Crohn's Disease

I. Definition

Crohn's Disease (CD) is a chronic, relapsing-remitting inflammatory bowel disease (IBD) characterised by patchy transmural inflammation, which may affect any part of the GI tract ^[1]. Let's break the name and definition down:

• Crohn's — named after Dr. Burrill Crohn who described it in 1932
• Patchy — the inflammation is not continuous; there are "skip lesions" (diseased segments interspersed with normal bowel)
• Transmural — "trans" = through, "mural" = wall; inflammation penetrates the full thickness of the bowel wall (mucosa → submucosa → muscularis propria → serosa). This is fundamentally different from UC which is limited to mucosa/submucosa, and it explains why CD causes fistulae, abscesses, and strictures while UC generally does not ^[1][2].
• Any part of the GI tract — from mouth to perianal area, though it most commonly affects the terminal ileum ± colon ^[2]

Indeterminate colitis accounts for ~10-15% of IBD patients who fail to be classified between UC vs CD, either due to inadequate tissue biopsy or a truly indeterminate form of disease. Surgical treatment for these patients follows UC principles ^[1][2].

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II. Epidemiology

Incidence and Prevalence

• Incidence is rising globally, particularly in newly industrialised countries in Asia (including Hong Kong), though overall rates remain lower than in the West ^[1]
• CD prevalence: urban > rural areas, higher socioeconomic classes — this supports the "hygiene hypothesis" (see Etiology) ^[1]
• Hong Kong context: IBD incidence has been rising steadily since the 1980s. The HK IBD registry shows CD incidence approximately 1-2 per 100,000 — lower than Western countries (5-10 per 100,000) but rapidly increasing ^[1]

Age and Gender

• Peak age of onset for CD: in the third decade (i.e., 20–30 years old) ^[1]
• There is a possible second smaller peak around 50–70 years (bimodal distribution)
• Gender: CD F > M globally, but M > F in East Asia ^[1] — this is an important exam distinction. In Hong Kong, there is a slight male predominance, which is the opposite of Western data ^[1]

East vs. West Differences (High Yield for HKU Exams)

East Asian IBD (including Hong Kong) differs from Western IBD ^[1]:

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III. Risk Factors

Established Risk Factors for Crohn's Disease

1. Smoking — Smoking is a risk factor for Crohn's disease (but NOT ulcerative colitis — in fact, smoking is PROTECTIVE for UC) ^[2]

   • Why? Smoking impairs Th1/Th17 immune regulation, reduces mucosal blood flow, and alters the gut microbiome. CD is predominantly a Th1/Th17-mediated disease, and smoking amplifies this pathway. UC is predominantly Th2-mediated, and nicotine appears to enhance mucus production and colonic mucosal blood flow, which are protective in UC.
   • Smoking doubles the risk of CD, increases the risk of relapse, the need for surgery, and post-operative recurrence

2. Prior appendicectomy — Prior appendicectomy is a risk factor for Crohn's disease (conversely, protective for UC) ^[2]

   • The mechanism is debated: appendicectomy may alter the gut immune landscape, removing an immune regulatory organ (the appendix contains significant lymphoid tissue)

3. Family history — Family history of IBD ^[2]

   • First-degree relative with CD increases risk 5-20×
   • Concordance rate in monozygotic twins ~50% for CD (vs. ~15% for UC), indicating a stronger genetic component in CD
   • Less family clustering in East Asia compared to West ^[1]

4. Infectious gastroenteritis — Infectious gastroenteritis in the prior 1 year is a risk factor ^[2]

   • Likely through disruption of the mucosal barrier and alteration of the gut microbiome, triggering an abnormal immune response in genetically susceptible individuals

5. Drug history

   • NSAIDs can trigger flares (they inhibit protective prostaglandin synthesis in the gut, disrupt the mucosal barrier, and may increase intestinal permeability) ^[3]
   • Oral contraceptives — modest increased risk, possibly through microvascular thrombosis
   • Isotretinoin — previously suggested but now considered controversial

6. Diet

   • High refined sugar, low fibre, high fat, high processed food diets are associated with increased risk
   • Western diet in Asia may explain the rising incidence

7. Genetic factors

   • NOD2/CARD15 gene mutation (chromosome 16) — the most well-established genetic association with CD (particularly ileal disease and stricturing phenotype)
     • NOD2 is an intracellular receptor for bacterial muramyl dipeptide. Mutation → defective innate immune response to gut bacteria → paradoxical chronic inflammation
   • ATG16L1 and IRGM genes — involved in autophagy (cellular "self-eating" of damaged organelles/bacteria). Mutations impair bacterial clearance
   • IL23R gene — involved in Th17 differentiation

   • 200 susceptibility loci identified by GWAS

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IV. Anatomy and Function (Relevant to CD)

Understanding the anatomy is critical because CD's transmural, skip-lesion pattern directly determines its clinical manifestations and complications.

Terminal Ileum — The Most Common Site

• The terminal ileum is the last ~20-30 cm of the ileum before the ileocaecal valve
• Functions: absorption of vitamin B12 (cobalamin) and bile salts
  • B12 absorption occurs ONLY in the terminal ileum → CD affecting this area → B12 deficiency → megaloblastic anaemia, subacute combined degeneration of the spinal cord
  • Bile salt absorption occurs in the terminal ileum → malabsorption of bile salts → bile salt diarrhoea (bile salts reach the colon and stimulate secretion) AND gallstone formation (reduced bile salt pool → cholesterol supersaturation of bile) ^[2]
• Contains the highest concentration of Peyer's patches (organized lymphoid tissue) — the initial site of immune activation in CD

Bowel Wall Layers (Why Transmural Matters)

This is why fistula formation and abscess formation are features of CD but NOT UC ^[1][2]. In UC, inflammation is limited to mucosa/submucosa and never penetrates deeply enough to form fistulae.

Mesentery

• CD characteristically involves mesenteric fat wrapping ("creeping fat" / "fat wrapping") — the mesenteric fat hypertrophies and wraps around the inflamed bowel segment
• This is thought to be an attempt by the mesentery to contain transmural inflammation
• On surgical inspection, this is pathognomonic of CD

Perianal Anatomy

• Perianal disease occurs in up to 40% of CD patients ^[1] — a very common and debilitating manifestation
• The perianal region includes the anal canal, internal and external sphincters, and the ischiorectal and intersphincteric spaces
• Perianal CD includes: fistulae-in-ano, perianal abscesses, skin tags, fissures, and anorectal strictures

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V. Etiology and Pathophysiology

The pathogenesis of Crohn's disease involves a complex interplay of four key elements. Think of it as a "perfect storm":

The Four-Hit Model

1. Genetic Susceptibility

• NOD2/CARD15 (chromosome 16q12): The most important genetic risk factor

  • NOD2 = "nucleotide-binding oligomerisation domain-containing protein 2" — an intracellular pattern recognition receptor (PRR) in macrophages and dendritic cells
  • Normally recognises muramyl dipeptide (MDP), a component of bacterial peptidoglycan → triggers NF-κB pathway → appropriate antimicrobial response + defensin production
  • Mutation → impaired bacterial sensing → defective defensin production → bacteria breach the mucosal barrier → compensatory over-activation of adaptive immunity → chronic inflammation
  • Associated with ileal disease and stricturing phenotype

• ATG16L1 and IRGM — autophagy genes

  • Autophagy = "auto" (self) + "phagy" (eating) — cellular housekeeping that clears intracellular bacteria and damaged organelles
  • Defective autophagy → impaired clearance of intracellular bacteria (e.g., adherent-invasive E. coli) → persistent immune stimulation

• IL23R — interleukin-23 receptor

  • IL-23 drives Th17 cell differentiation → IL-17 production → mucosal inflammation
  • Variants can be protective or risk-enhancing

2. Environmental Triggers

• Smoking (see Risk Factors)
• Diet: Western diet (high sugar, fat, processed food; low fibre) alters microbiome composition
• Antibiotics: Early-life antibiotic exposure may alter the developing microbiome
• Hygiene hypothesis: Growing up in overly hygienic environments → reduced microbial exposure in childhood → immature immune regulation → exaggerated response to commensal bacteria later in life. This explains the higher prevalence in urban > rural areas and higher socioeconomic classes ^[1]
• Infections: Prior GI infections may trigger disease in susceptible individuals
• Stress: Does not cause CD but can trigger flares via the gut-brain axis (cortisol → altered gut permeability and immune function)
• Vitamin D deficiency: Vitamin D is immunomodulatory; deficiency is associated with increased CD risk and disease activity

3. Gut Microbiome Dysbiosis

• CD patients have reduced microbial diversity, particularly:
  • Reduced Firmicutes (especially Faecalibacterium prausnitzii — a butyrate producer with anti-inflammatory properties)
  • Increased Proteobacteria (especially adherent-invasive E. coli — AIEC)
• Butyrate is a short-chain fatty acid that is the primary energy source for colonocytes and has anti-inflammatory effects. Its reduction → mucosal energy deficit → barrier dysfunction
• Whether dysbiosis is a cause or consequence of CD remains debated, but it clearly perpetuates the inflammatory cycle

4. Epithelial Barrier Defect

• Increased intestinal permeability ("leaky gut") is a feature of CD, even in unaffected relatives of CD patients
• Defective tight junctions, reduced mucus layer, and impaired Paneth cell function (Paneth cells secrete defensins — antimicrobial peptides)
• Barrier breach → luminal bacteria/antigens access the lamina propria → immune activation

Immune Pathways in CD

• CD is primarily a Th1 and Th17-mediated disease (in contrast to UC which is Th2-mediated)
• Key cytokines:
  • TNF-α: The master pro-inflammatory cytokine in CD → drives macrophage activation, granuloma formation, and tissue destruction. This is the therapeutic target of anti-TNF agents (infliximab, adalimumab)
  • IFN-γ: Produced by Th1 cells → activates macrophages
  • IL-12 and IL-23: Drive Th1 and Th17 differentiation respectively. Ustekinumab targets IL-12/23
  • IL-17: Produced by Th17 cells → recruits neutrophils, perpetuates mucosal inflammation
  • α4β7 integrin: A homing molecule on T cells that directs them to the gut. Vedolizumab blocks this

Granuloma Formation

• Non-caseating granulomas are the histological hallmark of CD (found in ~30-50% of biopsies)
• A granuloma is an organised collection of macrophages (epithelioid cells) ± multinucleated giant cells, surrounded by a collar of lymphocytes
• They form because macrophages cannot fully clear the antigenic stimulus → they aggregate and wall it off
• MUST exclude TB when granulomas are found — TB granulomas are typically caseating (central necrotic cheese-like material), but this distinction is not always clear on biopsy, and TB is common in Hong Kong ^[2]

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VI. Classification

Montreal Phenotypical Classification [1][2]

This is the standard classification system for CD, classifying by Age at diagnosis, Location, and Behaviour:

Clinical Subtypes of CD [2]

Disease Activity — Crohn's Disease Activity Index (CDAI) [2]

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VII. Clinical Features

The clinical features of CD are directly determined by the disease location, behaviour, and severity. The transmural nature of inflammation is the root cause of most unique CD features.

