Ulcerative colitis

Ulcerative colitis is an inflammatory bowel disease (IBD) characterized by chronic mucosal inflammation of the rectum, colon, and cecum. Common symptoms include bloody diarrhea, abdominal pain, and fecal urgency. Laboratory findings typically show elevated inflammatory markers (e.g., ESR, CRP) and elevated fecal calprotectin. Although not required for diagnosis, the presence of perinuclear antineutrophil cytoplasmic autoantibodies (pANCA) is suggestive of ulcerative colitis. Definitive diagnosis requires endoscopy, which may show changes to superficial vascular patterns, friable mucosa, and erosions and/or ulcerations. 5-Aminosalicylic acids (e.g., mesalamine) are the mainstay of treatment for mild-to-moderate disease. Patients who experience severe episodes often require corticosteroids or other immunosuppressants to achieve remission. In distal colitis, medications may be administered rectally (e.g., via enema), whereas more proximal inflammation requires oral treatment. Proctocolectomy is curative and indicated in patients with complicated ulcerative colitis or dysplasia. Patients with ulcerative colitis are at increased risk of developing colorectal cancer and should undergo regular endoscopic surveillance.

• Prevalence
  • Approximately 600,000 adults in the US are affected by ulcerative colitis. ^[1]
  • Ethnicity
    • Higher in White populations than in Black, Hispanic, or Asian populations
    • Highest among individuals of Ashkenazi Jewish descent
• Peak incidence
  • 15–35 years of age ^[2]
  • Another smaller peak may be observed in individuals > 55 years of age. ^[3]
  • Similar for men and women ^[4]

Epidemiological data refers to the US, unless otherwise specified.

Risk factors ^[3][5][6]

• Genetic predisposition (e.g., HLA-B27 association)
• Ethnicity (White populations, individuals of Ashkenazi Jewish descent)
• Family history of inflammatory bowel disease
• Episodes of previous intestinal infection
• Increased fat intake (especially saturated fat and animal fat)
• Oral contraceptive use
• NSAIDs may exacerbate ulcerative colitis.

Protective factors ^[5][6]

• Appendectomy
• Smoking

Classification of ulcerative colitis by disease extent ^[2]

The extent of disease is classified based on endoscopic findings.

Classification of ulcerative colitis by severity ^[2][7]

There are several classification systems that can be used to assess disease severity. Criteria include:

• Endoscopic findings
  • Ulcerative colitis endoscopic index of severity (UCEIS)
  • Mayo endoscopic score ^[8]
• Clinical presentation
  • Simple clinical colitis activity index (SCCAI)
  • Truelove and Witts severity index for ulcerative colitis ^[9]
• A combination of both endoscopic findings and clinical presentation
  • Mayo score for ulcerative colitis activity
  • American College of Gastroenterology (ACG) ulcerative colitis activity index
• Other: response to medication, disease course, and the patient's quality of life
• Remission criteria (ACG): no diarrhea, no visible blood in stools, no fecal urgency, fecal calprotectin < 150–200 mcg/g, normal laboratory values, and normal endoscopy findings ^[2]

Treatment recommendations by the ACG are based on the ACG ulcerative colitis activity index, while recommendations by the American Gastroenterological Association (AGA) are based on a combination of the Truelove and Witts severity index and the Mayo score for ulcerative colitis activity. There is significant overlap among the criteria used in all ulcerative colitis severity indices.

The exact mechanism is unknown but studies suggest that ulcerative colitis is caused by abnormal interactions between host immune cells and commensal bacteria. ^[5][6]

• Dysregulation of intestinal epithelium: increased permeability for luminal bacteria → activation of macrophages and dendritic cells → antigen presentation to macrophages and naive CD4+ cells leads to:
  • Secretion of proinflammatory cytokines (IL-6, IL-12, TNF-α) and chemokines (CXCL1, CXCL3, and CXCL8) → recruitment of other immune cells (e.g., neutrophils) to the site
  • Differentiation of naive CD4+ cells to Th2 effector cells
  • Recruitment of natural killer cells
• Dysregulation of the immune system: upregulation of lymphatic cell activity (T cells, B cells, plasma cells) in bowel walls → enhanced immune reaction and cytotoxic effect on colonic epithelium → inflammation with local tissue damage (ulcerations, erosions, necrosis) in the submucosa and mucosa
  • Autoantibodies (pANCA) against cells of the intestinal epithelium
  • Th2 cell-mediated response
• Pattern of involvement
  • Ascending inflammation that begins in the rectum and spreads continuously proximally throughout the colon
  • Inflammation is limited to the mucosa and submucosa.

