Crohn's Disease
Summary
Crohn's disease is a chronic, relapsing inflammatory bowel disease (IBD) characterised by transmural inflammation affecting any part of the gastrointestinal tract from mouth to anus. It classically involves the terminal ileum and right colon, but can affect any site in a discontinuous pattern ("skip lesions"). Histologically, non-caseating granulomas are pathognomonic. The clinical course is marked by periods of remission and flare. Common presentations include abdominal pain, diarrhoea (usually non-bloody), weight loss, and fatigue. Complications include strictures, fistulae, abscesses, and perianal disease. Treatment involves induction of remission (corticosteroids, enteral nutrition) and maintenance therapy (thiopurines, biologics such as anti-TNF agents). Surgery is reserved for complications but does not cure the disease.
Key Facts
- Distribution: Mouth to anus; terminal ileum most common (~50%); skip lesions
- Inflammation: Transmural (full thickness) — distinguishes from UC
- Histology: Non-caseating granulomas (40-60%); lymphoid aggregates
- Macroscopic features: Cobblestone mucosa; deep ulcers; strictures; fistulae
- Symptoms: Diarrhoea (often non-bloody), abdominal pain (RIF), weight loss, fatigue
- Extra-intestinal manifestations: Arthritis, uveitis, erythema nodosum, pyoderma gangrenosum
- Treatment: Steroids (induction); Thiopurines (maintenance); Biologics (anti-TNF, vedolizumab, ustekinumab)
- Surgery: 50-80% require surgery in lifetime; does NOT cure (recurrence common)
Clinical Pearls
"Skip Lesions = Crohn's": Unlike ulcerative colitis (continuous from rectum), Crohn's has discontinuous ("skip") lesions with normal bowel in between.
"Terminal Ileum Is the Hotspot": The terminal ileum is involved in ~50% of cases. Right iliac fossa pain and a palpable mass may mimic appendicitis.
"Transmural = Complications": Full-thickness inflammation leads to strictures, fistulae, and abscesses. UC is mucosal only and doesn't form fistulae.
"Surgery Doesn't Cure": Unlike UC, surgery is not curative in Crohn's. Recurrence at the anastomosis site is common. Avoid extensive resections.
"Biologics Have Transformed Treatment": Anti-TNF agents (infliximab, adalimumab), vedolizumab (anti-α4β7 integrin), and ustekinumab (anti-IL-12/23) have dramatically improved outcomes in moderate-severe Crohn's.
Why This Matters Clinically
Crohn's disease is a lifelong condition with significant morbidity. Early diagnosis, aggressive treatment of inflammation to achieve mucosal healing, and appropriate use of biologics can prevent complications and preserve bowel function. Understanding the distinction from UC and the indications for surgery is essential.[1,2]
Incidence & Prevalence
| Parameter | Data |
|---|---|
| Incidence | 5-10 per 100,000/year (UK) |
| Prevalence | ~150 per 100,000 |
| Peak age | 15-30 years (second peak 50-70) |
| Sex ratio | Slight female predominance |
| Geography | Higher in northern latitudes; Western countries |
Risk Factors
| Factor | Notes |
|---|---|
| Genetics | NOD2/CARD15 mutations; family history (10% have affected relative) |
| Smoking | Major modifiable risk factor; worsens disease; increases surgery risk |
| Western diet | Possible link (low fibre, high fat/sugar) |
| Appendicectomy | Protective for UC; NOT for Crohn's |
| NSAIDs | May trigger flares |
Pathophysiological Mechanism
Step 1: Genetic Susceptibility
- NOD2/CARD15, ATG16L1, IL23R mutations
- Defective innate immune response to gut bacteria
Step 2: Environmental Trigger
- Gut dysbiosis; altered microbiome
- Impaired mucosal barrier
Step 3: Dysregulated Immune Response
- Th1/Th17 predominant response
- Excessive TNF-α, IL-12, IL-23 production
- Granuloma formation
Step 4: Transmural Inflammation
- Full-thickness bowel wall involvement
- Lymphoid aggregates; fibrosis
Step 5: Complications
- Strictures (fibrosis)
- Fistulae (track formation)
- Abscesses
Montreal Classification
| Parameter | Classification |
|---|---|
| Age at diagnosis (A) | A1: <16 years; A2: 17-40 years; A3: >40 years |
| Location (L) | L1: Ileal; L2: Colonic; L3: Ileocolonic; L4: Upper GI (modifier) |
| Behaviour (B) | B1: Non-stricturing, non-penetrating; B2: Stricturing; B3: Penetrating; p: Perianal modifier |
