• Clinical science

Ulcerative colitis

Summary

Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) characterized by chronic mucosal inflammation of the colon and cecum. Common symptoms include bloody diarrhea, abdominal pain, and fever. Laboratory findings typically show elevated inflammatory markers and the presence of autoantibodies (pANCA). Definitive diagnosis requires biopsies showing abnormal colonic mucosa and characteristic histopathology. Aminosalicylic acid derivatives are the mainstay of treatment, although severe episodes typically require corticosteroids and immunosuppressants to achieve remission. In the case of distal colitis, some drugs may be administered topically (e.g., via enema), whereas more proximal inflammation requires systemic treatment. Proctocolectomy is curative and indicated for complicated UC or dysplasia. Individuals with UC are predisposed to colorectal cancer and should thus undergo regular surveillance colonoscopy.

Epidemiology

  • Prevalence
    • Approx. 600,000 adults in the U.S. are affected by UC [1]
    • Ethnicity
      • Higher in the white than in the black, Hispanic, or Asian populations
      • Highest among individuals of Ashkenazi Jewish descent.
    • Slightly higher in men than women [2]
  • Peak incidence
    • 15–35 years [3]
    • Another smaller peak may be observed in individuals > 55 years [4]

References: [5][4][6][2]

Epidemiological data refers to the US, unless otherwise specified.

Classification

Truelove and Witts' severity index [7]

Criteria Mild Moderate Severe
Bowel movements/day < 4 4–6 > 6
Blood in stools Intermittent Frequent Continuous
Temperature < 37.5°C (99.5°F) ≤ 37.8°C (99.68°F) > 37.8°C (100.4°F)
Heart rate < 90/min ≤ 90/min > 90/min
Hemoglobin > 11.5 g/dL ≥ 10.5 g/dL < 10.5 g/dL
ESR < 20 mm/h ≤ 30 mm/h > 30 mm/h

Montreal classification of extent and severity of ulcerative colitis [8]

Disease extent/severity Localization/definition
E1: Ulcerative proctitis Mucosal involvement limited to the rectum
E2: Left-sided/distal ulcerative colitis Mucosal involvement limited to part of the colorectum distal to the splenic flexure
E3: Extensive ulcerative colitis/pancolitis Mucosal involvement extends to proximal of the splenic flexure
S0: Clinical remission No mucosal involvement, asymptomatic
S1: Mild ulcerative colitis ≤ 4 stools/day (with or without blood), no signs of systemic illness, ESR normal
S2: Moderate ulcerative colitis > 4 stools/day, only minimal signs of systemic illness
S3: Severe ulcerative colitis ≥ 6 stools/day with blood, heart rate ≥ 90/min, temperature ≥ 37.5°C (99.5°F), Hb < 10.5 g/dL, ESR > 30 mm/h

Pathophysiology

Pathogenesis

The exact mechanism is unknown but studies suggest that ulcerative colitis is the result of abnormal interactions between host immune cells and commensal bacteria. [9][2]

  • 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 pro-inflammatory 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 NK cells
  • Dysregulation of the immune system: upregulation of lymphatic cell activity in bowel walls (T cells, B cells, plasma cells) → enhanced immune reaction and cytotoxic effect on colonic epitheliuminflammation with local tissue damage (ulcerations, erosions, necrosis) in the submucosa and mucosa
  • Pattern of involvement
    • Ascending inflammation beginning in the rectum and spreading continuously proximally throughout the colon
    • Mucosal and submucosal inflammation

The rectum is always involved in UC!

Risk factors [9][2][4]

  • 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 (esp. saturated fat and animal fat)
  • Oral contraceptive intake
  • NSAIDs may exacerbate UC

Protective factors [9][2]

References:[5]

Clinical features

Intestinal symptoms

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

Extraintestinal symptoms

Primary sclerosing cholangitis (PSC) is often associated with inflammatory bowel disease, especially UC. However, only around 4% of people with inflammatory bowel disease develop PSC!

To remember the characteristics of ulcerative colitis, think “ULCCCERS” for Ulcers, Large intestine, Continuous/Colon cancer/Crypt abscesses, Extends proximally, Red diarrhea, Sclerosing cholangitis

Course of the disease

  • Chronic intermittent
    • Most common course
    • Exacerbation is followed by complete remission.
  • Chronic continuous
    • Complete remission does not occur.
    • Severity of the disease varies.
  • Acute fulminant

References:[12][13][5][14]

Subtypes and variants

Backwash ileitis

  • Definition: inflammation of the terminal ileum in the context of ulcerative colitis
  • Epidemiology: affects approx. 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 ulcerative colitis from Crohn disease

References:[15]

Diagnostics

Laboratory tests

Endoscopy

Endoscopy (e.g., colonoscopy) with histological examination is considered the best test to definitively diagnose UC.

