Gastrointestinal · PANCE / PANRE

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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Question 1GastrointestinalMedium
A 55-year-old man with ulcerative colitis is hospitalized with 8 bloody stools per day, a temperature of 39.0°C, and diffuse abdominal tenderness. WBC is 18,000/mm3 and albumin is 2.4 g/dL. Stool studies, including Clostridioides difficile testing, are negative. Abdominal radiograph shows no colonic dilation. He has received intravenous methylprednisolone for 72 hours with minimal improvement. Which of the following is the most appropriate next step in management?
  • AUrgent full colonoscopy with biopsies
  • BIntravenous ciclosporin or infliximab
  • CContinued intravenous methylprednisolone
  • DHigh-dose oral mesalamine induction
Reveal answer & full explanation
Correct answer: B — Intravenous ciclosporin or infliximab
  • AUrgent full colonoscopy with biopsies
  • BIntravenous ciclosporin or infliximab
  • CContinued intravenous methylprednisolone
  • DHigh-dose oral mesalamine induction

Why Intravenous ciclosporin or infliximab is correct

  • This is acute severe ulcerative colitis by Truelove and Witts criteria: more than 6 bloody stools per day with systemic toxicity (fever, leukocytosis, hypoalbuminemia)
  • Failure to respond to intravenous corticosteroids by about 72 hours (the Oxford day-3 assessment) defines steroid-refractory disease
  • Per current ACG guidance, the next step after intravenous steroid failure is medical rescue therapy with intravenous ciclosporin or infliximab, with surgical consultation for colectomy if rescue fails
  • Delaying rescue therapy after steroid failure increases the risk of complications and emergency colectomy
  • Negative stool studies and the absence of colonic dilation on the radiograph make medical rescue, rather than urgent surgery, appropriate here

Why the others are wrong

  • Urgent full colonoscopy with biopsies — full colonoscopy carries a substantial perforation risk in acute severe colitis and adds little once infection is excluded; if mucosal assessment is needed, a limited flexible sigmoidoscopy is used instead (buzzword-matching on 'get tissue before escalating therapy')
  • Continued intravenous methylprednisolone — continuing steroids beyond 72 hours of nonresponse does not improve outcomes and only delays effective rescue therapy (premature closure on 'give the steroids more time')
  • High-dose oral mesalamine induction — mesalamine induces remission in mild-to-moderate ulcerative colitis and is inadequate for acute severe disease (right-drug-wrong-severity)
Question 2GastrointestinalMedium
A 45-year-old man with ulcerative colitis involving the entire colon (pancolitis) for 15 years undergoes surveillance colonoscopy that shows mild chronic inflammation. Multiple biopsies from a flat area of the transverse colon are read as 'indefinite for dysplasia' by a single pathologist. He is maintained on mesalamine and remains clinically well. Which of the following is the most appropriate next step in management?
  • ARepeat colonoscopy in 3-6 months
  • BContinue annual surveillance
  • CIncrease mesalamine and repeat in 12 months
  • DProceed to colectomy
Reveal answer & full explanation
Correct answer: A — Repeat colonoscopy in 3-6 months
  • ARepeat colonoscopy in 3-6 months
  • BContinue annual surveillance
  • CIncrease mesalamine and repeat in 12 months
  • DProceed to colectomy

Why Repeat colonoscopy in 3-6 months is correct

  • 'Indefinite for dysplasia' is a noncommittal pathology read with high interobserver variability, frequently driven by active inflammation; it is not itself an indication for surgery.
  • Per AGA/SCENIC guidance, optimize inflammation control and repeat colonoscopy in 3–6 months, ideally with chromoendoscopy and expert gastrointestinal-pathologist review, before any management change.
  • This confirms or refutes true dysplasia before committing the patient to a major intervention.

Why the others are wrong

  • Continue annual surveillance — defers reassessment far too long for an indefinite read; premature closure that under-responds to the finding.
  • Increase mesalamine and repeat in 12 months — controlling inflammation is reasonable, but a 12-month interval delays needed re-evaluation (right-idea-wrong-timing).
  • Proceed to colectomy — surgery is reserved for confirmed high-grade (or multifocal/endoscopically unresectable low-grade) dysplasia, not an unconfirmed indefinite read; anchoring on cancer risk.
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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 CriterionMildModerateSevere
Stools/day<44-6≥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
CRPNormalMild rise>30 mg/L
Truelove and Witts severity criteria for ulcerative colitis — guide hospitalization and rescue therapy decisions.

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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