Histological Features
| Feature | Notes |
|---|---|
| Non-caseating granulomas | Pathognomonic (40-60%); collections of epithelioid histiocytes |
| Transmural inflammation | Affects all layers of bowel wall |
| Lymphoid aggregates | Deep in the wall |
| Skip lesions | Normal bowel between affected segments |
| Fissuring ulcers | Deep knife-like ulcers |
Symptoms
| Symptom | Frequency | Notes |
|---|---|---|
| Diarrhoea | 80% | Usually non-bloody (unless colonic involvement) |
| Abdominal pain | 70% | Often RIF; colicky; post-prandial |
| Weight loss | 50-70% | Malabsorption; reduced intake |
| Fatigue | Common | Chronic disease; anaemia |
| Mouth ulcers | 10-20% | Aphthous ulcers |
| Perianal symptoms | 30% | Fistulae; abscesses; skin tags |
Signs
| Sign | Notes |
|---|---|
| RIF mass | Inflamed terminal ileum or abscess |
| Perianal disease | Fistulae; skin tags; abscesses |
| Anaemia | Pallor (iron deficiency; B12 in ileal disease) |
| Malnutrition | Cachexia; low BMI |
| Clubbing | Occasionally |
Extra-Intestinal Manifestations
| System | Manifestations |
|---|---|
| Joints | Peripheral arthritis (correlates with disease activity); Ankylosing spondylitis; Sacroiliitis |
| Skin | Erythema nodosum (correlates with activity); Pyoderma gangrenosum |
| Eyes | Uveitis; Episcleritis |
| Liver | Primary sclerosing cholangitis (more common in UC); Fatty liver |
| Haematological | Anaemia; VTE risk |
| Renal | Oxalate stones (ileal disease) |
Red Flags
[!CAUTION] Red Flags — Urgent Assessment:
- Bowel obstruction (obstipation, distension, vomiting)
- Severe perianal disease (abscess, complex fistula)
- High-output fistula (malnutrition, dehydration)
- Sepsis (abscess, perforation)
- Toxic megacolon (colonic dilatation, sepsis)
Abdominal Examination
| Finding | Significance |
|---|---|
| RIF mass | Inflamed terminal ileum; abscess |
| Tenderness | Active inflammation; abscess |
| Distension | Obstruction |
| Surgical scars | Previous bowel resection |
| Visible peristalsis | Obstruction |
Perianal Examination
| Finding | Notes |
|---|---|
| Skin tags | Large, elephant-ear tags common |
| Fistula openings | External openings with discharge |
| Abscess | Tender swelling |
| Scarring | Previous surgery/disease |
Nutritional Assessment
- BMI
- Mid-arm circumference
- Albumin
- Signs of specific deficiencies (glossitis, koilonychia, angular stomatitis)
Blood Tests
| Test | Finding |
|---|---|
| FBC | Anaemia (iron, B12, folate); Thrombocytosis; Leukocytosis |
| CRP / ESR | Elevated (correlates with activity) |
| Albumin | Low (malnutrition, active disease) |
| LFTs | May be abnormal (PSC, fatty liver) |
| Vitamin B12 | Low in ileal disease |
| Iron, Ferritin | Low (GI blood loss, malabsorption) |
Faecal Markers
| Test | Notes |
|---|---|
| Faecal calprotectin | Elevated; correlates with intestinal inflammation; used for diagnosis and monitoring |
| Stool culture | Exclude infection (C. diff, etc.) |
Endoscopy
| Procedure | Findings |
|---|---|
| Colonoscopy + Ileoscopy | Gold standard; cobblestoning; deep ulcers; skip lesions; strictures |
| Histology | Granulomas; transmural inflammation |
| Upper GI endoscopy | If upper GI symptoms |
| Capsule endoscopy | For small bowel assessment (exclude stricture first) |
Imaging
| Modality | Use |
|---|---|
| MR Enterography | Small bowel assessment; strictures; fistulae; preferred for monitoring |
| CT Abdomen | Abscess; perforation; obstruction (acute setting) |
| Pelvic MRI | Perianal fistula assessment (complex anatomy) |
Management Algorithm
CROHN'S DISEASE MANAGEMENT
↓
┌────────────────────────────────────────────────────────────┐
│ INITIAL DIAGNOSIS │
├────────────────────────────────────────────────────────────┤
│ ➤ Confirm diagnosis: Endoscopy + Biopsy + Imaging │
│ ➤ Exclude infection (stool culture, C. diff) │
│ ➤ Montreal classification (age, location, behaviour) │
│ ➤ Assess severity (symptoms, CRP, faecal calprotectin) │
│ ➤ Screen for TB/Hep B before biologics │
└────────────────────────────────────────────────────────────┘
↓
┌────────────────────────────────────────────────────────────┐
│ INDUCING REMISSION │
