Crohn's Disease
Crohn's disease is a chronic transmural granulomatous inflammatory bowel disease that can affect any part of the gastrointestinal tract from mouth to anus, most commonly the terminal ileum and colon, characterized by skip lesions, noncaseating granulomas, and a tendency toward fistula formation.
Crohn's Disease
Crohn's disease (CD) is a chronic, relapsing-remitting, transmural inflammatory disorder that can affect any part of the gastrointestinal tract from mouth to anus, though it has a strong predilection for the terminal ileum and ileocaecal region [1][2].
Breaking down the name and key descriptors:
- Crohn's — named after Dr Burrill Crohn, who described the disease in 1932 (originally "regional ileitis")
- Transmural — "trans" = through, "mural" = wall; the inflammation goes through all layers of the bowel wall (mucosa → submucosa → muscularis → serosa), unlike ulcerative colitis (UC) which is limited to the mucosa/submucosa
- Granulomatous — characterised histologically by non-caseating granulomas (though only present in ~35% of biopsies) [3]
Crohn's disease is one of the two major forms of inflammatory bowel disease (IBD), the other being ulcerative colitis. The distinction matters enormously because management, complications, and prognosis differ.
Key Distinction from UC
Crohn's = transmural, skip lesions, any part of GIT, granulomas possible, rectal sparing common. UC = mucosal only, continuous from rectum proximally, no granulomas, rectum always involved.
2. Epidemiology
- Incidence: Highest in North America and Northern Europe (~5–12/100,000/year); historically lower in Asia but rapidly rising
- Prevalence: ~100–300/100,000 in Western countries
- The incidence of CD has been steadily increasing in Asia over the last two decades, paralleling industrialisation and westernisation of diet [2]
- Incidence in Hong Kong: approximately 1/100,000 (historically lower than Western figures but rising) [3]
- Gender: M > F (or at least M ≈ F) in Chinese populations; in Western data there is a slight female predominance [2][3]
- The senior notes specifically state: "Crohn's and UC in China tends to affect males more → with time this ratio will be equalized" [2]
- Age of onset: Crohn's tends to have earlier onset than UC — typically 15–35 years (peak in 2nd–3rd decade), with a smaller second peak around 50–70 years. "Crohn's tends to have earlier onset age, UC is 10 years later" [2]
- Family clustering: "Tends to be clustered in families → Crohn's technically not a genetic disease, but this link is probably due to shared environment" [2]
High Yield: In Hong Kong, IBD incidence is rising. CD onset is younger than UC. Male predominance in Chinese populations.
- First peak: 15–35 years (most common)
- Second smaller peak: 50–70 years
- This bimodal pattern is less pronounced in Asian populations
3. Risk Factors
| Category | Risk Factor | Mechanism / Explanation |
|---|---|---|
| Smoking | Increases risk AND severity of CD | Nicotine impairs mucosal blood flow, alters cytokine balance (↑Th1), and disrupts the mucosal barrier. Paradoxically protective in UC. [1][2] |
| Family history of IBD | First-degree relatives have 5–20× increased risk | Shared genetic susceptibility and shared environment [2][3] |
| Prior appendicectomy | Risk factor for CD (contrast: protective in UC) | Mechanism unclear; may relate to altered mucosal immune homeostasis [3][4] |
| Infectious GE in prior 1 year | Recent enteric infection ↑ risk | Post-infectious dysbiosis may trigger immune dysregulation [4] |
| Diet | Refined sugars, low-fibre diet, spicy food | Western-type diet alters gut microbiota composition and disrupts epithelial barrier integrity [3] |
| Drugs | NSAIDs, OCP, antibiotics | NSAIDs disrupt mucosal prostaglandin-mediated cytoprotection; antibiotics disrupt commensal flora; OCP may promote microvascular thrombosis [3] |
| Genetics | NOD2/CARD15 gene polymorphisms (SNP8, 12, 13) | See genetics section below [2] |
Smoking and IBD — Classic Exam Question
Smoking increases the risk and severity of Crohn's disease, but appears to reduce the risk of developing ulcerative colitis. "Will sometimes see smokers who quit smoking, then develop ulcerative colitis." [2]
This is one of the most commonly tested points in IBD.
4. Anatomy and Function — Why the Terminal Ileum?
Understanding where Crohn's likes to sit helps you understand why it presents the way it does:
-
Terminal ileum (last ~20–30 cm of small bowel before the ileocaecal valve):
- Contains the largest concentration of Peyer's patches (organised lymphoid tissue in the gut wall) — these are the "sampling stations" of the gut immune system
- Site of bile acid reabsorption (enterohepatic circulation) — inflammation here → bile acid malabsorption → watery diarrhoea, steatorrhoea
- Site of vitamin B12 absorption — inflammation/resection → B12 deficiency → megaloblastic anaemia, neurological complications
- The ileocaecal valve creates a relative area of faecal stasis → prolonged antigen exposure → immune activation
-
Entire GI tract: Unlike UC, CD can involve any segment — mouth (oral ulcers/aphthae), oesophagus, stomach, duodenum, jejunum, ileum, colon, rectum, and anus. But most commonly it sits in the terminal ileum ± proximal colon.
Although Crohn's can affect the entire GI tract, where is it most commonly localised? [2]
| Location | Frequency |
|---|---|
| Small intestine AND colon (ileocolonic) | 40–55% |
| Terminal ileum, ileocolonic region | Most common overall |
| Small intestine only | ~20–30% |
| Colon only | ~20–30% |
| Anorectal disease (fistula, fissure, abscess) | 30–40% |
| Upper GI (mouth, oesophagus, stomach, duodenum) | < 5% in isolation |
Why the terminal ileum? The high density of Peyer's patches means antigen sampling is maximal here. In a genetically susceptible host with an abnormal immune response, this is where the "first hit" is most likely to occur. The relative stasis at the ileocaecal valve prolongs exposure to luminal antigens and bacteria.
5. Aetiology and Pathophysiology
The etiology of IBD is generally unknown. The current model is a multifactorial interplay between:
- Genetic susceptibility
- Environmental triggers (diet, infection, smoking)
- Immunological dysregulation
- Gut microbiota (dysbiosis)
Think of it as: Genetic soil + Environmental seed + Immune storm + Microbial shift = Disease
"Probably one of the most important one [environmental factor] → our genetics haven't changed a lot" [2] — this is the key insight. The rapid rise in CD incidence in Asia tracks with westernisation of diet and lifestyle, not with genetic changes.
-
NOD2 gene (also called CARD15) SNP8, 12, 13 — the most well-validated susceptibility gene for CD [2]
- NOD2 = Nucleotide-binding Oligomerisation Domain-containing protein 2
- NOD2 is an intracellular pattern recognition receptor (innate immune system) expressed in monocytes, macrophages, dendritic cells, and Paneth cells (in the crypts of Lieberkühn)
- It recognises muramyl dipeptide (MDP), a component of bacterial peptidoglycan
- Normal function: NOD2 activation → NF-κB signalling → appropriate antimicrobial response (defensin production, autophagy)
- Mutant NOD2: Loss-of-function → inadequate bacterial sensing → impaired clearance of intracellular bacteria → paradoxical excessive inflammatory response
- NOD2 mutations are more common in Caucasians and are extremely rare in Chinese populations — "not in Chinese, more in Caucasians" [2]
-
Other genes: ATG16L1, IRGM (autophagy genes), IL23R, LRRK2 — all converge on themes of barrier integrity, bacterial handling, and immune regulation
-
"Extremely rare genes will create a subtype of neonatal Crohn's → not in Chinese, more in Caucasians" [2]
Genetics vs Environment
The rapid rise of CD in Hong Kong/Asia cannot be explained by genetics alone — it takes thousands of years for allele frequencies to shift meaningfully in a population. The driver is environmental: westernised diet (high fat, refined sugar, low fibre), urbanisation, improved hygiene (hygiene hypothesis), antibiotic use, and changes in gut microbiota composition.
