative colitis and highlights the role of the interprofessional team in evaluating and improving care for patients with this condition.


  • Explain the history and physical examination of patients with ulcerative colitis.
  • Outline evaluation of patients with ulcerative colitis.
  • Describe treatment considerations for patients with ulcerative colitis.
  • Identify interprofessional team strategies for improving care coordination and outcomes in patients with ulcerative colitis.


Ulcerative colitis is an idiopathic inflammatory condition of the colon which results in diffuse friability and superficial erosions on the colonic wall associated with bleeding. It is the most common form of inflammatory bowel disease worldwide. It characteristically involves inflammation restricted to the mucosa and submucosa of the colon. Typically, the disease starts in the rectum and extends proximally in a continuous manner. In the United States, the disease accounts for a quarter-million provider visits annually, and medical costs directly related to the disease are estimated to exceed four billion dollars annually.[1][2][3] Ulcerative has no cure and is a lifelong disorder with a significant impact on both physical and mental health.


The specific cause of inflammatory bowel disease is not known. There seems to be a primary genetic component since the most important independent risk factor is a family history of the disease (8% to 14% of patients). A first-degree relative of a patient with ulcerative colitis has a four times higher risk of developing the disease. Additionally, ulcerative colitis has a higher incidence in Jewish populations than other ethnicities.

Although there is little evidence to support this, it has been postulated that alterations in the composition of the gut microbiota and defects in mucosal immunity could lead to ulcerative colitis. Autoimmunity may also play an important role in the etiology of ulcerative colitis.[4][5]

Some evidence suggests that smoking may be protective but so far no one has been able to confirm a direct relationship between the two.


Worldwide, the highest incidence and prevalence of inflammatory bowel diseases are seen in Northern Europe and North America. Inflammatory bowel disease is closely linked to a westernized environment and lifestyle. Ulcerative colitis has an incidence of 9 to 20 cases per 100,000 persons per year. Its prevalence is 156 to 291 cases per 100,000 persons per year. Compared to Crohn disease, ulcerative colitis has a greater prevalence in adults. When considering the pediatric population; however, ulcerative colitis is less prevalent than Crohn disease.

Ulcerative colitis has a bimodal pattern of incidence. The main onset peaks between the age of 15 and 30 years. A second, and the smaller peak of incidence occurs between the age of 50 and 70 years. Though some studies show a slight predilection for men, most studies note no preference regarding sex. There is an increased prevalence of ulcerative colitis in nonsmokers or those who recently quit smoking. Additionally, smokers diagnosed with ulcerative colitis tend to have milder disease, fewer hospitalizations, and need for less medication. There is evidence, though weak, that non-steroidal anti-inflammatory drug use is associated with the onset or relapse of ulcerative colitis.

There is also an association of inflammatory bowel disease with the removal of an inflamed appendix. Appendectomy before the age of twenty is associated with a decreased incidence of ulcerative colitis; whereas the opposite is true for Crohn disease. In fact, appendectomy has been shown to reduce the risk of developing ulcerative colitis by 69%.[6][7]


The pathophysiology of ulcerative colitis involves defects in the epithelial barrier, immune response, leukocyte recruitment, and microflora of the colon.[8][9]

The epithelial barrier has a defect in colonic mucin, and possibly tight junctions, leading to increased uptake of luminal antigens. The lamina propria of the mucosa also has an increased number of activated and mature dendritic cells which include a large number of toll-like receptors (TLR), specifically TLR2 and TLR4. There also seems to be an atypical T-helper (Th) cell response in patients with ulcerative colitis, specifically Th2, which exerts a cytotoxic response against epithelial cells. Other immune-related factors that play a role in the pathophysiology of ulcerative colitis include tumor necrosis factor-alpha (TNF-alpha), interleukin 13, and natural killer T-cells. Levels of IgM, IgA, and IgG are elevated in inflammatory bowel disease; however, a disproportionate increase in IgG1 antibodies is found in patients diagnosed with ulcerative colitis.