The rectum is always involved in ulcerative colitis.

Intestinal symptoms

• Bloody diarrhea with mucus
• Fecal urgency
• Abdominal pain and cramps
• Tenesmus

Extraintestinal symptoms of ulcerative colitis

• General: fatigue, fever
• Skeletal: (most common extraintestinal manifestation of ulcerative colitis): osteoarthritis, ankylosing spondylitis, sacroiliitis ^[11][12]
• Ocular: uveitis, episcleritis, iritis
• Biliary: primary sclerosing cholangitis (it is rare for patients with ulcerative colitis to develop PSC, but up to 90% of all patients with PSC will also have ulcerative colitis)
• Cutaneous
  • Erythema nodosum
  • Pyoderma gangrenosum
  • Aphthous stomatitis
  • Pyostomatitis vegetans
    • A very rare condition that is associated with other cutaneous diseases and inflammatory bowel disease, particularly ulcerative colitis
    • Manifests with multiple aphthae and pustules of the oral mucosa
• In children and adolescents: growth retardation and delayed puberty

PSC is often associated with inflammatory bowel disease, especially ulcerative colitis. However, only approximately 4% of patients with inflammatory bowel disease develop PSC.

“ULCCCERS:” Ulcers, Large intestine, Continuous/Colon cancer/Crypt abscesses, Extends proximally, Red diarrhea, and Sclerosing cholangitis are the characteristics of ulcerative colitis.

Disease course

• Chronic intermittent
  • Most common course
  • Exacerbation is followed by complete remission.
• Chronic continuous
  • Complete remission does not occur.
  • Disease severity varies.
• Acute fulminant
  • Sudden onset
  • Severe diarrhea, dehydration, shock

Backwash ileitis

• Definition: inflammation of the terminal ileum in the context of ulcerative colitis
• Epidemiology: affects approximately 10–20% of all patients diagnosed with ulcerative colitis
• Localization: typically affects an area a few centimeters proximal to the ileocecal valve
• Pathophysiology: The pathological mechanism is not fully understood.
• Differential diagnosis: Clinically, backwash ileitis is hardly relevant but its presence makes it harder to differentiate between ulcerative colitis and Crohn disease.

Approach ^[2][13]

• Evaluate patients with hematochezia and fecal urgency for ulcerative colitis.
• Rule out infectious gastroenteritis.
• Consult gastroenterology for ileocolonoscopy with histological examination to:
  • Definitively diagnose ulcerative colitis
  • Determine the extent of disease in ulcerative colitis and severity of ulcerative colitis
• Identify signs of acute severe ulcerative colitis (ASUC).
• Consider CT or MRI abdomen if direct endoscopy is contraindicated.
• Assess for the presence of extraintestinal symptoms of ulcerative colitis.

Laboratory studies ^[2][13]

Stool testing for causes of gastroenteritis is indicated in all patients. Blood tests are not routinely required for diagnosis but help assess disease activity and severity.

• Blood tests
  • CBC: anemia, leukocytosis, thrombocytosis ^[4]
  • ESR, CRP: Elevated levels may indicate active ulcerative colitis and often correlates with disease severity.
  • Hypoalbuminemia: associated with a poor prognosis and more severe disease ^[4]
  • ALP, GGT: elevated in patients with concurrent PSC
  • Perinuclear ANCA (pANCA) ^[2]
    • Not routinely recommended
    • Elevated in up to 70% of patients with ulcerative colitis
• Stool diagnostic studies
  • Stool test for Clostridioides difficile infection ^[4]
  • PCR panel for other enteric infections: depending on the patient's symptoms and risk factors for diarrhea
  • Stool culture and microscopy: to assess for bacteria and ova and parasites if a stool PCR panel is not available
  • Fecal calprotectin: can help assess for mucosal inflammation

Diagnosis of ulcerative colitis does not require the measurement of CRP, ESR, or hemoglobin levels but they are used to determine disease severity.

