Ulcerative Colitis – 13 Interesting Facts

What is an Ulcerative Colitis

Ulcerative colitis is long-lasting (chronic) swelling (inflammation) of the large intestine (colon). Sores (ulcers) may also form on the colon.

Ulcerative colitis is closely related to another condition of inflammation of the intestines that is called Crohn disease. Together, they are frequently referred to as inflammatory bowel disease (IBD).

Interesting Facts

  1. Ulcerative colitis is idiopathic, chronic inflammatory bowel disease characterized by recurring episodes of mucosal inflammation limited to the colon. Disease generally involves rectum with variable extension proximally in a continuous manner
  2. Disease is characterized by periods of relapse and remission presenting with bloody diarrhea, abdominal pain, urgency, and tenesmus
  3. Extraintestinal manifestations may include axial and peripheral arthropathies, ocular disease (eg, episcleritis, uveitis), dermatologic (eg, erythema nodosum, pyoderma gangrenosum), and primary sclerosing cholangitis
  4. Endoscopy (eg, colonoscopy, sigmoidoscopy) confirms presumptive diagnosis, further excludes alternate diagnosis, and defines extent of intestinal involvement
  5. Treatment is based on severity of symptoms and endoscopic extent of inflammation in consultation with a gastroenterologist; medical management is based on induction and maintenance of remission instituted in a step-up approach
  6. 5-aminosalicylic acid is the mainstay of treatment of mild to moderate disease 1
  7. Use corticosteroids followed by transition to a long-term, steroid-sparing agent (eg, thiopurine, anti–tumor necrosis factor, adhesion molecule inhibitor) for patients who have not responded to 5-aminosalicylate therapy and those presenting with more moderate to severe disease 1 2
  8. Disease remission is maintained by use of 5-aminosalicylic acid and/or thiopurine and/or anti–tumor necrosis factor therapy
  9. Flare in disease often requires topical and systemic steroids to reinduce remission 2
  10. Proctocolectomy is required for the up to 15% of patients who have not responded to medical therapy who develop severe complications (eg, toxic megacolon, perforation, malignancy) 1 2
  11. Periodic monitoring for colonic neoplasia is an important aspect of disease management
  12. Possible gastrointestinal complications of disease include bleeding, toxic or fulminant colitis, megacolon with or without toxicity, and increased risk for colorectal cancer
  13. Other conditions and complications associated with disease include osteopenia and osteoporosis, thromboembolic events from hypercoagulable state, anemia, and drug-related increased risk for opportunistic infection and lymphoma

What are the causes?

Ulcerative colitis is caused by increased activity of the immune system in the intestines. The immune system is the system that protects the body against harmful bacteria, viruses, fungi, and other things that can make you sick. When the immune system overacts, it causes inflammation. The cause of the increased immune system activity is not known.

What increases the risk?

Risk factors of ulcerative colitis include:

  • Age. This includes:
    • Being 15–30 years old.
    • Being older than 60 years old.
  • Having a family history of ulcerative colitis.
  • Being of Jewish descent.

What are the signs or symptoms?

Common symptoms of ulcerative colitis include rectal bleeding and diarrhea. There is a wide range of symptoms, and a person’s symptoms depend on how severe the condition is. Additional symptoms may include:

  • Pain or cramping in the belly (abdomen).
  • Fever.
  • Fatigue.
  • Weight loss.
  • Night sweats.
  • Rectal pain.
  • Feeling the immediate need to have a bowel movement.
  • Nausea.
  • Loss of appetite.
  • Anemia.
  • Joint pain or soreness.
  • Eye irritation.
  • Certain skin rashes.

How is this diagnosed?

Ulcerative colitis may be diagnosed by:

  • Medical history and physical exam.
  • Blood tests and stool tests.
  • X-rays.
  • CT scans.
  • Colonoscopy. For this test, a flexible tube is inserted into your anus and your colon is examined.
  • Examination of a tissue sample from your colon (biopsy).

How is this treated?

Treatment for ulcerative colitis may include medicines to:

  • Decrease inflammation.
  • Control your immune system.

Surgery may also be necessary.

Follow these instructions at home:

Medicines and vitamins

  • Take medicines only as directed by your doctor. Do not take aspirin.
  • Ask your doctor if you should take any vitamins or supplements.


  • Exercise regularly.
  • Limit alcohol intake to no more than 1 drink per day for nonpregnant women and 2 drinks per day for men. One drink equals 12 ounces of beer, 5 ounces of wine, or 1½ ounces of hard liquor.

Eating and drinking

  • Drink enough fluid to keep your urine clear or pale yellow.
  • Ask your health care provider about the best diet for you. Follow the diet as directed by your health care provider. This may include:
    • Avoiding carbonated drinks.
    • Avoiding popcorn, vegetable skins, nuts, and other high-fiber foods when you have symptoms of ulcerative colitis.
    • Eating smaller meals more often.
    • Keeping a food diary. This may help you to find and avoid any foods that make you feel not well.
  • Limit your caffeine intake.

General instructions

  • Keep all follow-up appointments as directed by your health care provider. This is important.

Contact a health care provider if:

  • Your symptoms do not improve or get worse with treatment.
  • You continue to lose weight.
  • You have constant cramps or loose bowels.
  • You develop a new skin rash, skin sores, or eye problems.
  • You have a fever or chills.

Get help right away if:

  • You have bloody diarrhea.
  • You have severe pain in your abdomen.
  • You vomit.

Ulcerative Colitis in Children

Ulcerative colitis is long-lasting (chronic) inflammation of the large intestine (colon). Sores (ulcers) may also form on the colon.

Ulcerative colitis, along with a closely related condition called Crohn disease, is often referred to as inflammatory bowel disease.

What are the causes?

Ulcerative colitis is caused by increased activity of the immune system in the intestines. The immune system is the system that protects the body against harmful bacteria, viruses, and other things that can make a person sick. The cause of increased activity of the immune system is not known.

What increases the risk?

This condition is more likely to develop in:

  • People who have a family history of ulcerative colitis.
  • People of Jewish descent.

What are the signs or symptoms?

Common symptoms of this condition include:

  • Diarrhea.
  • Blood in the stool.
  • Cramps in the abdomen, especially with bowel movements.
  • A strong and sudden need to have a bowel movement (bowel urgency).
  • Painful straining to pass stool.
  • Fever.
  • Weight loss.
  • Loss of appetite.
  • Tiredness (fatigue).

Less common symptoms include:

  • Constipation.
  • Slow growth.
  • Skin rashes.
  • Pain and problems in the joints.
  • Irritation of the eyes.
  • Delayed puberty.
  • Irregular menstrual periods.
  • Problems with other organs in the body.

Symptoms range from mild to severe. They may come and go.

How is this diagnosed?

This condition may be diagnosed with:

  • A medical history.
  • A physical exam.
  • Tests, including:
    • Blood tests.
    • Stool tests.
    • X-rays.
    • CT scans.
    • Endoscopy. In this test, the lining of the colon is examined with a flexible tube that has a light and a camera at the end (endoscope).
    • A biopsy. In this test, a tissue sample is taken from the colon and examined under a microscope.
    • A barium enema. In this test, a chalky fluid called barium is given as an enema. Then, X-rays are taken of the bowel.

How is this treated?

There is no cure for this condition, but it can be managed. Treatment depends on the child’s age and the severity of the disease. Treatment often involves medicines to reduce inflammation or to help with symptoms. Some medicines can affect growth, so children who take medicines may need to have their height and weight checked often. They may also need to take nutritional supplements.

Severe flare-ups may need to be treated at a hospital. Treatment in a hospital may involve:

  • Resting the bowel. This involves not eating or drinking for a period of time.
  • Giving medicines through an IV tube.
  • Giving fluids and nutrition through:
    • An IV tube.
    • A tube that is passed through the nose and into the stomach (nasogastric tube or NG tube).
  • Surgery to remove the affected part of the colon. This may be done if other treatments are not helping.

This condition increases the risk of colon cancer, so children who have this condition will need to be watched for colon cancer throughout life.

Follow these instructions at home:

  • Keep a diet journal to help identify foods that cause your child’s condition to flare up.
  • Have your child avoid foods that cause the condition to flare up.
  • Give over-the-counter and prescription medicines only as told by your child’s health care provider.
  • Have your child eat a well-balanced diet.
  • Give your child vitamins as needed.
  • Keep all follow-up visits as told by your child’s health care provider. This is important.

Contact a health care provider if:

  • Your child has a flare-up even with treatment.
  • Your child’s condition gets worse.
  • Your child has new symptoms.
  • Your child is depressed.
  • Your child is avoiding school or other activities.
  • Your child has a fever.

Get help right away if:

  • Your child has severe bleeding from the rectum.
  • Your child has severe abdominal pain.
  • Your child’s abdomen swells (abdominal distension).
  • Your child’s abdomen is tender to the touch.
  • Your child who is younger than 3 months has a temperature of 100°F (38°C) or higher.

Detailed Information


  • Failure to exclude infectious causes for symptoms at presentation can lead to unnecessary testing and evaluation for ulcerative colitis; 3 failure to exclude infectious causes for symptom flares can lead to unnecessary morbidity 1
  • Administer narcotic pain medications sparingly as they can render clinical abdominal examination less reliable and potentially precipitate colonic distention and megacolon 3
  • Failure to administer thromboembolic prophylaxis to hospitalized patients with ulcerative colitis can lead to increased morbidity; bloody stool is not a contraindication for low-molecular-weight heparin prophylaxis 4
  • Avoid using corticosteroids to maintain remission because there is high risk for morbidity and mortality associated with corticosteroid use; use alternate available effective therapies (eg, 5-aminosalicylic acid, infliximab, thiopurines) whenever possible 5

Urgent Action

  • Immediately refer patients who have massive hemorrhage, bowel perforation, or toxic megacolon to a general or colorectal surgeon for emergent surgical intervention 3


Clinical Clarification

  • Ulcerative colitis is an idiopathic, chronic inflammatory bowel disease characterized by recurring episodes of mucosal inflammation limited to the colon; disease generally involves the rectum and may remain localized or extend proximally 1 6
  • Extraintestinal manifestations may include axial and peripheral arthropathies, ocular disease (eg, episcleritis, uveitis), dermatologic conditions (eg, erythema nodosum, pyoderma gangrenosum), and primary sclerosing cholangitis 1
  • Patients with disease that extends beyond the rectum are at risk for colon cancer