A. Symptoms

1. Gastrointestinal Symptoms

a) Chronic Diarrhoea (most common presenting symptom)

• Mechanism: Multifactorial:
  • Mucosal inflammation → impaired water/electrolyte absorption → osmotic and secretory diarrhoea
  • Bile salt malabsorption (terminal ileal disease) → bile salts reach colon → stimulate colonic secretion (secretory diarrhoea)
  • Bacterial overgrowth in strictured/stagnant loops → deconjugation of bile salts → fat malabsorption → steatorrhoea
  • Fistulae bypassing absorptive surface → reduced transit time
• CD diarrhoea is typically non-bloody (unless colonic involvement) — this contrasts with UC where bloody diarrhoea is the hallmark
• When the colon is involved, there may be fresh blood in stool and urgency ^[5]

b) Abdominal Pain

• Typically right lower quadrant (RLQ) pain — because the terminal ileum/ileocaecal region is the most commonly affected ^[2][6]
• Mechanism: Transmural inflammation → serosal irritation → localised peritoneal pain in the RLQ
• Pain may be colicky (crampy, intermittent) — especially with stricturing disease → partial small bowel obstruction (SBO) → waves of peristalsis against obstruction
• Post-prandial pain — eating stimulates peristalsis → bowel contracts against a stricture → pain → patient stops eating → weight loss (this is "food fear")
• The RLQ mass from ileocaecal CD is a classic exam finding

c) Nausea and Vomiting

• More common in CD than UC because CD can affect the upper GI tract
• In moderate-severe disease: intermittent vomiting ^[2]
• In stricturing disease: vomiting due to small bowel obstruction

d) Perianal Symptoms

• Perianal disease in up to 40% of CD patients ^[1]
• Perianal pain, discharge (purulent or faecal), swelling
• Symptoms include: perianal abscess (throbbing pain, swelling, fever), fistula-in-ano (persistent discharge), anal fissure (sharp pain on defecation), skin tags (painless but characteristic — "sentinel tags")
• Mechanism: Transmural inflammation extends through the rectal wall into the perianal tissues → tracks through tissue planes → abscess → fistula

e) Oral Symptoms

• Oral aphthous ulcers — small, painful ulcers on the buccal mucosa, gums, or tongue
• Mechanism: CD can affect any part of the GI tract including the oral mucosa; aphthous ulcers represent mucosal inflammation
• Present in ~10% of CD patients; may be the first manifestation

f) Dysphagia / Odynophagia

• Rare; occurs with oesophageal or gastric CD
• Upper GI CD with stricturing may cause dysphagia

2. Systemic/Constitutional Symptoms

a) Weight Loss

• Very common and multifactorial:
  • Reduced oral intake ("food fear" — eating provokes pain)
  • Malabsorption (inflamed mucosa, reduced absorptive surface, bile salt malabsorption)
  • Increased catabolism from chronic inflammation (TNF-α, IL-6 → systemic inflammatory response → muscle wasting)
  • Protein-losing enteropathy (inflamed mucosa leaks protein into the lumen)
• In severe disease: cachexia with BMI < 18 ^[2]

b) Fever

• Low-grade fever in active disease (pro-inflammatory cytokines act on the hypothalamus)
• High fever suggests complication: abscess, perforation, or superimposed infection

c) Fatigue

• Anaemia (iron deficiency from chronic blood loss or malabsorption; B12 deficiency from terminal ileal disease; anaemia of chronic disease from chronic inflammation)
• Chronic inflammation itself causes fatigue via cytokine-mediated effects on the CNS

d) Growth Retardation (Paediatric CD)

• CD presenting before puberty can cause delayed growth and delayed puberty
• Mechanism: Chronic inflammation → high TNF-α/IL-6 → suppresses growth hormone axis; malnutrition; corticosteroid use further impairs growth

3. Extraintestinal Manifestations (EIMs)

Extraintestinal manifestations are fewer in East Asian CD compared to Western CD ^[1], but they still occur and are high-yield for exams.

EIMs can be classified by whether they correlate with disease activity or are independent of disease activity:

EIMs that Correlate with Disease Activity (flare when gut disease flares):

EIMs Independent of Disease Activity (persist even when gut disease is quiescent):

EIMs Specific to CD (due to terminal ileal disease/malabsorption):

B. Signs

1. General Examination

• Cachexia / wasting: In severe disease; BMI < 18 — chronic inflammation + malabsorption + reduced intake
• Pallor: Anaemia (iron deficiency, B12 deficiency, anaemia of chronic disease)
• Clubbing: Digital clubbing can occur in CD (mechanism: circulating vasodilators from chronic inflammation → increased blood flow to fingertips → connective tissue hypertrophy)
• Oral aphthous ulcers: Visible on inspection of the oral cavity
• Skin signs: Erythema nodosum (shins), pyoderma gangrenosum (legs, peristomal)
• Eye signs: Episcleritis (red eye without pain/visual loss), anterior uveitis (painful red eye with photophobia)
• Joint signs: Swollen joints (peripheral arthropathy), restricted spinal mobility (sacroiliitis/AS)

2. Abdominal Examination

• RLQ tenderness — most common abdominal sign; reflects terminal ileal/ileocaecal inflammation ^[6]
• RLQ mass — tender mass in moderate disease ^[2]; this represents a phlegmon (inflamed adherent loops of bowel) or an inflammatory mass/abscess
  • Why RLQ? Because the terminal ileum and caecum are in the right iliac fossa
  • This can mimic appendicitis or appendicular mass — a critical differential in a young patient presenting with RLQ pain ^[6]
• Abdominal distension — if bowel obstruction is present (stricturing disease)
• Visible peristalsis — in thin patients with SBO, you may see bowel peristalsis through the abdominal wall
• Surgical scars — previous bowel resections, stoma sites (CD patients often require multiple surgeries)
• Abdominal tenderness — generalised if peritonitis (from perforation), localised to area of active disease
• Fullness/asymmetry — inflammatory mass or abscess

3. Perianal Examination (CRITICAL — Never Skip in CD!)

• Perianal skin tags — large, oedematous, "elephant ear" skin tags are virtually pathognomonic of CD
• Fistula openings — external openings visible perianally; may have purulent or faecal discharge
• Perianal abscess — tender, fluctuant, erythematous swelling
• Anal fissure — classically lateral in CD (vs. posterior midline in idiopathic/benign fissure) — because CD fissures arise from transmural inflammation, not from tearing of the anoderm
• Anorectal stricture — on digital rectal examination (DRE), the examiner may feel narrowing
• Faecal soiling — from fistula or sphincter damage

4. Signs of Complications

• Signs of SBO: Abdominal distension, high-pitched/tinkling bowel sounds, visible peristalsis, vomiting
• Signs of abscess: Localised tenderness, fever, swinging pyrexia, palpable mass
• Signs of fistula: Abnormal openings (enterocutaneous fistula on the abdominal wall), pneumaturia or recurrent UTIs (enterovesical fistula), faeculent vaginal discharge (enterovaginal fistula)
• Signs of perforation: Peritonism (board-like rigidity, rebound tenderness, guarding), absent bowel sounds, tachycardia, hypotension

5. Nutritional Deficiency Signs

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VIII. Disease Pattern Comparison: CD vs UC [1][2]

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IX. Specific Pathological Features Explained

Skip Lesions

• Diseased segments separated by completely normal bowel
• Why? CD inflammation starts at Peyer's patches (discrete lymphoid follicles) → disease begins at these focal points → doesn't spread continuously like UC

Cobblestone Mucosa

• Deep linear ulcers with intervening oedematous mucosa
• The "cobblestones" are the islands of surviving swollen mucosa between ulcer tracks

Creeping Fat

• Mesenteric fat hypertrophy that wraps around the bowel
• The mesentery actively participates in CD inflammation — mesenteric adipocytes produce pro-inflammatory adipokines (TNF-α, leptin)
• Pathognomonic surgical finding

String Sign (on barium studies/CT)

• Severe narrowing of a bowel segment (typically terminal ileum) → a thin line of barium
• Represents a fibrostenotic stricture

Rose-Thorn Ulcers

• Deep, narrow, penetrating ulcers that project into the bowel wall on barium studies
• Named because they look like thorns on a rose stem
• Reflect the transmural nature of CD ulceration

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Active Recall - Crohn's Disease: Definition to Clinical Features

1. A 25-year-old male smoker in Hong Kong presents with chronic diarrhoea and RLQ pain. Colonoscopy shows skip lesions with deep ulcers and non-caseating granulomas in the terminal ileum. What is the diagnosis, and what critical differential must be excluded in Hong Kong? Why?

Your answer

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Diagnosis: Crohn's disease. Must exclude intestinal TB because TB is endemic in HK, both cause granulomatous terminal ileitis. TB granulomas are typically caseating; send tissue for AFB stain/culture and TB PCR. If uncertain, trial of anti-TB therapy may be given.

2. Explain why smoking is a risk factor for Crohn's disease but protective for ulcerative colitis.

Your answer

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CD is Th1/Th17-mediated; smoking amplifies Th1 responses, impairs mucosal blood flow, and alters gut microbiome. UC is Th2-mediated; nicotine enhances mucus production and colonic blood flow, which are protective. Smoking doubles CD risk, increases relapse and surgical rates.

3. List the Montreal classification categories for Crohn's disease and state the most common location and behaviour.

Your answer

Grade

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Age: A1 (less than 16), A2 (17-40), A3 (over 40). Location: L1 ileal (24.5%), L2 colonic (32.3%), L3 ileocolonic (43.1% - most common), L4 isolated upper GI. Behaviour: B1 inflammatory (65.2% - most common), B2 stricturing (25.1%), B3 penetrating (16.1%), P perianal modifier (24.5%).

4. Why does Crohn's disease cause fistulae and abscesses but ulcerative colitis does not?

Your answer

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CD inflammation is transmural (full thickness: mucosa to serosa). When inflammation breaches the serosa, it can track to adjacent structures forming fistulae or become walled-off forming abscesses. UC inflammation is limited to mucosa/submucosa and never penetrates deeply enough.

5. A CD patient with terminal ileal disease develops gallstones and calcium oxalate kidney stones. Explain the pathophysiology of each.

Your answer

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Gallstones: terminal ileal bile salt malabsorption leads to depleted bile salt pool causing cholesterol supersaturation of bile forming cholesterol gallstones. Kidney stones: unabsorbed bile salts and free fatty acids bind calcium in the gut lumen, leaving oxalate free to be absorbed causing hyperoxaluria and calcium oxalate renal stones.

6. List 4 key differences between East Asian and Western IBD as stated in the lecture slides.

Your answer

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1. More male prevalence with CD in East Asia (vs F > M in West). 2. Less family clustering. 3. Lower rates of surgery (5-8%). 4. Higher rates of penetrating and perianal disease in CD. Also: fewer EIMs, less PSC with UC.