Leukocyte recruitment is affected on two fronts. There is an upregulated release of the chemoattractant CXCL8 in ulcerative colitis so that leukocytes are recruited to the mucosa from systemic circulation. Additionally, there is an upregulation of mucosal addressin cellular adhesion molecule-1 (Mad-CAM1) on the endothelium of mucosal blood vessels which promotes leukocyte adhesion and extravasation into mucosal tissue.

Studies have shown that enteric microflora is important in the pathogenesis and severity of inflammation and disease phenotype. Ulcerative colitis seems to also result, in part, from a homeostatic imbalance between enteric microflora and the host's mucosal immunity. This results in an aberrant response to non-pathogenic bacteria.


Histologically, the mucosal layer of the colon in a patient with ulcerative colitis includes infiltrates of varying density and composition, depending on the stage of the disease. These infiltrates primarily consist of lymphocytes, plasma cells, and granulocytes, with the latter being more prominent during acute flares of the disease. Additionally, goblet cell depletion, ulcerations, and alterations in mucosal crypts are sometimes apparent. These findings might also be present on histological evaluation of the distal ileum, even though ulcerative colitis is a disease confined to the colon. This is backwash ileitis.

History and Physical

The main symptom of ulcerative colitis is bloody diarrhea, with or without mucus. Associated symptoms also include urgency or tenesmus, abdominal pain, malaise, weight loss, and fever, depending on the extent and severity of the disease. The onset of the disease is typically gradual, and patients will likely experience periods of spontaneous remission and subsequent relapses. Factors that typically exacerbate ulcerative colitis include smoking cessation and nonsteroidal anti-inflammatory drug use.

There are some extraintestinal manifestations (EIMs) that are also present in 10% to 30% of patients with ulcerative colitis. Extraintestinal manifestations associated with disease activity include episcleritis, scleritis, and uveitis, peripheral arthropathies, erythema nodosum, and pyoderma gangrenosum. Extraintestinal manifestations independent of colitis activity include axial arthropathies, sacroiliitis, and ankylosing spondylitis. A significant hepatic extraintestinal manifestation of ulcerative colitis includes primary sclerosing cholangitis and is associated with a greater risk of colorectal cancer.


Diagnosis of ulcerative colitis is made clinically with supportive findings on endoscopy, biopsy, and by negative stool examination for infectious causes. Because colonic infection can produce clinical findings indistinguishable from idiopathic ulcerative colitis, microbiologic studies for bacterial infection and parasitic infestation should be included in the initial evaluation.[10][11]

Radiologic examinations are not critical for the diagnosis but may be useful. Patients with longstanding ulcerative colitis may show a "stove-pipe" sign on double-contrast barium enema (DCBE).

Colonoscopy or proctosigmoidoscopy might reveal loss of typical vascular pattern, granularity, friability, and ulceration which involve the distal rectum and proceed proximally in a symmetric, continuous, and circumferential pattern. The disease can range from isolated to the rectum and sigmoid colon (proctitis) to disease of the entire colon (pancolitis). Population-based studies show that, upon presentation, proctitis is found in 30% to 60% of patients, left-sided colitis is found in 16% to 45%, and pancolitis is found in 14% to 35%.

Laboratory evaluation will usually reveal an increase in inflammatory factors (ESR, CRP, leukocytosis), especially during an acute flare. Regardless of disease stage, 60% to 70% of ulcerative colitis patients are positive for perinuclear antineutrophil cytoplasmic antibodies (P-ANCA). P-ANCA is also found in a small number of patients with Crohn disease. In addition to P-ANCA, anti-saccharomyces cerevisiae antibodies (ASCA) are found in both Crohn disease and ulcerative colitis but are more prevalent in Crohn disease, therefore testing for both P-ANCA and ASCA has some utility in distinguishing types. Testing for carcinoembryonic antigen (CEA) can also be helpful in ulcerative colitis as higher levels can indicate a flare.