  • Proposed American College of Gastroenterology Ulcerative Colitis Activity Index 5
    • Remission
      • Formed stools with no blood
      • Normal hemoglobin
      • Erythrocyte sedimentation rate less than 30 and normal C-reactive protein
      • Fecal calprotectin less than 150 to 200 mcg/g
      • Endoscopic index of severity score: 0 to 1
    • Mild disease
      • Fewer than 4 stools daily, with intermittent blood in stool
      • Normal hemoglobin
      • Erythrocyte sedimentation rate less than 30
      • C-reactive protein elevated
      • Fecal calprotectin greater than 150 to 200 mcg/g
      • Endoscopic index of severity score: 2 to 4
    • Moderate to severe disease
      • More than 6 stools daily, frequently bloody and often associated with urgency
      • Hemoglobin less than 75% of reference range
      • Erythrocyte sedimentation rate greater than 30 and elevated C-reactive protein
      • Fecal calprotectin greater than 150 to 200 mcg/g
      • Endoscopic index of severity score: 5 to 8
    • Fulminant disease
      • More than 10 bowel movements daily
      • Continuous bleeding and urgency
      • Blood transfusion requirement
      • Erythrocyte sedimentation rate greater than 30 and elevated C-reactive protein
      • Fecal calprotectin greater than 150 to 200 mcg/g
      • Endoscopic index of severity score: 7 to 8
  • Toronto Consensus Guidelines for Nonhospitalized Ulcerative Colitis classification based on extent of disease 7
    • Proctitis: inflammation limited to within 18 cm of the anal verge or distal to the rectosigmoid junction
    • Proctosigmoiditis: inflammation limited to rectum and sigmoid colon but not involving the descending colon
    • Left-sided colitis (distal colitis): inflammation extending anywhere from sigmoid to splenic flexure
    • Extensive colitis: inflammation extending beyond splenic flexure but sparing cecum
    • Pancolitis: inflammation extending beyond splenic flexure and involving cecum
  • Montreal World Congress of Gastroenterology classification based on the extent and severity of ulcerative colitis 8 9
    • Extent 9
      • E1 (proctitis): inflammation limited to the rectum
      • E2 (left-sided, distal colitis): affects rectum and left colon (distal to the splenic flexure) 10
      • E3 (pancolitis): affects the rectum and colon proximal to the splenic angle 10
    • Severity 9
      • S0 remission: no symptoms
      • S1 mild: fewer than 4 stools/day (with or without blood), absence of systemic symptoms, normal inflammatory markers
      • S2 moderate: 4 stools/day (with or without blood), minimal signs of systemic symptoms
      • S3 severe: 6 or more bloody stools per day with a least 1 sign of systemic toxicity (eg, pulse 90 beats/minute or higher, temperature 37.5°C or higher, hemoglobin concentration less than 10.5 g/dL, erythrocyte sedimentation rate 30 mm/hour or greater)


Clinical Presentation


  • Classic presentation includes bloody diarrhea with prominent rectal urgency and tenesmus 5
  • Presentation varies depending on extent and severity of disease 2
    • Patients with isolated proctitis often present primarily with urgency and tenesmus
    • Patients with pancolitis often present with bloody diarrhea and abdominal pain
    • At diagnosis, most patients have mild to moderate symptoms and fewer than 15% present with severe disease 2
  • Onset is usually gradual with progression over weeks, but it may be acute 1
  • Extraintestinal manifestations
    • May precede gastrointestinal manifestations and occur in up to one-quarter of patients before formal diagnosis 2
    • Develop in about one-third of patients overall at some time during course of disease 2
  • The most common symptoms on initial presentation include the following: 11
    • Diarrhea (70%-90%) 11
    • Abdominal pain and cramping around time of defecation (30%-70%) 11
    • Weight loss (35%-45%) 11
    • Gross or occult rectal bleeding (50%-90%) 11
    • Growth impairment in children (5%) 11
    • Extraintestinal manifestation (2%-15%) 11
      • May present alone or in combination with gastrointestinal manifestations
      • Musculoskeletal
        • Small and large joint pain from peripheral arthropathies 5
          • Arthritis tends to be worse in the morning and improves throughout the day 1
          • Peripheral arthritis is divided into 2 subgroups 1
            • Type 1: acute pauciarticular arthritis involving fewer than 6 joints 1
              • Tends to flare with colitis and is often self-limited
            • Type 2: chronic polyarticular arthritis involving 6 or more joints 1
              • Often affects metacarpophalangeal joints
              • Synovitis tends to be migratory and lasts for months 1
        • Back pain and stiffness from axial arthropathies (eg, sacroiliitis, ankylosing spondylitis)
          • Symptoms can be debilitating and often improve with exercise 1
          • Occur more often in HLA-B27 positive patients 12
          • Manifestations are usually independent of disease activity 12
        • History of fractures from osteoporosis 11
      • Dermatologic
        • Painful red nodules under the skin primarily on the lower extremities (ie, erythema nodosum) 11
          • Erythema nodosum often appears at the same time as luminal disease activity 1
        • Necrosis of tissue leading to deep ulcerative wounds on the lower extremities from pyoderma gangrenosum 11
          • Pyoderma gangrenosum often appears independent of luminal disease activity 1
      • Ocular
        • Eye pain, eye redness, and watery eyes from episcleritis 11
        • Eye pain, blurred vision, eye redness, and photophobia from uveitis 11
      • Hepatobiliary
        • Primary sclerosing cholangitis (inflammation and fibrosis leading to progressive stricturing of intra- and extrahepatic bile ducts) is most often asymptomatic presenting with isolated elevation in alkaline phosphatase level
        • Occasionally primary sclerosing cholangitis presents with right upper quadrant abdominal pain, pruritus, fever, night sweats, and/or jaundice
  • Other symptoms may include
    • Nocturnal bowel movements 5
    • Fecal urgency 5
    • Fecal incontinence and fear of fecal incontinence 5
    • Low-grade fever 1
    • Fatigue 2
    • Paradoxical constipation
      • Occurs in up to 10% of patients with proctitis or left-sided colitis 2
    • Aphthous stomatitis 1

Physical examination

  • Vital signs are often within reference range unless the patient presents with signs of dehydration (tachycardia or hypotension) or anemia (tachycardia) 3
  • Abdominal examination
    • Mild abdominal distention may be present 3
    • Diffuse abdominal tenderness without rebound or guarding may be present 3
  • Rectal examination
    • Occult blood and/or gross blood may be detectable on digital examination
    • Anal fissures or skin tags may be present secondary to irritation from frequent stooling 2
  • Extraintestinal manifestations
    • Musculoskeletal
      • Limited spinal flexion in patients with axial arthritis 1
      • Joint swelling and tenderness in patients with arthritis 1
    • Dermatologic
      • Erythema nodosum
        • Tender red nodules under the skin primarily occurring on the lower extremities
      • Pyoderma gangrenosum
        • Deep ulcerative wounds on the lower extremities
    • Ocular
      • Conjunctival erythema, injection, and engorgement of episcleral vessels in episcleritis
      • Conjunctival erythema, decreased visual acuity, ciliary flush, constricted pupil in anterior uveitis
    • Hepatic
      • Hepatomegaly and jaundice with progressive portal hypertension and cirrhosis in patients with primary sclerosing cholangitis 1

Causes and Risk Factors


  • Dysregulated mucosal immune response to commensal gut flora occurs in genetically susceptible people; precise cause of bowel inflammation is not known 9 13
    • Several diverse environmental factors appear important in triggering inflammatory response
    • Presence of known genetic susceptibility loci account for a minor role in disease variance and have little current predictive capacity for phenotype 2
  • Known genetic associations include the following:
    • Presence of HLA class II DRB1*0103 haplotype is associated with ulcerative colitis 9
    • Genetic risk factors are under investigation; over 200 inflammatory bowel disease susceptibility loci are identified 2 13
      • Abnormalities in multiple loci are associated with both ulcerative colitis 12 and Crohn disease susceptibility; some loci are specific to individual disease 13
        • Although ulcerative colitis and Crohn disease share some genetic susceptibility factors, differing environmental and luminal factors are involved in the variable development and phenotype associated with each disease
      • Some known genetic risk factors for ulcerative colitis involve abnormalities in the following pathways:
        • Epithelial barrier function (eg, ECM1, HNF4A, CHD1, LAMB1) 12 1
        • Cytokines and inflammatory markers (eg, TNFRSF15, TNFRSF9, IL1R2, IL8RaIRB, IL7R) 1
        • Innate immune function (eg, PLA2G2E, CARD9) and immune regulatory function (eg, HLA-region, BTNL2, IFNg-IL25) 13
        • Apoptosis and autophagy (eg, DAP) 12
        • Transcriptional regulation (eg, PRDM1, IRF5, NKX2-3) 12
        • Interleukin-23 signaling (eg, IL23R, JAK2, STAT3, IL12B, PTPN2) 12
        • Helper T-cell types 1 and 17 (Th1 and Th17) differentiation (eg, IL10, IL7R, IL23R, IFN-γ) 12
        • Cellular homeostasis in response to endoplasmic reticulum stress (eg, ORMDL3) 13

Risk factors and/or associations

  • Peak age of disease onset is from 30 to 40 years; 2 a second, smaller peak incidence occurs from age 50 to 70 years
  • Familial inheritance is positive in 8% to 14% of affected patients 2
    • First degree relatives have a 4-fold increased risk compared with general population of developing disease 2
  • Ashkenazi Jewish population has a 3- to 5-fold higher rate of disease than that of other ethnic groups 9
  • Less frequent in Hispanic and African American populations 1
Other risk factors/associations
  • More common in developed countries 1of North America and regions of Western and Northern Europe 2
  • More common in urban compared with rural areas 2
  • Risk factors for development of disease or that potentially exacerbate disease 14 include the following:
    • Cigarette smoking cessation in former smokers 2 14
    • Previous enteric infection with Salmonella or Campylobacter within 1 year 1
    • Possibly, exposure to certain drugs (eg, tetracycline 1, NSAIDs 9, hormone replacement therapy, oral contraceptives) 1 9 2
  • Factors associated with decreased risk include
    • Removal of inflamed appendix before age 20 years 9 12
    • Appendicitis or mesenteric lymphadenitis in childhood 15
    • Breastfeeding for a duration of more than 3 months 9
    • Cigarette smoking 15

Diagnostic Procedures

Primary diagnostic tools

  • Diagnosis is based on a combination of symptoms, endoscopic findings, histology, and exclusion of alternate diagnosis 2
  • History and physical examination suggest diagnosis (eg, persistent bloody diarrhea, rectal urgency, tenesmus) 11
  • Obtain baseline laboratory tests at time of diagnosis or during disease flare or relapse 9
    • CBC, C-reactive protein, erythrocyte sedimentation rate, fecal calprotectin, lactoferrin) and establishes baseline electrolytes, renal function, iron studies, vitamin D level, and liver function 15
      • Not diagnostic but may reveal evidence of inflammation, chronic disease, or infection 15
    • Stool studies to exclude gastrointestinal infectious pathogens (eg, stool culture; Clostridium difficile assay; ova and parasite screens) 5 15
      • Infections can produce clinical findings indistinguishable from idiopathic ulcerative colitis
      • Infections can lead to exacerbations of disease; stool studies can exclude infections in patients with unexpected, severe, or atypical disease exacerbations 5
        • Test for cytomegalovirus in patients who relapse while on immunosuppressant therapy 15
      • Testing for sexually transmitted diseases (eg, Chlamydia trachomatis, HSV, Neisseria gonorrhoeaeTreponema pallidum) is recommended in patients at risk, such as men who have sex with men and patients with severe rectal symptoms
    • Autoantibody markers are not typically part of the primary diagnostic evaluation and have limited utility in diagnosing ulcerative colitis 1
      • No autoantibody marker or panel of markers alone are sensitive or specific enough to establish a diagnosis of ulcerative colitis 1
    • Assess immunization status before initiating immune modulating therapy: obtain hepatitis B surface antibody and serologies for hepatitis A, B, and C; measles; varicella; Epstein-Barr virus; and HIV. Consider screening for latent tuberculosis 16
  • Perform both endoscopy and biopsy to confirm presumptive diagnosis and to further exclude alternate diagnoses: 9
    • Endoscopic (eg, sigmoidoscopy, colonoscopy) evidence of continuous, circumferential colonic inflammation beginning in the rectum with possible proximal extension
    • Biopsy showing histopathology consistent with disease
  • Obtain abdominal radiography to assess for free air and significant colonic dilation in those patients:
    • With acute severe colitis 6 15
    • Requiring hospital admission 6
    • Suspected of having serious complications (eg, megacolon, perforation) 3
  • Classify disease severity and extent 17
    • Clinical disease severity is based on formal scoring tools 2
      • Several scoring tools are available (eg, Mayo score, Lichtiger Index, Simple Clinical Colitis Activity Index) to designate disease activity (ie, remission, mild, moderate, severe) 2
    • Extent of intestinal involvement is based on endoscopic findings
      • Several endoscopic scoring tools (eg, endoscopy subscore of Mayo score, Ulcerative Colitis Endoscopic Index of severity) are available to designate extent and severity of disease 2
      • Several histologic disease activity scoring tools (eg, Nancy Index, Robarts Histopathology Index) are available to classify disease based on pathologic findings 2


