Ulcerative Colitis

Ulcerative colitis (UC) is an idiopathic inflammatory condition that involves the mucosal surface of the colon. It is a type of inflammatory bowel disease (IBD), along with Crohn’s disease (CD). The rectum is always involved, and inflammation may extend proximally through the colon. Ulcerative colitis causes diffuse friability, erosions with bleeding, and loss of haustra, which are visible on endoscopy. Patients typically present with bloody diarrhea, colicky abdominal pain, tenesmus, and fecal urgency. Diagnosis is established via endoscopy with biopsy and by ruling out other causes of bloody diarrhea. Management is primarily through topical mesalamine, 6-mercaptopurine, or colectomy for severe cases. Complications include fulminant colitis, toxic megacolon, intestinal perforation, and increased risk of colorectal cancer.

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Epidemiology and Pathophysiology

Epidemiology

  • Incidence: bimodal distribution
    • 15–35 years (slightly older average than in Crohn’s disease [CD])
    • Smaller peak occurs between 50 and 70 years of age
  • Men > women
  • Disease risk is lower in smokers.
  • Most common among whites and eastern European (Ashkenazi) Jews
  • Incidence: 9–20 cases per 100,000 persons per year

Risk factors

An increased risk of developing ulcerative colitis (UC) may be associated with the following:

  • Genetics: HLA-B27 (encodes genes for the major histocompatibility complex [MHC])
  • Family history of irritable bowel syndrome (IBS) 
    • Twin concordance rate is 10%15%
    • First-degree relatives have a 4 times higher risk of developing UC.
  • Increased dietary fat intake
  • Nonsteroidal anti-inflammatory drug (NSAID) use
  • Psychological stress and intestinal infections may trigger disease onset.

Pathophysiology

The exact pathophysiology is unknown, but is likely associated with a combination of dysregulation of the intestinal epithelium and the immune system.

  1. Defects in the lamina propria and epithelial barrier of the gastrointestinal (GI) tract allow for more pathogens to penetrate → recruitment and activation of cytotoxic cells
  2. As well, pANCA (perinuclear antineutrophil cytoplasmic antibodies) are thought to recognize nonpathogenic bacteria and epithelial cells as pathogens.
  3. Excessive release of pro-inflammatory cytokines, especially from Th2 cells, which seem to target epithelial cells → intestinal inflammation
  4. Causes intestinal epithelium damage including ulcerations, erosions, and necrosis

The inflammation invariably involves the rectum and may extend proximally through the colon in a continuous fashion.

  • Skip lesions are not seen.
  • The small intestine is unaffected, except in severe cases of pancolitis.
  • Pancolitis: affects the entire colon
  • Ulcerative proctitis or ulcerative proctosigmoiditis: effects limited to the rectum or rectosigmoid

Clinical Presentation

The typical presentation for UC is a relapsing disorder that includes the following:

  • GI manifestations:
    • Bloody diarrhea that lasts from weeks to months (with or without mucus)
    • Fecal urgency and/or incontinence
    • Tenesmus
    • Colicky lower abdominal pain that is temporarily relieved by defecation
  • General manifestations:
    • Signs of anemia: fatigue, pallor, dyspnea, palpitations
    • Weight loss
    • Low-grade fever
  • Extraintestinal manifestations (in general, less common than in CD):
    • Primary sclerosing cholangitis (much more common in UC than CD)
    • Pyoderma gangrenosum: rapidly progressive painful, red papules → pustules → deep ulcers with central necrosis
    • Erythema nodosum: painful, red nodules that usually appear on the shins
    • Eye inflammation (episcleritis, uveitis)
    • Oral ulcerations (aphthous stomatitis)
    • Peripheral arthritis, ankylosing spondylitis, or osteoporosis
    • Aphthous ulcers
    • Deep venous thrombosis and/or pulmonary embolism
Table: Truelove and Witts’ severity index for ulcerative colitis
Ulcerative colitis is classified based on severity.
FeaturesMildModerateSevere
Stool frequency per day< 44–6> 6
Symptoms
  • Frank blood
  • Intermittently
  • Mild cramping
  • Mild-to-moderate
  • Frequently
  • Frank blood
  • Continuously
  • Severe cramping
Systemic toxicityNormal findings:
  • HR < 90
  • Afebrile
  • Hg > 11.5g/dL
Laboratory abnormalities:
  • HR < 90
  • Afebrile
  • Anemia (Hg 10.5–11.5g/dL)
Laboratory abnormalities:
  • HR > 90
  • Fever
  • Anemia (Hg < 10.5g/dL)
  • +/- rapid weight loss
Erythrocyte sedimentation rate (ESR)< 2020–30> 30