  • Typical findings: see “Gross pathology” below
  • Pattern of disease involvement [3]
    • Proctosigmoiditis: limited to the rectum, with possible sigmoid involvement
    • Left-sided colitis: extends distally to the splenic flexure
    • Extensive colitis: extends beyond the splenic flexure
  • Recommendations [3]
    • Evaluate the ileum to rule out Crohn disease
    • Stepwise biopsy (for findings, see "Pathology" below)
    • Colonoscopy is contraindicated in patients with acute flare because of the high risk of perforation but should be performed once symptoms improve.
      • Sigmoidoscopy may be considered as an alternative.

Observe caution in taking biopsies from patients with severe disease, as the risk of perforation is high.

Imaging [18][3]

Imaging studies may serve as useful adjunct diagnostic procedures for UC, particularly when it comes to detecting complications.

  • Radiography
    • Plain radiography
      • Typically normal in mild to moderate disease
      • Findings
        • Loss of colonic haustra (“lead pipe” appearance) may be seen in severe cases
        • Massive distention in cases of toxic megacolon
        • Pneumoperitoneum in cases of perforation
    • Barium enema radiography
      • Able to detect very early changes
      • Findings
        • Granular appearance of the mucosa
        • Deep ulcerations
        • Loss of haustra
        • Pseudopolyps that appear as filling defects
  • CT: Detection of bowel wall thickening is possible in severe disease.
  • MRI: can be helpful in assessing disease severity and extent of bowel wall involvement
  • Ultrasound: can detect bowel wall thickening (manifests with absent hyperechoic reflection from the lumen)

References:[16][17][5][14]

Pathology

Gross pathology

  • Early stages
    • Inflamed, erythematous, edematous mucosa
    • Friable mucosa; with bleeding on contact with endoscope
    • Fibrin-covered ulcers
    • Small mucosal ulcerations
    • Loss of superficial vascular pattern
  • Chronic disease
    • Loss of mucosal folds
    • Loss of haustra
    • Strictures
    • Pseudopolyps
      • Raised areas of normal mucosal tissue that result from repeated cycles of ulceration and healing
      • Ulceration → formation of granulation tissue → deposition of granulation tissue → epithelization
      • Morphologically resemble polyps but do not undergo neoplastic transformation
      • Found in advanced disease

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.

Histological findings

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

References:[5]

Differential diagnoses

Microscopic colitis

The differential diagnoses listed here are not exhaustive.

Treatment

Initially, UC is treated conservatively with drugs to induce and maintain disease remission. Curative proctocolectomy is generally indicated if medical therapy fails or complications arise.

General management

  • Rehydration
  • Supplementation of nutritional deficiencies (e.g., iron)
  • Supplementation of nutrition: severe cases may warrant consideration of a feeding tube or parenteral nutrition.

Medical therapy [3]

Supportive care

Recommended medical therapy by the severity of disease [3]

Mild disease

Moderate disease

Severe or refractory disease

Systemic corticosteroids should only be used for the treatment of an active flare and are not recommended as a maintenance medication for ulcerative colitis!

Surgical intervention

  • Goal
  • Indications
    • Emergent: Acute complications despite adequate conservative management (e.g., toxic megacolon, perforation, sepsis, uncontrolled bleeding, etc.)
    • Elective: epithelial dysplasia, severe relapses, long-term dependence on steroids, impairment of the patient's general condition
  • Procedure: 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 (reservoir for feces) and thus a continence-conserving connection between the ileum and anus.
  • Complications
    • Anastomotic leak
    • Pouchitis (↑ stool frequency, malaise, and possibly incontinence caused by bacterial overgrowth)

In contrast to Crohn disease, ulcerative colitis can be cured surgically (proctocolectomy)!

Definition of remission

  • Clinical
    • No diarrhea
    • No (visible) blood in stools
    • No discomfort caused by intestinal or extraintestinal manifestations
  • Endoscopic: no tissue damage caused by inflammation

References:[5][19][20][21]

Complications

References:[18][22]

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

Prognosis

On average, the life expectancy of patients with UC is normal. [5]