Ulcerative Colitis (UC)
Chronic mucosal inflammation beginning at the rectum and extending proximally in a continuous pattern.
Also known as: UC, ulcerative colitis, ulcerative proctitis, pancolitis
Overview
Chronic, idiopathic, immune-mediated inflammatory bowel disease characterized by continuous mucosal inflammation that begins in the rectum and extends proximally to a variable extent. Inflammation is limited to the mucosa and submucosa.
Epidemiology
Incidence 10-20 per 100,000/year in North America; prevalence ~500 per 100,000 (more common than Crohn). Bimodal peaks at 15-30 and 50-70. Slight male predominance. Higher in Ashkenazi Jews, Northern European descent.
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Risk factors
- Family history (HLA-DR2, multiple susceptibility loci)
- NON-smoking — smoking is PARADOXICALLY PROTECTIVE; cessation can precipitate first flare
- Recent appendectomy is protective
- NSAID use can trigger flares
- Stress and infections may trigger relapses but do not cause UC
Pathophysiology
Aberrant Th2-skewed mucosal immune response to commensal microbiota in genetically susceptible hosts. Epithelial barrier dysfunction, increased permeability, and dysregulated regulatory T cells. Continuous mucosal inflammation starts at the rectum and progresses proximally without skip lesions.
Clinical presentation
Symptoms
- Bloody diarrhea (HALLMARK)
- Tenesmus and urgency
- Lower abdominal cramping, especially LLQ
- Passage of mucus and pus
- Fatigue, weight loss, fever in moderate/severe disease
- Extraintestinal: arthritis (peripheral/axial), uveitis/episcleritis, erythema nodosum, pyoderma gangrenosum, primary sclerosing cholangitis (UC > Crohn association)
Signs / physical exam
- Lower abdominal tenderness
- Pallor (anemia)
- Fever, tachycardia (severe disease)
- Distension and absent bowel sounds suggest toxic megacolon
- Extraintestinal findings as above
Classic findings
Young adult with weeks of bloody diarrhea, tenesmus, and urgency; LLQ tenderness; flexible sigmoidoscopy reveals continuous mucosal inflammation starting at the rectum.
Differential diagnosis
- Crohn colitis — Skip lesions, transmural disease, terminal ileal involvement, fistulas, perianal disease, granulomas
- Infectious colitis (C. diff, Shigella, Salmonella, Campylobacter, E. coli O157, amebiasis, CMV) — Acute onset, exposure, positive stool studies; ALWAYS check at first presentation and each flare
- Ischemic colitis — Older patient, watershed distribution (splenic flexure, rectum spared), thumbprinting on imaging
- Radiation proctitis — Prior pelvic radiation; telangiectatic mucosa
- Microscopic colitis — Chronic watery, NON-bloody diarrhea; macroscopically normal colonoscopy; biopsy diagnostic
- Diverticulitis-associated segmental colitis — Sigmoid; spares rectum; older patient
- Behçet, Sweet syndrome, GVHD — Systemic features; histology
Diagnostic workup
Diagnostic criteria
Composite of clinical (bloody diarrhea, urgency), endoscopic (continuous mucosal erythema, friability, ulceration starting at rectum), and histologic (crypt distortion, basal plasmacytosis, crypt abscesses; NO granulomas) findings, after exclusion of infection. Severity by Truelove and Witts criteria or Mayo Score.