  • Stool studies to exclude infection
    • Stool culture 11
      • Perform bacterial stool culture to exclude enteric infections with bacterial pathogens (eg, SalmonellaShigellaYersiniaCampylobacter, Escherichia coli O157:H7)
    •  assay Clostridium difficile
      • Exclude Clostridium difficile with molecular testing (eg, polymerase chain reaction) or glutamate dehydrogenase screening with confirmatory toxin assay 18
        • Polymerase chain reaction test 18
          • Provides fast, highly sensitive, and highly specific results to detect Clostridium difficile toxin-producing gene
        • Glutamate dehydrogenase screening with confirmatory toxin assay
          • High sensitivity but low specificity 18
          • Immunoassay for toxin A and toxin B: sensitivity is over 75% and specificity is over 80% 18
      • Multiple assays may be required to diagnose Clostridium difficile in patients with established inflammatory bowel disease because false negative test results are common in this patient population 14
    • Ova and parasite stool microscopy examination
      • Exclude parasitic causes (eg, EntamoebaCryptosporidiumCyclosporaGiardia)
      • If suspicion is high, evaluate for protozoan parasites (eg, GiardiaCryptosporidiumEntamoeba histolytica) using commercial ELISA and direct fluorescent antigen kits 19
      • In patients living in nonendemic areas, evaluation to exclude  organisms may require serologic testing Entamoeba
  • Stool markers of inflammation
    • Fecal calprotectin level
      • Protein detectable in stool serves as a nonspecific marker for inflammation (neutrophils) in the intestine
        • Sensitive markers of intestinal inflammation when elevated 10
        • Elevated fecal calprotectin level does not distinguish among causes of intestinal inflammation 2
        • Low fecal calprotectin level can help exclude inflammatory bowel disease
          • Associated with less than 1% chance of ulcerative colitis diagnosis 2
      • Useful to monitor effectiveness of treatment and diagnose relapse 5 10
        • Monitor levels to assess for endoscopic remission after patient achieves clinical remission
          • Level of less than 150 mg/kg is consistent with endoscopic remission (sensitivity 79%, specificity 75%) 2
        • Levels that indicate risk for relapse in the near future in asymptomatic patients:
          • 2 or more elevated levels at 1- to 3-month intervals correspond to 53% to 83% probability of relapse in the next 2 to 3 months 20
          • 2 or more levels within reference range at 1- to 3-month intervals correspond to 67% to 94% probability of remaining in remission for the next 2 to 3 months 20
    • Stool lactoferrin level
      • Sensitivity and specificity are lower than fecal calprotectin for active inflammation
  • Baseline serum indices of inflammation and metabolic status include
    • CBC 6
      • Assess for anemia, leukocytosis, and thrombocytosis 2
    • C-reactive protein level or erythrocyte sedimentation rate 1
      • Inflammatory markers are often elevated when disease is severe 2
      • Levels within reference range do not exclude disease activity and may occur in patients with mild to moderate disease 1
      • Baseline level used to monitor response to treatment 15
    • Comprehensive metabolic panel 15
      • Documents baseline renal function, and levels of electrolytes 6, alkaline phosphatase, albumen, and liver enzymes
      • Assess for the following potential abnormalities:
        • Electrolyte abnormalities associated with diarrhea
        • Hypoalbuminemia is associated with severe disease and is a predictor of need for colectomy and of poor response to biologic drugs 2
        • Elevations in alkaline phosphatase and liver enzyme levels are associated with primary sclerosing cholangitis
  • Autoantibody markers
    • Perinuclear antineutrophil cytoplasmic antibodies are found in 15
      • Up to 65% of patients with ulcerative colitis
      • Less than 10% of patients with Crohn disease
    • Currently have no role in establishing or excluding diagnosis or determining prognosis 5
  • Evaluate patients who have severe or refractory colitis for cytomegalovirus
    • Cytomegalovirus has been associated with severe, refractory disease 12
    • Histologic, immunochemical, serologic, culture, and DNA testing is available. 12 Optimal method has not been established, but generally it is accepted that histology or immunohistochemistry is superior to serologic tests 15


  • Upright abdominal radiograph
    • Not diagnostic for ulcerative colitis; may show signs of complications (eg, free air, dilated bowel)
    • Megacolon is defined by total or segmental nonobstructive midtransverse colon dilation to 5.5 cm or greater 2
  • CT enterography/magnetic resonance enterography 6
    • Not diagnostic for ulcerative colitis; may show bowel wall thickening
    • Helps identify other causes of abdominal pain (eg, Crohn disease, diverticulitis) 3


Lower gastrointestinal endoscopy (eg, colonoscopy, sigmoidoscopy)
General explanation
  • Nonsurgical procedure used to examine epithelium, collect tissue cultures, and collect biopsies of the large intestine using a flexible fiberoptic endoscope
  • Sigmoidoscopy examines the rectum and distal sigmoid colon with a sigmoidoscope
  • Colonoscopy examines the entire large intestine using colonoscope; colonoscope can evaluate first few centimeters of ileum if ileocecal valve is intubated
  • Requires adequate bowel preparation and conscious sedation or general anesthesia
  • To confirm diagnosis, exclude alternate diagnoses, assess location and extent of disease, and obtain tissue biopsies for histopathologic examination
  • To assess severity of disease, confirm active inflammation, and exclude alternate diagnoses for cause of flare in patients requiring hospital admission 6
  • Peritonitis
  • Relative contraindications include severe colitis owing to increased risk of perforation 6
  • Gastrointestinal bleeding
  • Perforation
  • Abdominal pain
  • Ileus
Interpretation of results
  • Characteristic endoscopy findings include the following:
    • Mucosal inflammation beginning in the distal rectum and extending proximally in a symmetric, continuous, circumferential pattern that does not extend past the terminal ileum 11
      • At diagnosis, 30% to 60% have proctitis, 16% to 45% have left-sided colitis, and 4% to 35% have pancolitis 2
      • Patchy cecal inflammation around appendiceal orifice (ie, cecal patch) is common in patients with distal disease 1 14
      • Backwash ileitis may occur in patients with cecal inflammation and appears as mild, diffuse ileal inflammation endoscopically 14
      • Skip areas with patchy inflammation; rectal sparing can be present in treated patients 14
    • Mucosal inflammatory changes include granularity, friability, erythema, spontaneous bleeding, loss of normal vascular pattern, erosion, and ulceration 14
    • Clear demarcation often occurs between area of inflammation and healthy-appearing mucosa 2
  • Confirmatory histopathologic findings include the following:
    • Disease limited to the mucosal layers 1
    • Histologic inflammation may be noted in healthy-appearing mucosal areas 2
    • Findings consistent with chronic active colitis include 1
      • Varying degrees of increased lymphocytes, plasma cells, and granulocytes in lamina propria (basal plasmacytosis)
      • Distortion of the crypt architecture with shortening and disarray of the crypts, crypt atrophy, crypt abscesses, and crypt branching
      • Epithelial cell abnormalities with the presence of Paneth cell metaplasia and mucin depletion
    • Backwash ileitis has characteristic findings of mild villous atrophy and only scattered crypt abscesses 14
    • Findings that favor ulcerative colitis over other causes include the following:
      • Lack of noncaseating granulomas (epithelioid granulomas) 12 or microscopic focality favors ulcerative colitis over Crohn disease 14
      • Lack of specific findings consistent with infectious cause (eg, caseating granulomas in tuberculosis, trophozoites in amebiasis, pseudomembranes in Clostridium difficile colitis, ova in schistosomiasis, viral inclusions in herpetic or cytomegalovirus colitis, tissue culture for Neisseria gonorrhea14
      • Lack of other histopathologic findings that support an alternate diagnosis including ischemia; radiation, collagenous, and microscopic colitis; drug-induced colitis; solitary rectal ulcer syndrome; and diverticulosis 14
  • Evaluation for infectious cause of manifestations
    • Immunoperoxidase staining results should be negative for cytomegalovirus
    • Culture results should be negative for sexually transmitted disease pathogens (eg, HSV, Neisseria gonorrhoeae)

Other diagnostic tools

Differential Diagnosis

Most common

  • Infectious colitis (Related: ) 22Acute diarrhea in adults
    • Inflammation of the colon caused by a variety of bacterial, viral, and parasitic causes can present similarly to ulcerative colitis with abdominal pain, diarrhea with or without blood, and fever
    • Differentiate by specific stool studies to exclude infectious etiologies (eg, bacterial stool culture, Clostridium difficile testing, ova and parasites screen, serologic testing for amoeba, cytomegalovirus studies)
    • Occasionally endoscopy findings are helpful to exclude infectious causes for colitis (eg, caseating granulomas in tuberculosis, trophozoites in amebiasis, pseudomembranes in Clostridium difficile colitis, ova in schistosomiasis, viral inclusions in herpetic or cytomegaloviral colitis, tissue culture for Neisseria gonorrhea23
  • Sexually transmitted disease Chlamydia infections
    • Organisms such as , , HSV, and syphilis can mimic proctitis caused by ulcerative colitis (eg, urgency, tenesmus, rectal bleeding) Chlamydia trachomatisNeisseria gonorrhoeae2
    • May occur in people who engage in anal intercourse
    • Diagnose and differentiate by history and specific testing for sexually transmitted disease
  • 24Crohn disease
    • Inflammatory bowel disease characterized by inflammation that can manifest in any region of the gastrointestinal tract
    • Both Crohn disease and ulcerative colitis can present with abdominal pain, weight loss, diarrhea with or without blood, and extraintestinal manifestations
      • Lack of gross blood in stool and presence of perianal disease (eg, fistula, abscess) is suggestive of Crohn disease
    • Differentiate Crohn disease from ulcerative colitis with endoscopy and biopsy findings. Crohn disease:
      • Is more likely to involve multiple areas of the entire gastrointestinal tract (from mouth to anus) 14
      • Has mucosal inflammation less likely to involve the rectum
      • Causes skip lesions in the gastrointestinal tract rather than continuous inflammation and ulceration
      • Is more likely to have transmural (deep) inflammation rather than disease limited to the mucosal bowel layers
      • Is more likely to cause stenosis of the bowel segments and fistula (eg, anal, perianal fistula) 2
    • Up to 5% of cases are diagnosed as indeterminate colitis when ulcerative colitis and Crohn disease cannot be differentiated based on clinical, radiologic, and endoscopic criteria 6
  • 25Diverticulitis
    • Inflammatory process by which bacteria proliferate in an existing colonic diverticulum can present with colitis symptoms similar to those of ulcerative colitis
    • Both diverticulitis and ulcerative colitis cause abdominal pain, diarrhea, and fever, but hematochezia is less likely in diverticulitis
    • Diverticulitis can be definitively diagnosed by a CT scan of the abdomen that shows inflammation in colonic diverticulum
  • Ischemic colitis 26
    • Presents with manifestations similar to those of ulcerative colitis with abdominal pain and bloody diarrhea
    • Typically occurs in elderly patients with cardiovascular disease risk factors (eg, smoking, diabetes)
    • History may identify episode of systemic low blood flow
    • Differentiate from ulcerative colitis by characteristic colonoscopy and biopsy findings. Macroscopic ulceration typically involves sigmoid, descending, and transverse colon, and is most marked around splenic flexure
  • Solitary rectal ulcer syndrome 27
    • Several different clinical processes (eg, NSAIDs, ergotamine suppositories, paradoxic contraction of the pelvic floor muscles, rectal prolapse, trauma) can result in development of localized rectal ischemia and mucosal ulceration
    • Presents similar to ulcerative colitis with bleeding, abdominal pain, tenesmus, and altered bowel habits 28
    • Differentiate from ulcerative colitis by characteristic colonoscopy and biopsy findings; macroscopic findings include a solitary ulcer involving the rectal wall
  • Colorectal cancer
    • Presents with manifestations similar to those of ulcerative colitis with abdominal pain, rectal bleeding, anemia, tenesmus, and change in bowel habits; abdominal or digital rectal examination may identify a mass
    • Typically a disease of the elderly with a mean age of presentation of 70 years in people without other significant risk for disease (eg, genetic predisposition, long-standing inflammatory bowel disease) 29
    • Differentiate from ulcerative colitis by characteristic colonoscopy and biopsy findings; macroscopic findings include mass lesions or polyps with malignant features (eg, irregular contours, contact bleeding, deformities, abnormal vasculature)