Testing for fecal calprotectin also has some utility in the diagnosis of ulcerative colitis, though it is nonspecific. Fecal calprotectin correlates with increased neutrophils in the intestine and therefore can be helpful in ruling out inflammatory bowel disease. Studies show that less than 1% of patients with low fecal calprotectin are likely to suffer from inflammatory bowel disease.

An endoscopy (colonoscopy) must be done at some point which will reveal:

  • Fragile mucosa
  • Granular mucosa
  • Loss of vascular pattern
  • Presence of erosions and pseudopolyposis

Multiple biopsies should be obtained to confirm the diagnosis.

When a diagnosis of ulcerative colitis is made, the most common classification system used to determine the extent and severity of the disease is the Montreal classification system. Extent (E) is determined by endoscopic evaluation and includes E1 (Proctitis), E2 (left-sided or distal colitis), and E3 (pancolitis). Symptoms and systemic findings determine severity (S). It ranges from S0 (remission) to S3 (severe).

Treatment / Management

Treatment choice for patients with ulcerative colitis is based on both the extent of the disease and the severity. The prognosis during the first decade after diagnosis is often generally good, and most patients go into remission. Rectal application of medical therapy, via suppository or enema, is usually appropriate for isolated distal disease (proctitis); however, a rectal application is usually used in combination with systemic therapy to help target the distal colon and therefore decrease tenesmus. [6][12][13]

First-line treatment is sulfasalazine and 5-aminosalicylates, given orally or rectally, which have a remission rate of about 50%. Glucocorticoids, orally or rectally, can be added for those who fail to achieve remission within two weeks. Except for glucocorticoids, all of these medications can be used in the maintenance of remission. Additionally, there is some evidence that probiotics are helpful in attaining remission. Fecal microbiota transplantation also shows promise in the treatment of ulcerative colitis to help establish healthy gut microbiota.

If patients are refractory to glucocorticoids, thiopurines or biological drugs can be added to therapy. Thiopurines are immunosuppressants such as azathioprine or 6-mercaptopurine. Biological drugs include anti-TNF-alpha drugs, such as infliximab, adalimumab, and golimumab. Infliximab is the most widely used for ulcerative colitis and can be used in severe cases during hospital admissions. The newest class of biological drugs are anti-adhesion molecule inhibitors, such as vedolizumab, which blocks alpha-4-beta-7 integrin.

Since patients with ulcerative colitis have reduced expression of peroxisome proliferator-activated receptor-gamma (PPAR-gamma) in their colonocytes, future treatment may include (PPAR-gamma) agonistic activity. PPAR-gamma is a negative regulator of NF-KB-dependent inflammation. Novel 5-aminosalicylic acid (5-ASA) analogs are being developed that have greater PPAR-gamma activity. Cardiotoxicity and metabolic toxicity restrict the use of existing PPAR-gamma agonists.

Colectomy is curative in patients with ulcerative colitis since the disease is restricted to the colon. Indications for surgery are a failure of medical therapy, intractable fulminant colitis, toxic megacolon, perforation, uncontrollable bleeding, intolerable side effects of medications, strictures, unresectable high-grade or multifocal dysplasia, cancer, or growth retardation in children. The procedure of choice is proctocolectomy with ileal pouch-anal anastomosis (IPAA); however, in patients who are ineligible for IPAA proctocolectomy with ileostomy is a viable alternative.

Because of the risk of colon cancer, colonoscopy is recommended at regular intervals.

All patients need maintenance therapy to prevent relapse. Oral aminosalicylates are the drugs of choice but others may respond to azathioprine and 6-mercaptopurine.

There is no specific diet for patients with ulcerative colitis but many develop lactose intolerance. Unlike Crohn disease, there is no role for elemental or parenteral nutrition.