Hypoalbuminemia and elevated CRP suggest a poor prognosis. Other poor prognostic factors include < 40 years of age at diagnosis, extensive ulcerative colitis, and severe disease based on endoscopic evaluation scores. ^[14][15]

Endoscopy ^[2][4]

• Ileocolonoscopy
  • Recommended method for diagnosis and disease monitoring ^[4]
  • Severe disease is a relative contraindication.

• Sigmoidoscopy
  • Indications
    • Initially used as an alternative to colonoscopy, e.g., in ASUC
    • Monitoring treatment response
  • Findings are similar to colonoscopy findings.
• EGD: recommended for patients with upper gastrointestinal symptoms to rule out Crohn disease

Patients with severe ulcerative colitis have a high risk for colonic perforation; therefore, caution should be used when performing biopsies.

Imaging ^[2][16]

Imaging studies are not routinely recommended; for diagnosing ulcerative colitis but may be used as an adjunct to endoscopy, particularly for the detection of complications; , or if endoscopy is not possible. ^[4]

Abdominal x-rays ^[2][4][17]

• Indication: initial and serial evaluation of suspected ASUC
• Findings
  • Typically normal in mild-to-moderate disease
  • Loss of colonic haustra (lead pipe appearance) may be seen in severe cases
  • May show signs of complications, e.g.:
    • Toxic megacolon: massive distention
    • Ulceration: segmental dilation with irregular edges outlined by gas ^[17]
    • Perforation: pneumoperitoneum ^[18]

CT or MRI abdomen ^[18]

• Indications
  • Patients with abdominal symptoms that cannot be explained by the disease activity seen on endoscopy
  • To evaluate for:
    • Proximal disease involvement if endoscopy is not possible
    • Complications, e.g., bowel perforation
    • Differential diagnoses, e.g., Crohn disease
• Findings
  • Loss of haustra
  • Increased bowel wall thickness
  • Mural hyperenhancement
  • Signs of complications (similar to abdominal x-ray findings)

Barium enema radiography ^[17]

The role of barium enema is limited, as it is less sensitive than other imaging modalities and is contraindicated in patients with obstruction or perforation.

• Indication: : can be considered for assessment of the proximal colon if colonoscopy is contraindicated
• Findings
  • Granular appearance of the mucosa
  • Deep ulcerations
  • Loss of haustra
  • Pseudopolyps that appear as filling defects

Abdominal ultrasound ^[17][18]

• Indication: monitoring disease activity and treatment response
• Findings: increased bowel wall thickness

Gross pathology

See “Endoscopic findings in ulcerative colitis” in “Diagnostics.”

Histological findings

• Early stages
  • Granulocyte (neutrophil) infiltration: limited to mucosa and submucosa
  • Crypt abscesses: an infiltration of neutrophils into the lumen of intestinal crypts due to a breakdown of the crypt epithelium
• Chronic disease
  • Lymphocyte infiltration
  • Mucosal atrophy
  • Altered crypt architecture
    • Branching of crypts
    • Irregularities in size and shape
  • Epithelial dysplasia

In ulcerative colitis, the extent of intestinal inflammation is limited to the mucosa and submucosa. In contrast, Crohn disease shows a transmural pattern of intestinal involvement.

Noncaseating granulomas are seen in Crohn disease but are not a feature of ulcerative colitis!

