Ulcerative colitis
Description
- Continuous mucosal inflammation from the rectum extending proximally; colon only
- Rectum is involved in essentially all untreated cases - rectal sparing suggests Crohn or topical therapy already given
- Mucosa + submucosa only. Transmural inflammation only in fulminant disease/toxic megacolon
Extent (Montreal)
| E1 Proctitis | Rectum only (~30%) |
| E2 Left-sided | Up to splenic flexure (~40%) |
| E3 Extensive/pancolitis | Beyond splenic flexure (~30%) |
- Extent determines route of therapy (topical vs oral) and cancer surveillance
- Backwash ileitis in pancolitis - still UC
Histology
- Crypt architectural distortion, crypt abscesses, goblet cell depletion, basal plasmacytosis
- No granulomas
Epidemiology
- Prevalence ~0.3% Australia; among the highest globally
- Peak 15-30 yrs, second peak 50-70
- M = F
- Disease of ex- and never-smokers - onset often follows smoking cessation
- Appendicectomy before age 20 is protective
Aetiopathogenesis
- Barrier failure + dysregulated mucosal response to commensal flora in a susceptible host
- Atypical Th2 profile, IL-13, NKT cells; converges on TNF/IL-23 pathways
- MZ twin concordance ~15% (vs ~50% Crohn - environment dominates in UC)
- HLA-DRB1*0103 - severe extensive disease
- pANCA positive ~60-70% (ASCA in Crohn)
- Smoking and appendicectomy both protective - opposite to Crohn
Diagnosis
Clinical
- Bloody diarrhoea with mucus/pus, tenesmus, urgency, crampy pain
- Proctitis may present with constipation + rectal bleeding rather than diarrhoea
- Nocturnal symptoms, weight loss, fever in severe disease
Establishing the diagnosis
1. Exclude infection - stool MCS, C. difficile toxin, +/- CMV in refractory disease
2. Colonoscopy + biopsy - continuous confluent erythema, loss of vascular pattern, friability, granularity, ulceration; clear demarcation from normal proximal mucosa
3. Faecal calprotectin raised
Severity (Truelove & Witts)
| Mild | <=4 stools/day +/- blood, no systemic upset, normal ESR |
| Moderate | >4 stools/day, minimal systemic toxicity |
| Severe | >=6 bloody stools/day PLUS one of: HR >90, temp >37.8, Hb <105 g/L, ESR >=30 |
- Severe = admit, IV steroids, surgical review - not an outpatient problem
In acute severe colitis
- AXR: colonic diameter >6 cm = toxic megacolon
- Barium enema and full colonoscopy contraindicated - perforation. Limited unprepped flexible sigmoidoscopy is safe and gives CMV histology
- Daily FBE, CRP, UEC, stool chart; VTE prophylaxis
- Loss of haustra + mucosal islands on AXR = severe
Management
Verified against ECCO Therapeutics in UC: Medical Treatment 2026, ACG 2025 update and the AGA living guideline.
