Lucan · Conditions

Ulcerative colitis

Australian guidance: eTG Gastrointestinal — IBD + GESA

1. Definition and epidemiology

Ulcerative colitis is a chronic relapsing inflammatory bowel disease characterised by continuous mucosal inflammation confined to the colon, always involving the rectum and extending proximally in a contiguous pattern toward the caecum. Australia has one of the highest incidence rates globally, estimated at 12 to 15 per 100,000 person-years, with prevalence exceeding 200 per 100,000 and rising. Onset peaks in the second to fourth decades with a smaller secondary peak in the sixth decade; there is no marked sex predominance. Unlike Crohn disease, inflammation is generally limited to the mucosal layer and does not involve the full bowel wall thickness, and skip lesions do not occur (eTG IBD; GESA Clinical Update 2018).

2. Pathophysiology

Ulcerative colitis arises from an abnormal mucosal immune response in a genetically susceptible host. Genome-wide association studies have identified over 200 susceptibility loci, including variants in genes encoding epithelial barrier proteins (notably MUC2, encoding intestinal mucin) and innate immune mediators. Defective barrier function allows luminal bacterial antigens to penetrate the surface epithelium, triggering a Th2-skewed cytokine response dominated by IL-4, IL-5, IL-13, and IL-33, in contrast to the Th1 or Th17 predominance of Crohn disease. The resulting eosinophilic and mast-cell-rich lamina propria infiltrate, combined with neutrophil migration into crypts forming crypt abscesses, destroys the surface epithelium. Repeated cycles of mucosal destruction and regeneration lead to architectural distortion, glandular branching, and goblet cell depletion visible on histology. Inflammation remains confined to mucosa and submucosa; the muscularis propria is spared except in fulminant colitis, where transmural extension can precipitate toxic megacolon (Robbins Ch 17).

3. Clinical presentation and diagnostic criteria

The cardinal presentation is bloody diarrhoea with mucus, tenesmus, and colicky left iliac fossa pain. Stool frequency and urgency reflect disease severity. Disease extent is classified using the Montreal classification as proctitis (up to 15 cm from the anal verge), left-sided colitis (to the splenic flexure), or extensive colitis or pancolitis (beyond the splenic flexure). Systemic features including fever, tachycardia, and anaemia indicate moderate to severe disease. Remission is defined clinically as a stool frequency of 0 to 1 per day above baseline with no rectal bleeding and a normal physician global assessment.

Extraintestinal manifestations occur in 25 to 40 percent of patients and include peripheral arthropathy (correlates with bowel activity), ankylosing spondylitis, primary sclerosing cholangitis (PSC, more strongly associated with ulcerative colitis than with Crohn disease), erythema nodosum, pyoderma gangrenosum, and anterior uveitis. Diagnosis requires colonoscopy with segmental biopsies after exclusion of infectious colitis, particularly Clostridioides difficile, Campylobacter, Shigella, and cytomegalovirus in immunocompromised patients. Microscopic and collagenous colitis must be considered when the colon appears endoscopically normal but histological inflammation is present, and ischaemic colitis must be considered in older patients with cardiovascular risk factors (eTG IBD).

4. Investigations and AU-specific cutoffs

Baseline blood work includes full blood count (anaemia reflects chronic blood loss; thrombocytosis occurs in active disease), CRP and ESR (CRP above 10 mg/L supports active flare; CRP above 45 mg/L in acute severe colitis predicts failure to respond to intravenous corticosteroids within 3 days), serum albumin (below 30 g/L indicates severe disease and nutritional compromise), iron studies, and vitamin D. Faecal calprotectin is the preferred non-invasive mucosal biomarker; a level above 250 micrograms per gram has high sensitivity for active mucosal inflammation and is used in Australia to monitor treatment response and guide colonoscopy timing. A level below 50 micrograms per gram in a patient in clinical remission supports endoscopic healing.

Stool cultures and Clostridioides difficile PCR must be sent at every flare to exclude infectious triggers (eTG IBD). Flexible sigmoidoscopy is sufficient for initial assessment of proctitis and left-sided disease; full colonoscopy is performed once the patient is stable to confirm disease extent and obtain segmental biopsies. CT abdomen and pelvis is performed urgently if toxic megacolon or perforation is suspected; a colonic diameter above 6 cm on plain abdominal film warrants urgent surgical review. Thiopurine methyltransferase (TPMT) and NUDT15 genotyping are mandatory before commencing azathioprine or 6-mercaptopurine to detect patients at risk of severe myelosuppression.

5. Management

Management follows a treat-to-target framework endorsed by GESA, with the primary target being endoscopic mucosal healing (Mayo endoscopic subscore 0 to 1) and a secondary target of clinical remission assessed by the partial Mayo score or patient-reported outcome measures. Targets are reassessed at 8 to 12 weeks for clinical response and at 6 months for endoscopic response (eTG IBD; GESA Clinical Update 2018).