| Factor | Effect on CD | Mechanism |
|---|---|---|
| Smoking | ↑ Risk, ↑ severity, ↑ relapse, ↑ need for surgery | Impairs mucosal blood flow, shifts immune balance to Th1, disrupts mucosal barrier |
| Diet (Western) | ↑ Risk | High refined sugar, high fat, low fibre → dysbiosis, ↓ SCFA production, ↑ mucosal permeability |
| NSAIDs | ↑ Risk of flare | Direct mucosal injury (↓ prostaglandins → ↓ mucosal blood flow, ↓ mucus secretion) |
| OCP | Modest ↑ risk | Microvascular thrombosis |
| Antibiotics | ↑ Risk | Disrupts commensal flora → dysbiosis |
| Appendicectomy | ↑ Risk (for CD) | Unclear; may remove a regulatory immune compartment |
| Hygiene hypothesis | ↑ Risk in "cleaner" environments | Reduced early-life microbial exposure → inadequate immune "education" |
| Infectious GE | ↑ Risk within 1 year | Post-infectious immune priming, altered microbiome |
This is the core of CD — understanding it helps you understand every clinical feature:
Step-by-step pathogenesis:
Detailed breakdown:
- Barrier defect: In genetically susceptible individuals, the intestinal epithelial barrier is "leaky" — tight junctions are less effective, Paneth cell defensin production is reduced (especially with NOD2 mutations), and the mucus layer is thinner
- Antigen exposure: Luminal bacteria and their products cross into the lamina propria
- Innate immune failure: Defective sensing by NOD2/pattern recognition receptors → paradoxically, instead of a clean, contained antimicrobial response, you get a persistent, uncontrolled inflammatory cascade
- Adaptive immune polarisation: Dendritic cells present antigens to T cells in a Th1/Th17-skewed manner:
- Th1 cells → produce IFN-γ and TNF-α → activate macrophages → granuloma formation
- Th17 cells → produce IL-17 → neutrophil recruitment → tissue damage
- Key cytokines: IL-12 (drives Th1), IL-23 (drives Th17), TNF-α (master pro-inflammatory cytokine)
- Transmural inflammation: Unlike UC (where inflammation stays in the mucosa), the Th1-driven macrophage-granuloma response in CD penetrates the full thickness of the bowel wall → this is why CD causes fistulae (inflammatory tract burns through the wall to adjacent structures), strictures (chronic inflammation → fibrosis of all layers), and abscesses (transmural penetration → walled-off infection)
Why transmural? Because Th1/macrophage-driven granulomatous inflammation is inherently a "deep" process — macrophages are recruited deep into the tissue, and granulomas are organised structures that form in the submucosa and deeper layers. In contrast, UC is Th2-driven with neutrophilic infiltration that stays superficial.
- Patients with CD have reduced microbial diversity — fewer Firmicutes (especially Faecalibacterium prausnitzii, which produces anti-inflammatory short-chain fatty acids like butyrate) and more Enterobacteriaceae (including adherent-invasive E. coli)
- This creates a vicious cycle: inflammation → dysbiosis → more inflammation
- The microbiome is now considered the "trigger" that keeps pulling the immune system into an inflammatory state in a genetically susceptible host
6. Classification
The Montreal classification is the internationally used system to categorise CD by age at diagnosis, location, and behaviour:
| Parameter | Classification | Details |
|---|---|---|
| A (Age at Dx) | A1 | ≤ 16 years |
| A2 | 17–40 years (most common) | |
| A3 | > 40 years | |
| L (Location) | L1 | Ileal |
| L2 | Colonic | |
| L3 | Ileocolonic (most common) | |
| L4 | Isolated upper GI (modifier, can be added to L1–L3) | |
| B (Behaviour) | B1 | Non-stricturing, non-penetrating (inflammatory) |
| B2 | Stricturing (fibrostenotic) | |
| B3 | Penetrating (fistulising) | |
| p | Perianal disease modifier (added to B1–B3) |
Phenotypes: inflammatory (30%), fibrostenotic (50%), fistulising (20%) [3]
This is important because disease behaviour determines management:
-
B1 — Inflammatory (non-stricturing, non-penetrating) (~30%)
- Active mucosal/transmural inflammation without mechanical complications
- Responds to anti-inflammatory and immunomodulatory therapy
-
B2 — Fibrostenotic (stricturing) (~50%)
- Chronic inflammation → fibrosis → luminal narrowing → bowel obstruction
- Why? Repeated cycles of transmural inflammation → healing by fibrosis → progressive narrowing
- Fibrotic strictures do NOT respond to anti-inflammatory drugs — they need endoscopic balloon dilatation or surgical resection
-
B3 — Penetrating (fistulising) (~20%)
- Inflammation burrows through the full thickness of the bowel wall → creates abnormal connections (fistulae) between:
- Bowel and bowel (entero-enteric)
- Bowel and skin (enterocutaneous)
- Bowel and bladder (enterovesical → pneumaturia, recurrent UTI)
- Bowel and vagina (enterovaginal → passage of stool/flatus per vagina)
- Perianal fistulae (very common in CD)
- Can also form intra-abdominal abscesses
- Inflammation burrows through the full thickness of the bowel wall → creates abnormal connections (fistulae) between:
Disease Behaviour Evolves Over Time
Most patients begin with B1 (inflammatory) disease. Over 20 years, ~50% will progress to either B2 (stricturing) or B3 (penetrating). This is why early, effective therapy ("treat-to-target") is advocated — to prevent structural damage.
- Crohn's Disease Activity Index (CDAI): The classic research tool; scores based on number of liquid stools, abdominal pain, general well-being, complications, use of anti-diarrhoeal drugs, abdominal mass, haematocrit, body weight
- < 150 = remission
- 150–220 = mild
- 220–450 = moderate
- > 450 = severe
- Harvey-Bradshaw Index (HBI): Simplified version of CDAI (5 items); commonly used in clinical practice
- Simple Endoscopic Score for Crohn's Disease (SES-CD): Endoscopic assessment
7. Clinical Features
The clinical features of Crohn's disease are best understood by tracing them back to the underlying transmural, skip-lesion, granulomatous inflammation that can occur anywhere from mouth to anus.
7.1 Symptoms
i. Abdominal Pain
- Crampy abdominal pain [4]
- Typically in the right lower quadrant (RLQ) — because the terminal ileum and caecum are the most commonly affected sites
- Pathophysiology: Transmural inflammation results in fibrotic stricture leading to obstruction [4]
- The pain may be colicky (comes and goes in waves) when there is partial obstruction, or constant when there is active inflammation or abscess
- Post-prandial exacerbation ("food fear") — eating triggers peristalsis → pain as bolus hits a narrowed or inflamed segment → patients may reduce oral intake → weight loss
ii. Diarrhoea
- Prolonged and fluctuates over a period of time [4]
- Less commonly bloody compared to UC — but occult blood may be present
- Watery but non-bloody ± steatorrhoea [3]
- Pathophysiology [4]:
- Excessive fluid secretion and impaired fluid resorption in inflamed bowels — inflammatory mediators (prostaglandins, cytokines) stimulate chloride secretion and inhibit sodium/water absorption
- Bile salt malabsorption due to inflamed or resected terminal ileum — the terminal ileum is where bile salts are actively reabsorbed; if inflamed or resected, bile salts reach the colon → stimulate colonic water and electrolyte secretion → watery diarrhoea. If > 100 cm of ileum is affected/resected, total bile salt pool is depleted → inadequate fat emulsification → steatorrhoea
- Bacterial overgrowth from small bowel strictures and enterocolonic fistula — stasis proximal to strictures allows bacterial proliferation → bacteria deconjugate bile salts → fat malabsorption; bacteria also produce gas and osmotically active metabolites → bloating and diarrhoea
iii. Steatorrhoea
- Pale, greasy, smelly and bulky stool that floats on water and difficult to flush away [4]
- Steatorrhoea may lead to malnutrition, clotting abnormalities, osteomalacia and hypocalcaemia causing tetany [4]
- Why? Fat-soluble vitamins (A, D, E, K) require bile salts for absorption. If bile salts are malabsorbed:
- Vitamin K deficiency → clotting abnormalities (↓ factors II, VII, IX, X)
- Vitamin D deficiency → osteomalacia (adults), rickets (children), hypocalcaemia → tetany
- Vitamin A deficiency → night blindness, xerophthalmia
- Vitamin E deficiency → peripheral neuropathy
- Why? Fat-soluble vitamins (A, D, E, K) require bile salts for absorption. If bile salts are malabsorbed:
- Pathophysiology [4]:
- Bile acid malabsorption due to an inflamed or resected terminal ileum
- Bacterial overgrowth from small bowel strictures and enterocolonic fistula
iv. Haematochezia (Blood in Stool)
- Stool may reveal presence of microscopic levels of blood [4]
- Gross bleeding is less frequent than ulcerative colitis [4]
- Why? CD's inflammation is transmural and often in the small bowel, which has less propensity for surface bleeding compared to UC's diffuse mucosal ulceration in the colon
- When colonic CD is present, frank blood per rectum is more common
v. Constitutional Symptoms
- Fever [4]
- Result of inflammatory process itself (pro-inflammatory cytokines like IL-1, IL-6, TNF-α act as endogenous pyrogens)
- Result of perforation with a complicating bowel infection (abscess)
- Fatigue — multifactorial: anaemia, malnutrition, chronic inflammation (cytokine-mediated), sleep disruption
- Anorexia — inflammatory cytokines suppress appetite via hypothalamic pathways
