Inflammatory bowel disease
Description
- Chronic relapsing immune-mediated gut inflammation. Two phenotypes + IBD-unclassified (~10% of colitis)
UC vs Crohn - the discriminators
| UC | Crohn | |
|---|---|---|
| Site | Colon only, rectum always, continuous retrograde | Mouth -> anus, skip lesions |
| Depth | Mucosa/submucosa | Transmural |
| Histology | Crypt abscesses, goblet cell depletion, no granuloma | Non-caseating granuloma (~30%), goblet cells preserved |
| Complications | Toxic megacolon, dysplasia | Strictures, fistulae, abscess, perianal disease |
| Smoking | Protective | Harmful |
| Serology | pANCA+ | ASCA+ |
| Surgery | Curative (colon removed) | Never curative - recurs at anastomosis |
- Backwash ileitis in UC pancolitis does not make it Crohn
- Rectal sparing or perianal disease = Crohn until proven otherwise
Epidemiology
- Prevalence ~0.3-0.5% in Australia; among the highest globally
- Bimodal onset: peak 15-30 yrs, second smaller peak 50-70
- UC ~ Crohn incidence; Crohn rising fastest, esp. paediatric
- Ashkenazi Jewish 2-4x
- Incidence rising in newly industrialised countries - environment, not genes
Aetiopathogenesis
- Genetically susceptible host + environmental trigger -> loss of tolerance to commensal microbiota -> sustained mucosal inflammation
- Defective barrier + dysregulated innate/adaptive response
Genetics
- >240 susceptibility loci; concordance MZ twins Crohn ~50%, UC ~15%
- NOD2/CARD15 - Crohn only; ileal, stricturing, early onset
- IL23R, ATG16L1 (autophagy), HLA-DRB1*0103 (UC)
- Monogenic very-early-onset IBD: IL10/IL10R defects - age <6
Environment
- Smoking: inc Crohn risk + worse course; dec UC risk (UC is a disease of ex-smokers)
- Appendicectomy protective against UC
- Antibiotics in childhood, NSAIDs, Western diet, urban living
- Breastfeeding protective
Immunology
- Crohn: Th1/Th17, IL-12/IL-23, TNF, IFN-gamma
- UC: Th2-like, IL-13, atypical NKT
- Both converge on TNF and IL-23 - the drug targets
Diagnosis
- Diagnosis = compatible clinical picture + endoscopy + histology, after excluding infection
- Always stool MCS, C. difficile toxin, +/- parasites before committing
Alarm features (vs IBS)
- Weight loss, rectal bleeding, nocturnal diarrhoea, short history, abnormal bloods
- Age of onset >50 or <20, FHx, anaemia
Faecal calprotectin
- Neutrophil cytosolic Ca-binding protein released with mucosal damage
- Separates IBD from IBS, and tracks activity over time
- <50 ug/g -> IBD unlikely; >250 ug/g -> active inflammation
- Also raised by NSAIDs, infection, coeliac, neoplasia - not IBD-specific
Examination clues
- Growth retardation/muscle wasting, pallor, glossitis, clubbing
- Multiple abdominal scars in a young patient = Crohn
- Aphthous ulcers, erythema nodosum, pyoderma gangrenosum
- Perianal tags/fissures/fistulae, uveitis/episcleritis
Investigations
- Bloods: FBE (anaemia, thrombocytosis), CRP/ESR, albumin, iron, B12, folate, vit D
- Normal CRP does not exclude active disease, esp. isolated ileal Crohn
- Ileocolonoscopy + biopsy = the diagnostic test (multiple segments incl. terminal ileum + rectum)
- MR enterography at diagnosis in Crohn - extent, strictures, fistulae; preferred over CT (radiation, young patients, repeated imaging)
- Pelvic MRI for perianal fistulising disease
- AXR if severe colitis: colonic diameter >6 cm = toxic megacolon
- Barium enema and colonoscopy contraindicated - perforation
Management
Targets have shifted: symptom control alone is inadequate. Treat-to-target (STRIDE-II) = symptomatic response early, then clinical remission + normal CRP/calprotectin, then endoscopic healing as the long-term target.
Disease phase axis
A. Induction
- 5-ASA - UC only (mesalazine oral +/- topical). Minimal role in Crohn
- Corticosteroids - prednisolone; budesonide MMX (UC) or ileal-release budesonide (ileocaecal Crohn), lower systemic exposure
- Never a maintenance drug - steroid dependence is a trigger to escalate
- Advanced therapy - see below
- Exclusive enteral nutrition - induction in paediatric Crohn, mucosal healing without steroids
B. Maintenance
- 5-ASA (UC), thiopurines, methotrexate (Crohn), advanced therapy continued
- Steroids never
C. Surgery - see below
Advanced therapies
The old anti-TNF-then-vedolizumab ladder is obsolete. Both AGA living guidelines and ECCO 2026 now place higher-efficacy agents first in moderate-severe disease.
