Ulcerative Colitis (UC)

Definition and Epidemiology

Ulcerative colitis is a chronic inflammatory bowel disease (IBD) that causes continuous mucosal inflammation confined to the colon and rectum. Unlike Crohn disease, it does not affect the small intestine (though "backwash ileitis" - a spillover effect - can occasionally occur at the terminal ileum and should not be confused with true ileal involvement).

Peak age of onset: 20-40 years, with a smaller second peak beyond the 7th decade
Sex distribution: equal in males and females (F:M ratio ~1:1)
Inflammation starts in the rectum and extends proximally in a continuous pattern - there are no skip lesions (unlike Crohn disease)

Pathology

Gross/Endoscopic findings:

Mild disease: granular, hyperemic, edematous mucosa with loss of the normal mucosal vascular pattern
Moderate disease: friable mucosa that bleeds easily on touch
Severe disease: frank mucosal ulceration extending into the lamina propria
Chronic disease: pseudopolyp formation (from epithelial regeneration after recurrent attacks - a marker of more severe disease), loss of normal colonic fold pattern, colonic shortening and narrowing

Histopathology:

Early/acute: epithelial necrosis, acute inflammatory infiltrate in the lamina propria, cryptitis and crypt abscesses
Chronic: predominant lymphocytic infiltrate and distortion of crypt architecture
Key distinguishing features: crypt distortion, continuous mucosal inflammation from rectum, absence of granulomas, absence of small bowel disease

Inflammation in UC is superficial/mucosal - it does not penetrate transmurally (unlike Crohn disease).

Clinical Features

Symptoms:

Bloody diarrhea (hallmark)
Abdominal pain / tenesmus (feeling of incomplete evacuation)
Weight loss
Fatigue and fever in severe disease

Extraintestinal manifestations:

Inflammatory arthropathies (most common)
Primary sclerosing cholangitis (most common hepatobiliary manifestation)
Skin: erythema nodosum, pyoderma gangrenosum
Eyes: uveitis, episcleritis
Bone involvement

UC vs Crohn Disease - Key Differences

Feature	Ulcerative Colitis	Crohn Disease
Sites involved	Colon only	Esophagus to anus
Skip lesions	No	Yes
Transmural inflammation	No	Yes
Ulceration pattern	Continuous	Usually discrete
Fistulas	No	Yes
Strictures	No	Yes
Perianal disease	No	Yes

Diagnosis

Endoscopy is the gold standard - findings start in the rectum and extend proximally in a continuous pattern.

Serologic markers (supportive, not diagnostic):

pANCA (perinuclear antineutrophil cytoplasmic antibodies): positive in ~55% of UC patients
ASCA (anti-Saccharomyces cerevisiae antibodies): present in <15% of UC patients (more specific for Crohn)
ASCA-positive + pANCA-negative pattern is 93% specific for Crohn disease

Lab findings:

Anemia (from chronic disease or blood loss)
Elevated ESR and CRP (nonspecific markers of active disease)
Elevated fecal calprotectin in active disease
Hypoalbuminemia in active/severe disease

Radiology: CT and MRI enterography are preferred over barium studies; useful to assess complications.

Treatment

Mild to Moderate Disease

5-aminosalicylates (5-ASA) - first-line agents for induction and maintenance of remission
- Proctitis: mesalazine suppositories (≥500 mg/day PR)
- Proctosigmoiditis: mesalazine enemas (can reach the splenic flexure)
- Left-sided or extensive colitis: combined topical + oral mesalazine (≥3 g/day PO) - superior to oral alone
- Sulfasalazine is an alternative (3-6 g/day)
Corticosteroids if 5-ASA fails:
- Budesonide (colonic release, rectal enema, or foam formulations) limits systemic steroid exposure
- Topical hydrocortisone (suppository, enema, or foam) for mild-moderate proctitis/proctosigmoiditis
- Oral prednisone 0.5-1 mg/kg/day for left-sided or pancolitis unresponsive to mesalazine; taper once symptoms improve
Immunomodulators (azathioprine 2 mg/kg/day PO) if steroids fail

Moderate to Severe Disease

IV corticosteroids - mainstay of inpatient management for severe flares
Infliximab (anti-TNF-α) - rescue therapy; preferred over cyclosporine in most centers for ease of use and fewer side effects
Cyclosporine (2-4 mg/kg IV/day) - alternative rescue therapy but significant toxicity (myelosuppression, nephrotoxicity, hepatotoxicity, electrolyte disturbances, risk of opportunistic infections including Pneumocystis pneumonia)
Vedolizumab - approved for moderate-severe UC resistant to immunomodulators, steroids, or anti-TNF therapy
Antibiotics should be considered in severe disease or with immunosuppressive drug use
Avoid anticholinergics, antidiarrheals, narcotics, and procedures (colonoscopy, barium enema) that increase risk of toxic megacolon
Early surgical consultation recommended for hospitalized patients

Maintenance of Remission

5-ASA agents are the mainstay of maintenance
Azathioprine for patients with more aggressive disease

Complications

Toxic Megacolon

A feared, life-threatening complication. Involves pathologic dilation of the colon from inflammation of smooth muscle layers, leading to muscle paralysis, dilation, and potentially perforation.

Triggers: anticholinergics, antimotility agents, narcotics, antidepressants. Signs: >10 stools/day, continuous bleeding, abdominal distention, fever, severe systemic toxicity.

Toxic Megacolon Secondary to Ulcerative Colitis - plain abdominal radiograph showing massively dilated colon with pseudopolyps visible as smooth indentations along the colonic margin

Toxic megacolon secondary to UC. The smooth indentations along the colon margin represent pseudopolyps. (Rosen's Emergency Medicine)

Colorectal Cancer Risk

Long-standing UC significantly increases colorectal cancer risk - this can be an indication for colectomy.

Surgery

Colectomy is curative for UC (unlike Crohn disease, where surgery is not curative).

Indications: disease refractory to medical management, toxic megacolon, massive bleeding, cancer
~3% require colectomy at 1 year, ~7% at 5 years, ~10% at 10 years (better medical therapy has reduced this)
Standard operation: proctocolectomy with Brooke ileostomy
Anal-sparing option: ileal pouch-anal anastomosis (IPAA) - 30 cm of terminal ileum fashioned into a J-pouch and pulled through the anal canal; preserves anal function
Complication of IPAA: pouchitis (inflammation of the ileal pouch), treated with metronidazole 500 mg TID or ciprofloxacin 500 mg BID for 2 weeks

Sources: Goldman-Cecil Medicine (26th ed.), Rosen's Emergency Medicine, Katzung's Basic & Clinical Pharmacology (16th ed.)

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