- Weight loss [4]
- Result of malabsorption
- Decreased oral intake in patients with obstructing segments of bowel ("food fear" — eating triggers pain)
- Increased metabolic demand from chronic inflammation
vi. Oral Symptoms
- Oral ulcers (aphthous ulcers), stomatitis [3]
- Aphthous ulcers are shallow, painful ulcers on the buccal mucosa, tongue, or lips
- These represent the "mouth-to-anus" nature of CD — the oral cavity is part of the GI tract
- Can also have granulomatous cheilitis (swelling of the lip due to granulomatous inflammation)
vii. Anorectal Symptoms
- Anal fissures, anal fistulae, perianal abscess (periproctitis) [2][3]
- Anorectal disease: 30–40% of CD patients [2]
- Perianal disease is so characteristic of CD that its presence should always raise suspicion
- Why is perianal disease so common? The transmural nature of inflammation allows tracts to form through the rectal/anal wall → fistulae and abscesses. Fissures may be atypical (lateral, deep, multiple, non-midline) — unlike the simple posterior midline fissures seen in the general population
- Anal skin tags — large, oedematous, "elephant ear" skin tags are characteristic of CD [5]
viii. Obstructive Symptoms
- Nausea, vomiting (especially with proximal small bowel obstruction)
- Abdominal distension, colicky pain
- Borborygmi (loud bowel sounds)
- Absolute constipation (no flatus or stool) in complete obstruction
- Small bowel (SB) / large bowel (LB) obstruction [3]
- Pathophysiology: Chronic transmural inflammation → fibrosis → stricture → mechanical obstruction
ix. Symptoms of Fistulae
- Enterovesical fistula: pneumaturia (air in urine), faecaluria (stool in urine), recurrent UTIs
- Enterovaginal fistula: passage of stool/flatus per vagina
- Enterocutaneous fistula: discharge of bowel content through the skin (often post-surgical)
- Entero-enteric fistula: malabsorption (bypasses absorptive surface), diarrhoea
- Pallor, dyspnoea, palpitation, fatigue [4]
- Causes of anaemia in CD:
- Iron deficiency → chronic blood loss (microscopic haematochezia), malabsorption of iron (duodenal/jejunal disease)
- Vitamin B12 deficiency → terminal ileal disease or resection (B12 is absorbed in the terminal ileum)
- Folate deficiency → proximal small bowel disease (folate is absorbed in the jejunum), or drug-related (methotrexate, sulfasalazine)
- Anaemia of chronic disease → hepcidin upregulation from IL-6 → iron sequestration in macrophages
7.2 Signs
- Cachexia / wasting — chronic malabsorption + reduced intake + increased metabolic demand
- Pallor — anaemia (multifactorial as above)
- Clubbing — associated with chronic malabsorption and active inflammatory bowel disease; mechanism not fully understood but may relate to VEGF release from inflamed bowel
- Dehydration — from diarrhoea and poor oral intake
- Growth retardation / delayed puberty — in paediatric CD, this may be the presenting feature before any GI symptoms appear; caused by malnutrition and chronic inflammation suppressing growth hormone axis
- Oral aphthous ulcers — on inspection of the oral cavity [3][5]
- Palpable mass at RLQ (25%) [3]
- This is a hallmark finding — represents a thickened, inflamed loop of terminal ileum, or an inflammatory phlegmon/abscess
- Why RLQ? Because the terminal ileum and caecum sit in the RLQ
- Tenderness — typically RLQ, may be diffuse in extensive disease
- Distension — if there is bowel obstruction
- Surgical scars — patients with CD often have had multiple surgeries (resections, abscess drainages); look for midline laparotomy scars, RIF scars, stoma sites
- Stoma — some patients will have an ileostomy or colostomy
- Enterocutaneous fistula openings — rarely, you may see discharge from an abdominal fistula
Physical examination of the perianal region: skin tags, fissures, fistulas, abscess, PR exam [5]
- Skin tags — large, fleshy, oedematous tags (different from the small, flat tags seen normally)
- Fissures — may be atypical: lateral position, deep, multiple, painless (vs. the classic posterior midline painful fissure of idiopathic anal fissure)
- Fistulae — external openings around the anus, may be discharging pus or faecal material; can be multiple and complex
- Abscess — perianal swelling, redness, tenderness, fluctuance
- Digital rectal examination — may reveal induration, tenderness, stricture, or internal fistula openings
Goodsall's rule for perianal fistulae: If the external opening is anterior to the transverse anal line, the tract usually runs directly to the nearest crypt (radial). If posterior, the tract curves to the posterior midline of the anal canal. In CD, however, fistulae are often complex and Goodsall's rule is less reliable.
EIMs occur in 25–40% of CD patients and can sometimes precede GI symptoms. They are crucial to recognise both for diagnosis and management.
Extraintestinal inspections: mouth, eyes, skin and joints [5]
They can be classified by whether they correlate with disease activity or run an independent course:
EIMs that correlate with bowel disease activity (flare when bowel flares):
| System | Manifestation | Pathophysiology |
|---|---|---|
| Joints | Peripheral arthritis (Type 1: pauciarticular, large joint, asymmetric) | Immune complex deposition and cross-reactive immune responses; tracks with disease activity |
| Skin | Erythema nodosum — tender, raised, red-purple nodules on anterior shins | Delayed-type hypersensitivity reaction; often flares with bowel disease [7] |
| Eyes | Episcleritis — painless redness of the eye (injection of episcleral vessels) | Immune-mediated; tracks with bowel activity |
| Mouth | Aphthous ulcers | Direct GI manifestation |
EIMs that are independent of bowel disease activity (may persist despite disease control):
| System | Manifestation | Pathophysiology |
|---|---|---|
| Joints | Axial arthropathy (sacroiliitis, ankylosing spondylitis) | HLA-B27 associated; runs independently of bowel disease |
| Type 2 peripheral arthritis (polyarticular, small joints, symmetric) | Runs independently | |
| Skin | Pyoderma gangrenosum — deep, undermined, violaceous ulcers (often on shins/near stoma) | Neutrophilic dermatosis; runs independently; exhibits pathergy (worsens with trauma/surgery) |
| Eyes | Anterior uveitis/iritis — painful red eye, photophobia, blurred vision | Autoimmune; can occur independently of flares [8] |
| Hepatobiliary | Primary sclerosing cholangitis (PSC) — more associated with UC but can occur in CD | Immune-mediated bile duct destruction; progressive cholestatic liver disease; independent of bowel activity |
| Gallstones — due to bile acid malabsorption | Terminal ileal disease → ↓ bile salt pool → cholesterol supersaturation of bile → cholesterol gallstones [6] | |
| Renal | Renal stones (oxalate) — fat malabsorption → free fatty acids bind Ca²⁺ → free oxalate absorbed → calcium oxalate stones | |
| Haematological | Thromboembolic disease (DVT, PE) | Chronic inflammation → ↑ procoagulant factors, ↓ antithrombin, endothelial activation |
| Bone | Osteoporosis — multifactorial: malabsorption of Ca²⁺/Vit D, chronic steroid use, inflammatory cytokines | [6] |
| Hepatobiliary | Amyloidosis (secondary/AA) — rare, from chronic inflammation |
EIMs — Quick Memory Framework
Think: "A PIE SAG"
- Arthritis (peripheral + axial)
- Pyoderma gangrenosum
- Iritis / uveitis
- Erythema nodosum
- Sclerosing cholangitis
- Aphthous ulcers
- Gallstones / renal stones (metabolic consequences)
| Deficiency | Sign | Why? |
|---|---|---|
| Iron | Koilonychia, angular stomatitis, glossitis | Malabsorption + chronic blood loss |
| B12 | Glossitis, peripheral neuropathy, subacute combined degeneration | Terminal ileal disease/resection |
| Folate | Glossitis, macrocytic anaemia | Proximal SB disease; methotrexate/sulfasalazine |
| Vitamin D | Proximal myopathy, bone tenderness, tetany | Fat malabsorption (bile salt depletion) |
| Vitamin K | Easy bruising | Fat malabsorption |
| Zinc | Acrodermatitis, poor wound healing | Malabsorption |
| Albumin | Peripheral oedema | Protein-losing enteropathy + malabsorption + ↓ synthesis |
Understanding the pathology helps cement why CD behaves the way it does:
- Transmural inflammation with fistula [3]
- Lymphocytic infiltration, Goblet cells preserved [3]
- Non-caseating granuloma (35%) [3]
- Granulomas are collections of epithelioid macrophages ± multinucleated giant cells
- "Non-caseating" = no central cheesy necrosis (vs. TB which shows caseating granulomas with central necrosis)
- DDx: TB colitis (caseating granuloma, AFB stain & C/ST if suspected) [3] — this is critically important in Hong Kong
- Skip lesions — patchy inflammation with intervening normal mucosa (vs. UC which is continuous)
- Deep linear ulcers → cobblestone appearance [3] — islands of oedematous mucosa between deep longitudinal and transverse ulcers
- Submucosal fibrosis → stricture formation
- Fissuring ulcers → penetrate into deeper layers → fistula/abscess formation
- Creeping fat (pathognomonic) — mesenteric fat wraps around the serosal surface of the inflamed bowel segment
Cobblestone appearance: Imagine a cobblestone road — the "stones" are the swollen, relatively preserved mucosa, and the "gaps" between them are the deep linear ulcers. This is best seen endoscopically and grossly.