References

^[1] Lecture slides: Inflammatory bowel disease.pdf (p2, p4, p5, p6, p8) ^[2] Senior notes: felixlai.md (Inflammatory bowel disease — Crohn's disease section) ^[3] Senior notes: felixlai.md (Inflammatory bowel disease — Ulcerative colitis section, NSAID risk) ^[4] Senior notes: maxim.md (Surgical procedures for CD, management strategy by behaviour) ^[5] Lecture slides: GC 186. Lower and diffuse abdominal painfresh blood in stool.pdf ^[6] Lecture slides: GC 195. Lower and diffuse abdominal pain RLQ problems; pelvic inflammatory disease; peritonitis and abdominal emergencies.pdf

Differential Diagnosis of Crohn's Disease

When a patient presents with features suggestive of Crohn's disease — chronic diarrhoea, abdominal pain (especially RLQ), weight loss, perianal disease, or extraintestinal manifestations — you need a systematic approach to the differential. The key question is: "What else could cause chronic intestinal inflammation, RLQ pain, or bloody diarrhoea?"

The differentials can be organised anatomically and by mechanism. Think about what CD looks like clinically and what other conditions mimic those features.

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Approach to Differential Diagnosis

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Differential Diagnoses — Detailed Breakdown

1. Ulcerative Colitis (UC)

This is the most important differential because both are IBD and share many features ^[2].

Why is this distinction important?

• Surgical approach differs fundamentally: UC is curable by total proctocolectomy (remove colon + rectum → disease is gone). CD is NOT curable by surgery — disease can recur anywhere in the GI tract, so the surgical principle is preservation of bowel length ^[4]. If you misdiagnose UC as CD, you might under-operate; if you misdiagnose CD as UC and create an ileal pouch-anal anastomosis (IPAA), Crohn's recurrence in the pouch is devastating.
• Indeterminate colitis (10%) — when you genuinely cannot distinguish: treat surgically as UC ^[1][2]

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2. Intestinal Tuberculosis

This is the critical differential in Hong Kong where TB is endemic ^[5][2].

Why does intestinal TB mimic CD?

• Both cause granulomatous inflammation of the terminal ileum with strictures and mass formation. The ileocaecal region is the site of highest lymphoid tissue concentration — TB bacilli are ingested, survive in macrophages, and preferentially settle where lymphoid tissue is abundant (Peyer's patches), just like the immune-mediated process of CD.

Key approach in Hong Kong:

• MUST do AFB smear and culture with sensitivity testing on all biopsies to rule out enteric TB ^[2][3]
• If histology is equivocal, a therapeutic trial of anti-TB therapy (2 months) is sometimes given before committing to CD diagnosis and immunosuppressive therapy (which would be disastrous in TB)
• Tissue TB PCR (GeneXpert) has improved sensitivity
• IGRA (QuantiFERON) and Mantoux test assess exposure but cannot distinguish latent from active TB

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3. Infective Colitis / Ileitis [2][5]

Infections including E. coli, Salmonella, Shigella, Campylobacter, Yersinia and amebiasis should be excluded with stool studies ^[2].

Why must you exclude infection before diagnosing CD?

• Starting immunosuppressive therapy (steroids, biologics) in a patient with undiagnosed infection is dangerous — you would worsen the infection
• Infective colitis is self-limiting (days to weeks) while CD is chronic and relapsing
• A single episode of bloody diarrhoea with positive stool cultures = infection, not IBD
• However, note that infectious gastroenteritis in the prior 1 year is actually a risk factor for triggering CD onset in genetically susceptible individuals ^[2]

Key discriminating factors:

• Acute onset (days) vs. chronic/relapsing course (weeks-months) in CD
• Travel history (TOCC — travel, occupation, contacts, clusters)
• Stool cultures, microscopy for ova/parasites, C. difficile toxin PCR ^[3]

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4. Clostridium difficile (C. difficile) Infection [2][3]

C. difficile infection should be considered particularly in patients treated with antibiotics ^[2].

• Pseudomembranous colitis — C. difficile toxins A (enterotoxin) and B (cytotoxin) damage colonocytes → yellowish-white plaques (pseudomembranes) on endoscopy
• Why it matters in CD: C. difficile can superinfect patients with IBD who are on immunosuppression, causing a flare that looks like worsening disease but is actually infection. Always send C. difficile toxin PCR before escalating immunosuppression for an apparent flare ^[3]
• Distinguishing feature: Recent antibiotic use, abrupt watery diarrhoea (may become bloody), pseudomembranes on sigmoidoscopy

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5. Irritable Bowel Syndrome (IBS) [2]

Presents with chronic abdominal pain and altered bowel habits in the absence of an organic cause ^[2].

Why is this differential important?

• IBS is extremely common (10-15% of the population) while CD is rare (~0.1%). Many patients initially diagnosed with IBS actually have early or mild CD. The key is that IBS has no objective evidence of inflammation — if inflammatory markers are elevated, you must investigate further.
• Faecal calprotectin is the most sensitive marker of intestinal inflammation in IBD ^[3] and is the best screening test to differentiate IBD from IBS. A normal faecal calprotectin essentially excludes active IBD.

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6. Lactose Intolerance [2]

Intolerance to lactose-containing food such as dairy products. Presents with abdominal pain, diarrhoea and flatulence after ingestion of milk or milk-containing products ^[2].

• Why it mimics CD: Chronic diarrhoea and abdominal cramps after eating
• Why it's different: Symptoms are temporally related to lactose ingestion only, no systemic features, no weight loss, normal inflammatory markers, normal endoscopy
• Complication: CD patients can develop secondary lactose intolerance due to mucosal damage in the small bowel (brush border lactase is destroyed) — so both conditions can coexist
• Diagnosed by hydrogen breath test or trial elimination diet

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7. Colorectal Cancer (CRC) [6][7]

• CRC is a less common but serious cause of hematochezia ^[6]
• CRC can present with change in bowel habits, weight loss, anaemia, and bowel wall thickening on CT — all features overlapping with CD
• IBD (UC > CD) is a risk factor for CRC ^[7] — so CRC can develop ON TOP of existing CD
• CD patients with colonic involvement have increased CRC risk, necessitating surveillance colonoscopy
• Key distinguishing features: Older age (usually > 50), progressive unrelenting symptoms, obstructive features (change in stool calibre, tenesmus), mass on imaging, biopsy shows adenocarcinoma

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8. Ischaemic Colitis [6][8]

• Presents with rapid onset of abdominal pain, hematochezia or bloody diarrhoea ^[6]
• Typically in elderly patients with cardiovascular risk factors (HT, DM, AF, atherosclerosis) or thromboembolic risk factors (OCP) ^[8]
• Affects watershed zones: splenic flexure (Griffith's point) and rectosigmoid junction (Sudeck's point) ^[8]
• Key feature: generalised abdominal pain out of proportion to physical findings ^[8]
• Why it mimics CD: Segmental colonic inflammation, ulceration, stricture formation. However, ischaemic colitis is typically acute onset in elderly (not chronic relapsing in young patients), and the distribution follows vascular territories, not Peyer's patch distribution.

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9. Acute Appendicitis [5][9]

Sometimes misdiagnosed with acute appendicitis — incidental finding of inflamed terminal ileum during operation ^[5].

• Why it mimics CD: Both cause RLQ pain, fever, tenderness, and sometimes a RLQ mass
• Ileitis causes include: Crohn's disease, TB, Radiation enteritis, Bacterial infection (Campylobacter, Yersinia, Salmonella) ^[5]
• Key distinguishing features:
  • Appendicitis: Acute onset (hours), migratory pain (periumbilical → RLQ), anorexia, single episode
  • CD: Chronic/relapsing course (weeks-months), diarrhoea is prominent, associated features (perianal disease, weight loss, EIMs)
  • Pointing sign, Rovsing's sign, Psoas sign, Obturator sign are specific for appendicitis ^[9]
• Important scenario: A patient taken to theatre for suspected appendicitis is found to have a normal appendix but inflamed terminal ileum → this is acute ileitis → do NOT resect → biopsy and close → investigate for CD/infection post-operatively

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10. Diverticular Disease [10]

• Right-sided diverticulitis is more common in Asian populations ^[10] → RLQ pain mimicking CD or appendicitis
• Clinical triad of diverticulitis: lower abdominal pain (RLQ in Asia) + fever + leucocytosis ^[10]
• Can cause strictures, fistulae (most commonly colovesical), and abscesses — similar complications to CD
• Why it mimics CD: Both cause segmental inflammation, strictures, fistulae, and abscesses
• How to distinguish: Diverticulitis is acute, episodic; CT shows pericolonic inflammation with diverticula; older age group; no skip lesions; no perianal disease; no EIMs

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11. Radiation Colitis/Enteritis [5][6]

Occurs in weeks to years after abdominal or pelvic irradiation ^[2].

• History of radiation therapy for pelvic malignancy (cervical, prostate, rectal cancer)
• Acute radiation injury: within 6 weeks — diarrhoea, tenesmus, rectal bleeding
• Chronic radiation injury: months to years — strictures, fistulae, ulceration, bleeding
• Why it mimics CD: Chronic stricturing, fistulising colitis. But the distribution matches the radiation field exactly, and there is clear history of prior radiotherapy.
• Listed as a cause of ileitis ^[5] and PR bleeding ^[6]

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12. Medication-Associated Colitis [2]

NSAIDs can cause chronic diarrhoea and bleeding ^[2].

• NSAIDs inhibit COX → reduced prostaglandin synthesis → loss of mucosal protection → ulceration, strictures (NSAID diaphragm disease), and bleeding throughout the small and large bowel
• Can mimic CD both clinically and endoscopically (small bowel ulcers, strictures)
• History of NSAID use is the key discriminating factor; resolves on cessation

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13. Other Differentials

a) Small Bowel Lymphoma

• Can present with chronic abdominal pain, weight loss, malabsorption, and small bowel mass/stricture
• Particularly consider in immunosuppressed patients or those with coeliac disease
• Distinguished by biopsy showing lymphomatous infiltrate

b) Coeliac Disease

• Chronic diarrhoea, weight loss, malabsorption, iron/folate deficiency
• Affects the proximal small bowel (duodenum/jejunum) — different from CD which favours the terminal ileum
• Diagnosed by anti-tTG antibodies and duodenal biopsy showing villous atrophy
• No perianal disease, no fistulae, no granulomas

c) Meckel's Diverticulitis ^[5][9]

• Congenital remnant of the omphalomesenteric (vitelline) duct
• Rule of 2s: 2% of population, 2 feet from ileocaecal valve, 2 inches long, 2 types of ectopic tissue (gastric/pancreatic), presents before age 2 (in children)
• Can cause RLQ pain mimicking appendicitis or CD, or painless GI bleeding (ectopic gastric mucosa → acid → ulceration)

d) Solitary Rectal Ulcer Syndrome ^[2]

• Presents with abdominal pain, altered bowel habits and bleeding
• Has a characteristic appearance on histology with a thickened mucosal layer and distortion of crypt architecture ^[2]
• Usually associated with rectal prolapse or excessive straining

e) Behçet's Disease

• Systemic vasculitis causing oral ulcers, genital ulcers, uveitis, and GI ulceration (especially ileocaecal region)
• Can closely mimic CD — distinguish by the presence of genital ulcers and pathergy test

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Summary Table of Key Differentials

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Investigations to Differentiate (Brief Overview)

This will be covered in detail in the Diagnosis section, but the key tests used to differentiate CD from its mimics include:

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Active Recall - Crohn's Disease: Differential Diagnosis

1. A 28-year-old male in Hong Kong presents with RLQ pain, chronic diarrhoea, and weight loss. Colonoscopy shows terminal ileal ulceration with granulomas. What is the most important differential diagnosis to exclude in this setting, and how would you do it?

