Lucan · Conditions

Crohn's disease

Australian guidance: eTG Gastrointestinal — IBD + GESA IBD Guidelines

1. Definition and epidemiology

Crohn disease is a chronic relapsing transmural granulomatous inflammation that can affect any segment of the gastrointestinal tract from mouth to anus, with a predilection for the terminal ileum and right colon. Unlike ulcerative colitis, inflammation affects all layers of the intestinal mucosa in any part of the gastrointestinal tract and can be discontinuous (skip lesions), a defining distinction per eTG IBD. Australia has one of the highest incidence rates globally, estimated at 17 to 20 per 100,000 person-years with prevalence approaching 300 per 100,000, placing significant burden on secondary and tertiary gastroenterology services. Onset is bimodal, peaking in the second to fourth decades and again in the sixth to seventh decades, with no strong sex predominance.

2. Pathophysiology

Crohn disease arises from dysregulated mucosal immunity in a genetically susceptible host exposed to environmental triggers. NOD2 (CARD15) variants on chromosome 16 impair intracellular bacterial sensing in Paneth cells and macrophages, promoting aberrant Th1 and Th17 cytokine responses. Defective autophagy via ATG16L1 and IRGM mutations further impairs bacterial clearance. The resulting uncontrolled cytokine cascade, dominated by TNF-alpha, IL-12, and IL-23, drives transmural inflammation extending through the mucosa, submucosa, muscularis propria, and serosa. This transmural depth underlies the characteristic complications of fistula, stricture, and abscess formation. Granulomas, present in only 30 to 60 percent of biopsy specimens, reflect aggregation of epithelioid macrophages around intraluminal bacteria that have penetrated the bowel wall. Skip lesions with normal intervening mucosa between inflamed segments distinguish Crohn disease histologically and endoscopically from ulcerative colitis, in which inflammation is continuous and confined to the mucosal layer (Robbins Ch 17; eTG IBD).

3. Clinical presentation and diagnostic criteria

Presentation varies by disease location. Ileocolonic disease (approximately 45 percent of cases) causes right iliac fossa pain, diarrhoea, and weight loss; a tender mass may be palpable. Colonic-only disease mimics ulcerative colitis with bloody stool. Upper gastrointestinal involvement causes dysphagia, nausea, or epigastric pain. Perianal disease including fissures, skin tags, and fistulae occurs in 25 to 35 percent and may precede luminal symptoms by years.

Extraintestinal manifestations occur in 25 to 40 percent of patients. These include peripheral arthropathy (correlates with luminal activity), enteropathic arthritis and axial spondyloarthritis (both part of the spondyloarthritis spectrum sharing HLA-B27 association per eTG Rheumatology), primary sclerosing cholangitis (less common than in ulcerative colitis), erythema nodosum, pyoderma gangrenosum, anterior uveitis, and non-melanoma skin and nail lesions overlapping with psoriasis.

No single diagnostic criterion exists. Diagnosis requires integration of clinical, endoscopic, histological, and radiological findings after excluding infectious causes, particularly Mycobacterium tuberculosis, Yersinia, and Clostridioides difficile. Infectious colitis must be excluded by stool examination at every flare per eTG IBD. Microscopic and collagenous colitis should be considered when the colon appears endoscopically normal but histological inflammation is present.

4. Investigations and AU-specific cutoffs

Initial blood work includes full blood count (anaemia reflecting chronic blood loss or B12 or folate deficiency; thrombocytosis in active inflammation), CRP and ESR (CRP above 10 mg/L supports active flare), serum albumin (below 35 g/L indicates nutritional compromise and predicts steroid dependence), iron studies, B12, folate, zinc, and vitamin D. Faecal calprotectin is the preferred non-invasive mucosal biomarker; a level above 250 micrograms per gram has high sensitivity for active small bowel or colonic inflammation and is used in Australia to triage colonoscopy referrals and monitor treatment response. A level below 50 micrograms per gram reliably excludes significant mucosal disease.

Stool culture and Clostridioides difficile PCR are sent at every flare to exclude infectious triggers (eTG IBD). Ileocolonoscopy with segmental biopsies remains the diagnostic gold standard, assessing mucosal involvement and obtaining tissue for histology and culture. MRI enterography is the preferred cross-sectional modality for small bowel assessment; it avoids radiation and characterises mural thickness, enhancement pattern, mesenteric fat stranding, and complications such as fistula or stricture. CT enterography is used when MRI is unavailable or when urgent assessment for abscess or perforation is required. Capsule endoscopy identifies proximal small bowel lesions missed by colonoscopy but is contraindicated until stricture has been excluded by cross-sectional imaging.

