Crohn disease
Description
- Transmural, granulomatous inflammation, mouth to anus, discontinuous skip lesions
- Distribution: ileocolonic ~40%, ileal ~30%, colonic ~25%, isolated upper GI ~5%
Montreal classification
| Axis | Categories |
|---|---|
| A age at diagnosis | A1 <=16 / A2 17-40 / A3 >40 |
| L location | L1 ileal / L2 colonic / L3 ileocolonic / L4 isolated upper GI (modifier) |
| B behaviour | B1 non-stricturing non-penetrating / B2 stricturing / B3 penetrating; +p = perianal |
- Behaviour is not static - B1 progresses to B2/B3 in ~50% over 20 yrs. The point of early effective therapy is to stop that.
Epidemiology
- Prevalence ~0.2-0.3% in Australia, incidence still rising
- Peak onset 15-30 yrs; second peak 50-70
- F slightly > M in Western cohorts
- MZ twin concordance ~50% (vs ~15% UC)
- Ashkenazi Jewish 2-4x
Aetiopathogenesis
- Impaired innate handling of luminal bacteria in a genetically susceptible host -> persistent transmural Th1/Th17 response
Genetics
- NOD2/CARD15 - Crohn-specific; intracellular bacterial sensing
- Homozygous/compound heterozygous: ileal, stricturing, early-onset phenotype
- ATG16L1, IRGM - autophagy; IL23R (protective variants)
Environment
- Smoking: doubles risk, more surgery, more post-op recurrence, worse response to therapy
- Opposite direction to UC - the single most useful modifiable factor
- Childhood antibiotics, NSAIDs, appendicectomy (inc risk, unlike UC)
Why the complications happen
- Transmural inflammation -> fibrosis -> stricture
- Transmural inflammation -> sinus tract through the wall -> fistula / abscess
- Neither happens in mucosa-limited UC
Diagnosis
Presentation by behaviour
- Inflammatory (terminal ileal) - diarrhoea, RIF pain, low-grade fever, fatigue, weight loss, malnutrition
- Stricturing - post-prandial pain, bloating, nausea, vomiting; sub-occlusive episodes
- Penetrating/fistulising - by tract:
- Enterovesical: faecaluria, pneumaturia, recurrent UTI
- Rectovaginal: dyspareunia, vaginal stool discharge
- Entero-enteric: often silent, or presents as an abscess
- Psoas abscess - hip pain + fever from penetrating terminal ileal disease
- Perianal: tags, fissures, fistulae, abscess. May precede luminal disease by years
Investigations
- Ileocolonoscopy + biopsy = primary test
- Segmental discontinuous inflammation, aphthous -> longitudinal + serpiginous ulcers -> cobblestoning, strictures
- Histology: patchy transmural chronic inflammation, non-caseating epithelioid granulomas (~30% on biopsy), goblet cells preserved
- MR enterography at diagnosis - small bowel extent, strictures, fistulae. Preferred over CT: no radiation in a young patient facing decades of imaging
- Distinguishes inflammatory (T2 hyperintense, enhancing) from fibrotic stricture - determines drug vs surgery
- Pelvic MRI for perianal fistulising disease (Parks classification, abscess)
- Capsule endoscopy for isolated small bowel disease - contraindicated if stricture suspected (retention)
- Bloods/stool: anaemia, thrombocytosis, inc ESR/CRP, hypoalbuminaemia, faecal calprotectin
- Calprotectin more specific for bowel inflammation than CRP/ESR; CRP can be normal in isolated ileal disease
Differentials
| Discriminator | |
|---|---|
| UC | Continuous, rectum involved, mucosa-limited, bleeding/tenesmus/urgency, little perianal disease |
| Infectious enterocolitis | Onset <4 weeks; always exclude C. difficile after antibiotics |
| Microscopic colitis | Chronic watery diarrhoea, normal-looking mucosa, F >50; lymphocytic or collagenous on biopsy |
| Intestinal TB | Ileocaecal, caseating granulomas, ascites; treating as Crohn with anti-TNF is catastrophic - exclude before biologics |
| Behcet, NSAID enteropathy, lymphoma, Yersinia |
Management
Verified against AGA Living Guideline (Crohn disease) 2025-26 and ECCO. The step-up 5-ASA-first approach is no longer standard for anything but mild localised disease.