Your answer

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Intestinal TB is the most important differential in Hong Kong. Exclude by: AFB smear and culture on biopsy specimens, tissue TB PCR (GeneXpert), CXR for pulmonary TB, IGRA/Mantoux for latent TB. TB granulomas are caseating and larger; TB ulcers are transverse. If equivocal, trial of anti-TB therapy for 2 months before committing to immunosuppression.

2. How does faecal calprotectin help in the differential diagnosis of Crohn's disease? What is it and what does a normal result tell you?

Your answer

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Faecal calprotectin is a neutrophil-derived protein (60% of neutrophil cytosol) released during intestinal inflammation. It is the most sensitive marker of intestinal inflammation in IBD. A normal result (less than 50 microg/g) essentially excludes active IBD, helping differentiate IBD from IBS and other non-inflammatory causes. It also correlates with endoscopic disease activity and predicts relapse.

3. List 4 key clinical features that distinguish Crohn's disease from ulcerative colitis.

Your answer

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1. CD has skip lesions vs UC is continuous. 2. CD is transmural (full thickness) vs UC is mucosal/submucosal. 3. CD causes fistulae (common) vs UC never causes fistulae. 4. CD has perianal disease (up to 40%) vs UC rarely. Also acceptable: CD has rectal sparing, deep focal ulcers, non-caseating granulomas, ASCA positive; UC has pseudopolyps, shallow ulcers, pANCA positive.

4. Why is it dangerous to start immunosuppressive therapy for presumed Crohn's disease without first excluding infection and TB?

Your answer

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Immunosuppression (steroids, biologics like anti-TNF) suppresses the immune response. In undiagnosed infection, this would worsen the infection and potentially cause sepsis. In latent TB, anti-TNF agents block TNF-alpha which is critical for granuloma maintenance and TB containment, leading to reactivation and potentially disseminated TB. This is especially important in TB-endemic Hong Kong.

5. A patient with known Crohn's disease on azathioprine presents with acute watery diarrhoea after a course of amoxicillin. What diagnosis should you consider and how would you investigate?

Your answer

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C. difficile infection (pseudomembranous colitis). Investigate with stool C. difficile toxin PCR (toxins A and B). Important because C. difficile can superinfect IBD patients on immunosuppression after antibiotic use. Must exclude before escalating immunosuppression for a presumed CD flare.

References

^[1] Lecture slides: Inflammatory bowel disease.pdf (p2, p6, p9) ^[2] Senior notes: felixlai.md (Inflammatory bowel disease — Crohn's disease, differential diagnosis and diagnosis sections) ^[3] Lecture slides: Inflammatory bowel disease.pdf (p10, p11, p12) ^[4] Senior notes: maxim.md (Inflammatory bowel disease — surgical principles) ^[5] Lecture slides: GC 195. Lower and diffuse abdominal pain RLQ problems; pelvic inflammatory disease; peritonitis and abdominal emergencies.pdf (p20 — Ileitis) ^[6] Lecture slides: GC 186. Lower and diffuse abdominal painfresh blood in stool.pdf (p8 — Causes of PR bleeding) ^[7] Senior notes: maxim.md (Colorectal cancer — risk factors) ^[8] Senior notes: maxim.md (Ischaemic bowel — clinical features and pathogenesis) ^[9] Senior notes: maxim.md (Acute appendicitis — differential diagnosis) ^[10] Senior notes: maxim.md (Diverticular disease — clinical features)

Diagnostic Criteria, Algorithm, and Investigations for Crohn's Disease

Important Principle: There Is No Single Diagnostic Test for CD

This is a critical point to understand from first principles. Unlike many conditions where a single blood test or imaging study clinches the diagnosis, Crohn's disease has no pathognomonic test. The diagnosis is made by integrating clinical presentation, laboratory findings, endoscopic appearance, histology, and imaging — essentially a pattern recognition exercise that requires you to piece together multiple lines of evidence while actively excluding mimics (especially intestinal TB and infections in Hong Kong).

The ECCO (European Crohn's and Colitis Organisation) guidelines state: "The diagnosis of CD is confirmed by clinical evaluation and a combination of endoscopic, histological, radiological, and biochemical investigations. No single gold standard exists."

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Diagnostic Criteria

While there is no single set of universally accepted "diagnostic criteria" like the Jones criteria for rheumatic fever, the diagnosis of CD rests on demonstrating a characteristic constellation of findings:

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Diagnostic Algorithm

The approach to diagnosing CD follows a systematic pathway: History & Examination → Screening blood/stool tests → Endoscopy with biopsy → Cross-sectional imaging → Exclude mimics → Establish Montreal classification.

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Investigation Modalities — Detailed Breakdown

I. History and Physical Examination

Diagnosis begins with patient history and physical examination ^[3]:

History — systematically cover ^[3]:

• Bowel symptoms: Duration, frequency, consistency of diarrhoea; presence of blood/mucus; nocturnal symptoms (nocturnal diarrhoea is a red flag for organic disease — functional disorders spare sleep)
• Medications: NSAIDs (can trigger flares or cause NSAID enteropathy mimicking CD), antibiotics (C. difficile risk)
• Surgery: Previous appendicectomy (risk factor for CD), prior bowel resections
• Drug history: Immunosuppressants, biologics if known IBD
• Immunization status: Important before starting immunosuppression (need to ensure vaccinations are up-to-date, especially live vaccines which are contraindicated on biologics) ^[3]
• Travel history, sexual history (proctitis differentials: gonorrhoea, HSV, chlamydia), TB contacts, family history of IBD

Physical Examination ^[3]:

• General and abdomen: Nutritional status, pallor, fever, abdominal tenderness/mass, surgical scars
• Perianal region: skin tags, fissures, fistulas, abscess, PR exam — never skip this in suspected CD ^[3]
• Extraintestinal inspections: mouth, eyes, skin and joints ^[3] — oral aphthous ulcers, episcleritis/uveitis, erythema nodosum/pyoderma gangrenosum, peripheral arthropathy

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II. Laboratory Tests

A. Blood Tests

Blood tests: CBP, CRP, ESR, albumin, ferritin ^[3]

Additional blood tests:

• LFT: Elevated ALP/GGT may suggest primary sclerosing cholangitis (PSC); assess liver function before starting hepatotoxic drugs (methotrexate, azathioprine)
• RFT: Baseline renal function; oxalate nephropathy in terminal ileal disease
• Hepatitis serology, HIV, TB testing ^[3] — mandatory before starting immunosuppression/biologics
  • Hepatitis B reactivation can occur with anti-TNF therapy → screen HBsAg, anti-HBc, anti-HBs
  • HIV affects treatment decisions and differential diagnosis
  • TB screening (CXR + IGRA) is essential before anti-TNF therapy because TNF-α is critical for granuloma maintenance in TB

B. Serological Markers

How to use serology in practice:

• ASCA+/pANCA− → strongly suggests CD
• ASCA−/pANCA+ → strongly suggests UC
• Neither is diagnostic alone — they are adjuncts, not definitive tests
• Most useful in indeterminate colitis to help lean towards CD or UC

C. Stool Tests

Stool examination: culture, Cl. difficile toxin, calprotectin ^[3]

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III. Endoscopy

Endoscopy is the cornerstone of CD diagnosis because it allows direct visualisation of the mucosa AND tissue sampling for histology.

A. Colonoscopy [3]

Colonoscopy is the primary endoscopic investigation for both UC and CD ^[3].

Technique and requirements:

• Ileocolonoscopy — the scope must be passed through the ileocaecal valve to intubate the terminal ileum, as this is the most commonly affected site in CD. A colonoscopy that does not examine the terminal ileum is incomplete for IBD evaluation.
• Biopsy should be taken from the left and right colon and rectum even if normal in appearance to assess for microscopic inflammation ^[2]
• Multiple biopsies from at least 5 sites (terminal ileum, ascending colon, transverse colon, descending colon, rectum) — this is essential because CD can have microscopic inflammation even where the mucosa looks macroscopically normal
• MUST do AFB smear and culture with sensitivity testing to rule out enteric TB ^[2] — this is mandatory in Hong Kong

Endoscopic findings in CD ^[2]:

Contrast with UC endoscopic findings:

B. Sigmoidoscopy (for severe active disease) [3]

• In acute severe colitis, full colonoscopy is risky (risk of perforation in an acutely inflamed, thinned colon) → sigmoidoscopy is safer as it examines only the distal colon and rectum
• Allows assessment of disease extent and severity without the risks of full bowel preparation and full colonoscopy in a sick patient
• Biopsies can still be taken for histology and C. difficile toxin

C. OGD (for foregut symptoms in CD) [3]

• OGD is indicated when foregut symptoms are present — dysphagia, epigastric pain, nausea ^[3]
• Can reveal oesophageal, gastric, or duodenal CD (aphthous ulcers, strictures, granulomatous inflammation)
• Also important in paediatric CD where upper GI involvement is more common

D. Small Bowel Capsule Endoscopy (SBCE) [3]

• Small bowel capsule endoscopy — the patient swallows a small wireless camera capsule that transmits images as it traverses the GI tract ^[3]
• Excellent for visualising the small bowel mucosa (which is not reachable by standard colonoscopy or OGD)
• Detects aphthous ulcers, mucosal erosions, and strictures in the small bowel
• Critical limitation: Should be avoided in patients with suspected intestinal stricture due to possibility of retained capsule ^[2] — the capsule can get stuck proximal to a stricture, causing obstruction. A patency capsule (dissolvable) should be used first if stricture is suspected.

E. Single or Double Balloon Enteroscopy [3]

• Single or double balloon enteroscopy allows deep intubation of the small bowel — can reach areas inaccessible to standard endoscopy ^[3]
• Enables therapeutic intervention (biopsy, dilatation, haemostasis) in small bowel disease
• More invasive and time-consuming than capsule endoscopy; typically reserved for cases where capsule endoscopy detects an abnormality that requires biopsy or treatment

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IV. Histology

Biopsy specimens from colonoscopy undergo H&E staining. The key histological findings in CD:

Additional stains and tests on biopsy:

• AFB smear and culture — mandatory to exclude TB ^[2]
• TB PCR (GeneXpert) — higher sensitivity than AFB stain
• CMV immunohistochemistry — if deep ulcers in immunosuppressed patient (CMV superinfection)

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V. Cross-Sectional Imaging

Endoscopy only sees the mucosal surface. CD is transmural — you need cross-sectional imaging to see the full bowel wall, extraluminal complications (abscesses, fistulae), and mesenteric involvement.

A. MR Enterography (MRE) [3]

MRE is the preferred imaging modality for small bowel CD assessment ^[3].

B. CT Enterography (CTE) [3]

CTE is an alternative to MRE ^[3].