By extent and severity
A. Proctitis / distal disease
- Topical mesalazine suppository 1 g daily - more effective than oral 5-ASA alone for proctitis
- Add oral 5-ASA and/or topical steroid if inadequate
B. Left-sided / extensive, mild-moderate
- Oral mesalazine >=2.4 g/day + topical mesalazine enema - combination beats either alone
- Once-daily dosing = adherence, equal efficacy
- No response by 2-4 weeks -> oral prednisolone or budesonide MMX
- 5-ASA maintenance also reduces colorectal cancer risk - keep it going
C. Moderate-severe / steroid-dependent or refractory
- Advanced therapy. Higher-efficacy tier: infliximab, vedolizumab, ozanimod, etrasimod, upadacitinib, risankizumab, guselkumab
- Intermediate: golimumab, ustekinumab, tofacitinib, filgotinib, mirikizumab; adalimumab lower
- The old "anti-TNF first, then vedolizumab" sequence is superseded - choose by efficacy tier, speed of onset, safety profile and comorbidity
- Thiopurine - steroid-sparing maintenance; too slow (8-12 wks) for induction. After 5-ASA failure or post-rescue
- JAK inhibitors: fastest onset, oral. MACE/VTE/malignancy caution - age >65, smokers, CV risk
- S1P modulators: first-dose bradycardia, macular oedema, lymphopenia, live vaccines
D. Acute severe UC (ASUC) - a medical emergency
- IV hydrocortisone 100 mg QID (or methylprednisolone); nil 5-ASA, stop antimotility/opioids/anticholinergics
- Exclude C. difficile and CMV colitis
- Prophylactic LMWH - VTE risk is high despite rectal bleeding
- Day 3 assessment (Oxford/Travis criteria) - escalate if:
- Stool frequency >=8/day, OR
- 3-5 stools/day with CRP >45
- Rescue:
- Infliximab (accelerated dosing often used in severe disease/low albumin), OR
- IV ciclosporin if thiopurine-naive - UC only, never Crohn
- JAK inhibitors (tofacitinib, upadacitinib) increasingly used as rescue, incl. after infliximab failure - ~80% colectomy-free in cohort data; off-label, not yet in guidelines as first rescue
- Colectomy if no response to rescue within ~5-7 days - delay increases mortality; involve surgeons from day 1
Ciclosporin specifics
- IV then oral, bridging to a maintenance thiopurine
- Colectomy after ciclosporin rescue: 10-40% short term, ~50% at 3 yrs, ~58% at 7 yrs
- Avoid if cholesterol <3 mmol/L or low magnesium - seizure risk. Monitor levels, BP, renal function
Predictors of course - guide initial intensity
- Milder: limited extent, older age at diagnosis, smoking -> oral +/- topical 5-ASA
- Severe: extensive disease, young age, deep ulceration, ASUC at presentation -> 5-ASA + immunomodulator or straight to advanced therapy
Surgery - curative
- Proctocolectomy + ileal pouch-anal anastomosis (usually staged) or permanent ileostomy
- Indications: fulminant colitis/toxic megacolon, perforation, uncontrolled haemorrhage, medically refractory disease, high-grade dysplasia or cancer
- Post-pouch: 3-8 loose motions/day is expected, improves over the first year as capacity increases
- Loperamide (safe long-term), codeine, bulking agents; bananas/rice/pasta/white bread/cheese
- Cholestyramine if bile-acid perianal excoriation
- Pouchitis ~50% by 10 yrs -> ciprofloxacin or metronidazole; chronic pouchitis -> vedolizumab
Associations
The four classic
- Pyoderma gangrenosum (~5%) - pathergy: never debride
- Primary sclerosing cholangitis - UC >> Crohn; independent of colitis activity, unaffected by colectomy, multiplies CRC risk
- Autoimmune (chronic active) hepatitis
- Ankylosing spondylitis - HLA-B27
Other
- Erythema nodosum (~10%), type 1 and type 2 peripheral arthropathy, sacroiliitis
- Episcleritis, uveitis
- Anaemia (iron deficiency, anaemia of inflammation)
- VTE - risk raised throughout, highest during flare and admission
- Osteoporosis - disease + steroids
- pANCA positive in the majority
Natural history & complications
- Relapsing-remitting; ~50% relapse in any given year
- Proximal extension over time in ~20-30% of proctitis/left-sided disease
- Colectomy ~15% at 10 years, falling with advanced therapy
- ASUC affects ~15% at some point; ~30% of those come to colectomy in that admission
Colorectal cancer
- Risk driven by extent x duration x cumulative inflammation; PSC is the strongest multiplier
- Surveillance from 8 years after symptom onset; from diagnosis if PSC
- High-definition white light or chromoendoscopy with targeted biopsies
- Interval 1-5 yrs by extent, inflammation, dysplasia history, PSC, FHx
- 5-ASA maintenance is chemopreventive
- Colitis-associated cancer arises from flat dysplasia - it is not a polyp sequence
Prognostic markers
- Extensive disease, young age at onset, deep ulceration, need for steroids in the first year, high CRP
- Mortality overall close to background
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