Thiopurine methyltransferase (TPMT) and NUDT15 genotyping must be performed before starting azathioprine or 6-mercaptopurine to identify patients at risk of severe myelosuppression.

5. Management

Management follows a treat-to-target strategy endorsed by GESA, with the primary target being endoscopic remission (absence of mucosal ulceration) and a secondary target of clinical symptom remission assessed by the Harvey-Bradshaw Index or Crohn Disease Activity Index (CDAI). Targets are reassessed at 12 weeks for clinical response and at 26 weeks for endoscopic or biomarker-confirmed response.

Mild to moderate flares of ileocaecal disease are treated with budesonide 9 mg daily for up to 12 weeks, exploiting its high first-pass hepatic metabolism to minimise systemic corticosteroid effects. Systemic prednisolone 40 to 60 mg daily tapering over 8 to 12 weeks is reserved for moderate to severe or extensive disease. Neither budesonide nor prednisolone has a role in maintenance therapy; repeated or prolonged steroid use triggers early escalation to immunosuppressive or biologic therapy per GESA guidelines.

Thiopurines (azathioprine 2 to 2.5 mg/kg/day or 6-mercaptopurine 1 to 1.5 mg/kg/day) are conventional maintenance agents effective in approximately 50 to 60 percent of patients but slow-acting (3 to 6 months to full effect). Methotrexate 25 mg subcutaneously weekly with folic acid 5 mg weekly is an alternative in thiopurine-intolerant patients.

Biologic therapy is indicated for moderate to severe disease, corticosteroid dependence, or failure of immunosuppression. Anti-TNF agents (adalimumab subcutaneously preferred over infliximab intravenously for outpatient initiation) combined with a thiopurine reduce immunogenicity and sustain remission more effectively than either agent alone. Ustekinumab (anti-IL-12/23) and vedolizumab (gut-selective anti-integrin) are used in anti-TNF failure or where anti-TNF is contraindicated. Risankizumab (anti-IL-23) gained TGA approval in 2023 and is increasingly used in refractory disease. Surgical resection (commonly ileocaecal resection) is considered when medical therapy fails or complications arise; it is not curative given the risk of disease recurrence proximal to the anastomosis.

Exclusive enteral nutrition is first-line for induction in paediatric Crohn disease and an adjunct in adults with nutritional compromise or when corticosteroids are contraindicated.

6. Pharmacology and AU PBS notes

Adalimumab (Humira and biosimilars including Hadlima, Idacio, Amgevita) is PBS-listed under Section 100 Highly Specialised Drugs for luminal Crohn disease. PBS criteria require: confirmed diagnosis, failure of conventional therapy (corticosteroid plus thiopurine or methotrexate for at least 3 months at adequate dose), and CDAI above 300 or equivalent marker of severe disease. Infliximab (Remicade and biosimilars Inflectra, Renflexis, Flixabi) shares the same PBS access pathway. Prescribers must document response at 12 weeks (CDAI reduction above 100 points or remission) for PBS continuation authority.

Ustekinumab (Stelara) is PBS-listed for Crohn disease refractory to at least one anti-TNF agent. Vedolizumab (Entyvio) is also PBS-listed for anti-TNF failure. Risankizumab (Skyrizi) has TGA approval for moderately to severely active Crohn disease in adults. Biosimilar substitution is recommended by GESA for new starts; switching stable patients carries low clinical risk per TGA guidance. Budesonide (Entocort, Budeflam) is not PBS-restricted for Crohn disease and is available on an ordinary prescription.

7. Complications and monitoring

Intestinal complications include fibrostenotic stricture causing subacute obstruction, penetrating disease with internal or external fistulae and intra-abdominal abscess, and perianal fistulising disease. Malabsorption of fat-soluble vitamins (A, D, E, K) and B12 is common with extensive ileal disease or prior ileal resection. Patients with colonic Crohn disease carry increased colorectal cancer risk; surveillance colonoscopy is recommended from 8 years after diagnosis using chromoendoscopy-guided biopsies every 1 to 2 years based on GESA guidance.

Bone density monitoring by DXA is recommended at diagnosis and periodically given cumulative corticosteroid exposure and vitamin D malabsorption. Thiopurine use carries a small but real risk of non-melanoma skin cancer and lymphoma; annual dermatological review and sun protection counselling are advised. 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. Post-operative Crohn recurrence at the anastomosis occurs in 50 to 80 percent endoscopically by 12 months; post-operative colonoscopy at 6 to 12 months guides ongoing therapy.

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