C. MRI Anal Canal [3]

MRI anal canal is the investigation of choice for perianal CD ^[3].

• 24.5% of patients with Crohn's disease have perianal disease; 83% required surgery ^[11]
• MRI and EAUS (endoanal ultrasound) necessary to document before the definitive treatment ^[11]
• MRI provides detailed soft tissue imaging of:
  • Fistula tracts (course, complexity, relationship to sphincter)
  • Abscesses (undrained collections)
  • Sphincter integrity
• Classification: Parks classification of fistulae (intersphincteric, transsphincteric, suprasphincteric, extrasphincteric)
• Essential for surgical planning — the surgeon needs to know exactly where the fistula tracks before operating

D. Plain Radiographs

E. Barium Studies (Historical but Still Referenced)

F. Ultrasound (USG)

• USG for diagnosis of ileal Crohn's disease ^[2] — bowel wall thickening > 3mm, hyperaemia on Doppler
• Endoanal USG can be used to identify fistula tracts ^[2] — alternative to MRI for perianal disease assessment
• Non-invasive, no radiation, inexpensive, but operator-dependent and limited by bowel gas

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VI. Disease Activity Assessment

Once the diagnosis is established, quantifying disease activity guides treatment decisions.

Crohn's Disease Activity Index (CDAI) [2]

The CDAI incorporates 8 variables over 7 days: number of liquid stools, abdominal pain rating, general well-being, extraintestinal features, anti-diarrhoeal use, abdominal mass, haematocrit, and body weight. It's primarily a research tool — in clinical practice, a combination of symptoms, CRP, calprotectin, and endoscopic findings guides management.

Harvey-Bradshaw Index (HBI) [12]

• A simplified version of CDAI (only 5 variables, no 7-day diary needed): general well-being, abdominal pain, number of liquid stools, abdominal mass, complications
• HBI > 15 = severe disease (indication for surgical consideration) ^[12]
• More practical for routine clinical use

Endoscopic Activity

• Simple Endoscopic Score for Crohn's Disease (SES-CD) — grades ulcer size, ulcerated surface area, affected surface area, and presence of narrowing
• Mucosal healing is now a key treatment target ("treat-to-target") — the goal is not just symptom control but endoscopic remission, as mucosal healing correlates with reduced complications, hospitalisations, and surgery

Faecal Calprotectin for Monitoring [3]

Faecal calprotectin is invaluable for monitoring:

• Well correlated with endoscopic disease activity ^[3]
• Predicts disease relapse, post-op relapse ^[3]
• Non-invasive alternative to repeated colonoscopy for tracking disease activity
• Rising calprotectin in clinical remission → subclinical inflammation → consider treatment intensification before clinical relapse

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VII. Montreal Classification — Established at Diagnosis

After completing the diagnostic workup, the patient is classified using the Montreal classification ^[1]:

The Montreal classification is established using the combination of endoscopy (location, fistulae), imaging (strictures, fistulae, abscesses), and clinical assessment (perianal disease). It is dynamic — a patient initially classified as B1 may progress to B2 or B3 over time, requiring reclassification and treatment adjustment.

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VIII. Pre-Treatment Screening Checklist

Before initiating therapy (especially immunosuppression/biologics), the following must be completed:

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Active Recall - Crohn's Disease: Diagnosis

1. What is faecal calprotectin, and why is it considered the gatekeeper test in the diagnostic workup of suspected IBD?

Your answer

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Faecal calprotectin is a neutrophil-derived protein (60% of neutrophil cytosol). It is the most sensitive marker of intestinal inflammation in IBD. A normal level (less than 50 microg/g) essentially excludes active IBD, differentiating it from IBS without invasive endoscopy. It correlates well with endoscopic disease activity and predicts disease relapse and post-operative relapse.

2. List the key endoscopic findings of Crohn's disease on ileocolonoscopy and explain the pathophysiological basis of cobblestone appearance.

Your answer

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Key findings: skip lesions, aphthous ulcers, solitary deep focal ulceration, cobblestone appearance, fistulae, abscesses, strictures, rectal sparing. Cobblestone appearance: deep longitudinal and transverse ulcers criss-cross the mucosa creating cracks, while intervening oedematous surviving mucosa forms raised islands (stones). This reflects the transmural nature of CD inflammation.

3. A colonoscopy biopsy in a young Hong Kong patient shows terminal ileal granulomas. What additional tests MUST be sent on the biopsy, and why?

Your answer

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MUST send AFB smear and culture with sensitivity testing, and TB PCR (GeneXpert), to rule out intestinal TB. In TB-endemic Hong Kong, intestinal TB causes granulomatous terminal ileitis indistinguishable from CD. TB granulomas are typically caseating; starting immunosuppression for misdiagnosed TB would be catastrophic.

4. Compare MR enterography and CT enterography for small bowel CD assessment. When would you prefer each?

Your answer

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MRE: preferred for routine assessment - no ionising radiation (critical for young patients needing repeated imaging), excellent soft tissue contrast, superior for fistulae and perianal disease, can distinguish active inflammatory from fibrostenotic strictures. CTE: preferred in acute presentations (faster, more widely available), better for abscesses. CTE disadvantage is cumulative radiation dose.

5. What pre-treatment screening investigations are mandatory before starting anti-TNF therapy for Crohn's disease, and why?

Your answer

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1. TB screening (CXR plus IGRA/Mantoux): anti-TNF blocks TNF-alpha which maintains granulomas containing TB - risk of latent TB reactivation. 2. Hepatitis B serology (HBsAg, anti-HBc, anti-HBs): risk of HBV reactivation with immunosuppression. 3. HIV testing: affects treatment decisions. 4. Immunisation status: live vaccines contraindicated on biologics. 5. Baseline TPMT/NUDT15 if using thiopurines.

6. State the CDAI score ranges for mild, moderate, and severe Crohn's disease, and the HBI threshold indicating severe disease warranting surgical consideration.

Your answer

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CDAI: mild 150-220, moderate 220-450, severe greater than 450. HBI greater than 15 indicates severe disease and is an indication for surgical consideration. CDAI greater than 450 also indicates severe disease with features such as cachexia (BMI less than 18), abscess formation, obstruction, or persistent symptoms despite intensive treatment.

References

^[1] Lecture slides: Inflammatory bowel disease.pdf (p2, p8) ^[2] Senior notes: felixlai.md (Inflammatory bowel disease — Crohn's disease, diagnosis section) ^[3] Lecture slides: Inflammatory bowel disease.pdf (p10, p11, p12) ^[4] Senior notes: maxim.md (Inflammatory bowel disease — surgical principles) ^[11] Lecture slides: Inflammatory bowel disease.pdf (p45 — Perianal CD) ^[12] Lecture slides: Inflammatory bowel disease.pdf (p27 — Indications for surgery, HBI)

Management of Crohn's Disease

Overarching Principles

Before diving into specific drugs and procedures, let's establish the philosophy of CD management. This is fundamentally different from UC management because CD is NOT curable by surgery — it can recur anywhere in the GI tract after resection. Every management decision must be understood through this lens.

Principles of management ^[2]:

• To induce and maintain remission taking into account disease activity, disease site, disease behaviour and patient preference ^[2]
• Trend towards early introduction of immunomodulators and biologics in patients with adverse prognostic factors ^[2]:
  • Young age < 40
  • Extensive small bowel disease
  • Perianal involvement
  • Presence of strictures
  • Presence of deep colonic ulcers
  • Steroids required in initial treatment
• Avoidance of triggering factors — smoking cessation ^[2]
• Treatment goals have evolved from symptom control to "treat-to-target": the modern goal is mucosal healing (endoscopic remission) because this reduces complications, hospitalisations, and need for surgery

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Management Algorithm Overview

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I. Medical Treatment

The medical management of CD uses drugs with distinct roles: induction (getting the inflammation under control quickly) vs maintenance (keeping it under control long-term). Understanding which drug does what — and why — is fundamental.

A. Antibiotics

Antibiotics ^[2]:

Why ciprofloxacin and metronidazole specifically?

• Metronidazole ("metro" = relating to the uterus historically, but it's actually a nitroimidazole) — effective against anaerobic bacteria and some protozoa. The gut, especially the colon, is an anaerobic environment, so metronidazole targets the predominant colonic flora. Also has immunomodulatory properties.
• Ciprofloxacin — a fluoroquinolone effective against gram-negative aerobes. The combination covers a broad spectrum of gut bacteria.

Limitations: Metronidazole causes peripheral neuropathy with prolonged use (damages nerve axons — metallic taste and tingling are early warning signs). Ciprofloxacin can cause tendinopathy.

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B. 5-Aminosalicylates (5-ASA)

5-aminosalicylates (5-ASA) ^[2]:

Key drug distinctions:

Why sulfasalazine only works in the colon — explained from first principles: Sulfasalazine = sulfapyridine + 5-ASA linked by an azo bond. This bond is resistant to gastric acid and small bowel enzymes. Only colonic bacteria (which produce azoreductases) can cleave the bond → 5-ASA is released locally in the colon. For ileal disease, you need mesalamine formulations that release 5-ASA in the small bowel (e.g., Pentasa uses ethylcellulose-coated microgranules that release 5-ASA throughout the GI tract).

Adverse effects:

• Mesalamine: Nephrotoxicity ^[2] — interstitial nephritis (monitor renal function)
• Sulfasalazine: Nausea, headache, fever, agranulocytosis, pancreatitis, SJS ^[2]. Also associated with "sulfa" allergy and pregnancy complications including kernicterus (crosses placenta) and neural tube defects (inhibits absorption and metabolism of folic acid) ^[2] — always co-prescribe folic acid 5mg daily if using sulfasalazine in women of childbearing age

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C. Glucocorticoids

Glucocorticoids ^[2]:

Key drug distinctions:

Why budesonide for ileocaecal disease specifically? Budesonide modified-release formulations (e.g., Entocort) are designed to release the drug in the ileum and right colon — exactly where ileocaecal CD occurs. Because of the extensive first-pass hepatic metabolism (~90% is inactivated on first pass through the liver), systemic steroid side effects are minimised. However, this also means it's less potent than prednisolone for widespread or severe disease.

Critical rules about steroids in CD:

• Calcium and vitamin D supplements required for osteoprotective effect if prescribed for more than 12 weeks ^[2]
• Never use steroids for maintenance — they don't prevent relapse and cause cumulative toxicity (osteoporosis, cataracts, diabetes, adrenal suppression, avascular necrosis)
• Steroid-dependent = patient relapses when steroids are tapered or within 3 months of stopping → needs immunomodulator or biologic
• Steroid-refractory = no response despite adequate dose → needs escalation to biologic

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D. Immunomodulators

Immunomodulators ^[2]:

These are the bridge between steroids (short-term induction) and long-term maintenance. Their onset of action is slow (2-3 months), so they cannot be used alone for acute flares.

Thiopurines: Azathioprine (AZA) / 6-Mercaptopurine (6-MP)

Methotrexate (MTX)

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E. Biologic Therapies

This is the most important and rapidly evolving area of CD management. Biologics are monoclonal antibodies that target specific components of the inflammatory cascade.