  • From Ungaro R et al: Ulcerative colitis. Lancet. 389(10080):1756-70, 2017, Figure 4.Suggested treatment approach algorithm for mild to moderate ulcerative colitis. – Based on Toronto Consensus and European Crohn’s and Colitis Organisation guidelines. For patients needing and responding to steroids, the choice for maintenance medication can be either 5-ASA, thiopurine, or a biological drug. 5-ASA can be considered if partial initial response and first course of steroids. Thiopurines can be used if no response to 5-ASA, low risk of complications, and first course of steroids. Biological drugs should be used if unable to taper steroids, second course of steroids, or higher risk of complications.
  • From Ungaro R et al: Ulcerative colitis. Lancet. 389(10080):1756-70, 2017, Figure 5.Suggested treatment approach algorithm for moderate to severe ulcerative colitis. – Based on Toronto Consensus and European Crohn’s and Colitis Organisation guidelines. 5-ASA, mesalamine (5-aminosalicylic acid); anti-TNF, anti-tumor necrosis factor drug; DI, dose intensification.
  • From Ungaro R et al: Ulcerative colitis. Lancet. 389(10080):1756-70, 2017, Supplementary algorithm.Acute severe ulcerative colitis treatment algorithm.
  • From Ungaro R et al: Ulcerative colitis. Lancet. 389(10080):1756-70, 2017, Supplementary Figure 4.Step-up approach to treatment based on disease severity.


  • Induce and maintain steroid-free clinical and endoscopic gross (macroscopic) and deep (microscopic) remission 2
  • Alleviate pain and improve patient’s quality of life 1
  • Decrease risk of complications and monitor for neoplasia 1


Admission criteria

General hospital admission for parenteral steroids is necessary with the following: 1

  • Severe or fulminant colitis 1
  • Failure of outpatient medical therapies 3 or persistence of moderate to severe symptoms despite oral corticosteroids 1

General hospital admission for further management is indicated with the following:

  • Inability to tolerate oral intake owing to nausea or vomiting 3
  • Emergent surgical procedures for complications required or elective procedures for recalcitrant disease planned
  • Recalcitrant or severe opportunistic infection secondary to immunosuppressive therapies 3
Criteria for ICU admission
  • Toxic megacolon
  • Severe hemorrhage
  • Suspected sepsis with hypotension refractory to fluid administration

Recommendations for specialist referral

  • Consult a gastroenterologist for all patients with disease for diagnostic recommendations, treatment recommendations, and monitoring
  • Consult general surgeon or colorectal surgeon for surgical treatment options for patients with the following:
    • Suspected complications (eg, toxic megacolon, bowel obstruction, perforation, severe hemorrhage, malignancy) 3
    • Recalcitrant or severe disease 3
    • Admission requirement for severe colitis
  • Consult ophthalmologist for patients with ocular manifestations of disease for diagnostic recommendations, treatment recommendations, and monitoring
  • Consult rheumatologist for patients requiring management of arthritis for treatment recommendations

Treatment Options

General approach to treatment

  • Clinical severity of symptoms (eg, mild, moderate, severe, fulminant) and endoscopic extent of inflammation determine approach to therapy 5
    • Consider early use of biologic drugs in patients with severe disease who require admission and in patients with steroid-refractory disease 2
    • Proctitis may require only topical therapy whereas extensive disease often requires systemic therapy 2
  • Medical management is based on induction and then maintenance of remission 13
    • Remission targets include clinical symptom resolution (eg, cessation of rectal bleeding, improved bowel habits) and endoscopic healing; deep remission is a combination of the two and is the preferred goal of treatment 2 5
    • Medications are continued or added once remission is achieved to maintain remission status 2
    • Overall, optimal medical management is highly individualized
    • Fecal microbiota transplantation is an emerging therapy that may be considered in the context of a clinical trial 30 31
  • Treatment is often instituted in a rapid step-up approach in consultation with a gastroenterologist 1
    • Treat-to-target approach is employed to monitor for efficacy of treatment 2
    • Regular follow-up is required to evaluate progress toward clinical and endoscopic disease control target goals
  • Several guidelines are available to assist with treatment decisions; specific recommendations may vary
    • American College of Gastroenterology clinical guideline on ulcerative colitis in adults, 2019 5
    • Toronto Consensus clinical practice guidelines on medical management of nonhospitalized ulcerative colitis, 2015 7
    • Third European Evidence-Based Consensus on diagnosis and management of ulcerative colitis, 2017 4 15
    • American Gastroenterological Association clinical practice guidelines on management of mild-moderate ulcerative colitis, 2019 31 32

Remission induction in active ulcerative colitis

  • Mild to moderate active disease
    • First line treatment is 5-aminosalicylic acid (ie, sulfasalazine, olsalazine, mesalamine, balsalazide); standard dose mesalamine or diazo-bonded 5-aminosalicylic acid is preferred form 31 2 5
      • Preparation indicated depends on extent of disease
        • Topical treatment 14
          • Suppositories are effective with disease extending to about 10 cm
          • Foam is effective with disease extending up to about 15 to 20 cm
          • Enemas reach the splenic flexure
        • Oral therapy is definitively indicated when extent of inflammation extends proximal to the reach of topical therapy 14
      • Preferred initial treatment of proctitis and proctosigmoiditis is topical 5-aminosalicylic acid 4 7 9 33
      • Preferred initial treatment of left-sided and extensive colitis is combined oral and topical 5-aminosalicylic acid 2 4 7
      • Concurrent use of both oral and rectal formulations is more effective than either treatment alone, and combined oral and topical mesalazine and high-dose mesalazine are more effective than standard dose. High-dose therapy may be used in patients with suboptimal response to standard doses 35 31 14 34
    • Use steroids to induce remission when symptoms persist despite optimal dosage of induction medications 1
      • Topical steroids may be used as a second line add-on treatment in patients with disease limited to the area distal to the splenic flexure 2
      • Start a course of oral steroids if symptoms persist after 14 to 21 days of first line treatment or if sustained relief of symptoms is not achieved by 30 to 40 days with treatment 10
      • Oral steroids with minimal systemic activity (eg, budesonide Multi Matrix, prolonged release beclomethasone dipropionate) are an alternative to oral steroids with relatively more systemic activity (eg, prednisone) in patients who do not respond to induction regimen 2
      • Response is usually apparent by 2 weeks then steroids may be tapered; consensus on tapering protocol is not available 2
        • A common approach to taper is taper by 5 to 10 mg/week until reaching 20 mg, then decrease by 2.5 to 5 mg/week until completed 2
      • Avoid long-term use of corticosteroids because they are not acceptable for maintaining disease remission 9 14
      • Transition to maintenance medications
        • Transition to 5-aminosalicylic acid regimen to maintain remission in patients with mild flare with recent diagnosis or previously naive to 5-aminosalicylic acid 2
        • Transition to alternate, step-up, steroid-sparing agents (eg, thiopurine and/or biologic drug [anti–tumor necrosis factor agent, anti-integrin therapy]) to maintain remission in patients with the following: 1 2
          • Poor prognostic factors (eg, young age at disease onset, extensive colitis, deep ulcerations)
          • Not well controlled on aminosalicylates alone 9
          • Corticosteroid-dependent disease or require 2 or more courses of oral steroids in a year 2
  • Moderate to severe active disease 7
    • Oral steroids are first line 2 5
      • High dose 5-aminosalicylic acid (4.8 mg/day of mesalamine) may be used as adjunct in patients with moderate disease but is not indicated for severe colitis
    • In patients who do not require urgent hospitalization, may use anti–tumor necrosis factor therapy with infliximab, adalimumab, or golimumab if disease is not improving with optimal dose of oral steroids 5
    • Vedolizumab or tofacitinib may be used if disease is refractory to anti–tumor necrosis factor agents 5
    • Failure of optimized biologic drug (ie, anti–tumor necrosis factor, vedolizumab) may require colectomy 2
    • Transition patient to maintenance medications (eg, 5-aminosalicylic acid, thiopurine, biologic drug) once response is achieved
  • Acute severe disease
    • Patients presenting with toxicity require hospital admission for a course of IV steroids 5
      • IV corticosteroid failure rate is 20% to 40% for patients with severe colitis requiring admission 14
    • In patients requiring admission for severe disease, discontinue any 5-aminosalicylate–based medication owing to possible paradoxic worsening of colitis attributable to 5-aminosalicylic acid 6
      • Lack of significant improvement within 3 to 5 days is an indication for treatment with rescue IV infliximab (preferred), tacrolimus, cyclosporine, or colectomy 1 4
    • Antibiotics
      • According to most experts, antibiotics show no therapeutic benefit in absence of proven infection and are rarely indicated, even in patients requiring admission 5
      • Indicated only for patients with suspected extraluminal complications or signs of toxicity (eg, fulminant colitis, toxic megacolon) 5
      • Select and start in consultation with a specialist (eg, gastroenterologist, surgeon), based on patient presentation, hospital-directed protocol, and regional antimicrobial susceptibilities
    • Exclude superimposed infection in patients with severe colitis
      • Exclude Clostridium difficile and enteric pathogens in all patients 14
        • Vancomycin is preferred initial antibiotic for Clostridium difficile 5
      • Before escalating immunosuppressive therapy, exclude cytomegalovirus with sigmoidoscopic biopsy and viral culture in patients not responding to maximal medical therapy 2 5
        • Treat promptly with ganciclovir, if cytomegalovirus is identified 5