Endoscopic findings in CD [3]:
- Patchy inflammation with skip lesions
- Deep linear ulcers (cobblestone appearance)
- Stricture, abscess, fistula
- Rectum usually spared (in contrast to UC where rectum is always involved)
Why skip lesions? The immunological process in CD is driven by focal areas of immune activation, likely at Peyer's patches and other lymphoid aggregates. Inflammation begins at these discrete sites and spreads transmurally, but adjacent segments may be completely spared — giving the characteristic "patchy" or "skip" pattern.
| Feature | Crohn's Disease | Ulcerative Colitis |
|---|---|---|
| Location | Any part GIT (mouth to anus); MC terminal ileum | Rectum ± colon (always starts at rectum) |
| Distribution | Skip lesions, patchy | Continuous, from rectum proximally |
| Depth | Transmural (all layers) | Mucosal/submucosal only |
| Rectal involvement | Often spared | Always involved |
| Bleeding | Less common, occult | Bloody diarrhoea is hallmark |
| Perianal disease | Very common (30–40%) | Uncommon |
| Fistulae | Common | Very rare |
| Strictures | Common (fibrostenotic) | Uncommon (if present, worry about malignancy) |
| Granulomas | Non-caseating (35%) | Absent |
| Smoking | Risk factor | Protective |
| Appendicectomy | Risk factor | Protective |
| Cobblestone appearance | Yes | No |
| Pseudopolyps | Can occur | Common |
| Malignancy risk | Increased (especially colonic CD) | Higher (especially if pancolitis for > 8–10 years with concurrent PSC) |
Why is it crucial to rule out infection in the diagnosis of IBD? Which infection are you thinking of? [2]
Especially Tuberculosis. [2]
Some of the biologics (i.e. anti-TNF-alpha) will suppress the host's ability to contain TB → TB reactivation. [2]
This is critically important in Hong Kong, where TB prevalence remains significant. CD and intestinal TB can look virtually identical clinically and endoscopically:
| Feature | Crohn's Disease | Intestinal TB |
|---|---|---|
| Granuloma | Non-caseating | Caseating |
| AFB stain | Negative | May be positive |
| TB culture | Negative | May be positive |
| Quantiferon/T-SPOT | Usually negative | Usually positive |
| CXR | Normal | May show pulmonary TB (though extrapulmonary TB may have normal CXR) |
| Response to anti-TB Rx | No | Yes (therapeutic trial sometimes used) |
| Ileocaecal valve | Patulous (gaping) | Strictured/fibrotic |
| Ulcers | Longitudinal | Transverse (along lymphatic channels) |
TB vs CD — Must Know
Before starting biologics (anti-TNF), you MUST screen for latent TB (CXR + Quantiferon/T-SPOT). If latent TB is present, treat with isoniazid ± rifampicin before commencing anti-TNF therapy. Failure to do so can cause fatal disseminated TB reactivation.
"No single test or gold standard" for diagnosis of IBD [2]. Diagnosis is based on a combination of endoscopic, radiological, pathological, and biochemical findings [2].
Investigations to work up a potential case of IBD [2]:
- CBC — anaemia (Fe, B12, folate, ACD), high WBC (active inflammation, abscess, steroid use)
- CRP / ESR — markers of active inflammation
- Stool studies — WBC, bacteria, parasites (especially amoeba — rare but can cause colitis) [2]
- Fecal calprotectin — "In active intestinal inflammation, neutrophils migrate into mucosa, lead to leakage of calprotectin" → helps differentiate IBD from IBS (low = IBS more likely; high = IBD more likely, but not 100% specific) [9]
- Serology — "helpful but not diagnostic" [2]
- Ileo-colonoscopy with biopsy — minimum 2 biopsies from each segment: TI, ascending colon, transverse colon, descending colon, sigmoid, rectum [3]
- Gold standard assessment
- Sigmoidoscopy is sufficient for acute severe colitis [3]
- CT/MR enteroclysis/enterography — first-line for small bowel assessment [2]
- "Patient may have undiagnosed strictures causing capsule retention" [2] — hence CT/MR enterography is preferred over capsule endoscopy as first-line for small bowel evaluation in known/suspected CD
- CT scan — for diagnosis and complications (abscess, perforation, fistula) [2]
- Small bowel series (barium follow-through) — now largely replaced by CT/MR enterography [2]
High Yield Summary
Definition: Crohn's disease is a chronic, relapsing-remitting, transmural, granulomatous inflammatory disorder affecting any part of the GIT (mouth to anus), most commonly the terminal ileum and ileocaecal region.
Epidemiology (HK): Incidence ~1/100,000 (rising), M ≥ F in Chinese populations, earlier onset than UC (peak 15–35y).
Risk Factors: Smoking (↑ risk — opposite for UC), FHx IBD, prior appendicectomy (↑ risk — opposite for UC), infectious GE in past year, NSAIDs, OCP, antibiotics, Western diet, NOD2 mutations (rare in Chinese).
Pathophysiology: Genetically susceptible host + environmental trigger → mucosal barrier defect → luminal antigens cross epithelium → exaggerated Th1/Th17 immune response → TNF-α, IL-12, IL-23 → transmural granulomatous inflammation → ulceration, fibrosis, fistulae.
Key Locations: Ileocolonic (40–55%) > SB only / colon only (~20–30% each); anorectal disease 30–40%.
Phenotypes: Inflammatory (30%), fibrostenotic (50%), fistulising (20%).
Clinical Features:
- Symptoms: RLQ crampy abdominal pain (stricturing/obstruction), watery non-bloody diarrhoea ± steatorrhoea (bile acid malabsorption), constitutional symptoms (fever, weight loss, fatigue), oral ulcers, perianal symptoms (fissure, fistula, abscess), anaemic symptoms.
- Signs: Palpable RLQ mass (25%), perianal disease (skin tags, fissures, fistulae, abscess), cachexia, pallor, clubbing, nutritional deficiency signs.
- Extraintestinal: Arthritis, erythema nodosum, pyoderma gangrenosum, uveitis/episcleritis, PSC, gallstones, renal stones, osteoporosis, thromboembolic disease.
Pathology: Transmural inflammation, non-caseating granulomas (35%), skip lesions, cobblestone appearance, creeping fat. DDx TB colitis (caseating granulomas — must rule out before biologics).
Fecal calprotectin: Differentiates IBD from IBS (high = IBD likely); ASCA associated with CD, pANCA with UC — but serology is not diagnostic.
Active Recall - Crohn's Disease (Definition, Epidemiology, Aetiology, Clinical Features)
[1] Lecture slides: GC 033. Chronic diarrhea_irritable bowel syndrome and inflammatory bowel disease.pdf [2] Senior notes: Block A - Chronic diarrhoea_ irritable bowel syndrome and inflammatory bowel disease.pdf (pp. 31–41) [3] Senior notes: Maksim Medicine Notes.pdf (p. 129) [4] Senior notes: MBBS Final MB (Medicine) (Felix PY Lai).pdf (pp. 855–857); MBBS Final MB (Surgery) (Felix PY Lai).pdf (pp. 650–652) [5] Lecture slides: Inflammatory bowel disease.pdf (p. 10) [6] Senior notes: Block A - Upper abdominal pain_ peptic ulcer; pancreatitis and gallstone.pdf (p. 26); Block A - Back pain in an elderly woman_ osteoporosis and related fractures.pdf (p. 15) [7] Senior notes: Ryan Ho Rheumatology.pdf (p. 157) [8] Senior notes: Ryan Ho Opthalmology.pdf (p. 131) [9] Senior notes: Block A - Gastrointestinal Data Interpretation.pdf (p. 6)
Differential Diagnosis of Crohn's Disease
Crohn's disease is a clinical chameleon. Because it can affect any part of the GIT, produce transmural or superficial inflammation, mimic infections, and present with a bewildering range of intestinal and extra-intestinal features, the differential diagnosis is broad. The specific differentials you consider depend on the dominant clinical presentation:
- Is the patient presenting with chronic diarrhoea?
