Key Facts

Crohn's disease is a chronic, relapsing inflammatory bowel disease characterised by transmural, granulomatous inflammation that can affect any part of the GI tract. Along with ulcerative colitis, it constitutes the two main forms of IBD.

Epidemiology

UK prevalence is approximately 145 per 100,000 (rising). Incidence is ~7-10 per 100,000 per year. Peak onset 15-30 years (second smaller peak at 50-70 years). Slight female predominance. Higher incidence in Northern European and North American populations. Incidence is rising in previously low-incidence populations (Asia, Africa).

Aetiology

Multifactorial: genetic susceptibility + environmental triggers + immune dysregulation + altered microbiome:

• Genetics: >200 susceptibility loci identified; NOD2/CARD15 (chromosome 16) — first Crohn's gene identified; ATG16L1 (autophagy); IL23R
• Smoking: strongest modifiable risk factor (2x risk, doubles relapse rate)
• Appendicectomy: may increase risk (opposite to UC)
• Microbiome: reduced diversity (particularly Firmicutes); increased Enterobacteriaceae
• NSAIDs: may trigger flares

Pathophysiology

Genetically determined defects in innate immunity (NOD2 — pattern recognition receptor for muramyl dipeptide) and autophagy lead to impaired handling of intraluminal bacteria. This triggers an excessive adaptive immune response with Th1/Th17 polarisation, producing TNF-α, IL-12, IL-23, and IFN-γ. Transmural inflammation causes the hallmark features: deep ulceration, non-caseating granulomata, fibrosis (strictures), and sinus tract formation (fistulae).

Typical Presentation

• Chronic diarrhoea (usually non-bloody, unlike UC)
• Abdominal pain (often RIF — terminal ileal disease)
• Weight loss and malnutrition
• Fatigue
• Low-grade fever

Disease Location-Specific Features

• Ileal: RIF pain, diarrhoea, B12/bile acid malabsorption, risk of stricture/obstruction
• Colonic: diarrhoea (may be bloody), similar to UC but rectal sparing common
• Perianal: fistulae, abscesses, skin tags — present in 30-40%
• Upper GI: mouth ulcers, dysphagia, gastric outlet obstruction (rare)

Extra-Intestinal Manifestations

• Musculoskeletal: peripheral arthropathy (Type I — large joints, correlates with disease activity; Type II — small joints, independent), sacroiliitis, ankylosing spondylitis (HLA-B27)
• Skin: erythema nodosum (correlates with disease activity), pyoderma gangrenosum (independent)
• Eyes: anterior uveitis, episcleritis
• Hepatobiliary: PSC (rare — more common in UC), gallstones (bile acid malabsorption)
• Renal: oxalate stones (fat malabsorption → increased oxalate absorption)

Red Flags

• Acute abdominal pain with distension (obstruction/perforation)
• Perianal sepsis (abscess requiring drainage)
• Significant GI bleeding
• High-output fistula (dehydration, electrolyte derangement)
• Nutritional failure (BMI <18.5, hypoalbuminaemia)

Bedside

• Stool: faecal calprotectin (>200 μg/g strongly suggests IBD), stool cultures (exclude infection including C. difficile)
• Perianal examination: skin tags, fistula openings, abscess

Bloods

• FBC: anaemia (iron, B12, folate deficiency), raised platelets (inflammation)
• CRP/ESR: disease activity markers
• Albumin: nutritional status and disease severity
• U&Es, LFTs: baseline; LFTs for PSC screening
• Iron studies, B12, folate: nutritional deficiencies
• TPMT/NUDT15: before starting thiopurines (azathioprine/mercaptopurine)

Imaging

• MR enterography (MRE): gold standard for small bowel assessment — strictures, fistulae, inflammation, abscess
• Pelvic MRI: perianal disease assessment (fistula mapping)
• CT abdomen: if acute presentation (perforation, abscess, obstruction)
• Abdominal USS: thickened bowel wall, abscess detection

Special Tests

• Ileocolonoscopy + biopsies: gold standard for diagnosis — assess from terminal ileum to rectum
  • Findings: aphthous ulcers, deep serpiginous ulcers, cobblestoning, skip lesions, relative rectal sparing
  • Histology: non-caseating granulomata (30-50%), transmural inflammation, lymphoid aggregates
• Upper GI endoscopy: if upper GI symptoms
• Capsule endoscopy: small bowel assessment if MRE inconclusive (ensure no stricture first)
• Montreal classification: age at diagnosis (A1/A2/A3), location (L1-L4), behaviour (B1-B3 + p for perianal)

Non-pharmacological

• Smoking cessation: most important modifiable factor — doubles relapse rate if continues
• Nutritional support: dietitian involvement; correct deficiencies
• Exclusive enteral nutrition (EEN): first-line for inducing remission in children/adolescents (equal to steroids); used adjunctively in adults
• MDT approach: gastroenterologist, surgeon, dietitian, IBD nurse specialist, psychologist

Pharmacological

• Inducing remission:
  • Mild-moderate: budesonide 9 mg OD for 8 weeks (ileal/right-sided); oral prednisolone 40 mg OD tapering over 8 weeks (extensive/severe)
  • Moderate-severe/steroid-dependent: anti-TNF therapy (infliximab 5 mg/kg IV at 0, 2, 6 weeks then 8-weekly; OR adalimumab 160 mg then 80 mg then 40 mg EOW)
  • Refractory: vedolizumab (anti-α4β7 integrin), ustekinumab (anti-IL12/23), risankizumab (anti-IL23)
• Maintaining remission:
  • Thiopurines: azathioprine 2-2.5 mg/kg/day or mercaptopurine 1-1.5 mg/kg/day (check TPMT/NUDT15)
  • Methotrexate: 15-25 mg/week SC/IM (second-line maintenance)
  • Biologics: continued anti-TNF, vedolizumab, ustekinumab — most effective for maintaining remission
• Perianal disease: antibiotics (metronidazole 400 mg TDS + ciprofloxacin 500 mg BD), anti-TNF (infliximab most evidence), seton drainage
• 5-ASAs (mesalazine): limited role in Crohn's (unlike UC); may have modest benefit in mild colonic Crohn's

Surgical/Interventional

• Surgery needed in ~50% within 10 years of diagnosis
• Ileocaecal resection: for refractory ileal disease or stricture (LIR!C trial — comparable to infliximab for limited ileocaecal Crohn's)
• Stricturoplasty: bowel-preserving option for short strictures
• Abscess drainage: percutaneous or surgical
• Seton insertion: for perianal fistulae
• Defunctioning stoma: for severe perianal or colonic disease

Referral Criteria

• All IBD to gastroenterology for specialist management
• IBD nurse specialist for ongoing support
• Surgical referral for complications (stricture, abscess, fistula)
• Fertility/obstetric counselling before pregnancy (optimise disease control)

Crohn's disease is a lifelong condition with relapsing-remitting course. ~50% require surgery within 10 years of diagnosis. Post-operative recurrence is common (~50% endoscopic recurrence at 1 year). Smoking cessation reduces relapse by 50%. Biologics have significantly improved outcomes — reduced hospitalisation and surgery rates. Mortality is slightly increased compared to general population (standardised mortality ratio 1.2-1.5). Colorectal cancer risk is increased in Crohn's colitis (similar magnitude to UC — surveillance colonoscopy recommended).

Montreal Classification

Crohn's vs Ulcerative Colitis