Differential Diagnosis

In patients presenting with lower abdominal pain and bloody diarrhea, the following differentials should be considered:

  • Crohn disease
  • Parasitic colitis
  • Tuberculosis
  • Radiation colitis
  • Colon cancer
  • Toxic megacolon
  • Bacterial/viral gastroenteritis


The severity of ulcerative colitis is graded from mild to severe depending upon rectal bleeding:

  • Mild: Fewer than four rectal bleeding episodes per day
  • Moderate: More than four rectal bleeding episodes per day
  • Severe: More than four rectal bleeding episodes  per day and the patient has systemic features of an illness combined with hypoalbuminemia


Ulcerative colitis is a lifelong illness but the overall mortality is not greater than in the general population. However, mortality is increased in patients who develop shock and surgical complications. When the muscularis propria is involved it may damage the nerves resulting in dilatation, aperistalsis, and ischemia (toxic megacolon). Today, toxic megacolon is the most common cause of death in ulcerative colitis. At least 5% of patients develop colon cancer and this risk increases with the duration of the disease. Unlike Crohn disease, stricture formation is rare.


Ulcerative colitis is a lifelong disease with periods of remission and relapse. Following complications can occur in patients suffering from ulcerative colitis:

  • Leak from anastomosis
  • Pelvic abscess
  • Enterocutaneous fistulas
  • Pouch prolapse, pouchitis
  • Incontinence
  • Sexual dysfunction
  • Toxic  megacolon
  • Colon/rectal cancer

Deterrence and Patient Education

American College of Gastroenterology has made guidelines on preventive care in patients with ulcerative colitis. These recommendations include:

  • Screening for skin malignancies irrespective of the use of biological agents
  • Assessing bone mineral density
  • Be vaccinated against herpes zoster
  • Vaccinated against pneumococcus, H. influenzae, and the flu virus
  • Should not travel to areas of yellow fever without first consulting with an infectious disease expert
  • Be screened for depression and anxiety
  • Women with ulcerative colitis should get annual cervical cancer screening

Pearls and Other Issues

There is an increased risk of colorectal cancer in patients with ulcerative colitis. The risk is cumulative, with a 2% chance of colorectal cancer after ten years of diagnosis, 8% after 20 years, and 20% to 30% after 30 years. Two factors associated with increased risk of colorectal cancer are the duration and extent of the disease.

Enhancing Healthcare Team Outcomes

Ulcerative colitis is a systemic disorder with no cure. The disorder has numerous extraintestinal involvement in addition to the colon. Thus, it is best managed by an interprofessional team. All patients with the disorder need lifelong monitoring. Because of the risk of colorectal cancer, surveillance colonoscopy should occur every 1-2 years. Further, since patients are often treated with biological agents, they need to undergo screening for melanoma and nonmelanoma skin cancer.

The pharmacists should assist the team by educating the patient on the importance of medication compliance to avoid relapse. The nurse should encourage regular vaccinations, hand washing, and cancer screening. A dietary consult should be obtained to educate the patient on foods to eat and what not to eat, especially if they have a stoma. In addition, a stoma nurse should be involved in the teaching of stoma care.

An infectious disease nurse should monitor the patient in the outpatient setting to ensure that they are not immunocompromised. Social workers should be involved to ensure that the patient has ample support and finances; so that the treatments are not missed. Patients with risk factors for osteoporosis need screening for bone mineral density periodically. Patients should be encouraged to undergo annual vaccination against influenza and pneumococcus. Finally, many patients with ulcerative colitis develop depression and anxiety and should be referred to a mental health counselor.[14][15]


Ulcerative colitis has no cure and despite treatment, many continue to have increased bouts of stool frequency. An increase in mortality is usually seen in elderly patients, those with complications like infection, shock, anemia, and those who require repeated surgical interventions. Data show that when the disease involves the muscularis propria, it can lead to bowel dysmotility, necrosis, and gangrene. A certain number of patients also develop toxic megacolon with poor outcomes. It is estimated that about 5% of patients will develop colorectal cancer over time. The risk of colon cancer is higher in patients with pancolitis and in patients whose disease started before the age of 15. Overall, the quality of life in patients with ulcerative colitis is poor.[16][17] (Level 5)

Article Details

Article Author

Whitney D. Lynch

Article Editor:

Ronald Hsu


6/11/2022 12:07:24 AM



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