- Is the chief complaint RLQ abdominal pain (mimicking appendicitis)?
- Is it bloody diarrhoea (mimicking UC or infectious colitis)?
- Is it perianal disease (fistula, abscess)?
- Is it a small bowel stricture on imaging?
- Is it weight loss and malabsorption?
The approach below is organised by clinical presentation, then we will provide a unified diagnostic algorithm.
When a patient presents with chronic diarrhoea ( ≥ 4 weeks), the first question is: organic or functional?
Fecal calprotectin is the pivotal screening test here [9][10]:
- "Neutrophil-derived protein, 60% of neutrophil cytosol" [10]
- "Most sensitive marker of intestinal inflammation in IBD" [10]
- "Well correlated with endoscopic disease activity" [10]
- "Predict disease relapse, postoperative relapse" [10]
- In active intestinal inflammation, neutrophils migrate into mucosa, lead to leakage of calprotectin [9]
- Low → IBS more likely; High → IBD more likely (but not 100% specific, as anything causing intestinal inflammation and damage will raise calprotectin) [9]
The chronic diarrhoea differential can be split into three major categories [11]:
| Type | Examples | Key Features |
|---|---|---|
| Inflammatory | IBD (CD, UC), chronic infections (TB, C. difficile), colorectal CA, ischaemic colitis | Mucoid/bloody stools, PMN in stools |
| Watery | Secretory (VIPoma, carcinoid, bile salt malabsorption), osmotic (lactase deficiency, laxative abuse), motility (IBS, hyperthyroidism) | Watery; secretory persists with fasting, osmotic/motility improves |
| Fatty | Malabsorptive enteropathy (coeliac, CD, short gut), pancreatic insufficiency (chronic pancreatitis, CF) | Steatorrhoea, weight loss, nutritional deficiency |
Key point: Crohn's can appear in all three categories — inflammatory diarrhoea from colonic disease, watery diarrhoea from bile salt malabsorption, and fatty diarrhoea from extensive small bowel disease. This is why it is a great mimicker.
2. Systematic Differential Diagnosis by Category
The single most important differential when considering Crohn's colitis. The distinction has major implications for surgery (total colectomy can cure UC; surgery in CD is never curative).
| Feature | Crohn's Disease | Ulcerative Colitis |
|---|---|---|
| Distribution | Skip lesions, any part of GIT | Continuous, starts at rectum, extends proximally |
| Depth | Transmural | Mucosal only |
| Rectal involvement | Often spared | Always involved |
| Perianal disease | Common (30–40%) | Uncommon |
| Bleeding | Less common, often occult | Bloody diarrhoea is the central feature |
| Fistulae/strictures | Common | Rare (stricture in UC → think malignancy) |
| Granulomas | Non-caseating (35%) | Absent |
| Smoking | Risk factor | Protective |
| Serology | ASCA+ | pANCA+ |
"Was difficulty distinguishing between UC and CD in the colectomy specimen" — when distinction is truly impossible on colectomy, this is called indeterminate colitis [2]. About 5–15% of IBD cases affecting only the colon cannot be definitively classified.
Indeterminate Colitis / IBD-Unclassified
When colonoscopic and histological features overlap and you genuinely cannot distinguish CD from UC (especially in isolated colonic disease), the term IBD-unclassified (IBD-U) is used. This matters because it affects surgical planning — an ileal pouch-anal anastomosis (IPAA) is generally only offered for UC, not CD (high failure rate in CD due to recurrence in the pouch).
"Why is it crucial to rule out infection in the diagnosis of IBD? Which infection are you thinking of? — Especially Tuberculosis" [2]
"Some of the biologics (i.e. anti-TNF-alpha) will suppress the host's ability to contain TB → TB reactivation" [2]
This cannot be overstated. In Hong Kong, TB remains prevalent, and intestinal TB can be virtually indistinguishable from CD clinically and endoscopically.
| Feature | Crohn's Disease | Intestinal TB |
|---|---|---|
| Granuloma | Non-caseating | Caseating |
| AFB stain | Negative | May be positive |
| TB culture/PCR | Negative | May be positive |
| Quantiferon/T-SPOT | Usually negative | Usually positive |
| CXR | Normal | May show pulmonary TB |
| Ulcers | Longitudinal | Transverse (along lymphatics) |
| Ileocaecal valve | Patulous (gaping open) | Strictured/fibrosed/fish-mouth deformity |
| Ascites | Uncommon | More common (peritoneal TB) |
| Response to anti-TB Rx | No improvement | Improvement within 2–3 months |
| Histology | Non-caseating granuloma (35%) | Caseating granuloma, AFB stain & C/ST if suspected [3] |
Laboratory tests should include: Hepatitis serology, HIV, TB testing [10]
Practical approach in HK: If there is any doubt, do a therapeutic trial of anti-TB medications for 2–3 months. If the patient improves, it was TB. If not, proceed with IBD management. Always screen with CXR + Quantiferon/T-SPOT before starting biologics.
"Infection including E. coli, Salmonella, Shigella, Campylobacter, Yersinia and amebiasis should be excluded with stool studies" [4]
"C. difficile infection should be considered particularly in patients treated with antibiotics" [4]
Stool examination: culture, Cl. difficile toxin, calprotectin [10]
| Organism | Key Features | Why It Mimics CD |
|---|---|---|
| Yersinia enterocolitica | RLQ pain, terminal ileitis, mesenteric lymphadenitis | Almost identical presentation to ileal CD; even causes granulomas! |
| Campylobacter jejuni | Bloody diarrhoea, fever, abdominal pain | Colonic inflammation mimics IBD |
| Salmonella spp. | Fever, bloody diarrhoea | Ileocolitis pattern possible |
| Shigella spp. | Bloody mucoid diarrhoea, tenesmus | Mimics UC/Crohn's colitis |
| E. coli (EHEC/EIEC) | Bloody diarrhoea, HUS risk (EHEC) | Colonic inflammation |
| Entamoeba histolytica | Rare but can cause colitis [2] | Flask-shaped ulcers; can mimic IBD; check stool for parasites |
| C. difficile | Pseudomembranous colitis, especially post-antibiotics | Can complicate existing IBD or mimic de novo presentation |
| CMV colitis | In immunosuppressed patients | Can reactivate in patients already on immunosuppression for IBD — always consider if a patient on azathioprine/anti-TNF flares |
Key principle: Infectious colitis is usually acute (< 4 weeks) and self-limiting, whereas CD is chronic and relapsing. However, some infections (TB, Yersinia, amoeba) can present chronically and truly mimic CD.
"Presents with chronic abdominal pain and altered bowel habits in the absence of an organic cause" [4]
IBS is a functional gastrointestinal disorder — there is no structural inflammation. It is diagnosed using the Rome IV criteria (recurrent abdominal pain ≥ 1 day/week in the last 3 months, associated with defecation, change in frequency, change in form).
How to distinguish from CD:
- IBS: No red flags (weight loss, anaemia, PR bleeding, fever, raised inflammatory markers), normal fecal calprotectin, no nocturnal symptoms (IBS rarely wakes patients at night)
- CD: Red flags present, raised calprotectin/CRP, may have nocturnal diarrhoea, perianal disease, EIMs
Fecal calprotectin: Low → IBS more likely; High → IBD more likely [9]
"Antibodies are useless in diagnosing IBD" [9] — don't rely on ASCA/pANCA to distinguish IBS from IBD; use calprotectin and endoscopy.