| Class | Agents | Notes |
|---|---|---|
| Anti-TNF | infliximab, adalimumab, golimumab (UC) | Only class with good fistula + EIM evidence. Infliximab = ASUC rescue |
| Anti-integrin | vedolizumab | Gut-selective, safest, slow onset. Ineffective for EIMs |
| IL-12/23 | ustekinumab | |
| IL-23 | risankizumab, mirikizumab, guselkumab | Now higher-efficacy tier in both UC and Crohn |
| JAK | upadacitinib, tofacitinib (UC) | Fastest onset - useful in ASUC/steroid-refractory. MACE/VTE/malignancy warnings: age >65, smokers, CV risk |
| S1P modulator | ozanimod, etrasimod (UC) | Oral. Bradycardia at initiation, macular oedema, lymphopenia |
- Combination anti-TNF + thiopurine dec immunogenicity, inc levels (SONIC)
- Therapeutic drug monitoring for loss of response: low level + no antibody -> dose up; low level + high antibody -> switch within or out of class
Thiopurines
- Azathioprine / 6-mercaptopurine. Slow onset (8-12 weeks) - not for induction alone
- Indications: maintenance, steroid-sparing, fistulising/perianal disease, post-op relapse prevention in Crohn
- Check TPMT/NUDT15 before starting
- Monitor FBE + LFT; risks: myelosuppression, pancreatitis, hepatotoxicity, non-melanoma skin cancer, NHL (esp. M >50 or <30), hepatosplenic T-cell lymphoma (young males on combination therapy)
Surgery
- UC - proctocolectomy + ileal pouch-anal anastomosis, or permanent ileostomy
- For fulminant colitis/toxic megacolon, refractory disease, high-grade dysplasia or cancer
- Post-pouch: 3-8 loose motions/day expected, settles over the first year
- Loperamide (safe long-term), codeine, bulking agents, low-residue foods; cholestyramine if bile-acid excoriation
- Pouchitis ~50% at 10 yrs -> ciprofloxacin/metronidazole
- Crohn - stricture, penetrating disease (perforation/abscess/phlegmon), internal fistula, perianal disease, refractory colitis
- Resect minimum length; stricturoplasty preserves bowel
- Post-op prophylaxis within 4 weeks in high risk (smoker, penetrating disease, prior resection); colonoscopy at 6-12 months
Every patient
- Smoking cessation - the single highest-yield intervention in Crohn
- Vaccinate before immunosuppression: live vaccines contraindicated once on it
- Bone density, vit D, calcium if repeated steroids
- Iron (IV preferred if active disease), B12 after ileal resection
- Skin surveillance + sun protection; cervical screening
- VTE prophylaxis in every IBD admission - inc risk even when bleeding
Associations
Split by whether they track gut activity - determines whether treating the bowel fixes them.
Activity-related
- Oral aphthous ulcers
- Erythema nodosum (UC ~10%, Crohn ~15%)
- Type 1 peripheral arthropathy - pauciarticular (<5 joints), large joints, asymmetric
- Episcleritis (2-5%) - mild burning/itch, no vision loss
- Anaemia
- Thromboembolism
Activity-independent
- PSC - UC >> Crohn; does not improve with colectomy; inc colorectal cancer risk
- Ankylosing spondylitis (~10%, Crohn > UC); sacroiliitis equal in both, HLA-B27
- Type 2 peripheral arthropathy - polyarticular, small joints, chronic
- Uveitis (0.5-3%) - pain, photophobia, blurred vision, headache. Sight-threatening - same-day ophthalmology
- Pyoderma gangrenosum (UC ~5%, Crohn ~2%) - pathergy: do not debride
- Renal (oxalate) and gallstones - Crohn after ileal resection
Other
- Psoriasis; autoimmune hepatitis; metabolic bone disease
- Amyloidosis (AA) - long-standing Crohn
Natural history & complications
- Relapsing-remitting. ~50% in remission at any time; ~10-15% chronic continuous
- Crohn: progressive bowel damage - inflammatory -> stricturing/penetrating over years
- ~50% need surgery within 10 yrs; ~50% of those need a second operation
- UC: ~15% colectomy at 10 yrs (falling with advanced therapy)
- Proximal extension of UC over time in ~20-30%
Colorectal cancer
- Risk driven by extent x duration x inflammation burden; PSC is a multiplier
- Surveillance colonoscopy from 8 years after symptom onset (immediately at PSC diagnosis)
- Chromoendoscopy or high-definition white light with targeted biopsies
- Interval 1-5 yrs by risk
- Crohn: also small bowel adenocarcinoma, anal cancer in chronic perianal fistulising disease
Mortality and disability
- Overall mortality close to background in UC; modestly raised in Crohn
- Short bowel syndrome after repeated resections
- Depression/anxiety in ~1/3 - independently worsens disease course
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