Diagnosis

Laboratory studies:

  • Complete blood count will show anemia, leukocytosis, and thrombocytosis (occasionally).
  • Complete metabolic panel to check if chronic diarrhea has caused electrolyte imbalance 
  • ↑ ESR

Stool studies: may be used to exclude other causes of inflammatory diarrhea (e.g., infection)

Abdominal imaging:

  • X-ray, computed tomography (CT) and/or magnetic resonance imaging (MRI):
    • Nonspecific findings: thickened bowel wall, colon dilation
    • Barium enema: micro-ulcerations, loss of haustra with “lead pipe” appearance, and granular mucosa
  • Colonoscopy with biopsy:
    • Helps to determine the extent of disease
    • Contraindicated during an acute exacerbation due to risk of intestinal perforation
    • Macroscopic findings:
      • Diffuse and continuous mucosal inflammation always involving the rectum
      • Neutrophil infiltration limited to the mucosa and submucosa
      • Friable mucosa
      • Loss of haustra, giving the GI tract a “lead pipe” appearance
      • Pseudopolyps: raised areas caused by recurrent ulceration, healing, and scarring of the mucosa
    • Microscopic findings:
      • Crypt abscesses
      • Broad-based ulcers that don’t penetrate the muscularis propria 
      • No granuloma formation
      • GI bleeding
      • Epithelial metaplasia
      • Submucosal fibrosis and mucosal atrophy

Management

Medical therapies for UC depend on the severity of the disease. The 2 main therapeutic goals are:

  1. Terminating an acute, symptomatic attack
  2. Preventing recurrent attacks

General therapeutic measures

  • Preventative care: colonoscopy to screen for colorectal cancer (higher risk in patients with UC)
    • 810 years after initial diagnosis 
    • Every 12 years thereafter
  • Targeted medical therapy:
    • Corticosteroids
      • For acute disease flare-ups
      • Duration is limited due to complications of long-term use
    • 5-ASA agents (topical or oral mesalamine, sulfasalazine)
    • Immunomodulators (6-mercaptopurine)
    • Anti-TNF therapies (infliximab, adalimumab)
    • Antidiarrheal agents
  • Surgical intervention:
    • Colectomy
      • Considered curative
      • Reserved for severe diseases, ineffective medical therapy, refractory toxic megacolon, or biopsy-proven malignancy
    • Required in case of complications
Colectomy and ileal pouch-anal anastomosis

Colectomy and ileal pouch-anal anastomosis

Image by Lecturio.

Management by severity

  • Mild-to-moderate disease: 
    • Topical mesalamine (via suppository or enema) for acute flares
    • If no response in 4 weeks, consider adding a topical/oral corticosteroid or an oral 5-ASA agent
  • Moderate-to-severe disease: 
    • Oral corticosteroid and 5-ASA agent for acute flares
    • If no response, consider adding anti-TNF therapies
    • Patients who achieve remission are maintained on oral mesalamine +/- an anti-TNF agent.
  • Severe-fulminant or refractory disease: 
    • Keep nothing by mouth (NPO) for 2448 hours, administer IV fluids, monitor electrolytes, and transfuse for anemia, as needed.
    • IV corticosteroids
    • For patients who do not respond to corticosteroids within 47 days, further management includes infliximab/cyclosporine.
    • In the case of toxic megacolon, broad-spectrum antibiotics may be added to reduce septic complications.