- Risk factors: > 50 years, male, smoker, FHx, Hx of IBD, polyps and colorectal CA [11]
- Bowel habits: alternating constipation and diarrhoea, pencil thin stools, tenesmus [11]
- Constitutional symptoms: loss of appetite, loss of weight, malaise [11]
- Can present with bowel wall thickening on CT — similar appearance to CD stricture
- Iron deficiency anaemia (especially right-sided colonic cancer)
- Important because long-standing colonic CD is itself a risk factor for colorectal cancer
Practical point: Any stricture in the colon, especially in a patient with long-standing colonic CD, must be biopsied to rule out malignancy.
| Feature | Acute Appendicitis | CD (Ileocaecal) |
|---|---|---|
| History | Acute onset (hours); periumbilical → RLQ migration | Chronic/subacute; weeks-months of RLQ pain, diarrhoea |
| Peritoneal signs | Typically present (McBurney's point tenderness, guarding, rebound) | Usually less prominent unless perforation/abscess |
| Diarrhoea | Uncommon | Common |
| Systemic features | Acute fever, anorexia | Chronic weight loss, malabsorption features |
| Perianal disease | Absent | May be present (very suggestive of CD) |
- In practice, a young patient taken to theatre for suspected appendicitis may have the appendix found to be normal with a thickened, inflamed terminal ileum — this is how CD is sometimes first diagnosed!
- "Prior appendicectomy is a risk factor for Crohn's disease" [4] (or at least associated — it may be that some patients who underwent appendicectomy actually had undiagnosed CD at the time)
"Diarrhoea rather than abdominal pain is the predominant symptom [in IBD vs diverticulitis]" [12]
| Feature | Diverticulitis | Crohn's (Colonic) |
|---|---|---|
| Age | Typically > 50 (Western) | Typically 15–35 |
| Location | Left lower quadrant (sigmoid) | Can be anywhere; RLQ if ileocaecal |
| CT features | Pericolonic fat stranding, focal wall thickening, diverticulae | Skip lesions, transmural enhancement, abscess/fistula |
| Histology | No granulomas | Non-caseating granulomas (35%) |
| Chronic course | Usually single acute episodes | Relapsing-remitting |
- Can coexist: CD patients can have diverticular disease
"Presents with rapid onset of abdominal pain, haematochezia or bloody diarrhoea" [12] "Patients usually have risk factors for ischaemic colitis including advanced age, hypertension, DM, dehydration, laxative use or haemodialysis" [12]
- Ischaemic colitis typically affects the "watershed" areas (splenic flexure, rectosigmoid junction)
- Acute onset in an elderly patient with cardiovascular risk factors
- "Thumbprinting" on plain AXR/CT due to submucosal oedema and haemorrhage
- Very different demographic and tempo from CD
"Occurs in weeks to years after abdominal or pelvic irradiation" [4]
- History of prior radiotherapy is the key clue
- Typically affects the rectum/sigmoid (pelvic radiation) or small bowel (abdominal radiation)
- Can cause chronic diarrhoea, bleeding, strictures — mimicking CD
- Biopsy shows radiation changes (telangiectasia, fibrosis, atypical fibroblasts)
"NSAIDs can cause chronic diarrhoea and bleeding" [4]
- NSAIDs can cause a de novo enteropathy/colitis or trigger flares of pre-existing IBD
- Mechanism: inhibition of prostaglandin-mediated mucosal cytoprotection → mucosal ulceration
- Other drugs: mycophenolate, ipilimumab (checkpoint inhibitor colitis — increasingly important), olmesartan
"Presents with abdominal pain, altered bowel habits and bleeding" [4] "Has a characteristic appearance on histology with a thickened mucosal layer and distortion of crypt architecture" [4]
- Associated with excessive straining, rectal prolapse
- Ulcer typically on anterior rectal wall
- Distinguished by histology (fibromuscular obliteration of the lamina propria)
- "Celiac → extremely rare in our locality → villous atrophy" [2]
- Presents with chronic diarrhoea, malabsorption, steatorrhoea, weight loss
- Distinguished by: positive anti-tTG/anti-endomysial antibodies, villous atrophy on duodenal biopsy, improvement on gluten-free diet
- Very rare in Chinese populations but should be considered in non-Chinese patients in HK
- Primary intestinal lymphoma (especially in the ileum/ileocaecal region) can mimic CD
- Features: mass lesion, bowel wall thickening, obstruction, B symptoms (fever, weight loss, night sweats)
- Biopsy is essential for distinction
- Non-Hodgkin lymphoma (especially MALT lymphoma, mantle cell lymphoma with "lymphomatous polyposis") should be considered
- Systemic vasculitis that can cause intestinal ulceration (especially ileocaecal region)
- Classic triad: recurrent oral ulcers + genital ulcers + uveitis
- Can cause deep, punched-out intestinal ulcers that mimic CD
- More common in East Asian and Middle Eastern populations
| Presentation | Key Differentials to Consider |
|---|---|
| Chronic diarrhoea | UC, IBS, infectious colitis (TB, Yersinia, amoeba, CMV, C. diff), coeliac, microscopic colitis, colorectal CA, bile salt malabsorption, chronic pancreatitis |
| RLQ pain | Acute appendicitis, Yersinia ileitis, intestinal TB, lymphoma, ovarian pathology (torsion, ectopic pregnancy — in females), caecal carcinoma |
| Bloody diarrhoea | UC, infectious colitis (Shigella, Campylobacter, EHEC, amoeba), ischaemic colitis, radiation colitis, colorectal CA |
| Perianal disease | Idiopathic fistula-in-ano, perianal abscess (cryptoglandular), pilonidal sinus, hidradenitis suppurativa, perianal TB, rectal CA, lymphogranuloma venereum (LGV) |
| Small bowel obstruction | Adhesions (post-surgical), small bowel tumour (lymphoma, carcinoid), TB stricture, radiation stricture |
| Weight loss + malabsorption | Coeliac disease, chronic pancreatitis, small bowel lymphoma, Whipple's disease, short gut syndrome |
"No single test or gold standard — Diagnosis via multiple means: endoscopic, radiological, pathological, biochemical findings" [2]
- Patient history: bowel symptoms, medications, surgery, drug history, immunisation status
- Physical examination: general and abdomen, perianal region (skin tags, fissures, fistulas, abscess, PR exam), extraintestinal inspections (mouth, eyes, skin and joints)
Laboratory tests [10]:
- Blood tests: CBP, CRP, ESR, albumin, ferritin
- pANCA (UC), ASCA (CD) — helpful but not diagnostic [2]
- Hepatitis serology, HIV, TB testing
- Stool examination: culture, Cl. difficile toxin, calprotectin
Imaging and endoscopy [10]:
- Colonic (UC/CD): Colonoscopy; Sigmoidoscopy for severe active disease
- Small bowel (CD): MR enterography (MRE) or CT enterography (CTE); Small bowel capsule endoscopy (SBCE); Single or double balloon enteroscopy
- Foregut symptoms (CD): OGD
- Perianal (CD): MRI anal canal
Capsule Endoscopy — Caution in CD
"Patient may have undiagnosed strictures causing capsule retention" [2]. Always perform CT/MR enterography first in suspected CD to rule out strictures before considering capsule endoscopy. A patency capsule can also be used to test for safe passage before deploying a video capsule.
Endoscopic findings in CD vs UC [3]:
| CD | UC |
|---|---|
| Patchy inflammation with skip lesions | Continuous lesions |
| Deep linear ulcer (cobblestone appearance) | Superficial broad-based ulcer |
| Stricture, abscess, fistula | Clear demarcation between inflamed and normal mucosa |
| Rectum usually spared | Rectal involvement |
| — | Touch friability, petechiae, bleeding |
| — | Caecal patch (in E2 disease) |
Histological findings [3]:
| CD | UC |
|---|---|
| Transmural inflammation with fistula | Mucosal inflammation, without fistula |
| Lymphocytic infiltration, Goblet cells preserved | Neutrophilic infiltration |
| Non-caseating granuloma (35%) | No granuloma, no Goblet cells |
| DDx: TB colitis (caseating granuloma, AFB stain & C/ST if suspected) | — |
| Condition | Key Distinguishing Feature from CD |
|---|---|
| Ulcerative colitis | Continuous from rectum, mucosal only, bloody diarrhoea, no granulomas |
| Intestinal TB | Caseating granulomas, AFB+, transverse ulcers, responds to anti-TB Rx |
| Infectious colitis | Acute onset, positive stool cultures, self-limiting |
| IBS | Functional, no inflammation, low calprotectin, Rome IV criteria |
| Colorectal cancer | Older age, iron deficiency, mass on imaging/endoscopy |
| Appendicitis | Acute onset, peritoneal signs, no diarrhoea, no chronicity |
| Diverticulitis | LLQ, older age, diverticulae on CT, no granulomas |
| Ischaemic colitis | Elderly, CVS risk factors, acute onset, watershed areas |
| Lymphoma | Mass lesion, B symptoms, biopsy diagnostic |
| Coeliac disease | Anti-tTG+, villous atrophy, responds to GFD, rare in Chinese |
| Behçet's disease | Oral + genital ulcers, uveitis, punched-out ileocaecal ulcers |
High Yield Summary — DDx of Crohn's Disease
- Always rule out TB before starting biologics — especially in Hong Kong. Caseating granulomas + AFB stain + C/ST + Quantiferon/T-SPOT. Anti-TNF can reactivate latent TB.