Risk stratification drives everything
Predictors of a disabling course -> early advanced therapy, not step-up:
- Age at onset <40
- Fistulising or perianal disease at presentation
- Early requirement for corticosteroids
- Deep ulceration at endoscopy
- Extensive small bowel involvement
- Smoking
- Weight loss >5 kg
- High serological antibody titres
Induction
- Ileocaecal budesonide 9 mg for mild-moderate localised disease - lower systemic exposure than prednisolone
- Prednisolone for moderate-severe; wean over 8-12 weeks
- Steroid dependence or a second course within 12 months = escalate
- Exclusive enteral nutrition - as effective as steroids for induction in children, mucosal healing without steroid toxicity
- Advanced therapy where risk factors present, started early rather than after failure
- Higher-efficacy tier: infliximab, adalimumab, ustekinumab, risankizumab, mirikizumab, guselkumab, vedolizumab
- Upadacitinib and certolizumab positioned lower for advanced-therapy-naive patients
- 5-ASA has essentially no role - do not maintain a Crohn patient on mesalazine
Maintenance
- Thiopurine (azathioprine/6-MP) - onset 8-12 wks; check TPMT/NUDT15 first
- Methotrexate - Crohn-specific evidence (weak in UC); weekly SC/IM
- For thiopurine intolerance/failure, or combined with anti-TNF to reduce immunogenicity
- Folate cover; teratogenic - contraception in both sexes
- Advanced therapy continued, with drug-level monitoring on loss of response
Perianal / fistulising disease
- Examination under anaesthesia + pelvic MRI first - drain sepsis before immunosuppression
- Seton for complex fistula
- Infliximab is the best-evidenced agent for fistula closure
- Antibiotics (metronidazole, ciprofloxacin) adjunctive
Treat to target
- Early: symptomatic response
- Intermediate: clinical remission + normal CRP and calprotectin
- Long-term: endoscopic healing
- Symptoms alone correlate poorly with mucosal inflammation - do not titrate on symptoms
Surgery
- Never curative - recurrence at the anastomosis is the rule
- Indications: fixed stricture, perforation/abscess/phlegmon, internal fistula, refractory perianal or colonic disease, dysplasia
- Resect minimum length; stricturoplasty for short fibrotic small bowel strictures
- Post-op prophylaxis within 4 weeks if high risk (smoker, penetrating disease, prior resection, <30 yrs); colonoscopy at 6-12 months (Rutgeerts score) to guide escalation
Adjuncts
- Smoking cessation - highest-yield single intervention
- Nutrition: iron, B12 after ileal resection or >20 cm ileal disease, fat-soluble vitamins, vit D/calcium
- Bile-salt diarrhoea after ileal resection -> cholestyramine
- Vaccination before immunosuppression; skin and cervical surveillance; VTE prophylaxis when admitted
Associations
Extra-intestinal
- Oral aphthous ulcers; orofacial granulomatosis
- Episcleritis, uveitis
- Peripheral arthritis (type 1 tracks activity, type 2 does not); ankylosing spondylitis / sacroiliitis (HLA-B27)
- Erythema nodosum (~15%); pyoderma gangrenosum (~2%)
- Digital clubbing
- PSC (far more UC)
- Metabolic bone disease
Consequences of ileal disease/resection
- Gallstones - dec bile salt reabsorption
- Oxalate renal stones - 10-20% after small bowel resection
- Fat malabsorption -> Ca binds fat -> free oxalate absorbed (enteric hyperoxaluria)
- B12 deficiency, fat-soluble vitamin deficiency, bile-salt diarrhoea
Complications
- Psoas abscess, intra-abdominal abscess, free perforation (uncommon - walled off)
- Short bowel syndrome
- AA amyloidosis in long-standing disease
Natural history & complications
- B1 -> B2/B3 progression in ~50% by 20 years
- ~50% require surgery within 10 years; ~50% of those a second operation
- ~10-15% run a chronic continuous course
Malignancy
- Colorectal cancer - highest with extensive colonic involvement; surveillance as for UC (from 8 years)
- Small bowel adenocarcinoma - rare but markedly increased relative risk, chronically inflamed ileum
- Anal cancer complicating chronic perianal fistulising disease
- B-cell non-Hodgkin lymphoma
- Drug-attributable: thiopurines -> NHL (M >50 or <30) and non-melanoma skin cancer; hepatosplenic T-cell lymphoma with combined thiopurine + anti-TNF in young males; biologics -> melanoma
Monitor
- Calprotectin + CRP periodically; endoscopy to confirm healing and after surgery
- Growth and puberty in adolescents
- Bone density, iron, B12, vit D
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