Maintenance treatment

  • Depending on response to induction medications, either 5-aminosalicylic acid regimen, thiopurine, or biologic agent may be used to maintain remission in most patients
    • First line therapy is 5-aminosalicylic acid 13
      • Patients with extensive disease or with frequent relapses may benefit from a higher dose of maintenance therapy 36
    • Step-up therapy is indicated in patients with steroid-dependent disease, poor prognostic factors, or poor control with frequent relapse on first line agents 2 13
      • Second line treatment is a thiopurine immunomodulator (azathioprine and 6-mercaptopurine) 13 37
        • A thiopurine can be added to 5-aminosalicylic acid therapy to increase efficacy 13
      • Alternate second line treatment includes
        • Anti–tumor necrosis factor agents for patients who have a contraindication to thiopurines, develop significant adverse effects to thiopurines, or have disease recalcitrant thiopurine therapy 1
        • Combination of both azathioprine and infliximab may be more effective than either agent alone 2
        • Anti-integrin therapy (antiadhesion molecule inhibitors) 2
    • Consider potential risks and benefits when deciding to use combination therapy (eg, azathioprine, infliximab)
      • May improve treatment outcome and reduce risk of antibody formation to certain biologic drugs (ie, tumor necrosis factor agents)
      • May be associated with increased risk of opportunistic infection and malignancy (eg, skin cancer, lymphoma)
  • Maintenance treatment of first episode of disease limited to rectum is individualized
    • Maintenance treatment often is not recommended after the first episode of disease limited to rectum

Treatment of flare or disease

  • Depends on severity and extent of disease and presence or absence of associated infection (Clostridium difficile, fecal pathogens) 2
  • First step is to optimize medications by reviewing dose, administration, and adherence 2
    • Monitoring therapeutic drug concentrations may be indicated (eg, thiopurines, anti–tumor necrosis factor)
  • Patients may require medications to reinduce remission (eg, systemic or topical steroids) and step-up maintenance therapy 2


  • Required for 15% to 27% of patients in whom medical therapy fails 1 6
    • Prolonged salvage IV immunosuppressive therapy for severe disease is associated with increased morbidity and mortality
    • Surgery is indicated when salvage therapy is ineffective by day 7 of treatment (eg, corticosteroids, infliximab, cyclosporine) 38
    • Risk for colectomy requirement include 2
      • Age under 40 years at diagnosis
      • Extensive disease
      • Need for systemic steroids
      • Elevated inflammatory markers
  • Main options include total proctocolectomy with permanent ileostomy or the ileal pouch anal anastomosis procedure 14
    • Elective procedures
      • Ileal pouch anal anastomosis procedure is the most commonly performed and the elective procedure of choice 5 12
        • Advantage over traditional proctocolectomy with ileostomy is preservation of anal sphincter function 12
        • Accomplished in 1, 2, or 3 stages, depending on patient’s clinical status at time of surgery and surgeon’s judgment and experience 14
      • Total proctocolectomy with permanent ileostomy is a less preferred procedure owing to high rates of gastrointestinal outlet obstruction with this procedure over time 14
    • Emergent procedure
      • Subtotal colectomy without removal of the rectal stump with temporary ileostomy is the preferred emergent procedure 9
        • After recovery, restorative surgery with construction of ileal pouch anal anastomosis can be performed

Drug therapy

  • 5-aminosalicylic acid and derivatives
    • Specific dosage is variable and dependent on individual response weighed with the appearance of adverse effects; commonly used dosage is listed and complete dosage regimens are available in guidelines 7 14
      • Efficacy is similar between different 5-aminosalicylic acid formulations (eg, sulfasalazine, olsalazine, mesalamine, balsalazide)
      • Sulfasalazine metabolized to 5-aminosalicylic acid is often not as well-tolerated as parent compound drugs 2
      • In general, daily doses of oral 5-aminosalicylic acid of 2 g or higher are more effective at inducing and maintaining remission than lower doses 2 36
      • Many experts recommend starting oral 5-aminosalicylic acid at a dose of 2 to 2.4 g/day and increasing up to 4.8 g/day if needed; 7 2 patients with moderate disease may benefit more from higher dosage than patients with milder disease 36
      • Response often begins within 14 days; may take up to 8 weeks on effective dose for symptomatic remission 2
      • Overall at least 50% to 70% of patients achieve remission with optimal 5-aminosalicylic acid induction therapy 12 39
      • Continue patients on same drug for maintenance if remission is achieved with 5-aminosalicylic acid 2 7
      • Patients with extensive disease or frequent relapses may benefit from higher oral maintenance dosage 36
    • Common adverse reactions that may limit use include increased diarrhea, nausea, vomiting, dyspepsia, anorexia, and headache. Less common but serious adverse reactions include allergic reactions, pancreatitis, hepatotoxicity, drug-induced connective tissue disease, bone marrow suppression, interstitial nephritis and nephrotoxicity, hemolytic anemia or megaloblastic anemia, and possible abnormal sperm counts, motility, and morphology 1 14
    • Sulfasalazine 1
      • Sulfasalazine Oral tablet; Children and Adolescents 6 years and older: Initially, 40 to 60 mg/kg/day PO given in 3 to 6 divided doses; recommended maintenance dose is 30 mg/kg/day PO divided every 6 hours. Patients should take a folic acid supplement.
      • Sulfasalazine Oral tablet; Adults: Initially, 1 gram PO every 6 to 8 hours. May start at 500 mg every 6 to 12 hours and titrate to response and tolerance to limit GI side effects. Usual maintenance dose: 500 mg PO every 6 hours, adjust to response and tolerance. Suggested Max: 4 grams/day PO. Higher doses may increase risk of adverse effects and toxicity. Patients should take a folic acid supplement.
      • Doses up to 4 to 6 g daily for adults has been recommended by the American College of Gastroenterology for both induction and remission dosage. Daily doses exceeding 4 g may have an increased risk of gastrointestinal adverse effects 14
    • Mesalamine 1
      • Induction of remission 5 9
        • Delayed-release tablets (ie, Asacol HD)
          • Mesalamine Gastro-resistant tablet; Adults: 1,600 mg PO 3 times daily for 6 weeks; total dose: 4.8 grams/day.
        • Controlled-release preparation (ie, Pentasa)
          • Mesalamine Oral capsule, extended-release; Adults: 1 gram PO 4 times daily. Treatment duration in controlled trials was up to 8 weeks.
        • Suppository
          • Mesalamine Rectal suppository; Adults: 1,000 mg PR once daily at bedtime for 3 to 6 weeks depending on symptoms and sigmoidoscopic findings. Safety and effectiveness beyond 6 weeks have not been established.
        • Enema
          • Mesalamine Rectal enema, suspension [Sulfite-free]; Adults: 4 grams PR enema each night and retained for 8 hours if possible; use for 3 to 6 weeks depending on symptoms and sigmoidoscopic findings.
      • Maintenance of remission 5 9
        • Delayed-release tablets (ie, Asacol HD)
          • Mesalamine Gastro-resistant tablet; Adults: 2.4 grams PO once daily with a meal.
        • Controlled-release preparation (ie, Apriso)
          • Mesalamine Oral capsule, extended-release; Adults: 1,500 mg PO once daily in the morning.
        • Suppository (proctitis)
          • Mesalamine Rectal suppository; Adults: 500 mg PR twice daily retained in the rectum for 1 to 3 hours or more if possible. Alternatively, 1000 mg at bedtime. 14
        • Enema (distal colitis)
          • Mesalamine Rectal enema, suspension; Adults: 2 to 4 g PR enema nightly. 14
  • Corticosteroids
    • Patients on long-term steroids are at risk of adrenal insufficiency if steroids are discontinued or tapered too rapidly; therefore, they require steroid replacement at periods of increased stress (eg, surgery) 14
    • Use to induce remission; avoid use of steroids for long-term maintenance of disease remission 14
      • Optimum duration of oral corticosteroid treatment and tapering protocol is not available 9
    • Adverse effects of oral steroid use include cushingoid features, emotional and psychiatric disturbances, infections, glaucoma, cataracts, gastroduodenal mucosal injury, skin striae, impaired wound healing, metabolic bone disease, osteonecrosis, hyperglycemia, sodium and fluid retention, hypokalemia, metabolic alkalosis, hyperlipidemia, and accelerated atherogenesis 1 14
    • Budesonide 1 7 40
      • Distal colitis treatment 2 mg enema (not available in the United States) 14
      • Budesonide Oral tablet, extended-release; Adults: 9 mg PO once daily in the morning for up to 8 weeks.
    • Prednisone 1
      • Prednisone Oral tablet; Adults: Initially, 40 mg to 60 mg PO once daily; clinical response is expected within 5 to 7 days of treatment. Max: Use of more than 60 mg/day is not more effective. Use for the shortest duration possible, with early initiation of steroid-sparing therapy. The prednisone taper should be guided by symptoms, cumulative steroid exposure, and the onset of alternative therapies. The ACG states that systemic corticosteroids should not be used long-term maintenance of remission in patients with UC.
    • Hydrocortisone 14
      • Distal colitis treatment topical foam or enema 14
        • Hydrocortisone Acetate Rectal foam; Adults: One applicatorful (90 mg hydrocortisone acetate) PR once daily or twice per day for 2 to 3 weeks; every second day thereafter. Because of the potential complications of steroid use, use the lowest dose possible for the shortest duration possible.
        • Hydrocortisone Rectal enema, suspension; Adults: 100 mg PR, as a retention enema, nightly for 21 nights or until remission. If clinical/proctologic improvement fails to occur within 2 or 3 weeks, discontinue. Difficult but responding cases may require 2 or 3 months of treatment. Avoid abrupt discontinuation if used longer than 21 nights; withdraw gradually (e.g., PR every other night for 2 to 3 weeks, then discontinue). Because of the potential complications of steroid use, use in the lowest dose possible for the shortest duration possible.
      • Severe colitis requiring hospitalization 6 14
        • Hydrocortisone Sodium Succinate Solution for injection; Children and Adolescents: 0.56 to 8 mg/kg/day or 20 to 240 mg/m2/day IM/IV given in 3 to 4 divided dose is the FDA-approved general dosage range; adjust to patient response. Because of the potential complications of steroid use, use in the lowest dose possible for the shortest duration possible.
        • Hydrocortisone Sodium Succinate Solution for injection; Adults: 100 mg IV every 8 hours for up to 5 days. 14
      • Oral dosage
        • Hydrocortisone Oral tablet; Children and Adolescents: 0.56 to 8 mg/kg/day or 16 to 240 mg/m2/day PO given in 3 to 4 divided doses. Adjust according to patient response. Because of the potential complications of steroid use, use in the lowest dose possible for the shortest duration possible.
        • Hydrocortisone Oral tablet; Adults: 20 to 240 mg (base)/day PO in 2 to 4 divided doses. Because of the potential complications of steroid use, use in the lowest dose possible for the shortest duration possible.
    • Methylprednisolone 1 6
      • Severe colitis requiring hospitalization 5
        • Methylprednisolone Sodium Succinate Solution for injection; Children and Adolescents: 1 to 1.5 mg/kg/day (Max: 60 mg/day) IV or IM in 1 to 2 divided doses for 2 to 4 weeks; transition to oral corticosteroids as soon as feasible; slowly taper over several weeks after response achieved. Pulse methylprednisolone (20 to 30 mg/kg/day [Max: 1 gram/day] IV for 3 days) has also been used to induce remission in children with moderate to severe UC. Because of the potential complications of steroid use, use selectively and in the lowest dose and shortest duration possible.
        • Methylprednisolone Sodium Succinate Solution for injection; Adults: 20 mg IV every 8 hours for up to 5 days.
  • Thiopurines 1
    • Check thiopurine methyl-transferase activity before starting therapy; 0.3% of patients have low to absent activity and 11% have intermediate activity of this metabolic enzyme 14
      • Dosage adjustment is necessary in patients with intermediate activity; avoid use in patients who lack enzyme activity 1
      • Patients with lower enzyme activity are at increased risk of severe myelotoxicity 14
    • Check baseline CBC and liver function tests before starting therapy 2
    • Primary indications and use include
      • Main use is for maintenance of remission; primary benefit is steroid-sparing effect 1
        • Maintenance agent in patients with mild to moderate disease difficult to control with first line 5-aminosalicylic acid 2
        • Maintenance agent for mild to severe disease unresponsive to corticosteroids or corticosteroid-dependent disease (eg, inability to wean from steroids) 14
        • Maintenance agent after successful treatment with cyclosporine 6
        • Adjunctive agent for use in combination with infliximab 6
    • Onset of action is delayed; up to 3 to 6 months of treatment may be required before optimal effects are appreciated 14
    • Major adverse effects include bone marrow suppression, increased risk of infection, hepatotoxicity, allergic reaction, pancreatitis, skin cancer, abnormal Papanicolaou smear results, and lymphoma 1 14
    • Azathioprine 1 5
      • Azathioprine Oral tablet; Children 3 years and older: 2 to 2.5 mg/kg/day PO is the usual target (goal) dose range for maintenance treatment. Children less than 6 years may require up to 3 mg/kg/day PO. Consider TPMT genotyping or enzymatic activity testing prior to initiating therapy to guide dose adjustments. Review drug interactions. Not recommended as induction therapy.
      • Azathioprine Oral tablet; Adults: 2 to 2.5 mg/kg/day PO is the usual initial and maximal target (goal) dose range for maintenance treatment. Initially, 25 to 50 mg PO once daily, then titrated to goal therapy, is commonly utilized. Consider TPMT genotyping or enzymatic activity testing prior to initiating therapy to guide dose adjustments. Review drug interactions. Not recommended as induction therapy.
    • Mercaptopurine 1
      • Mercaptopurine Oral tablet; Adults: 1.5 mg/kg/day PO is the usual target (goal) dose for maintenance treatment. Initially, 25 to 50 mg PO once daily, then titrated to goal therapy, is commonly utilized. Consider TPMT genotyping or enzymatic activity testing prior to initiating therapy to guide dose adjustments. Review drug interactions. Not recommended as induction therapy.
  • Anti–tumor necrosis factor agents 1
    • Before administering anti–tumor necrosis factor medications, screen for the following: 1
      • Chronic hepatitis B: HBsAg, anti-HBs, and core antibody 14
      • Latent tuberculosis: chest radiograph, PPD, and/or interferon-γ release assay 6
    • Obtain baseline CBC, liver function tests, and renal function tests before starting therapy 2
    • Use to induce or maintain remission; effective alone or used in combination with thiopurines 1
    • Some experts advocate for concomitant use of thiopurine with anti–tumor necrosis factor agent to minimize risk of developing drug antibody 1
    • Major adverse reactions include infusion reactions, autoimmune responses, increased risk of infection, lymphoma, skin cancer, hepatic carcinoma, and possibly other malignancies. Rare adverse reactions include hepatotoxicity, development or exacerbation of multiple sclerosis or optic neuritis, lupuslike reaction, and worsening of congestive heart failure in patients with preexisting cardiac disease 1 14
    • Incidence of infusion reactions is decreased by regular 8-week dosing intervals and concomitant immunosuppressive (eg, thiopurine) treatment 14
      • Premedicate patients with previous mild to moderate infusion reaction with antihistamines and corticosteroids 14
    • Failure to respond clinically to induction therapy with adequate drug levels precludes further use of drug within same class 5
    • Infliximab 1 14
      • Monoclonal antibody to tumor necrosis factor 6
      • Primary indications include
        • Patients with mild to severe extensive colitis: to treat active disease by inducing and maintaining remission 5
        • Outpatients with moderate to severe disease: to treat those who do not respond to oral corticosteroids 6
        • Hospitalized patients with severe active disease who have not responded to corticosteroids: as salvage therapy 6
      • Involves a 2-hour IV infusion of monoclonal antibody to tumor necrosis factor-α in a monitored setting
      • Onset of action may be noted within days after first dose; full effect may be delayed up to 6 to 12 weeks 1
      • Presence of hypoalbuminemia may require higher dosage 41
      • Contraindications include active infection, untreated latent tuberculosis, preexisting demyelinating disorder or optic neuritis, moderate to severe congestive heart failure, and current or recent malignancies 14
      • Infliximab (Murine) Solution for injection; Children and Adolescents 6 to 17 years: 5 mg/kg IV infusion at weeks 0, 2, and 6 as induction therapy, then a maintenance regimen of 5 mg/kg IV infusion every 8 weeks.
      • Infliximab (Murine) Solution for injection; Adults: Induction: 5 mg/kg IV infusion at weeks 0, 2, and 6. Maintenance: 5 mg/kg IV infusion every 8 weeks thereafter.
    • Adalimumab 1
      • Adalimumab Solution for injection; Adults: 160 mg subcutaneously given as 4 injections on day 1 or as 2 injections on days 1 and 2, then 80 mg subcutaneously at 2 weeks later (day 15). Then, 2 weeks later (day 29), start 40 mg subcutaneously every other week. Aminosalicylates and/or corticosteroids may be continued. If necessary, azathioprine and 6-mercaptopurine (6-MP) may be continued during treatment.
    • Golimumab 1
      • Golimumab Solution for injection; Adults: 200 mg subcutaneously on week 0, followed by 100 mg subcutaneously at week 2 for induction. For maintenance, give 100 mg subcutaneously every 4 weeks starting at week 6.
  • Calcineurin inhibitor
    • Cyclosporine 1 6
      • Drug prevents clonal expansion of T-cell subsets 6
      • Obtain baseline magnesium, cholesterol, and creatinine levels before starting drug: dose to trough level 200 to 400 ng/mL 1 1 6
      • Contraindications include renal insufficiency, infection, and hypocholesterolemia owing to increased risk of seizures 6
      • Rescue treatment of severe disease when IV steroids and infliximab fail. Second line induction medication only, not a long-term maintenance treatment option 1
      • Transition patients responding to cyclosporine infusion to oral dosage regimen with goal of transition to thiopurine for long-term maintenance treatment 6
      • Common adverse effects include paresthesias, hypertension, hypertrichosis, headache, abnormal liver function tests, hyperkalemia, and gingival hyperplasia; severe adverse reactions limiting use include nephrotoxicity, infection, and seizures 1 14
      • Cyclosporine Solution for injection; Adults: The American College of Gastroenterology (ACG) states that 2 mg/kg IV is the targeted cyclosporine dose for rescue treatment of acute severe ulcerative colitis (ASUC); other options include infliximab IV. Higher cyclosporine doses of 4 mg/kg IV do not have greater efficacy based on available data. Cyclosporine or infliximab use should be restricted to those failing IV corticosteroid therapy except in patients who have contraindications or intolerance to corticosteroids.
  • Selective adhesion molecule inhibitor 1
    • Vedolizumab 1
      • Check baseline CBC level and test liver and renal function before starting of therapy 2
      • Indicated for moderate to severe disease to induce and maintain remission when standard treatment fails 1 42
      • May be used as a first line biologic treatment based on expert opinion (limited data) 2
      • Drug is a humanized monoclonal antibody that inhibits adhesion molecule a4β7 heterodimer, which blocks leukocyte migration and resultant gut inflammation 1
      • Adverse effects include infusion reactions and nasopharyngeal infection 1
      • Vedolizumab Solution for injection; Adults: Induction: 300 mg IV over 30 minutes at weeks 0, 2, and 6. Maintenance: 300 mg IV every 8 weeks.
  • Janus kinase inhibitor
    • Tofacitinib 5
      • Tofacitinib Oral tablet; Adults: INDUCTION: 10 mg PO twice daily for at least 8 weeks; then, transition to maintenance therapy. If needed, continue 10 mg twice daily for a maximum of 16 weeks. Discontinue induction dose after 16 weeks if an adequate response not achieved. MAINTENANCE: 5 mg PO twice daily. Limit the use of 10 mg twice daily beyond induction to those with loss of response and use for the shortest duration. Do not use with other UC biologic therapies or with potent immunosuppressants. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