- UC vs CD: Continuous vs skip, mucosal vs transmural, rectal involvement vs sparing, bloody diarrhoea vs non-bloody, no granulomas vs non-caseating granulomas.
- IBS vs IBD: Fecal calprotectin is the key discriminator — low favours IBS, high favours IBD. Serology (ASCA/pANCA) is not diagnostic.
- Infectious colitis: Exclude with stool culture, O&P, C. diff toxin. Yersinia can closely mimic CD (terminal ileitis + granulomas).
- Colorectal cancer: Any colonic stricture in IBD must be biopsied. CRC can complicate long-standing colonic CD.
- No single gold standard — diagnosis is multimodal: clinical + endoscopic + radiological + pathological + biochemical.
Active Recall - Differential Diagnosis of Crohn's Disease
References
[2] Senior notes: Block A - Chronic diarrhoea_ irritable bowel syndrome and inflammatory bowel disease.pdf (pp. 13, 26, 41) [3] Senior notes: Maksim Medicine Notes.pdf (p. 129) [4] Senior notes: MBBS Final MB (Medicine) (Felix PY Lai).pdf (p. 868); MBBS Final MB (Surgery) (Felix PY Lai).pdf (pp. 644, 665) [5] Lecture slides: Inflammatory bowel disease.pdf (p. 10) [9] Senior notes: Block A - Gastrointestinal Data Interpretation.pdf (p. 6) [10] Lecture slides: Inflammatory bowel disease.pdf (pp. 11–12) [11] Senior notes: Ryan Ho Fundamentals.pdf (p. 290) [12] Senior notes: MBBS Final MB (Surgery) (Felix PY Lai).pdf (p. 644)
Diagnostic Criteria, Diagnostic Algorithm & Investigations for Crohn's Disease
"No single test or gold standard" [2]
"Diagnosis via multiple means: endoscopic, radiological, pathological, biochemical findings" [2]
This is a foundational concept. Unlike, say, rheumatic fever (Jones criteria) or SLE (SLICC criteria), Crohn's disease has no validated set of diagnostic criteria that you tick off a checklist. Instead, the diagnosis is a convergence of evidence across four pillars:
| Pillar | What You're Looking For |
|---|---|
| Clinical | Compatible history (chronic diarrhoea, RLQ pain, perianal disease, weight loss, EIMs), physical signs |
| Endoscopic | Skip lesions, deep ulcers, cobblestone appearance, rectal sparing, strictures/fistulae |
| Histological | Transmural inflammation, non-caseating granulomas, focal chronic inflammation |
| Radiological | Bowel wall thickening, strictures, fistulae, abscesses, skip involvement on cross-sectional imaging |
The diagnosis is made when these four pillars converge to form a consistent picture, and infectious mimics (especially TB) are excluded.
Why No Gold Standard?
CD is a heterogeneous disease — it varies in location (mouth to anus), depth (transmural), behaviour (inflammatory vs stricturing vs fistulising), and severity. No single test captures all of this. A biopsy can be normal in skip areas. Imaging may miss early mucosal disease. Blood tests are non-specific. Only by combining all modalities can you confidently diagnose CD.
While there are no "criteria" per se, the ECCO guidelines (current standard, updated 2023) provide a structured diagnostic approach:
A diagnosis of CD should be considered when a patient presents with:
- Chronic or nocturnal diarrhoea
- Abdominal pain (especially RLQ)
- Weight loss
- Perianal disease (fistulae, skin tags, abscess)
- Extraintestinal manifestations (arthritis, eye/skin involvement)
- Family history of IBD
- Growth failure in children
The diagnosis is confirmed by demonstrating:
- Characteristic endoscopic and/or radiological appearances, AND
- Histological evidence of chronic granulomatous inflammation (though granulomas are present in only ~35%), AND
- Exclusion of infections (especially TB, Yersinia, amoeba, C. difficile)
The following algorithm integrates the clinical approach from the lecture slides and senior notes into a practical diagnostic pathway:
4. Investigation Modalities — Detailed Breakdown
Patient history [5]:
- Bowel symptoms
- Medications
- Surgery
- Drug history
- Immunisation status
Physical examination [5]:
- General and abdomen
- Perianal region: skin tags, fissures, fistulas, abscess, PR exam
- Extraintestinal inspections: mouth, eyes, skin and joints
Why immunisation status? Patients with CD are likely to require immunosuppressive therapy (steroids, thiopurines, biologics). Before starting these, you need to ensure vaccinations are up to date — especially live vaccines (varicella, MMR, BCG) which are contraindicated once immunosuppression begins. Hepatitis B status must also be known (risk of reactivation on anti-TNF). This is why the history specifically includes immunisation status and why hepatitis serology is part of the workup.
4.2 Laboratory Investigations
"Blood tests: CBP, CRP, ESR, albumin, ferritin" [10]
| Test | What You're Looking For | Interpretation / Pathophysiology |
|---|---|---|
| CBP (Complete Blood Picture) | Anaemia, high WBC [2] | Anaemia: iron deficiency (chronic blood loss, malabsorption), B12 deficiency (terminal ileal disease), folate deficiency, anaemia of chronic disease. Leukocytosis: active inflammation, abscess, or steroid use. Thrombocytosis: reactive (acute phase response). |
| CRP | Acute phase reactant | Produced by the liver in response to IL-6. Correlates with disease activity. Normal CRP does NOT exclude CD (some patients with isolated ileal disease have normal CRP). |
| ESR | Acute phase reactant | Slower to rise and fall than CRP. Elevated in active inflammation. |
| Albumin | Nutritional and disease activity marker | Low albumin reflects: protein-losing enteropathy (transmural inflammation → lymphatic leakage), malabsorption, reduced intake, and active inflammation (negative acute phase reactant — the liver preferentially makes CRP/fibrinogen instead of albumin). Hypoalbuminaemia is a marker of severe disease. |
| Ferritin | Iron stores | May be falsely normal or elevated in active inflammation (ferritin is also an acute phase reactant). True iron deficiency may coexist with elevated ferritin if inflammation is present → check transferrin saturation as well. |
| LFT | Liver function | Screen for concurrent PSC (↑ ALP, ↑ GGT, cholestatic pattern); drug-induced hepatotoxicity (azathioprine, methotrexate). |
| RFT | Renal function | Baseline before starting nephrotoxic drugs; also screen for renal stones (oxalate). |
| Vitamin B12 / Folate | Nutritional deficiency | B12: absorbed in terminal ileum → low in ileal CD/post-resection. Folate: absorbed in proximal jejunum → low in proximal SB disease; also depleted by methotrexate and sulfasalazine. |
"Stool examination: culture, Cl. difficile toxin, calprotectin" [10]
| Test | Purpose | Key Points |
|---|---|---|
| Stool culture | Exclude bacterial infection (Salmonella, Shigella, Campylobacter, Yersinia, E. coli) | Must be done before diagnosing IBD — especially on first presentation |
| Stool O&P | Ova and parasites — especially amoeba [2] | "Amoeba, rare but can cause colitis" [2] — Entamoeba histolytica causes flask-shaped colonic ulcers mimicking IBD |
| Cl. difficile toxin | Exclude C. difficile colitis | Especially important in patients already on antibiotics or immunosuppression |
| Fecal calprotectin | "Most sensitive marker of intestinal inflammation in IBD" [10] | "Neutrophil-derived protein, 60% of neutrophil cytosol" [10]. "Well correlated with endoscopic disease activity" [10]. "Predict disease relapse, postoperative relapse" [10]. Low = IBS more likely; High = IBD more likely [9]. Normal value < 50 μg/g. Values > 250 μg/g highly suggestive of active IBD. |
Fecal Calprotectin — The Key Screening Test
Fecal calprotectin is arguably the most important non-invasive investigation in the IBD workup. It acts as a gatekeeper to endoscopy:
- If low ( < 50 μg/g) → IBD is very unlikely → consider functional causes (IBS) → avoids unnecessary colonoscopy
- If high ( > 50, especially > 250 μg/g) → proceed to colonoscopy
- "Not 100% specific, as anything causing intestinal inflammation and damage will raise calprotectin" [9] — infections, NSAIDs, CRC can also elevate it
It is also used for monitoring: tracking response to therapy, predicting relapse, and detecting postoperative recurrence.