Anti-TNF-α Agents

Biologic therapies (Anti-TNFα) ^[2]:

Pre-treatment screening — MANDATORY ^[2]:

MUST screen for TB with CXR / QuantiFERON-TB Gold + HBV infection with HBsAg ^[2]:

• Requires TB prophylaxis with isoniazid or rifampicin ^[2] — if latent TB is detected, treat with isoniazid 9 months (or rifampicin 4 months) BEFORE or concurrently with anti-TNF
• Requires HBV prophylaxis with entecavir ^[2] — if HBsAg positive or anti-HBc positive, start antiviral prophylaxis to prevent reactivation

Key drugs:

Stopping rules:

• Do not stop anti-TNF easily unless there is deep remission of at least 18 months with normal blood and endoscopic parameters ^[2]
• Deep remission = clinical remission + biochemical remission (normal CRP, calprotectin) + endoscopic remission (mucosal healing)

Contraindications ^[2]:

Adverse effects ^[2]:

• Reactivation of infection (e.g. TB/HBV)
• Lymphoma (especially hepatosplenic T-cell lymphoma — rare but often fatal, particularly in young males on combination AZA + anti-TNF)
• Non-melanoma skin cancer
• Infusion reactions (infliximab — acute anaphylactoid reactions; delayed serum sickness-like reactions)
• Anti-drug antibodies → loss of response (more common with infliximab due to chimeric structure; co-administration with AZA reduces antibody formation — this is the rationale for combination therapy)

Other Biologics (Beyond Anti-TNF)

For patients who fail or are intolerant of anti-TNF agents:

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F. Small Molecules

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II. Surgical Treatment

Surgical treatment is NOT curative in Crohn's disease and is mainly used to treat complications only ^[2].

This is the most important principle. Unlike UC where total proctocolectomy removes ALL diseased tissue (because UC only affects the colon/rectum), CD can recur anywhere in the GI tract after resection. Therefore:

Surgical principles ^[4]:

• Preservation of bowel length (should document residual SB length) ^[4] — repeated resections can lead to short bowel syndrome (< 200 cm of remaining small bowel → malabsorption, dependence on TPN)
• Conservative and minimal resection as possible ^[2]
• Extended resection does not decrease recurrence ^[2] — you don't need wide margins. Even a 2cm margin is sufficient because recurrence is driven by systemic immune factors, not "missed" disease at the resection margin
• Bypass is NOT recommended since there is risk of malignant transformation in the bypassed segment ^[2]

Indications for Surgery

Indications ^[2][12]:

Emergency:

• Fulminant colitis ^[4]
• Toxic megacolon: non-obstructive colonic dilatation with systemic toxicity ^[4]
• Impending perforation ^[4]
• Life-threatening haemorrhage ^[4]
• Perforation / Sepsis ^[2]

Elective:

• Persistent symptoms refractory to medical treatment ^[2]
  • CDAI > 450 ^[12]
  • Harvey-Bradshaw Index (HBI) > 15 ^[12]
• Strictures (intestinal obstruction) ^[2]
• Abscess ^[2]
• Fistula ^[2]
• Malignancy: treatment (e.g. biopsy-proven adenoCA) or prophylaxis (e.g. dysplasia on surveillance Bx) ^[4]
• Luminal complications: SBO, abscess, enterocutaneous fistula ^[4]
• Perianal diseases: abscess, fistula, anorectal stricture ^[4]
• Debilitating EIM, except EIM independent of colitis activity — sacroiliitis, hepatobiliary complications ^[4]

Key point from lecture slides: Rarely curative but lead to long-lasting remissions in some patients. Low threshold for ileocolic CD ^[12].

Surgical Procedures by Location and Behaviour

1. Small Bowel Involvement [2]

• Small bowel resection with primary anastomosis — remove the diseased segment and join the healthy ends

2. Large Bowel Involvement [2]

3. Ileocaecal CD [13]

80% of ileocaecal CD require surgery ^[13]. This is a remarkable statistic — the majority eventually need resection.

Key points from lecture slides ^[13]:

• An alternative to medical Tx in the early disease course — the LIR!C trial showed that laparoscopic ileocaecal resection is a valid alternative to infliximab for limited ileocaecal CD, with comparable quality of life at 1 year
• Technically more difficult due to: adhesion due to inflammation, phlegmon, shortened mesentery ^[13]
• Reduction of adhesive bowel obstruction (laparoscopic advantage) ^[13]
• Consider stopping medical Tx after one year of remission ^[13]
• From the Stevens et al. (Lancet 2020) data ^[14]: Resection group: 42% no Crohn's-related medication; 26% anti-TNF but none required 2nd OT. Infliximab group: 48% need resection — this demonstrates that early surgery for ileocaecal CD can reduce long-term medication burden

4. Strictures [2]

Management strategy for small bowel strictures ^[15]:

• If inflammatory → Medical therapy ^[15]
• If fibrostenotic → Stricturoplasty preferred; Resection if suspect malignancy or isolated stricture ^[15]

Why stricturoplasty over resection when possible? Because it preserves bowel length. CD patients may need multiple operations over their lifetime — if you resect every time, you'll eventually cause short bowel syndrome. Stricturoplasty widens the narrowed segment without sacrificing bowel.

Important exception: NO role for stricturoplasty in Crohn's colitis since there is a 7% risk of malignancy over 20 years ^[2] — large bowel strictures in CD should be resected, not stricturoplastied, because of the CRC risk.

Non-operative treatment for partial obstruction applies in several situations including Crohn's disease ^[16] — if the patient has partial SBO from a known CD stricture, initial conservative management (bowel rest, IV fluids, nasogastric decompression) may resolve the episode without surgery.

5. Fistula Management

Enterocutaneous fistula: abnormal communications between 2 epithelialised surfaces ^[4].

Causes: FRIEND ^[4] — Foreign body, Radiation, Inflammation/infection, Epithelialization, Neoplasm, Distal obstruction.

SNAP management principle ^[2]:

Enterocutaneous fistula specific management ^[4]:

• Delineate anatomy of fistula: CT abdomen
• Replace fluid and electrolytes, chart fistula output
• Wound care, e.g. negative pressure wound therapy (NPWT)
• Bowel rest → drugs (loperamide, octreotide) → endoscopic/surgical closure ^[4]

6. Perianal CD [11]

This is high-yield and has its own dedicated algorithm from the lecture slides.

Key facts ^[11]:

• 24.5% of patients with Crohn's disease have perianal disease
• 83% required surgery
• More complicated courses of fistula tract
• MRI and EAUS necessary to document before the definitive treatment
• Anti-TNF ± AZA and/or seton drainage

Perianal CD Treatment Algorithm ^[11][17]:

Step-by-step explanation:

1. Clinical assessment: exclude abscess — undrained sepsis will NOT respond to biologics. You must drain pus first.
2. Antibiotics (ciprofloxacin/metronidazole) + AZA; MRI and endoscopy to delineate the anatomy ^[17]
3. EUA (examination under anaesthesia) ± drainage ± seton — a seton is a suture/silastic loop threaded through the fistula tract that keeps it draining and prevents abscess re-accumulation. It establishes a "controlled fistula" while the inflammation is treated medically. ^[4]
4. Infliximab induction (5 mg/kg at 0, 2, 6 weeks) ^[17]
5. If complete response → remove seton at week 6 → continue infliximab 8-weekly → eventual MRI assessment → if healed, stop IFX and continue AZA ^[17]
6. If partial response → adalimumab ^[17]
7. If no response → consider surgical intervention (defunctioning stoma ± proctectomy) ^[4][17]

Surgical options for perianal CD ^[2][4]:

• Simple fistula: Fistulotomy ^[2]
• Complex fistula: Seton drainage / Azathioprine / Biologics (Infliximab/Adalimumab) ^[2]
• If failed: defunctioning stoma ± proctectomy ^[4]

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III. Nutritional Support

Nutrition is a critical and often underappreciated pillar of CD management:

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IV. Post-Operative Prophylaxis Against Recurrence

Since CD recurs after surgery (endoscopic recurrence at the neo-terminal ileum in ~70-80% at 1 year without prophylaxis), post-operative prophylaxis is essential:

• Colonoscopy at 6-12 months post-surgery to assess for recurrence (Rutgeerts score)
• Faecal calprotectin predicts post-op relapse ^[3] — rising calprotectin before symptoms appear allows early intervention

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V. Management of Dysplasia / CRC Surveillance

IBD-associated CRC risk factors ^[18]:

• Primary sclerosing cholangitis; History of colorectal neoplasia; Family history of CRC in first-degree relative; Smoking
• Disease duration; Disease extent; Cumulative inflammatory burden; Active inflammation endoscopically or histologically
• Stricture (UC, longer disease duration, proximal location, symptoms); Shortened tubular colon; Pseudopolyps
• Early age of disease onset; Male sex

Management of dysplasia ^[19]:

• Endoscopically visible dysplasia:
  • Polypoid: polypectomy
  • Non-polypoid: endoscopic resection if complete resection possible
  • Surgery should be considered if not endoscopically feasible
• Endoscopically invisible dysplasia:
  • Associated with high rate of CRC
  • Referred to an experienced endoscopist
  • If LGD or no dysplasia: 5% LGD changed to HGD or CRC; Surveillance or surgery?
  • If invisible HGD or multifocal LGD, surgery should be offered

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Summary Table: Drug Classes at a Glance

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Active Recall - Crohn's Disease: Management

1. Why are corticosteroids used for induction but NEVER for maintenance in Crohn's disease? What do you use for maintenance instead?

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Steroids are effective for inducing remission by rapidly suppressing inflammation but are ineffective at preventing relapse (maintenance). Long-term steroid use causes cumulative toxicity: osteoporosis, diabetes, cataracts, adrenal suppression, avascular necrosis. For maintenance, use thiopurines (AZA/6-MP) as steroid-sparing agents, or biologics (anti-TNF, vedolizumab, ustekinumab) in moderate-severe disease.

2. List the contraindications to anti-TNF therapy and explain the mechanism for each.

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1. Active or latent untreated TB: TNF-alpha maintains granulomas containing TB bacilli; blocking TNF causes granuloma breakdown and disseminated TB. 2. Lymphoma: TNF has some anti-tumour activity; blocking may promote lymphoma. 3. Severe heart failure (NYHA III-IV): TNF paradoxically supports cardiac function in failing hearts. 4. Demyelinating disease (MS): TNF has complex roles in myelin maintenance. 5. Optic neuritis: related to demyelinating risk.

3. Describe the SNAP principle for managing fistulae in Crohn's disease.

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S = Sepsis control (antibiotics + CT-guided percutaneous abscess drainage). N = Nutrition support (TPN aids fistula closure, bowel rest reduces output). A = Anatomical delineation (imaging with fistulogram, CT or MR enteroclysis to locate fistula). P = Procedure (medical treatment with infliximab, OR surgical treatment with en-bloc resection of bowel + primary anastomosis + diverting stoma).

4. A patient with ileocaecal Crohn's disease has a 15cm fibrostenotic stricture of the terminal ileum. What surgical options are available and which would you choose?