Nondrug and supportive care

Symptomatic care

  • Pain 41
    • Primary long-term management strategy for pain control is disease control
    • Preferred medication for temporary relief of pain is acetaminophen
    • Tramadol and anxiolytics may be required for some hospitalized patients
    • Avoid NSAIDs owing to potential for worsening of disease
    • Avoid long-term use of narcotics
  • Diarrhea
    • Bulking agents may be preferred for temporary relief 43
      • Loperamide may be used for temporary relief; however, routine use is discouraged by many experts owing to increased risk for complications (eg, toxic megacolon) with use 43
      • Antidiarrheals can be used safely in most patients with J pouch or ileostomy and are frequently used in this setting
    • Avoid antidiarrheal agents in patients with extreme illness, evidence of obstruction or colonic dilation, fever, or abdominal tenderness 44


  • Recommend avoidance of certain drinks 41
    • Alcohol and sugary drinks may lead to worsening of diarrhea
    • Caffeinated beverages may lead to fluid loss due to diuresis
    • Carbonated drinks may result in increased abdominal cramping related to gas production
  • Encourage oral fluid replacement during non-NPO status with water and electrolyte-containing fluid 41
  • Hospitalized patients may require IV fluid resuscitation and replacements


  • No specific dietary recommendations are available; however, a few general dietary suggestions include the following:
    • During a flare: avoid high-fiber and high-fat diets 41
    • During remission: no significant limitations are recommended; however, high-fiber diet may be beneficial 41

Address additional health maintenance considerations at the time of diagnosis 45

  • Review routine vaccination status
    • Update any indicated vaccines and administer any live vaccines before treatment with immunosuppressants 45
      • Live attenuated vaccines are contraindicated in immunosuppressed patients 2
        • Live vaccines include bacille Calmette-Guérin; intranasal influenza; measles, mumps, rubella; varicella-zoster; rotavirus; zoster; smallpox; oral typhoid; oral adenovirus; and oral cholera 46
        • Do not administer live vaccines to patients planning immunosuppressive therapy within the next 6 weeks or to patients who have received immunosuppressive therapy within the past 3 months 47
      • Vaccinate nonimmune patients who are at risk for infection for hepatitis B, especially before administering anti–tumor necrosis factor drugs 45
      • Ensure routine vaccination for pneumococcus and tetanus-diphtheria with boosters every 5 years and influenza vaccine annually 2
      • Vaccinate at-risk patients—regardless of immunosuppression—for hepatitis A, meningococcus, and HPV 2
      • Vaccinate susceptible, nonimmunocompromised patients for varicella-zoster 2
  • Encourage adherence to guidelines for cervical dysplasia screening 14
    • Women with inflammatory bowel disease may be at increased risk for cervical dysplasia, and some of these populations have suboptimal frequency of Papanicolaou testing
  • Osteoporosis and osteopenia treatment and prevention 14
    • Encourage patient to change modifiable risk factors (eg, cigarette smoking, alcohol use, sedentary lifestyle)
    • In consultation with specialist (eg, gastroenterologist), consider bisphosphonates to prevent glucocorticoid-induced bone loss in high-risk patients 14
    • Prescribe a bisphosphonate (eg, alendronate, risedronate, etidronate, teriparatide, clodronate):
      • For patients with T scores below ₋2.5 14
      • For patients on long-term corticosteroids or with other important risk factors (eg, previous fractures) with T scores below ₋1.0 14
  • Optimize vitamin D and calcium status
    • May prevent flares and lower cancer risk 1
    • Recommend supplemental vitamin D and calcium in patients with vitamin D deficiency or insufficiency 2
    • Administer supplemental calcium and vitamin D during courses of oral steroids 2
  • Address comorbid conditions and provide resources 14
    • Anxiety and depression are more prevalent in patients with inflammatory bowel disease
    • Medication noncompliance may decrease with appropriate care for anxiety and depression
  • Provide disease-related anticipatory guidance and address other routine heath maintenance issues for patients with disease 14
    • Routine health checklists and guidance for preventive care are available 2
    • Outline anticipated monitoring regimen
  • Provide Pneumocystis jiroveci (carinii) prophylaxis with trimethoprim-sulfamethoxazole or dapsone for patients during periods requiring triple drug immunosuppression (eg, steroids, cyclosporine, thiopurine) 14
  • Provide anticipatory guidance regarding limitation of sun exposure and use of sunscreen to patients taking medications that increase risk for skin cancer (eg, thiopurines, anti–tumor necrosis factor agents) 2