Differential diagnosis considerations

• Crohn disease (see “Differential diagnostic considerations: Crohn disease and ulcerative colitis”)
• Exudative-inflammatory diarrhea
• Diverticular disease
• Appendicitis
• Ischemic colitis
• Infectious colitis
  • C. difficile colitis
  • Shigella dysenteriae
  • Salmonella enterocolitis
  • Escherichia coli colitis
  • Campylobacter enterocolitis
  • Yersiniosis
  • Tuberculosis
  • CMV colitis
• Radiation colitis
• Celiac disease
• Inflammatory diarrhea

Microscopic colitis ^[19][20]

• Definition: : an idiopathic, inflammatory form of colitis that is characterized by a normal macroscopic appearance of bowel on colonoscopy and collagenous or lymphocytic infiltrates on microscopy
• Histological subtypes
  • Collagenous colitis: characterized by proliferation of collagenous connective tissue that forms a thick subepithelial collagen band
  • Lymphocytic colitis: characterized by lymphocytic infiltrates and little to no proliferation of connective tissue
• Epidemiology ^[21]
  • Peak incidence: ∼ 60 years of age ^[22]
  • ♀ > ♂
  • Associated with autoimmune diseases (e.g., celiac disease, type 1 diabetes mellitus, autoimmune thyroiditis)
• Etiology: unknown
• Risk factors
  • Smoking
  • Frequent use of certain drugs, including:
    • NSAIDs
    • PPIs (especially lansoprazole)
    • SSRIs (especially sertraline)
    • Statins
• Clinical features
  • Chronic, nonbloody, watery diarrhea for > 4 weeks
  • Weight loss
  • Abdominal pain
  • Fecal urgency or incontinence
  • Nocturnal stools
• Treatment
  • Discontinue drugs associated with the condition if possible (e.g., NSAIDs, PPIs).
  • Symptomatic therapy (e.g., loperamide for mild diarrhea)
  • Corticosteroids

The differential diagnoses listed here are not exhaustive.

Approach ^[2]

• Choose medical therapy based on disease severity and disease extent.
• If remission is achieved, initiate maintenance therapy.
  • Continue the treatment used to achieve remission, with the exception of corticosteroids.
  • For patients who achieved remission with corticosteroids, consider thiopurine monotherapy.
• If remission is not achieved, escalate treatment.
• Monitor for complications related to the disease and treatment.
• Consult surgery for consideration of curative proctocolectomy if medical therapy is unsuccessful or complications occur.
• Screen for colorectal cancer and other common comorbidities (e.g., depression and anxiety).

While many patients with ulcerative colitis can be managed in an outpatient setting, patients with ASUC should be managed in the inpatient setting.

Management of acute severe ulcerative colitis

• The presence of both of the following indicates acute severe ulcerative colitis (ASUC): ^[2]
  • ≥ 6 bowel movements daily
  • ≥ 1 sign of systemic toxicity (e.g., tachycardia, fever, hemoglobin < 10.5 g/dL, ESR > 30 mm/hour)
• Admit all patients with ASUC to the hospital.
• Obtain a stool test for CDI.
• Consult gastroenterology to obtain urgent flexible sigmoidoscopy (ideally within 24 hours) and discuss management.
• Initiate treatment with IV corticosteroids (see “Induction of remission”).
• Provide supportive care with IV fluid resuscitation and electrolyte repletion as needed.
• Initiate DVT prophylaxis. ^[2]
• Closely monitor for:
  • Complications: using serial abdominal examinations and abdominal x-rays
  • Treatment response: based on symptoms, vital signs, physical examination findings, and serial CRP results
• Consult surgery if:
  • Complications arise (e.g., toxic megacolon, bowel perforation, hemorrhage, sepsis)
  • There is no improvement after 3–5 days of medical management ^[2]

Avoid NSAIDs, opioids, and anticholinergic medications in patients with ASUC.

Neither total parenteral nutrition nor empiric antibiotics are routinely indicated in ASUC.

Pharmacological therapy ^[2]

• Pharmacological therapy is used to induce and maintain disease remission.
• Goals of treatment
  • Initially: symptomatic remission ^[2]
  • Long-term: mucosal healing

Induction of remission

While treatment recommendations are based on mild-to-moderate, moderate-to-severe, and acute severe disease severity, the ACG ulcerative colitis activity index classifies disease severity as mild, moderate-to-severe, or fulminant.

