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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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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