Labs
- CBC (anemia, leukocytosis, thrombocytosis as inflammatory marker)
- CRP, ESR
- BMP, albumin (severity)
- LFTs (screen for PSC — alk phos disproportionately elevated)
- Stool studies — C. diff, culture, ova/parasites; CMV biopsy in steroid-refractory cases
- Fecal calprotectin (>250 supports active inflammation; useful for monitoring)
- Serology: pANCA+/ASCA- pattern supports UC over Crohn
- Pre-biologic screen: hepatitis B/C, HIV, TB (QuantiFERON), varicella titer
Imaging
- Flexible sigmoidoscopy at initial presentation (often sufficient for diagnosis in mild disease and avoids perforation risk in severe disease)
- Full colonoscopy with biopsies once stabilized to assess extent (proctitis, left-sided colitis, extensive/pancolitis)
- Abdominal radiograph if severe disease — assess colonic dilation (toxic megacolon if transverse colon >6 cm)
- CT abdomen/pelvis if abscess or perforation suspected
Diagnostic algorithm
| Truelove-Witts Criterion | Mild | Moderate | Severe |
|---|---|---|---|
| Stools/day | <4 | 4-6 | ≥6 bloody |
| Pulse | <90 | ≤90 | >90 |
| Temperature | <37.5°C | ≤37.8°C | >37.8°C |
| Hemoglobin | >11.5 g/dL | ≥10.5 g/dL | <10.5 g/dL |
| ESR | <20 | ≤30 | >30 |
| CRP | Normal | Mild rise | >30 mg/L |
Treatment
First-line
- Disease extent and severity determine therapy
- Mild-moderate proctitis or distal disease: topical 5-ASA — mesalamine suppository or enema; can add oral 5-ASA
- Mild-moderate extensive disease: oral 5-ASA — mesalamine, sulfasalazine, balsalazide — induction and maintenance
- Moderate-severe disease: oral corticosteroids for induction; transition to steroid-sparing maintenance
- Severe (hospitalized): IV corticosteroids (methylprednisolone 40-60 mg/day or hydrocortisone)
- Maintenance with 5-ASA, immunomodulators, or biologics depending on response
Second-line / adjunct
- Biologics: anti-TNF (infliximab, adalimumab, golimumab), vedolizumab (anti-integrin, gut-selective), ustekinumab (anti-IL-12/23), risankizumab/mirikizumab (anti-IL-23) for moderate-severe disease or steroid-refractory
- JAK inhibitors: tofacitinib, upadacitinib — induction and maintenance
- S1P receptor modulators: ozanimod, etrasimod — newer maintenance options
- Immunomodulators (azathioprine, 6-MP) — maintenance, often in combination with biologics
- Cyclosporine or infliximab — rescue therapy for acute severe UC failing 3-5 days of IV steroids
- Surgery: total proctocolectomy with ileal pouch-anal anastomosis (IPAA) — CURATIVE; for medically refractory disease, dysplasia, cancer, or toxic megacolon
Complications
- Toxic megacolon — colonic dilation >6 cm with systemic toxicity; surgical emergency; avoid antimotility agents, opioids, anticholinergics, barium enema
- Severe hemorrhage
- Perforation
- Colorectal cancer — risk rises 8-10 yr after diagnosis with extensive colitis; surveillance colonoscopy every 1-3 yr
- Primary sclerosing cholangitis (PSC) — accelerates CRC risk further; annual colonoscopy if PSC + UC
- Strictures (less common than Crohn; if present, exclude malignancy)
- Pouchitis after IPAA (treat with ciprofloxacin or metronidazole)
- VTE — risk 3× baseline during flares; prophylax hospitalized patients
PANCE pearls
- Bloody diarrhea + urgency + tenesmus in a young adult = UC until proven otherwise.
- Continuous inflammation starting at the rectum distinguishes UC from Crohn (skip lesions, terminal ileum).
- Smoking and appendectomy are paradoxically PROTECTIVE for UC. Smoking cessation can trigger first flare.
- Acute severe UC (Truelove-Witts): ≥6 bloody stools/day + ≥1 systemic sign (fever, tachycardia, anemia, ESR >30) — admit, IV steroids, day-3 reassessment for rescue therapy.
- Day-3 rule: if CRP >45 and >8 stools/day on IV steroids, rescue with infliximab or cyclosporine; failure → urgent colectomy.
- Toxic megacolon: stop antimotility, opioids, anticholinergics; bowel rest; broad-spectrum antibiotics; serial abdominal exams and films; surgical consultation.
- Colectomy is CURATIVE for colonic UC (unlike Crohn).
- CRC surveillance: chromoendoscopy or high-definition white-light colonoscopy every 1-3 yr starting 8 yr after diagnosis (immediately upon PSC diagnosis).
- Hospitalized IBD patients require VTE prophylaxis even during active bleeding — DVT risk outweighs minor bleeding risk.
References
- ACG 2019 — Rubin DT et al. ACG Clinical Guideline: Ulcerative Colitis in Adults. Am J Gastroenterol 2019;114:384-413
- AGA 2020 — Feuerstein JD et al. AGA Clinical Practice Guidelines on the Management of Moderate to Severe Ulcerative Colitis. Gastroenterology 2020;158:1450-1461
- ECCO 2022 — Raine T et al. ECCO Guidelines on Therapeutics in Ulcerative Colitis: Medical Treatment. J Crohns Colitis 2022;16:2-17
- Truelove-Witts — Truelove SC, Witts LJ. Cortisone in ulcerative colitis. BMJ 1955;2:1041
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