Acute management concerns and supportive care for hospitalized patients

  • Address hydration and nutritional status; address electrolytes abnormalities if present
    • Administer IV fluids and electrolyte supplementation; potassium supplementation of at least 60 mmol/day is often necessary 4
    • Aggressively correct electrolyte abnormalities (eg, hypokalemia, hypomagnesemia) in any patients with bowel dilation; hypokalemia and hypomagnesemia can exacerbate bowel dilation 5
    • Maintain NPO status for patients who show signs of severe toxicity (eg, fever, leukocytosis, worsening symptoms), fulminant colitis, or toxic megacolon owing to likely necessity for imminent surgical intervention 1
    • Provide nutritional support for malnourished patients 4
      • Enteral nutrition is preferred 4 5
      • Total parenteral nutrition is not necessary for bowel rest purposes but may be needed for patients with significant nutrition depletion 5
        • Associated with higher complication rates and does not improve outcomes
  • Place small bowel decompression tube in patients with small bowel ileus 14
    • Rotate patient frequently into the prone or knee-elbow position to aid evacuation of bowel gas
  • Discontinue any medications with anticholinergic or opiate properties in patients with either toxic signs (eg, fever, leukocytosis, worsening symptoms) or megacolon as these can precipitate colonic dilation and/or colonic atony 14
  • Discontinue use of NSAIDs owing to possible exacerbation of disease 4 6
  • Administer blood transfusions to maintain hemoglobin concentration above 8 to 10 g/dL 4
  • Venous thromboembolism prophylaxis 4
    • Venous thromboembolism occurs more frequently in hospitalized patients with ulcerative colitis compared with hospitalized controls 5
    • Hospitalized patients require prophylactic anticoagulation (eg, low-molecular-weight heparin) 1 38
    • Active ulcerative colitis with bloody bowel movements is not a contraindication to venous thromboembolism prophylaxis 1
Total proctocolectomy with permanent ileostomy or ileal pouch anal anastomosis

General explanation

  • Surgical removal of the diseased portion of the colon with diversion of the proximal bowel to either an ileostomy or ileoanal anastomosis formed by construction of an ileal pouch 1
  • Treating surgeon bases decision to surgically remove all or part of bowel on the patient’s overall health and need to reestablish bowel anatomy and function
  • Emergent surgery is often required for patients who have severe complications (eg, bowel perforation, uncontrolled hemorrhage) 2
  • Urgent surgery is most often performed for patients with severe ulcerative colitis unresponsive to intensive inpatient medical treatment 9
  • Elective surgery is most often performed for patients refractory to or intolerant of long-term maintenance treatments and patients who develop dysplasia or colorectal cancer 9
  • Staged repair is often required for patients undergoing emergent or urgent surgery 2
    • First stage involves subtotal colectomy and creation of temporary ileostomy
    • Second stage involves ileal pouch creation with anastomosis to anal canal with diverting ileostomy
    • Third stage involves ileostomy take down to restore intestinal continuity
  • Ileal pouch anal anastomosis procedure is increasingly performed by laparoscopic approach 38 48


  • Absolute indications 6
    • Bowel perforation 14
    • Uncontrolled hemorrhage 2
    • Toxic megacolon 41
    • Documented or strongly suspected malignancy 14
  • Other indications
    • Intractable fulminant colitis or acute severe colitis refractory to medical management 2 12
    • Medically refractory disease 2
    • Steroid dependence 13
    • Intolerable adverse effects of medication 14
    • Growth retardation in children 12
    • Strictures not amenable to endoscopic alleviation 12


  • Uncorrected bleeding dyscrasia


  • Early postoperative complications 49
    • Pelvic sepsis/abscess 14
    • Early postoperative small bowel obstruction 9
    • Fistula
  • General late postoperative complications
    • Anastomotic breakdown and leak 14
    • Bladder dysfunction 12
    • Hernia formation
  • Long-term postoperative complications after ileal pouch anal anastomosis
    • Pouchitis develops in up to 50% of patients 3 to 4 years after procedure; 9 pouchitis becomes chronic in up to 20% of patients 12
    • Pouch failure requiring excision and permanent diversion in up to 8% to 10% of patients 12
    • Bowel obstruction occurs in up to 30% of patients by 10 years 9
    • Anastomotic stricture develops in 8% to 14% of patients by 10 years 9
    • Erectile dysfunction and retrograde ejaculation 2
    • Female infertility and transient dyspareunia 14
    • Fecal incontinence 14
    • Cuffitis (inflammation of residual anal tissue at ileal-anal anastomosis site)
    • Pouch dysplasia or cancer

Interpretation of results

  • Surgical goal is removal of diseased bowel

Special populations

  • Pregnant women or women planning pregnancy 50
    • Most medications are safe during pregnancy
    • Many experts recommend discontinuing anti–tumor necrosis factor therapy around 32 weeks of gestation; however, consensus is lacking
    • Disease control before conception and throughout pregnancy is essential for successful pregnancy management in patients with inflammatory bowel disease
    • Base delivery method primarily on obstetric indications
      • Some experts recommend cesarean section for patients who have undergone ileal pouch anal anastomosis procedure (controversial) 38
    • Detailed recommendations for management of inflammatory bowel disease during pregnancy have been published by the American Gastroenterological Association 51
  • Male couples planning pregnancy 50
    • Men can experience reduced fertility or infertility when treated with sulfasalazine
      • Causes reversible semen abnormalities and infertility in up to 60% of men 50
  • Postmenopausal women 14
    • Calcium supplementation 1000 to 1500 mg/day and vitamin D 800 units/day
    • Estrogen replacement


  • Long-term care and health maintenance monitoring
    • Monitor for disease activity and treatment efficacy
      • Treatment goal targets include both symptom control (eg, diminished diarrhea, resolution of rectal bleeding) and endoscopic remission 2
      • Suggested follow-up includes the following:
        • Reevaluate for symptoms every 3 months until they resolve, then reassess maintenance regimen every 6 to 12 months to verify patient has control 2
        • Perform direct assessment of colon for endoscopic remission 3 to 6 months after starting a new treatment 2
        • Once in remission, noninvasive markers (eg, fecal calprotectin) and inflammatory markers (eg ,C-reactive protein, erythrocyte sedimentation rate) may be used to monitor disease activity 2 16
    • Monitor for primary sclerosing cholangitis
      • Experts suggest monitoring liver function about every 4 months and carbohydrate antigen 19-9 with magnetic resonance cholangiopancreatography about every 6 to 12 months, ongoing
    • Monitor for gastrointestinal malignancy
      • Guideline recommendations vary regarding colorectal cancer screening intervals 2
      • Most guidelines recommend annual or biannual surveillance colonoscopy with multiple biopsies at regular intervals after 8 to 10 years if inflammation extends beyond rectum 2 5
        • Detection of dysplasia is better with chromoendoscopy (ie, spraying colon mucosa with indigo carmine or methylene blue) than with white light colonoscopy using random biopsy technique 1
      • Begin screening patients immediately if primary sclerosing cholangitis develops 14
        • Use histopathology results from this screening to determine extent of disease to direct frequency of future screening 9
          • Patients with high-risk features (eg, stricture or dysplasia, extensive colitis with severe active inflammation, colorectal cancer in a first-degree relative younger than 50 years): repeat colonoscopy in 1 year 16
            • Also annually screen patients who have primary sclerosing cholangitis 1
          • Patients with intermediate risk factors (eg, extensive colitis with mild or moderate active inflammation, postinflammatory polyps, family history of colorectal cancer in a first-degree relative diagnosed at age 50 years or older): repeat colonoscopy in 2 to 3 years 16
          • Patients with neither intermediate nor high-risk features: repeat colonoscopy in 5 years 16
      • No surveillance recommendations are available for screening for dysplasia or adenocarcinoma in pouches
      • Follow standard colorectal cancer screening for patients with proctitis because patients are at no higher risk than general population for colorectal cancer 2
    • Monitor immunocompromised patients for other malignancy
      • Cervical cancer
        • Annual Papanicolaou testing is recommended 2
      • Skin cancer
        • Annual skin examination by dermatologist is recommended 2
    • Monitor for bone health
      • Patients with corticosteroid use beyond 2 to 3 1 consecutive months or recurrent corticosteroid use require DEXA bone scan monitoring 45
      • Measure serum concentration of 25(OH)D (vitamin D) at least once in all patients and supplement if deficient or insufficient 2
  • Monitoring based on medication profile
    • 5-aminosalicylic acid
      • Monitor clinically for paradoxical worsening of symptoms (eg, diarrhea) 1, which occurs in less than 5% of patients, and for other adverse drug reactions and effects 1
      • Monitor renal function with periodic serum creatinine levels to assess for rare occurrence of nephrotoxicity that often presents as an interstitial nephritis 1 14
        • Suggested monitoring frequency is at 3- to 6-month intervals during first year of treatment and yearly thereafter 14
      • Monitor for hepatotoxicity with periodic liver function testing 1
      • Monitor for clinical response to induction therapy
        • Lack of clinical response within 4 weeks indicates need to modify therapy 7
    • Thiopurines
      • Have dermatologist perform annual evaluation because there is increased risk for nonmelanoma skin cancer 1 2
      • Perform annual Papanicolaou test and document it because there is increased risk for cervical dysplasia 1
      • Monitor for bone marrow suppression, in particular leukopenia, using CBC frequently during initial stages of treatment and periodically thereafter 14
      • Monitor periodic liver function test results to screen for hepatotoxicity 1
      • Monitor clinically for other adverse drug reactions and effects
      • Therapeutic drug monitoring
        • Adequacy of dosage can be assessed with active metabolite concentration (ie, 6-thioguanine, 6MMPN concentrations) 2
    • Corticosteroids
      • Annual ophthalmologic examinations and possibly bone health assessments are recommended for patients taking steroids for long-term disease management 2 14
      • Exposure to 10 mg/day of prednisone f60 days or longer requires monitoring with DEXA bone scanning for osteopenia and osteoporosis 1
      • Suggested laboratory values to be monitored include hemoglobin A1C and vitamin D concentrations 1
      • Monitor clinically for other adverse drug reactions and effects
      • Monitor for response to oral corticosteroid induction treatment
        • Lack of response within 2 weeks indicates need to modify treatment approach 7
      • Monitor patients receiving IV corticosteroids for hyperglycemia, hypokalemia, sodium and fluid retention, and metabolic alkalosis 6
      • Monitor for response to parenteral corticosteroid treatment 6
        • Assess response to IV corticosteroid by treatment day 3 38 using clinical and C-reactive protein level/erythrocyte sedimentation rate biochemical markers; scoring systems to aid in decision are available 52 53
        • Consider early alternate therapeutic options for patients not responding to parenteral steroids (eg, infliximab, cyclosporine) 38
    • Infliximab
      • Monitor during administration for infusion reactions
        • Occur in about 10% of patients and are more common in patients with antibodies to infliximab 14
        • Mild to moderate reactions are most common (eg, flushing, headaches, dizziness, chest pain, cough, dyspnea, fevers, chills, pruritus) 14
        • Reactions during infusions often respond to temporarily halting infusion and slowing infusion rate 14
      • Monitor clinically for delayed hypersensitivitylike or serum sicknesslike reactions
        • Occur in 1% to 2% of patients and are most common in those who have had a long hiatus between infusions 14
        • Present with myalgias, arthralgias, fevers, or rashes
        • Reactions are often responsive to a brief course of corticosteroids 14
      • Monitor clinically for other adverse drug reactions and effects
      • Patients who require anti–tumor necrosis factor agents need to be evaluated yearly by a dermatologist owing to increased risk for melanoma 1 2
      • Monitor periodic liver function test results to screen for hepatotoxicity and hepatocarcinoma; periodic CBC and renal function testing is suggested 1 2
      • Monitor yearly with tuberculosis risk assessment and repeat testing if high risk (eg, travel to endemic region) 2
      • Monitor for response to anti–tumor necrosis factor induction therapy
        • Lack of response within 8 to 12 weeks indicates need to modify treatment approach 7
        • Suboptimal response to induction suggests need for dosage intensification to achieve complete remission 7
      • Therapeutic drug monitoring
        • Can assess adequacy of dosage by measuring periodic trough drug concentration 1 2
        • Check antidrug antibodies if symptoms recur or worsen on treatment before dosage escalation 1
          • Development of anti-drug antibodies is associated with decreased drug concentration and loss of clinical response 2
    • Calcineurin inhibitors
      • Monitor drug concentrations; dosage is based on goal trough measurement
        • Cyclosporine goal trough concentration is 200 to 400 ng/mL 1
      • Monitor magnesium, cholesterol, and creatinine levels 24 hours after starting treatment; 6 other suggested test results to monitor include BUN concentration, liver function test, and CBC 1
      • Maintain cholesterol above 120 mg/dL to reduce risk of seizures 6
      • Monitor clinically for other adverse drug reactions and effects
    • Selective adhesion molecule inhibitors
      • Suggested monitoring includes periodic CBC and liver and renal function testing 2