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Options: Heineke-Mikulicz stricturoplasty (short stricture less than 10cm - not suitable here), Finney stricturoplasty (long stricture 10-20cm - suitable for this 15cm stricture), endoscopic balloon dilatation (for short strictures only), or resection. Choose Finney stricturoplasty to preserve bowel length. Resection if malignancy is suspected. Extended resection does not decrease recurrence. No role for bypass due to malignant transformation risk in bypassed segment.

5. Outline the perianal CD treatment algorithm as described in the lecture slides, starting from initial assessment to management of non-responders.

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1. Clinical assessment to exclude abscess. 2. Antibiotics + AZA, MRI and endoscopy to delineate anatomy. 3. EUA with drainage and/or seton insertion. 4. Infliximab 5mg/kg at 0, 2, 6 weeks. 5. If complete response: remove seton at week 6, continue infliximab 8-weekly, MRI scan, then consider stopping IFX and continue AZA. 6. If partial response: try adalimumab, continue IFX and reassess 6-monthly. 7. If no response: consider surgical intervention (defunctioning stoma with or without proctectomy).

6. Why is TPMT/NUDT15 genotyping mandatory before starting azathioprine, and why is this particularly important in Hong Kong?

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TPMT and NUDT15 are enzymes that metabolise thiopurines. Genetic polymorphisms cause enzyme deficiency leading to toxic accumulation of 6-thioguanine nucleotides causing fatal bone marrow suppression (pancytopenia). NUDT15 polymorphisms are particularly common in East Asian populations including Hong Kong (up to 2% homozygous deficient). Testing before starting treatment identifies patients who need dose reduction or alternative therapy.

References

^[2] Senior notes: felixlai.md (Inflammatory bowel disease — Crohn's disease, treatment section) ^[3] Lecture slides: Inflammatory bowel disease.pdf (p11 — faecal calprotectin) ^[4] Senior notes: maxim.md (Inflammatory bowel disease — surgical management; Surgical procedures for CD) ^[11] Lecture slides: Inflammatory bowel disease.pdf (p45 — Perianal CD) ^[12] Lecture slides: Inflammatory bowel disease.pdf (p27 — Indications for surgery) ^[13] Lecture slides: Inflammatory bowel disease.pdf (p41 — Ileocaecal CD) ^[14] Lecture slides: Inflammatory bowel disease.pdf (p43 — Stevens et al. LIR!C trial data) ^[15] Lecture slides: Inflammatory bowel disease.pdf (p28 — Small bowel stricture) ^[16] Lecture slides: GC 194. Intestinal obstruction colorectal cancer.pdf (p27 — Non-operative treatment) ^[17] Lecture slides: Inflammatory bowel disease.pdf (p49 — Perianal CD algorithm) ^[18] Lecture slides: Inflammatory bowel disease.pdf (p52 — IBD-associated CRC risk factors) ^[19] Lecture slides: Inflammatory bowel disease.pdf (p55 — Management of dysplasia)

Complications of Crohn's Disease

Understanding the complications of CD flows directly from understanding the pathology: transmural inflammation of a chronic, relapsing disease that can affect any part of the GI tract. Almost every complication can be traced back to one of these three features. Let's work through them systematically.

The complications can be organised into:

1. Luminal/structural complications (direct consequences of transmural inflammation)
2. Perianal complications
3. Metabolic/nutritional complications (consequences of malabsorption)
4. Malignant complications
5. Extraintestinal manifestations (immune-mediated complications beyond the gut)
6. Treatment-related complications
7. Post-surgical complications

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I. Luminal / Structural Complications

These are the hallmarks of CD that distinguish it from UC. They all stem from the transmural (full-thickness) nature of CD inflammation.

1. Fistula Formation

Fistulas are communication that connect two epithelial-lined organs ^[2].

Pathophysiology — explained from first principles ^[2]:

1. Transmural inflammation leads to development of sinus tract — the inflammation erodes through the mucosa → submucosa → muscularis → serosa
2. Sinus tract that penetrates the serosa gives rise to fistulas — once the inflammation breaches the outer wall of the bowel, it can track to any adjacent structure
3. The sinus tract becomes epithelialised over time (lined by epithelium), which is why fistulae don't heal spontaneously — you can't easily close a tube that has its own lining

Types of fistula and their clinical presentations ^[2]:

Enterocutaneous fistula ^[4][20]:

Causes: FRIEND ^[4] — Foreign body, Radiation, Inflammation/infection, Epithelialization, Neoplasm, Distal obstruction.

Management follows the SNAP principle ^[2][20]:

• S — Sepsis control: Abscess drainage, antibiotics ^[20]
• N — Nutrition support: High vs low output; Nutritional assessment and support ^[20]
• A — Anatomy: CTE or MRE to delineate ^[20]
• P — Procedure: Medication adjustment; Closure with biological agents; En-bloc resection of involved bowel and fistula ^[20]

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2. Abscess Formation

Some sinus tracts may lead to abscess formation and present as acute localised peritonitis with fever, abdominal pain and tenderness ^[2].

Pathophysiology: Transmural inflammation breaches the serosa → a sinus tract develops → if the sinus is walled off by adjacent structures (omentum, mesentery, other bowel loops) instead of forming a free perforation, a contained collection of pus forms = abscess.

Types by location:

• Intra-abdominal (mesenteric, inter-loop, pelvic, subphrenic)
• Retroperitoneal (psoas abscess — a classic CD complication; presents with hip pain, flexion deformity of the hip, and swinging fever)
• Perianal (see below)

Clinical features:

• Persistent fever (especially swinging/spiking pyrexia) despite antibiotics
• No improvement in abdominal pain despite antibiotics
• Localised tenderness, palpable mass
• Leucocytosis, elevated CRP

Management: CT-guided percutaneous drainage + antibiotics. Surgical drainage if percutaneous drainage fails or is not feasible. Must drain abscess before starting biologics (undrained sepsis + immunosuppression = catastrophe).

Abscess perforation can lead to diffuse peritonitis ^[2] — a surgical emergency.

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3. Phlegmon Formation

Some sinus tracts may present as a phlegmon ^[2].

• Phlegmon is a walled-off inflammatory mass without bacterial infection ^[2] — think of it as an organised collection of inflamed, adherent bowel loops and mesentery, but without frank pus
• Phlegmon may be palpable on abdominal examination ^[2]
• Ileal involvement is suggested by a mass in the RLQ ^[2]
• Differentiated from abscess on CT: phlegmon = solid inflammatory mass without a fluid collection; abscess = rim-enhancing fluid collection
• Management: often responds to medical therapy (steroids, biologics); surgery may be needed if it doesn't resolve

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4. Stricture and Intestinal Obstruction

Strictures are common in CD ^[1] — they are listed as a key surgical complication ^[12].

Pathophysiology: Chronic transmural inflammation → fibrosis (replacement of normal tissue with collagen) → progressive luminal narrowing → intestinal obstruction. This is the natural progression of untreated or under-treated CD.

Two types of strictures — this distinction is CRITICAL for management:

Clinical features of obstruction:

• Colicky abdominal pain (waves of peristalsis against the obstruction)
• Abdominal distension
• Vomiting (bilious if distal to ampulla; faeculent if distal SBO)
• Obstipation (complete obstruction) or reduced stool/flatus (partial)
• High-pitched/tinkling bowel sounds → later absent bowel sounds

Important points:

• NO role for stricturoplasty in Crohn's colitis since there is a 7% risk of malignancy over 20 years ^[2]
• Bypass is NOT recommended since there is risk of malignant transformation in the bypassed segment ^[2]
• In CD, colonic strictures should be considered malignant until proven otherwise (biopsy essential)

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5. Perforation

Pathophysiology: Transmural inflammation can erode completely through the bowel wall → free perforation into the peritoneal cavity → generalised faecal/purulent peritonitis.

Types:

• Free perforation: Faecal contamination of the peritoneal cavity → generalised peritonitis → surgical emergency
• Contained perforation: Walled off by adjacent structures → forms abscess (see above)
• Perforation can also occur secondary to toxic megacolon (though this is more common in UC)

Clinical features:

• Sudden severe abdominal pain
• Peritonism: board-like rigidity, rebound tenderness, guarding
• Absent bowel sounds
• Tachycardia, hypotension, fever → septic shock
• CXR: pneumoperitoneum (free air under diaphragm) — though this may be absent in contained perforations

Management: Emergency laparotomy, resection of perforated segment, often with temporary stoma (anastomosis in the presence of peritoneal contamination is risky due to high leak rates).

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6. Severe Bleeding [2]

• Massive GI haemorrhage occurs but is less common than in UC or diverticular disease
• Arises from erosion of transmural inflammation into blood vessels in the bowel wall
• Management: resuscitation → endoscopic haemostasis if possible → angiographic embolisation → surgical resection of the bleeding segment if all else fails
• Listed as a surgical indication: Severe bleeding ^[2]

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7. Toxic Megacolon

Toxic megacolon is defined as total or segmental non-obstructive dilatation of colon ≥ 6 cm or caecum > 9 cm and the presence of systemic toxicity ^[2].

• More commonly associated with UC, but can occur in Crohn's colitis
• Pathophysiology: Severe transmural inflammation destroys the muscularis propria and neural plexus → loss of colonic tone → massive dilatation. The inflamed, thinned wall is at imminent risk of perforation.
• Presents with fever, tachycardia, hypotension, dehydration, electrolyte disturbances, anaemia, hypoalbuminaemia and mental changes ^[2]
• Diagnosis is made by plain AXR ^[2]
• Management: bowel rest and total parenteral nutrition, fluid and electrolyte replacement and corticosteroids ^[2]. If no response within 24-48 hours → emergency surgery (total colectomy + end ileostomy)
• Fulminant colitis and impending perforation: thumb-printing sign on AXR are surgical emergencies ^[4]

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II. Perianal Complications

Perianal diseases are common in CD, occurring in up to 40% of patients ^[1]. 24.5% of patients with Crohn's disease have perianal disease and 83% required surgery ^[11].

MRI and EAUS are necessary to document before the definitive treatment ^[11] — because the anatomy of perianal fistulae is complex (relationship to sphincter muscles) and determines the surgical approach.

Management: Anti-TNF ± AZA and/or seton drainage ^[11] (see Management section for full algorithm).

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III. Metabolic and Nutritional Complications

These arise primarily from terminal ileal disease or resection and chronic inflammation-driven malabsorption.

A. Malabsorption-Related

B. Gallstones (Cholelithiasis) [2]

Altered bile composition since resection of the ileum interrupts the enterohepatic circulation of bile acids and causes bile to be supersaturated with cholesterol ^[21].

Step-by-step pathophysiology:

1. Normal: bile salts are absorbed in the terminal ileum → return to the liver via portal circulation (enterohepatic circulation) → re-secreted into bile
2. Terminal ileal disease/resection → bile salt malabsorption → depleted bile salt pool
3. Bile becomes supersaturated with cholesterol (normally, bile salts keep cholesterol in solution)
4. Cholesterol precipitates → cholesterol gallstones
5. Additionally: reduced oral intake / TPN → bile stasis → further promotes stone formation ^[21]

C. Kidney Stones (Nephrolithiasis — Calcium Oxalate) [2]

Increased risk of calcium oxalate nephrolithiasis ^[21].