Complications

  • Fulminant colitis
    • Caused by colonic mucosal inflammation
    • Presents with > 10 bloody stools per day, abdominal pain and distension, and systemic symptoms of shock
    • Increases risk of developing toxic megacolon
  • Toxic megacolon
    • Involves inflammation extending beyond the mucosal layers to the muscular layers of the colon
    • Characterized by:
      • Colonic dilation of > 6 cm on plain film 
      • Signs of severe toxicity
    • Treatment involves nasogastric suction, NPO status, antibiotics, and corticosteroids.
  • Gastrointestinal bleeding: 
    • Can occur acutely during a flare or chronically
    • May lead to anemia
  • Intestinal perforation: usually caused by performing a colonoscopy during an acute flare
  • Large bowel obstruction: due to colonic stenosis produced by recurrent episodes of ulceration, healing, and scarring of the mucosa
  • Increased risk of colorectal cancer

Differential Diagnosis

The following conditions are differential diagnoses for ulcerative colitis:

  • Irritable bowel syndrome: presents with recurrent abdominal pain; however, IBS requires 2 or more of the following: abdominal pain that improves with defecation, change in stool frequency, or change in stool consistency (diarrhea-predominant, constipation-predominant, or mixed). Diagnosis is clinical, and the condition is not associated with structural abnormalities. 
  • Infectious colitis: presents with acute-onset fever and diarrhea. Common causative enteric pathogens include Shigella, Salmonella, Campylobacter, E. coli O157:H7, Yersinia, and Clostridioides difficile. These infections may be self-limiting or require antibiotic treatment and can be confirmed with stool cultures and polymerase chain reaction (PCR).
  • Radiation colitis: also presents with bloody diarrhea, but is usually preceded by pelvic irradiation (months/years ago). Histologic findings suggestive of radiation colitis include eosinophilic infiltrates, which can help to differentiate it from UC.
  • Diverticular disease: also presents with bleeding per rectum, but can be differentiated from IBD by the presence of characteristic diverticula on colonoscopy.
  • Crohn’s disease: presents with intermittent, crampy abdominal pain, and non-bloody diarrhea. This condition causes patchy, transmural inflammation that can affect any area of the GI tract; however, the terminal ileum and proximal colon are most commonly involved. Intestinal biopsy shows noncaseating granulomas.
    One of the most effective ways to learn about ulcerative colitis is to compare and contrast it with Crohn’s disease, the other form of IBD. The table below provides a comparison:
Table: Inflammatory bowel disease
Crohn’s diseaseUlcerative colitis
Pattern of involvementSkip lesions in any part of the GI tract:
  • Most commonly the terminal ileum and proximal colon
  • Rectal sparing
Continuous lesions:
  • More localized to the colon
  • Rectal involvement
GI symptomsUsually non-bloody diarrhea, may be bloody at timesBloody diarrhea
  • May present with mucus at times
  • Stool frequency: UC >> CD
Extraintestinal manifestationsCholelithiasis and nephrolithiasis with calcium oxalate stonesPrimary sclerosing cholangitis
  • Erythema nodosum
  • Pyoderma gangrenosum
  • Uveitis
  • Aphthous ulcers
  • Arthritis
Complications
  • Fistulas
  • Malabsorption or short bowel syndrome
  • Perianal fissures and fistulas
  • Toxic megacolon
  • Fulminant colitis
  • Gastrointestinal bleeding
  • Intestinal perforation
  • Bowel obstruction
  • Colorectal cancer
Macroscopic findingsTransmural inflammation
  • Cobblestone mucosa
  • Bowel wall thickening (“string sign” on barium swallow study)
Mucosal and submucosal inflammation
  • Friable mucosa
  • Loss of haustra (“lead pipe” appearance on abdominal X-ray)
  • Broad-based ulcers
Microscopic findings
  • Non-caseating granulomas
  • Lymphoid aggregates of lamina propria
  • No granulomas
  • Crypt abscesses and ulcers
  • Epithelial metaplasia
  • Neutrophil infiltration
Treatment
  • Corticosteroids
  • Antibiotics (ciprofloxacin, metronidazole)
  • Immunomodulators (azathioprine)
  • Anti-TNF agents (infliximab, adalimumab)
  • 5-ASA agents (mesalamine)
  • Immunomodulators (6-mercaptopurine)
  • Anti-TNF agents (infliximab)
  • Colectomy

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