├────────────────────────────────────────────────────────────┤
│ MILD-MODERATE ILEOCAECAL CROHN'S: │
│ ➤ Budesonide 9 mg OD (locally acting steroid) │
│ ➤ OR Systemic corticosteroids (Prednisolone) │
│ │
│ MILD-MODERATE COLONIC CROHN'S: │
│ ➤ Prednisolone 40 mg OD tapering │
│ ➤ Mesalazine NOT effective (unlike UC) │
│ │
│ MODERATE-SEVERE / EXTENSIVE: │
│ ➤ IV Hydrocortisone (if acute severe) │
│ ➤ Early biologics: Anti-TNF (Infliximab, Adalimumab) │
│ ➤ Vedolizumab or Ustekinumab (alternative) │
│ │
│ PAEDIATRIC: │
│ ➤ Exclusive Enteral Nutrition (EEN) first-line │
└────────────────────────────────────────────────────────────┘
↓
┌────────────────────────────────────────────────────────────┐
│ MAINTAINING REMISSION │
├────────────────────────────────────────────────────────────┤
│ FIRST-LINE: │
│ ➤ Azathioprine 2-2.5 mg/kg/day OR │
│ ➤ Mercaptopurine 1-1.5 mg/kg/day │
│ ➤ Check TPMT before starting (toxicity risk) │
│ │
│ BIOLOGIC MAINTENANCE: │
│ ➤ Anti-TNF: Infliximab 5 mg/kg q8 weeks; Adalimumab 40 │
│ mg every 2 weeks │
│ ➤ Vedolizumab 300 mg IV q8 weeks │
│ ➤ Ustekinumab q8-12 weeks │
│ │
│ STEROIDS ARE NOT FOR MAINTENANCE │
│ ⚠️ Steroid-dependency = escalate therapy │
└────────────────────────────────────────────────────────────┘
↓
┌────────────────────────────────────────────────────────────┐
│ SURGICAL MANAGEMENT │
├────────────────────────────────────────────────────────────┤
│ INDICATIONS: │
│ ➤ Failed medical therapy │
│ ➤ Stricture with obstruction │
│ ➤ Fistulae (especially complex) │
│ ➤ Abscess (drainage + antibiotics) │
│ ➤ Perforation │
│ ➤ Dysplasia/malignancy │
│ │
│ PRINCIPLES: │
│ ➤ Bowel-sparing: Limit resection length │
│ ➤ Strictureplasty for short strictures │
│ ➤ Recurrence at anastomosis common │
│ │
│ PERIANAL DISEASE: │
│ ➤ Abscess: Incision and drainage │
│ ➤ Fistula: Seton; biologics; complex surgery if needed │
└────────────────────────────────────────────────────────────┘
Biologic Agents
| Drug | Mechanism | Notes |
|---|---|---|
| Infliximab | Anti-TNF-α (chimeric) | IV infusion; requires IV access |
| Adalimumab | Anti-TNF-α (human) | Subcutaneous; self-administered |
| Vedolizumab | Anti-α4β7 integrin | Gut-selective; safer for elderly |
| Ustekinumab | Anti-IL-12/23 | Used in moderate-severe; q8-12 weeks |
Intestinal Complications
| Complication | Notes |
|---|---|
| Stricture | Fibrotic or inflammatory; causes obstruction |
| Fistula | Enteroenteric; enterocutaneous; enterovesical; rectovaginal |
| Abscess | Intra-abdominal or perianal; requires drainage |
| Perforation | Rare; surgical emergency |
| Malabsorption | B12 (ileal disease); fat-soluble vitamins; bile salt diarrhoea |
| Short bowel syndrome | After multiple resections |
Perianal Disease
| Manifestation | Notes |
|---|---|
| Skin tags | Often large; not usually surgically removed |
| Fissures | Often lateral (unlike typical midline) |
| Fistulae | Complex tracts; MRI useful |
| Abscesses | Require drainage |
| Stenosis | Rare |
Malignancy
| Cancer | Risk |
|---|---|
| Small bowel adenocarcinoma | Increased risk |
| Colorectal cancer | Increased if longstanding colonic disease; surveillance after 8 years |
Natural History
| Outcome | Notes |
|---|---|
| Relapsing course | Most patients; periods of remission and flare |
| Surgery | 50-80% require surgery within 10-15 years |
| Recurrence after surgery | Common (~50% at 5 years at anastomosis site) |
| Mucosal healing | Associated with better long-term outcomes |
Prognostic Markers
| Good Prognosis | Poor Prognosis |
|---|---|
| Colonic disease only | Ileal or ileocolonic disease |
| Non-stricturing, non-penetrating | Stricturing or penetrating behaviour |
| Non-smoker | Smoker |
| Early response to therapy | Steroid dependency |
| Mucosal healing | Persistent inflammation |
Key Guidelines
| Guideline | Organisation | Year | Key Points |
|---|---|---|---|
| Crohn's Disease Management (NG129) | NICE | 2019 | Diagnosis, treatment, monitoring |
| ECCO Guidelines | ECCO | 2020 | European IBD consensus |
Landmark Evidence
SONIC Trial (2010)
- Infliximab + Azathioprine superior to either alone for moderate-severe Crohn's
- Established combination therapy as standard
- PMID: 20410503
What is Crohn's disease?