Step-by-step pathophysiology ^[21]:

1. Normal: dietary calcium binds dietary oxalate in the gut lumen → insoluble calcium oxalate complex → excreted in stool (never absorbed)
2. In CD with fat malabsorption: unabsorbed fatty acids preferentially bind calcium in the gut lumen → calcium is unavailable to bind oxalate
3. Free oxalate remains in the gut lumen → absorbed in the colon → enters the bloodstream → filtered by kidneys → hyperoxaluria
4. Calcium binds to unabsorbed fatty acids leaving oxalate free to pass into the colon to be absorbed and then filtered by the kidneys ^[21]
5. In the renal tubules: oxalate + urinary calcium → calcium oxalate kidney stones

Prevention ^[21]:

• Increased fluid intake
• Low oxalate diet
• Correction of metabolic acidosis with potassium citrate (citrate inhibits calcium oxalate crystallisation)

D. Metabolic Bone Disease [21]

Primary due to malabsorption of calcium and vitamin D, both of which are consequences of fat malabsorption ^[21].

• Also contributed to by corticosteroid use (steroids → osteoblast apoptosis, reduced calcium absorption, increased renal calcium excretion)
• Increased risk for osteomalacia, osteopenia, osteoporosis and secondary hyperparathyroidism ^[21]
  • Osteomalacia = defective mineralisation of osteoid (soft bones)
  • Osteoporosis = reduced bone mass
  • Secondary hyperparathyroidism: low calcium → PTH secretion → bone resorption to maintain serum calcium
• Managed with magnesium, calcium and vitamin D supplements ^[21]
• DEXA scan for bone density monitoring

E. Short Bowel Syndrome

This is a complication of treatment rather than the disease itself — repeated bowel resections can lead to short gut syndrome ^[2].

• Defined as < 200 cm of remaining small bowel (or < 100 cm without colon)
• Loss of absorptive surface → global malabsorption → dependence on TPN
• Complications of short bowel syndrome include ^[21]: electrolyte deficiency (hypomagnesaemia, hypocalcaemia), trace element deficiency (zinc, copper, selenium), iron deficiency, essential fatty acid deficiency, metabolic bone disease, gallstones, kidney stones, oesophagitis/PUD (gastrin hypersecretion), TPN-associated complications (line infections, liver disease)
• This is precisely why surgical principle = preservation of bowel length ^[4] and conservative and minimum resection ^[12] are emphasised

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IV. Malignant Complications

Colorectal Cancer (CRC) [2]

CRC in IBD patients is preceded by dysplasia. Incidence of CRC in IBD: 18% after 30 years of colitis ^[22].

Pathophysiology: The dysplasia-carcinoma sequence in IBD differs from the sporadic adenoma-carcinoma sequence:

• Sporadic CRC: Normal mucosa → adenoma → carcinoma (discrete polyp)
• IBD-CRC: Chronic inflammation → flat dysplasia (not a polyp) → carcinoma. The chronic inflammatory milieu generates reactive oxygen species, DNA damage, and promotes clonal expansion of dysplastic cells across a wide field ("field cancerisation")

Risk factors for IBD-associated colorectal neoplasia ^[18]:

CRC Surveillance ^[23]:

AGA guideline 2010 ^[23]:

• Started at a maximum 8 years after UC or Crohn's colitis
• Optimal surveillance interval not clearly defined
• Left-sided or extensive colitis: within 1-2 years after initial screening colonoscopy
• After two negative examinations, every 1 to 3 years
• Individualised (i.e. presence of other risk factors)
• Primary sclerosing cholangitis: yearly
• Ulcerative proctitis: not considered at increased risk
• Ideally, surveillance colonoscopy should be performed when the disease is in remission

Surveillance methods ^[2]:

• Chromoendoscopy — highest yield for dysplasia detection; involves topical application of methylene blue or indigo carmine to enhance mucosal irregularities
• High-definition white light colonoscopy — alternative when chromoendoscopy yield is decreased
• Narrow band imaging (NBI) — does NOT enhance dysplasia detection ^[2]

Small Bowel Malignancy

• CD patients have a modestly increased risk of small bowel adenocarcinoma, especially in chronically inflamed segments
• Also increased risk of small bowel lymphoma (particularly with immunosuppressive therapy)
• The risk is lower than CRC risk but is important because small bowel cancers are difficult to detect early

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V. Extraintestinal Complications

These are immune-mediated manifestations occurring outside the GI tract. They were discussed in detail in the Clinical Features section but are also true complications of CD.

Extraintestinal manifestations ^[2][1]:

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VI. Treatment-Related Complications

The therapies we use for CD carry their own complications — an unavoidable trade-off:

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VII. Post-Surgical Complications

A. Post-Resection Recurrence

• The most important long-term surgical complication: CD recurs in ~70-80% at the neo-terminal ileum within 1 year of surgery (endoscopic recurrence), and ~50% will have clinical recurrence within 5 years without prophylaxis
• Why at the neo-terminal ileum? After ileocaecal resection, the new "terminal ileum" (the anastomotic site) is exposed to the faecal stream and bacterial load — the same factors that drive disease in the original terminal ileum
• Assessed by colonoscopy at 6-12 months post-op using the Rutgeerts score (i0-i4 grading of endoscopic recurrence at the anastomosis)
• Prevented by post-operative prophylaxis (AZA, anti-TNF) and smoking cessation (smoking is the strongest modifiable risk factor for post-surgical recurrence)

B. Short Bowel Syndrome (Discussed Above)

Repeated bowel resections can lead to short gut syndrome ^[2] — hence the emphasis on conservative and minimum resection ^[12] and preservation of bowel length ^[4].

C. Anastomotic Complications

• Anastomotic leak: Leakage at the surgical join → peritonitis, sepsis. Risk increased by malnutrition, steroids, and active disease at the resection margin.
• Anastomotic stricture: Fibrosis at the anastomotic site → narrowing → obstruction. Can be managed with endoscopic balloon dilatation.

D. Adhesive Small Bowel Obstruction

• Any abdominal surgery → adhesion formation → bands of fibrous tissue can kink or compress bowel → mechanical obstruction
• Laparoscopic ileocaecal resection reduces adhesion formation compared to open surgery → reduction of adhesive bowel obstruction ^[13]

E. Stoma-Related Complications [21]

If a stoma is created (ileostomy or colostomy), potential complications include:

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VIII. Complications Specific to Disease Behaviour

Pulling it all together according to the Montreal classification ^[1]:

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Active Recall - Crohn's Disease: Complications

1. A CD patient presents with recurrent UTIs and pneumaturia. What type of fistula is this, and what is the step-by-step pathophysiology of its formation?

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Enterovesical fistula (bowel to bladder). Pathophysiology: Transmural inflammation erodes through all bowel wall layers developing a sinus tract. The sinus tract penetrates the serosa and tracks to the adjacent bladder. Communication forms between bowel and bladder lumen. Bowel contents (gas, bacteria, faeces) enter the bladder causing pneumaturia (air in urine), faecaluria, and recurrent polymicrobial UTIs.

2. Explain the pathophysiology of calcium oxalate kidney stones in a patient with terminal ileal Crohn's disease.

Your answer

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Normally, dietary calcium binds dietary oxalate in the gut lumen forming insoluble calcium oxalate complex excreted in stool. In CD with terminal ileal disease, bile salt malabsorption leads to fat malabsorption. Unabsorbed fatty acids bind calcium preferentially, leaving free oxalate in the gut lumen. Free oxalate is absorbed in the colon, enters the bloodstream, filtered by kidneys causing hyperoxaluria. Oxalate combines with urinary calcium forming calcium oxalate kidney stones.

3. Why is short bowel syndrome a major concern in CD management, and what surgical principles are used to prevent it?

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CD is not curable by surgery and recurs after resection. Repeated resections progressively shorten the small bowel. Short bowel syndrome occurs when less than 200cm of small bowel remains, causing global malabsorption and TPN dependence. Prevention: preservation of bowel length (document residual SB length), conservative and minimum resection, stricturoplasty preferred over resection where possible, extended resection does not decrease recurrence.

4. List the risk factors for IBD-associated colorectal cancer and state when surveillance should begin.

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Patient-specific: PSC, history of colorectal neoplasia, FHx CRC in first-degree relative, smoking, early age of onset, male sex. Disease-specific: disease duration, extent, cumulative inflammatory burden, active inflammation. Endoscopic: stricture, shortened tubular colon, pseudopolyps. Surveillance begins at maximum 8 years after UC or Crohn's colitis (AGA 2010), repeated every 1-3 years. PSC patients require yearly surveillance.

5. A CD patient on azathioprine and infliximab develops persistent swinging fever and RLQ tenderness. CRP is markedly elevated. CT shows a rim-enhancing fluid collection adjacent to the terminal ileum. What is the diagnosis, the immediate management steps, and why must you address this before continuing biologics?

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Diagnosis: Intra-abdominal abscess. Immediate management: CT-guided percutaneous drainage plus IV antibiotics. Must drain abscess before continuing biologics because anti-TNF therapy causes immunosuppression. Undrained sepsis combined with immunosuppression leads to uncontrolled infection and septic shock. Only after sepsis is controlled can biologics be safely continued or restarted.

6. Compare inflammatory versus fibrostenotic strictures in CD: how do they differ on MRE and in management?

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Inflammatory stricture: MRE shows wall enhancement (gadolinium uptake indicates active inflammation), T2 hyperintensity (oedema), restricted diffusion. Management: medical therapy (steroids, biologics) as inflammation is reversible. Fibrostenotic stricture: MRE shows no enhancement, T2 hypointensity (fibrosis). Management: endoscopic balloon dilatation, stricturoplasty (small bowel), or resection (large bowel or suspected malignancy). Fibrosis does not respond to anti-inflammatory drugs.

References

^[1] Lecture slides: Inflammatory bowel disease.pdf (p6, p8, p9) ^[2] Senior notes: felixlai.md (Inflammatory bowel disease — Crohn's disease, complications and signs/symptoms of complications sections) ^[4] Senior notes: maxim.md (Inflammatory bowel disease — surgical management; Surgical procedures for CD) ^[11] Lecture slides: Inflammatory bowel disease.pdf (p45 — Perianal CD) ^[12] Lecture slides: Inflammatory bowel disease.pdf (p26, p27 — Surgery for CD) ^[13] Lecture slides: Inflammatory bowel disease.pdf (p41 — Ileocaecal CD) ^[15] Lecture slides: Inflammatory bowel disease.pdf (p28 — Small bowel stricture) ^[18] Lecture slides: Inflammatory bowel disease.pdf (p52 — IBD-associated CRC risk factors) ^[20] Lecture slides: Inflammatory bowel disease.pdf (p34 — Enterocutaneous fistula) ^[21] Senior notes: felixlai.md (Short bowel syndrome complications; CRC screening section) ^[22] Lecture slides: Inflammatory bowel disease.pdf (p51 — IBD-associated CRC) ^[23] Lecture slides: Inflammatory bowel disease.pdf (p56 — AGA guideline 2010)