Distal proctitis or proctosigmoiditis is treated with topical mesalazine suppositories (1 g nightly) or enemas (2 to 4 g), which are superior to topical corticosteroids for inducing remission. Oral mesalazine is added for inadequate response. Left-sided or extensive mild to moderate disease is treated with oral mesalazine 2 to 4 g daily; once-daily dosing is as effective as divided doses and improves adherence per GESA guidance. Combination oral plus topical mesalazine achieves remission more rapidly than either agent alone and is the preferred regimen for extensive mild to moderate disease.

Moderate to severe flares or mesalazine failure prompts oral prednisolone 40 mg daily tapered over 8 to 12 weeks. Acute severe colitis, defined by the Truelove and Witts criteria as 6 or more bloody stools per day plus at least one of tachycardia above 90 beats per minute, fever above 37.8 degrees Celsius, haemoglobin below 105 g/L, or ESR above 30 mm per hour, is a medical emergency requiring hospital admission, intravenous methylprednisolone 60 mg or hydrocortisone 400 mg daily, twice-daily stool charts, daily bloods, and early gastroenterology and surgical co-management. Failure to respond by day 3 triggers rescue therapy with intravenous cyclosporin 2 mg/kg daily or infliximab 5 mg/kg infusion; colectomy is considered within 5 to 7 days of failed rescue.

Thiopurines (azathioprine 2 to 2.5 mg/kg/day) are standard maintenance therapy for corticosteroid-dependent or frequently relapsing disease. Biologic therapy with anti-TNF agents (infliximab or adalimumab), vedolizumab (gut-selective anti-integrin), or ustekinumab (anti-IL-12/23) is indicated for moderate to severe disease refractory to or intolerant of thiopurines. Tofacitinib (a JAK1/3 inhibitor) is an oral small-molecule option for moderate to severe disease in adults. Surgical colectomy (total proctocolectomy with ileal pouch-anal anastomosis) is curative and is considered for medically refractory disease, dysplasia, or malignancy.

6. Pharmacology and AU PBS notes

Mesalazine (Pentasa, Asacol, Salofalk) is available in multiple delayed-release and controlled-release formulations; formulation choice depends on disease distribution. It is not PBS-restricted and is available on an ordinary prescription. Sulfasalazine is a cheaper alternative for patients with concomitant arthropathy but carries higher gastrointestinal and haematological side-effect burden.

Adalimumab (Humira and biosimilars Hadlima, Idacio, Amgevita) and infliximab (Remicade and biosimilars Inflectra, Renflexis) are PBS-listed under Section 100 Highly Specialised Drugs for ulcerative colitis. PBS criteria require confirmed moderate to severe disease, failure of corticosteroids and thiopurine at adequate dose for at least 3 months, and a partial Mayo score of at least 6 or a full Mayo score of at least 6 with an endoscopic subscore of at least 2. Response must be documented at 8 weeks (partial Mayo reduction of at least 3 points and at least 30 percent) to obtain a continuation authority. Vedolizumab (Entyvio) is PBS-listed for moderate to severe ulcerative colitis, including as a first-line biologic. Tofacitinib (Xeljanz) is PBS-listed for adults with moderate to severe ulcerative colitis who have failed at least one conventional therapy (corticosteroid, thiopurine, or aminosalicylate). Biosimilar substitution is endorsed by GESA for new starts.

7. Complications and monitoring

Acute severe colitis and toxic megacolon are the most immediately life-threatening complications. Long-term colorectal cancer risk is substantially elevated; risk correlates with disease extent, duration, and coexisting PSC. Surveillance colonoscopy is recommended starting 8 to 10 years after diagnosis for extensive colitis: annually in high-risk patients (PSC or previous low-grade dysplasia) and every 1 to 2 years in others, using chromoendoscopy with targeted biopsies per GESA guidelines. Long-term mesalazine use is associated with a modestly reduced colorectal cancer risk. PSC monitoring includes annual liver function tests and MRI cholangiography. Bone density is monitored at baseline and periodically given cumulative corticosteroid exposure. Patients on thiopurines require annual skin checks due to elevated non-melanoma skin cancer risk, and sun protection counselling should be provided. Patients commencing biologic therapy require tuberculosis screening (QuantiFERON-TB Gold) and hepatitis B serology before initiation; live vaccines are contraindicated during biologic or combination immunosuppressive therapy. Pouchitis, occurring in up to 50 percent of patients after ileal pouch-anal anastomosis, is treated with metronidazole or ciprofloxacin.

Written for Australian practice and grounded in the guidance named above. Study material only — not medical advice. Always check against current guidelines.