Crohn's disease is a lifelong condition that causes inflammation in the digestive system. It can affect anywhere from the mouth to the bottom, but most commonly affects the end of the small bowel (ileum) and the large bowel (colon).
What are the symptoms?
- Tummy pain (often on the right side)
- Diarrhoea (usually without blood)
- Tiredness and fatigue
- Weight loss
- Mouth ulcers
- Problems around the bottom (pain, discharge)
What causes it?
The exact cause is unknown, but it's thought to be an abnormal immune reaction in the gut, possibly triggered by bacteria. It runs in families and is made worse by smoking.
How is it treated?
- During flares: Steroids to reduce inflammation
- To keep it under control: Tablets called immunosuppressants (like azathioprine) or injections called biologics (like infliximab)
- Surgery: Sometimes needed for complications like blockages or fistulas
Can Crohn's be cured?
Crohn's cannot be cured, but it can be well-controlled with treatment. Many people live full, active lives. Stopping smoking is one of the most important things you can do to improve your disease.
Guidelines
- NICE. Crohn's disease: management (NG129). 2019. nice.org.uk/guidance/ng129
Key Trials
- Colombel JF, Sandborn WJ, Reinisch W, et al. Infliximab, azathioprine, or combination therapy for Crohn's disease (SONIC). N Engl J Med. 2010;362(15):1383-1395. PMID: 20410503
High-Yield Exam Topics
| Topic | Key Points |
|---|---|
| Distribution | Mouth to anus; skip lesions; terminal ileum most common |
| Inflammation | Transmural vs mucosal (UC) |
| Histology | Non-caseating granulomas |
| Complications | Strictures, fistulae, abscesses |
| Induction | Steroids (budesonide for ileocaecal); EEN in children |
| Maintenance | Thiopurines; biologics (anti-TNF, vedolizumab, ustekinumab) |
| Smoking | Worsens Crohn's (improves UC) |
Sample Viva Questions
Q1: How do you differentiate Crohn's disease from Ulcerative Colitis?
Model Answer:
| Feature | Crohn's Disease | Ulcerative Colitis |
|---|---|---|
| Distribution | Mouth to anus; skip lesions | Rectum → proximal; continuous |
| Inflammation | Transmural | Mucosal only |
| Histology | Non-caseating granulomas | Crypt abscesses; goblet cell depletion |
| Complications | Fistulae, strictures, abscesses | Toxic megacolon; Cancer (higher) |
| Bleeding | Usually non-bloody | Bloody diarrhoea |
| Perianal disease | Common (30%) | Rare |
| Surgery | Not curative; recurs | Curative (panproctocolectomy) |
| Smoking | Worsens disease | Protective |
Q2: What are the management options for moderate-severe Crohn's disease?
Model Answer: For moderate-severe Crohn's:
- Induction: Systemic corticosteroids (Prednisolone 40 mg tapering) OR early biologics if high-risk features
- Biologics: Infliximab (anti-TNF) or Adalimumab; Vedolizumab (gut-selective); Ustekinumab (anti-IL-12/23)
- Maintenance: Thiopurines (Azathioprine/Mercaptopurine) or ongoing biologics. SONIC trial showed combination infliximab + azathioprine is superior.
- Steroid-dependent disease: Escalate to biologics; steroids are NOT for maintenance
Q3: What are the indications for surgery in Crohn's disease?
Model Answer: Surgery is NOT curative in Crohn's (unlike UC). Indications:
- Failed medical therapy (refractory disease)
- Fibrotic stricture with obstruction (strictureplasty or resection)
- Fistulae (especially complex or symptomatic)
- Abscess (drainage ± resection)
- Perforation (emergency)
- Dysplasia or malignancy
Principles: Bowel-sparing surgery; limit resection length; recurrence at anastomosis is common. Post-operative medical prophylaxis (thiopurines, biologics) reduces recurrence.
Common Exam Errors
| Error | Correct Approach |
|---|---|
| Using mesalazine in Crohn's | Mesalazine is NOT effective for Crohn's (works in UC) |
| Prescribing steroids for maintenance | Steroids are induction only; escalate if steroid-dependent |
| Thinking surgery cures Crohn's | NOT curative; recurrence common |
| Confusing EEN with adult treatment | EEN is first-line in paediatric Crohn's, not adults |
Last Reviewed: 2025-12-24 | MedVellum Editorial Team
Medical Disclaimer: MedVellum content is for educational purposes and clinical reference. Clinical decisions should account for individual patient circumstances. Always consult appropriate specialists.