• Clinical science

Ulcerative colitis

Abstract

Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) with chronic mucosal inflammation of the colon and cecum. The main symptoms are bloody diarrhea, abdominal pain, and fever. Laboratory findings show elevated inflammatory markers and autoantibodies (pANCA). The diagnosis is confirmed through a colonoscopy with biopsies showing abnormal colonic mucosa and a characteristic histopathology. Mild to moderate episodes are primarily treated with aminosalicylic acid derivatives (5-ASA derivatives), severe episodes with corticosteroids and immunosuppressants. In the case of distal colitis, some drugs may be administered topically (e.g., via enema), whereas extensive 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 colonoscopy.

Epidemiology

  • Incidence: approx. 10–12 cases per 100,000 adults
  • Peak incidence: 15–35 years ; another smaller peak may be observed in individuals > 55 years
  • Sex: Prevalence is slightly higher in women
  • More common among Caucasian populations and Ashkenazi Jews than in African-American or Hispanic populations

References:[1][2][3]

Epidemiological data refers to the US, unless otherwise specified.

Classification

Truelove and Witts' severity index

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

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

  • The exact pathophysiology is unknown. Studies suggest that immune reactions play a role
  • Pattern of involvement: ascending inflammation beginning in the rectum and spreading continuously throughout the colon
  • Risk factors
    • Genetic predisposition (e.g., HLA-B27 association)
    • NSAIDs may exacerbate UC
  • Nicotine consumption has a protective effect

References:[1]

Clinical features

Intestinal symptoms

  • Bloody diarrhea with mucus
  • 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!

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:[4][5][1][6]

Subtypes and variants

Backwash ileitis

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

References:[7]

Diagnostics

Laboratory tests

Colonoscopy

  • Best test
  • Typical findings
    • Inflamed, reddened mucosa
    • Bleeding on contact with endoscope
    • Fibrin-covered ulcers
    • In advanced disease: formation of pseudopolyps on remaining islands of intact mucosa
  • Pattern of involvement
    • Proctosigmoiditis
    • Left-sided colitis
    • Extended colitis
    • Pancolitis
  • Recommendations
    • Evaluate the ileum to rule out Crohn disease
    • Stepwise biopsy (for findings, see "Pathology" below)
    • Observe caution in taking biopsies from patients with severe disease, as the risk of perforation is higher

Imaging

Imaging studies are valuable adjunct diagnostic procedures for UC, particularly when it comes to detecting complications. All procedures have a similar sensitivity and specificity.

  • Radiography
    • Plain radiography
      • Loss of colonic haustra ('lead pipe” appearance)
      • Massive distention with possible toxic megacolon
      • Pneumoperitoneum in cases of perforation
    • Barium enema radiography
      • Ability to detect very early changes: granular appearance of the mucosa
      • Deep ulcerations
      • Pseudopolyps that appear as filling defects
  • CT
    • Useful in differentiating between ulcerative colitis and Crohn disease if radiography is inconclusive
    • Assessing extent and localization of involvement of the intestinal wall
  • MRI
    • Differentiation between ulcerative colitis and Crohn disease
    • Assessment of severity of the disease and bowel wall involvement: depiction of all layers of the colonic wall possible
  • Ultrasound
    • Thickened bowel walls
    • Investigation of possible pathologies caused by PSC

References:[8][9][1][6]

Pathology

Gross pathology

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.

  • Early stages
    • Swelling of the mucosa caused by edema
    • Spotty intestinal bleeding, bleeding on contact
    • Loss of vascular pattern
    • Small mucosal ulcerations
  • Chronic disease
    • Loss of mucosal folds
    • Loss of haustra ('lead pipe' appearance)
    • Pseudopolyps

Histological findings

References:[1]

Differential diagnoses

Microscopic colitis

The differential diagnoses listed here are not exhaustive.

Treatment

UC is initially conservatively treated with drugs to induce and maintain disease remission. If medical therapy fails or complications arise, curative proctocolectomy is generally indicated.

General management

  • Rehydration
  • Supplementation in the case of deficiencies (e.g., iron)
  • In the case of a severe episode, consider a feeding tube or parenteral nutrition.
  • Physical therapy in the case of arthritis

Medical therapy

Therapeutic goal Drug
Symptomatic

Acute episode

 Mild disease
  • If 5-ASA is not tolerated: topical steroids (budesonide) as suppositories
Moderate disease
  • 1st-line treatment: oral and topical 5-ASAs
Severe disease
  • 1st-line treatment: high‑dose oral and topical 5-ASAs and oral corticosteroids
Steroid-refractory disease

Maintenance therapy

  • 1st-line treatment
    • Mild disease: oral or rectal 5-ASA
    • Moderate to severe disease: Combination of oral and rectal 5-ASA
    • Intolerance to 5-ASAs: probiotics (E. coli strain Nissle 1917)
  • Alternatives

Surgical intervention

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

References:[1][10][11][12]

Complications

References:[13][14]

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

Prognosis

  • On average, the life expectancy of patients with UC is normal.[1]