Colitis

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"ulcerative colitis" AND "management"

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Colitis

Colitis refers to inflammation of the colon. It is not a single disease but an umbrella term encompassing multiple distinct conditions with different causes, pathology, and management.

Classification: Types of Colitis

The major types, per Sleisenger & Fordtran's:

Category	Examples
Inflammatory Bowel Disease (IBD)	Ulcerative colitis, Crohn's colitis, IBD-unclassified
Infectious	Clostridioides difficile, Campylobacter, Salmonella, Shigella, E. coli O157, CMV, Entamoeba histolytica, TB
Ischemic	Reversible, non-gangrenous, ischemic stricture, toxic megacolon
Microscopic	Collagenous colitis, lymphocytic colitis
Drug-induced	NSAIDs, gold, checkpoint inhibitors (anti-CTLA4, anti-PD1)
Radiation	Post-pelvic radiotherapy
Diversion	Following bowel diversion surgery
Other	Eosinophilic colitis, Behcet disease, GVHD, sarcoidosis, SCAD

1. Ulcerative Colitis (UC)

Definition and Epidemiology

UC is a chronic idiopathic inflammatory disease of the colon, most commonly affecting adults in their 3rd to 4th decades of life. It is characterized by a lifelong relapsing-remitting course. Incidence has stabilized in Western Europe/North America but continues to rise in Eastern Europe, Asia, and the developing world.

Yamada's Textbook of Gastroenterology, 7th ed.

Pathogenesis

Multifactorial - involving genetic predisposition, environmental factors, epithelial barrier defects, dysregulated immune responses, and microbiological factors. Infectious enteritis may trigger mucosal immune activation in susceptible individuals. Unlike Crohn's disease, UC onset can be associated with smoking cessation (smoking provides partial symptomatic relief).

Distribution (Montreal Classification)

UC phenotypes by Montreal Classification

Inflammation begins in the rectum and extends proximally in a continuous, circumferential fashion:

Proctitis (30-60% of patients): rectal bleeding, tenesmus, urgency
Left-sided colitis (16-45%): above plus diarrhea, abdominal cramping
Extensive/pancolitis (15-35%): all of the above plus constitutional symptoms, fatigue, fever

At diagnosis: left-sided colitis ~40%, extensive colitis ~30%, proctitis ~30%.

Symptoms

Bloody diarrhea with mucopurulent discharge (most consistent feature)
Rectal urgency, tenesmus, sensation of incomplete evacuation
Colicky abdominal pain preceding bowel movements
Up to 10% have paradoxical constipation (especially proctitis/left-sided)
Severe/fulminant: fever, night sweats, weight loss

Extraintestinal Manifestations (7-17% of patients)

Arthritis (most common): peripheral pauciarticular (follows bowel activity) or axial spondyloarthropathy (independent of bowel activity; can be progressive)
Dermatological: pyoderma gangrenosum (1-5%), erythema nodosum
Ocular: uveitis, episcleritis
Hepatobiliary: primary sclerosing cholangitis

Gross and Microscopic Pathology

Gross pathology of ulcerative colitis - total colectomy, inflammatory polyps, mucosal bridges

Histopathology of UC: crypt abscesses, pseudopyloric metaplasia, mucosal-limited disease

Key features:

Diffuse, superficial (mucosal only) inflammation - does not extend beyond mucosa (key distinction from Crohn's)
Red, granular mucosa; crypt abscesses; loss of goblet cells
Crypt architectural distortion in chronic disease
Inflammatory polyps (pseudopolyps); mucosal bridges
Backwash ileitis in extensive colitis (distal ileum involved superficially)
Robbins, Cotran & Kumar Pathologic Basis of Disease

Diagnosis

Colonoscopy with biopsy - contiguous inflammation from rectum; granularity, friability, pseudopolyps
Histology confirms mucosal-limited disease
Stool cultures to exclude infection
Calprotectin (raised), CRP, ESR, CBC

Endoscopic distinction from Crohn's (Yamada's):

Feature	UC	Crohn's
Distribution	Contiguous (+++), circumferential	Patchy (+)
Rectal involvement	+++	+
Cobblestoning	+	+++
Ileal involvement	- (backwash only)	++++
Deep/linear ulcers	+	+++

Disease Activity (Truelove-Witts / Mayo Score)

	Mild	Moderate-severe	Fulminant
Stools/day	<4	>6	>10
Blood in stools	Small	Obvious	Continuous
Systemic signs	None	Present	Severe

Management

Step-up approach (conventional) or risk-stratified (modern):

Mild-moderate:

5-ASA (mesalamine/sulfasalazine) - first-line for mild-moderate UC and maintenance. Rectal formulations (suppositories, enemas) for proctitis/left-sided; oral for extensive. Sulfasalazine is linked by azo-bond to sulfapyridine; the 5-ASA component acts locally in the colon.
Combined oral + topical 5-ASA is superior to either alone

Moderate-severe:

Corticosteroids (prednisolone, budesonide MMX) for induction - not for maintenance
Biologics:
- Anti-TNF: infliximab, adalimumab, golimumab
- Anti-integrin: vedolizumab (gut-selective)
- Anti-IL-12/23: ustekinumab
JAK inhibitors: tofacitinib, upadacitinib, filgotinib (oral; small molecule)
Thiopurines (azathioprine, 6-MP): maintenance; often combined with biologics

Acute severe UC:

IV hydrocortisone; if refractory: rescue therapy with infliximab or ciclosporin
Colectomy if no response within 3-5 days ("rescue" threshold)

Surgery (~15% of patients): Proctocolectomy with ileal pouch-anal anastomosis (IPAA) - curative for intestinal disease; extraintestinal manifestations may persist. Historically up to 30% needed colectomy within 3 years, but this has fallen sharply with biologics.

A 2024 AGA network meta-analysis (PMID 39425738) compared advanced therapies for moderate-to-severe UC, providing updated evidence on relative efficacy ranking for biologic and small molecule agents.

Colorectal Cancer Risk

Risk begins after 8-10 years of extensive colitis. Surveillance colonoscopy is recommended. Colitis-associated dysplasia is flat and may be invisible, requiring systematic biopsies. Risk scales with extent and duration of disease.

2. Crohn's Colitis

Crohn's disease can affect any part of the GI tract from mouth to anus. When it involves the colon, it differs from UC in:

Skip lesions (patchy, discontinuous)
Transmural inflammation (vs. mucosal only in UC)
Cobblestone mucosa from linear ulcers + submucosal edema
Fistulae and abscesses (transmural fissures)
Non-caseating granulomas (~35% of cases) - hallmark
Creeping fat on serosa
Rectal sparing possible; ileal involvement frequent
Aphthous ulcers are the earliest lesion
Submucosal fibrosis and muscular hypertrophy cause strictures
Robbins, Cotran & Kumar Pathologic Basis of Disease

3. Microscopic Colitis

Encompasses collagenous colitis and lymphocytic colitis - considered variants of the same condition.

Key features:

Chronic, watery, non-bloody diarrhea
Normal colonoscopy (diagnosis requires biopsy)
Primarily affects middle-aged and older women
Associated with NSAIDs, PPIs, SSRIs, ranitidine

Histology:

Collagenous colitis: thickened subepithelial collagen band (>10 µm) + surface epithelial damage + lamina propria lymphocytosis
Lymphocytic colitis: increased intraepithelial lymphocytes (>20 per 100 epithelial cells) + lamina propria lymphocytosis; crypt architecture preserved
Robbins, Cotran & Kumar Pathologic Basis of Disease

Treatment: Stop offending drugs; budesonide (most effective); bismuth subsalicylate; cholestyramine

4. Ischemic Colitis

Results from reduced blood flow to the colon (usually the splenic flexure or rectosigmoid - "watershed zones")
Most common in the elderly with atherosclerosis; also post-aortic surgery, vasopressors, cocaine
Presents with sudden-onset left-sided abdominal pain, bloody diarrhea
Most cases are non-gangrenous and self-limiting
CT shows thumbprinting (submucosal edema); colonoscopy shows segmental, non-specific inflammation
Management: supportive (bowel rest, fluids); surgery for gangrene or stricture

5. Infectious Colitis

Major pathogens:

C. difficile: post-antibiotic, pseudomembranous colitis; toxin-mediated; treat with fidaxomicin/vancomycin
Campylobacter, Salmonella, Shigella: acute dysentery
E. coli O157:H7: hemolytic uremic syndrome risk; do NOT use antibiotics
Entamoeba histolytica: flask-shaped ulcers; treat with metronidazole + luminal agent
CMV colitis: in immunocompromised; linear punched-out ulcers; treat with ganciclovir

6. Indeterminate Colitis

About 10% of IBD cases cannot be clearly classified as UC or Crohn's. No small bowel involvement; continuous colonic pattern like UC but with some Crohn's features (patchy histology, perianal lesions, family history). Medical management overlaps sufficiently with both conditions to allow effective treatment.

Robbins, Cotran & Kumar Pathologic Basis of Disease

Summary Comparison: UC vs. Crohn's Colitis

Feature	Ulcerative Colitis	Crohn's Colitis
Location	Colon only (rectum always)	Any GI segment; may spare rectum
Pattern	Continuous, circumferential	Skip lesions, segmental
Depth	Mucosal only	Transmural
Granulomas	No	Yes (35%)
Fistulae/abscesses	Rare	Common
Strictures	Rare	Common
Smoking	Protective	Risk factor
Surgery	Colectomy = cure	Recurrence post-surgery
CRC risk	Yes (long-standing)	Yes (lower than UC)

Sources: Yamada's Textbook of Gastroenterology, 7th ed. | Sleisenger & Fordtran's Gastrointestinal and Liver Disease | Robbins, Cotran & Kumar Pathologic Basis of Disease | Fischer's Mastery of Surgery, 8th ed.

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