Ulcerative colitis

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.

• The exact pathophysiology is unknown. Studies suggest that immune reactions play a role
  • Autoantibodies (pANCA) against cells of the intestinal epithelium
  • Activation of lymphatic cells in bowel walls (T-cells, B-cells, plasma cells) → enhanced immune reaction and cytotoxic effect on colonic epithelium → inflammation with local tissue damage (ulcerations, erosions, necrosis) in the submucosa and mucosa
  • Th2 cells mediated
• 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]

Intestinal symptoms

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

Extraintestinal symptoms

• Uveitis , iritis, episcleritis
• Primary sclerosing cholangitis (PSC): up to 90% of all patients affected by PSC may also be diagnosed with UC
• Joints: arthritis, ankylosing spondylitis, sacroiliitis
• Skin manifestations: erythema nodosum, pyoderma gangrenosum, pyostomatitis vegetans (multiple aphthae and pustules of the oral mucosa)
• Episcleritis
• Aphtous stomatitis
• Fatigue
• Fever
• In children/adolescents: growth retardation and delayed puberty

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
  • Sudden onset
  • Severe diarrhea, dehydration, shock

References:^[4][5][1][6]

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]

Laboratory tests

• Blood
  • ↑ ESR, ↑ CRP, leukocytosis; , thrombocytosis in some cases
  • Anemia
  • ↑ Perinuclear ANCA (pANCA); : medium sensitivity but high specificity
  • In case of PSC: elevated gamma-glutamyl transferase
• Stool analysis
  • Test for bacteria to rule out other causes
  • Calprotectin and lactoferrin are indicators of mucosal inflammation

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]

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

• Early stages
  • Granulocyte (neutrophils) infiltration: limited to mucosa and submucosa
  • Crypt abscesses
• Chronic disease
  • Lymphocyte infiltration
  • Mucosal atrophy
  • Altered crypt architecture
    • Branching of crypts
    • Irregularities in size and shape
  • Epithelial dysplasia

References:^[1]

• Crohn disease, see Differential diagnostic considerations: Crohn disease and ulcerative colitis
• Exudative‑inflammatory diarrhea
• Infectious colitis (bacterial diarrhea)
• Diverticular disease
• Appendicitis
• Ischemic colitis
• Other infectious or noninfectious causes of diarrhea
• Radiation colitis

Microscopic colitis

• Forms: collagenous colitis and lymphocytic colitis
• Etiology: unknown
• Clinical findings
  • Chronic, non-bloody, watery diarrhea for > 4 weeks
  • Weight loss
  • Abdominal pain
• Pathological findings: In histological tests, tissue changes may be seen in the colon, despite its macroscopic appearance seeming normal during colonoscopy!
  • Collagenous colitis: significant proliferation of collagenous connective tissue
  • Lymphocytic colitis: mainly lymphocytic infiltrates with little/no proliferation of connective tissue
• Treatment
  • Cease nonsteroidal anti‑inflammatory drugs (NSAIDs may be a trigger for disease)
  • Symptomatic therapy (e.g., loperamide for mild diarrhea)
  • Corticosteroids

The differential diagnoses listed here are not exhaustive.

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		Short-term use in mild cases Antidiarrheal agents: loperamide Anticholinergic medication: propantheline, dicyclomine
Acute episode	Mild disease	1st-line treatment: topical 5-aminosalicylic acid derivatives (5-ASAs) administered as suppositories or enemas Mesalamine Sulfasalazine Olsalazine
		If 5-ASA is not tolerated: topical steroids (budesonide) as suppositories
	Moderate disease	1st-line treatment: oral and topical 5-ASAs
		Alternative: 5-ASAs in combination with topical corticosteroids
	Severe disease	1st-line treatment: high‑dose oral and topical 5-ASAs and oral corticosteroids
		If 1st line treatment was insufficient: IV corticosteroids
	Steroid-refractory disease	1st-line treatment: cyclosporine Alternatives Infliximab Tacrolimus Azathioprine
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 Azathioprine or 6-mercaptopurine Infliximab

Surgical intervention

• Goal
  • Curative approach with full recovery
  • Reduce risk of colorectal cancer
• Indications
  • Acute complications despite adequate conservative management (toxic megacolon, perforation, sepsis, uncontrolled bleeding, etc.)
  • Elective surgery in cases of epithelial dysplasia, severe relapses, long-term dependence on steroids, impairment of the patient's general condition
• Methods
  • Proctocolectomy with an ileal pouch-anal anastomosis (IPAA or J pouch)
• 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:^{[1][10][11][12]}

• Gastrointestinal bleeding (both acute and chronic)
• Toxic megacolon
• Perforation → peritonitis
• Fulminant colitis
• ↑ Risk of cancer (see colorectal carcinoma)
  • ↑ Duration and/or extent of disease → ↑ risk
  • Risk is not significantly increased in patients with mild UC
  • Colonoscopies with biopsies every 1–2 years are recommended 8–10 years after the initial diagnosis to screen for colorectal cancer
• Strictures
• Amyloidosis

References:^[13][14]

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