Complications and Prognosis


  • Gastrointestinal
    • Gastrointestinal bleeding
      • Acute severe hemorrhage occurs in up to 10% of patients 12
      • Chronic bleeding can lead to iron deficiency anemia 12
    • Toxic or fulminant colitis 12
      • Patients are at risk for progression to toxic megacolon, bowel perforation, and sepsis
      • Usually develops in patients with extensive colitis with severe inflammation
    • Megacolon
      • Defined as total or segmental nonobstructive dilation to 5.5 cm or larger; can be associated with or without toxicity 2
      • Toxic megacolon
        • Megacolon accompanied by fever, persistent tachycardia, intense pain, abdominal tenderness and distention, and severe leukocytosis
        • Often a significantly dilated transverse colon (greater than 8 cm) is apparent 41
        • Occurs in up to 7.9% of patients 3
        • Risk of death is high and perforation may occur
    • Colorectal cancer
      • One of the more common causes of mortality in patients with ulcerative colitis 54
      • Risk for colorectal cancer
        • Degree of risk is related to the duration of colitis, anatomic extent of colitis, and degree of microscopic inflammation over time
          • Increased duration of colitis is associated with increased cancer risk
            • Cancer risk is reported to be 1% and 2% per year after disease duration of 10 and 20 years, respectively 5
          • More extensive macroscopic inflammation increases risk
            • Patients with pancolitis have a 14.8-fold increased risk of colorectal cancer compared with the general population 9
            • Patients with left-sided colitis have an intermediate risk of colorectal cancer 9
            • Patients with isolated proctitis or proctosigmoiditis do not appear to be at increased risk of cancer 14
            • Development of dysplasia or adenocarcinoma in pouches is very infrequent 14
          • Increased degree of microscopic inflammation increases risk 55
            • Worsening microscopic inflammation severity scores increase risk 3- to 5-fold 14
        • Presence of primary sclerosing cholangitis increases risk
          • Patients with concomitant ulcerative colitis and primary sclerosing cholangitis have an up to 5-fold increased risk of colorectal cancer over patients with only ulcerative colitis 2
        • Familial inheritance of colorectal cancer further increases risk 3-fold over baseline increased risk 1
        • Other risk factors include numerous pseudopolyps, ongoing inflammation, male sex, shortened colon, and strictures 1
        • Decreased risk for colorectal dysplasia and cancer is associated with: 9
          • Use of thiopurines in patients with extensive disease
          • Use of ursodeoxycholic acid in patients with primary sclerosing cholangitis and concomitant ulcerative colitis
    • Bowel stricture is relatively uncommon 12
      • Can be associated with malignancy
    • Colonic dysmotility and anorectal dysfunction 2
      • May develop in some patients
    • Clostridium difficile colitis
      • Must be treated with vancomycin or fidaxomicin 41
  • Hematologic associations with disease
    • Hypercoagulable state 12
      • Increased risk of thromboembolic events, particularly in peripheral veins but may occur in arteries
        • Baseline risk for venous thromboembolism is 3- to 4-fold higher than in the general population 2
        • Thromboembolic event risk is highest during disease flare, hospitalization, and treatment with corticosteroids 2 6
    • Anemia 12
      • Chronic hemorrhage may cause iron deficiency anemia
      • Anemia of chronic disease, anemia of mixed origin, and autoimmune hemolytic anemia also may occur
  • Hepatobiliary conditions associated with disease
    • Primary sclerosing cholangitis
      • More common in people with more extensive colonic disease 1
      • Course does not parallel colonic disease activity 1
      • May present with elevated alkaline phosphatase and no other symptoms
      • Presence is a risk factor for colon cancer and cholangiocarcinoma 1
        • Ursodeoxycholic acid treatment reduces risk of developing colorectal neoplasia 14
    • Primary biliary cirrhosis 1
    • Autoimmune hepatitis 1
    • Fatty liver infiltration 12
    • Pancreatitis 1
  • Musculoskeletal conditions associated with disease
    • Osteopenia in up to 44% of patients 14
    • Osteoporosis in up to 12% of patients 14
    • Fractures
    • Osteonecrosis
    • Impaired growth in children 1
    • Peripheral arthritis 12
    • Axial arthropathies (eg, sacroiliitis, ankylosing spondylitis) 1
    • Myopathy 1
  • Ocular conditions associated with disease
    • Anterior chamber disease (eg, scleritis, episcleritis, uveitis, iritis, conjunctivitis) is most common 12
    • Optic neuritis 1
  • Cutaneous conditions associated with disease 1
    • Pyoderma gangrenosum
    • Erythema nodosum
    • Sweet syndrome
    • Aphthous ulcers
  • Psychiatric conditions associated with disease
    • Anxiety 14
    • Depression 1
  • Opportunistic infection
    • Steroids
      • More common in patients older than 50 years 14
      • Use increases risk for opportunistic infection 3-fold; risk is dose-related 14
    • Infliximab
      • Increases risk for infection from intracellular pathogens, especially extrapulmonary and disseminated tuberculosis 14
      • Increases risk for opportunistic infections that require macrophages for intracellular killing 14
      • Increases risk for reactivation of latent hepatitis B 14
    • Thiopurines
      • Increase risk of opportunistic infections 3-fold; further increased risk occurs in the setting of lower absolute lymphocyte counts and leukopenia 14
    • Combination therapy
      • Risk of opportunistic infection is synergistically increased with concomitant use of multiple immune modulating drugs (eg, corticosteroids, thiopurines, infliximab)
  • Malignancy
    • Lymphoma
      • Risk is increased in patients who have been treated with infliximab and thiopurines 14
    • Melanoma and nonmelanoma skin cancers 45
      • Increased risk associated with anti–tumor necrosis factor therapy and thiopurines
  • Long-term surgical complications
    • Pouchitis
      • May develop idiopathic inflammation in the newly established ileal pouch after the ileal pouch anal anastomosis procedure 5
        • Develops at least once in up to 46% of patients 2
      • Presents with increased stool frequency, rectal bleeding, abdominal cramping, rectal urgency, tenesmus, incontinence, fevers, and appearance of extraintestinal manifestations
      • Treat with a 2- to 4-week course of antibiotics (eg, ciprofloxacin 1000 mg/day, metronidazole 20 mg/kg/day) 2 56 after confirming diagnosis by observing characteristic endoscopic and histologic features 14
      • Minority may develop chronic pouchitis with symptoms persisting longer than 4 weeks of treatment or with frequent recurrences 2
      • Probiotics can be effective in preventing recurrence of pouchitis 12 56
    • Cuffitis 2
      • Residual rectal tissue at the anastomosis between ileum and anal canal (rectal cuff) may become inflamed
      • Typically presents with bleeding
      • Treat with 5-aminosalicylic acid suppositories


  • Clinical course of disease
    • Characterized by alternating periods of remission and relapse 9
      • Most experience relapsing and remitting disease course with periodic flares 57
      • Many with mild disease will remain in remission or have only mild symptoms 10 years from diagnosis 9
      • Minority experience continuing symptoms and are unable to achieve remission 57
      • In general, patients with proctitis experience a more benign disease course than patients with more extensive colitis
    • Progression of disease
      • Proximal extension of disease occurs in 10% to 19% of patients after 5 years and up to 28% of patients at 10 years 2
      • Patients are more likely to require biologic and immunosuppressant drugs and surgery when disease flare is associated with proximal extension of disease 2
    • Specific factors related to course of disease
      • Age
        • Milder disease is associated with disease onset after the age of 60 years 2
      • Patients with primary sclerosing cholangitis
        • Disease in these patients is more likely to be extensive, milder, and associated with rectal sparing and backwash ileus compared with disease in patients without associated primary sclerosing cholangitis 2
      • Risk factors for aggressive disease include: 2
        • Younger than 40 years at onset 2
        • Pancolitis
        • Lack of endoscopic healing in clinical remission
        • Deep ulcerations
        • High concentrations of perinuclear antineutrophil cytoplasmic antibodies
    • Diagnosis changes in a minority of patients (5%-10%) initially designated with ulcerative colitis to Crohn disease 2
  • Colectomy
    • Disease extent is an important predictor of need for colectomy 9
      • Patients with extensive disease have a risk 3.5- to 4-fold higher than patients with isolated proctitis 9
    • Overall colectomy is required in up to 15% of these patients; 2 most occur within 2 years of diagnosis 9
    • Colectomy rate for hospitalized patients with severe ulcerative colitis is 27% 6
  • Mortality
    • Despite the often severe disease manifestations, overall, patients with ulcerative colitis do not have an increased mortality risk compared with the general population 2
    • Mortality rate for hospitalized patients with acute severe ulcerative colitis is approximately 1% 6


1: Feuerstein JD et al: Ulcerative colitis: epidemiology, diagnosis, and management. Mayo Clin Proc. 89(11):1553-63, 2014

Cross Reference