Systemic corticosteroids should only be used for induction of remission. Steroid-sparing agents are preferred for maintenance of remission. ^[2]

Azathioprine may be considered in combination with anti-TNF therapy for induction of remission or as monotherapy for maintenance of remission; it is not recommended as monotherapy for induction of remission. ^[2]

Overview of 5-ASA and 5-ASA derivatives ^[2][14]

Supportive therapy ^[2]

• Treat pain as needed.
  • Nonpharmacological measures, e.g., heating pads
  • Consider acetaminophen, anxiolytics, and sedatives.
  • Avoid opioids and NSAIDs.
• Avoid parenteral nutrition unless required to improve nutritional status prior to colectomy. ^[2]
• Identify and treat any micronutrient deficiency.
• Currently, there is insufficient evidence to support the use of probiotics. ^[14]

Surgical treatment ^[2]

Ulcerative colitis can be cured surgically. Surgical treatment also reduces the risk of colorectal cancer.

• Indications
  • Complications of ASUC
    • Toxic megacolon
    • Bowel perforation
    • Multiorgan failure
    • Severe hematochezia
  • Refractory ulcerative colitis; (i.e., no response after; 3–5 days of medical management and/or corticosteroid dependence)
  • Dysplasia or carcinoma
• Procedure: : restorative proctocolectomy with an ileal pouch-anal anastomosis (IPAA or J pouch)
  • Resection of the entire colon and rectal mucosa while sparing the anal sphincters.
  • Loops of small intestine (serving as the pouch) are used to create an artificial rectum, resulting in a continence-conserving connection between the ileum and anus.
• Complications of surgery
  • Early (≤ 30 days): anastomotic leak, pelvic sepsis
  • Late: bowel stricture, bowel obstruction, fertility issues, sexual dysfunction ^[4]
  • Most common late postoperative issue: pouchitis (increased stool frequency, malaise, and possibly incontinence caused by bacterial overgrowth)

Poor nutritional status prior to colectomy in ulcerative colitis is associated with adverse patient outcomes. Optimize nutritional status prior to surgery.

Long-term management

• Disease monitoring
  • Assess treatment response using endoscopy or fecal calprotectin if endoscopy is not possible. ^[2]
  • Flexible sigmoidoscopy is recommended 3–6 months after starting a new treatment. ^[4]
  • Follow-up every 3 months until remission has been achieved, then every 6–12 months. ^[4]
• Colorectal cancer screening ^[2][26]
  • Start screening 8–10 years after the initial diagnosis or at the time of diagnosis of PSC.
    • Modality: ileocolonoscopy with biopsies
    • Interval: every 1–5 years

• ↑ Risk of cancer (see ”Long-term management” in “Treatment” for screening protocol)
  • Risk increases with duration and/or extent of disease (e.g., pancolitis).
  • Colorectal carcinoma risk is not significantly increased in patients with mild ulcerative colitis.
• Toxic megacolon
• Fulminant colitis: severe bowel inflammation that typically causes > 10 stools per day, lower gastrointestinal bleeding, abdominal pain, and abdominal distention
• Gastrointestinal bleeding (both acute and chronic)
• Perforation → peritonitis (see “Gastrointestinal perforation”)
• Colonic stricture
• Amyloidosis

References:^[13]

We list the most important complications. The selection is not exhaustive.

Inflammatory bowel disease in pregnancy ^[27][28]

Fertility and preconception counseling

• Fertility is not affected in women with IBD in remission and no history of abdominal surgery.
• Women with active disease have decreased fertility rates.
• Pharmacological therapy for IBD does not impact fertility.
• Active disease at conception increases the risk of persistently active disease during gestation.
• Active disease is associated with an increased risk of preterm birth and low birth weight.
• Patients who wish to conceive should be on appropriate pharmacological therapy to maintain disease remission.
• With the exception of methotrexate, all other treatments can be continued at conception.

Disease management during pregnancy

• Most medications used in the treatment of IBD are considered safe during pregnancy.
• Corticosteroids; are indicated for disease flares but should be avoided as maintenance therapy because of the increased risk of gestational diabetes, preterm birth, and low birth weight.
• 5-ASA, 5-ASA derivatives, immunomodulators, and biopharmaceuticals can be used during pregnancy.
• Monotherapy is preferred for maintenance treatment to reduce the risk of adverse effects.

On average, the life expectancy of patients with ulcerative colitis is normal.