"Serology → helpful, but not diagnostic" [2]
| Marker | Association | Clinical Utility |
|---|---|---|
| ASCA (Anti-Saccharomyces cerevisiae antibodies) | Crohn's disease [2][10] | Sensitivity ~50–60%, specificity ~85–95% for CD. ASCA = antibodies against the yeast Saccharomyces cerevisiae (baker's/brewer's yeast). Why would CD patients have these? Hypothesised to reflect abnormal mucosal permeability allowing luminal antigens (like yeast) to stimulate immune responses. |
| pANCA (Perinuclear anti-neutrophil cytoplasmic antibodies) | UC [2][10] | Present in ~60–70% of UC. Note: this is different from the c-ANCA in GPA (Wegener's). |
"Antibodies are useless in diagnosing IBD" [9]
This strong statement from the GI Data Interpretation tutorial emphasises that ASCA and pANCA should never be used alone to diagnose or exclude IBD. They can support a clinical picture but are insufficiently sensitive or specific to stand alone.
Practical approach: Order serology as part of the workup, but base your diagnosis on endoscopy + histology + imaging. If ASCA+ and pANCA−, it supports CD over UC. If ASCA− and pANCA+, it supports UC. But many patients are negative for both.
"Hepatitis serology, HIV, TB testing" [10]
| Test | Reason |
|---|---|
| Hepatitis B surface antigen, anti-HBs, anti-HBc | HBV reactivation risk with immunosuppression (steroids, thiopurines, anti-TNF). If HBsAg+ or anti-HBc+ with HBsAg−, need antiviral prophylaxis before immunosuppression |
| Hepatitis C antibody | Baseline screen |
| HIV testing | Immunosuppressive therapy; CMV colitis risk in HIV; differential diagnosis (HIV enteropathy) |
| TB screening: CXR + Quantiferon-TB Gold / T-SPOT.TB | "Especially Tuberculosis — some of the biologics (i.e. anti-TNF-alpha) will suppress the host's ability to contain TB → TB reactivation" [2]. Mandatory before anti-TNF therapy. |
TB Screening Is Non-Negotiable
In Hong Kong, every patient being considered for anti-TNF therapy must undergo TB screening (CXR + IGRA). TNF-α is critical for maintaining TB granuloma integrity. Anti-TNF → granuloma dissolution → disseminated TB. This has caused fatalities.
4.3 Endoscopic Investigations
"Imaging and endoscopy" [10]:
- "Colonic (UC/CD): Colonoscopy; Sigmoidoscopy (for severe active disease)"
- "Small bowel (CD): MR enterography (MRE) or CT enterography (CTE); Small bowel capsule endoscopy (SBCE); Single or double balloon enteroscopy"
- "Foregut symptoms (CD): OGD"
- "Perianal (CD): MRI anal canal"
Ileo-colonoscopy with biopsy: minimum 2 biopsies from each segment — TI, AC, TC, DC, sigmoid, rectum [3]
- This is the single most important diagnostic investigation
- Intubation of the terminal ileum is essential — CD has a predilection for the TI and will be missed if only the colon is examined
- Why minimum 2 biopsies from each segment? Because CD produces skip lesions — you need systematic sampling to detect patchy inflammation and to map disease extent. Taking biopsies from both normal-appearing and abnormal mucosa maximises diagnostic yield.
MUST do AFB smear and culture with sensitivity testing to rule out enteric TB [13]
Endoscopic findings in CD [3][13]:
| Finding | Description | Pathophysiological Basis |
|---|---|---|
| Skip lesions | "Skip areas of involvement with segments of normal appearing bowel interrupted by large areas of disease" [13] | Inflammation begins at discrete lymphoid aggregates (Peyer's patches) → patchy involvement |
| Deep linear ulcers | "Deep linear ulcer = 'cracks'" [13] | Transmural inflammation erodes deeply into the bowel wall |
| Cobblestone appearance | "Polypoid mucosal changes — inflamed tissues = 'stones'" [13] | Oedematous mucosa between deep criss-crossing ulcers creates a cobblestone pattern |
| Aphthous ulcers | Small, shallow, punched-out ulcers (earliest visible lesion) | Initial mucosal breach overlying lymphoid follicles |
| Strictures | Narrowing of lumen | Chronic transmural inflammation → fibrosis → luminal compromise |
| Fistulae | Abnormal connections between bowel and adjacent structures | Deep ulceration penetrates through all layers |
| Abscesses | Walled-off collections | Transmural penetration with bacterial contamination |
| Rectal sparing | Rectum appears normal | Unlike UC where rectum is always the starting point |
Endoscopic findings in UC (for comparison) [13]:
| Finding | Description |
|---|---|
| Uniform and continuous lesions | "Hyperaemic mucosa due to mucosal engorgement" |
| Diffuse granularity | "Diffuse granularity of mucosa" |
| Shallow ulceration | Superficial, broad-based |
| Touch friability, petechiae, bleeding | Mucosa bleeds on contact with endoscope |
| Pseudopolyps | "Hypertrophied masses of mucous membrane resembling polyps" — regenerating islands of mucosa surrounded by ulcerated areas |
| Caecal patch | Inflammation at caecum in E2 (left-sided) UC |
"Sigmoidoscopy is sufficient for acute severe colitis" [3]
- In acute severe colitis (Truelove and Witts criteria), full colonoscopy carries a risk of perforation due to the thinned, inflamed, and friable colonic wall
- Flexible sigmoidoscopy with limited insufflation and biopsies from the rectum and sigmoid is safer and sufficient to confirm IBD and exclude CMV/C. difficile superinfection
- Full colonoscopy should be deferred until the acute episode has settled
"Foregut symptoms (CD): OGD" [10]
- Indicated when CD is suspected in the upper GIT (oesophagus, stomach, duodenum)
- OGD permits duodenal biopsy [2] to diagnose:
- In paediatric IBD, OGD is routinely performed as part of the initial workup regardless of symptoms (higher incidence of upper GI involvement in children)
Small bowel capsule endoscopy (SBCE) [10]:
- Wireless capsule swallowed by patient; transmits images as it traverses the GIT
- Good for detecting mucosal lesions in the small bowel not reached by standard colonoscopy
- "Patient may have undiagnosed strictures causing capsule retention" [2] — always assess for strictures first (CT/MR enterography or a patency capsule)
Single or double balloon enteroscopy [10]:
- Allows direct visualisation, biopsy, and therapeutic intervention in the deep small bowel
- Push-and-pull technique with inflatable balloons to pleat the bowel onto the endoscope
- Reserved for cases where tissue diagnosis is needed from areas beyond reach of standard endoscopy
4.4 Radiological Investigations
"Small bowel (CD): MR enterography (MRE) or CT enterography (CTE)" [10]
"First line for small bowel assessment" [2]
"Name the preferred mode of radiological monitoring of disease in a young Crohn's patient? — MR enterography" [2]
MRE is the preferred cross-sectional imaging modality for CD, especially in young patients, because:
- No ionising radiation — CD is a lifelong disease requiring repeated imaging; cumulative radiation from repeated CT scans is a genuine concern in young patients
- Excellent soft-tissue contrast for assessing bowel wall inflammation, strictures, fistulae, abscesses, and mesenteric changes
- Can distinguish active inflammatory stricture (wall enhancement, oedema, restricted diffusion) from fibrotic stricture (no enhancement, no oedema) — this distinction determines whether medical therapy will help (inflammatory) or surgery/dilatation is needed (fibrotic)
Key MRE findings in CD:
| Finding | Significance |
|---|---|
| Bowel wall thickening ( > 3 mm) | Active inflammation or fibrosis |
| Mural hyperenhancement | Active inflammation (increased blood flow to inflamed wall) |
| Restricted diffusion (DWI) | Active inflammation (cellular infiltration restricts water movement) |
| Mural oedema (T2 hyperintensity) | Active inflammation |
| Mesenteric fat stranding / "comb sign" | Engorged vasa recta (mesenteric vessels) — sign of hyperaemia from active inflammation |
| Stricture with upstream dilatation | Significant luminal narrowing causing functional obstruction |
| Fistula | Enhancing tract connecting bowel to bowel/skin/bladder/vagina |
| Abscess | Rim-enhancing fluid collection |
| Skip involvement | Segments of normal bowel between affected areas |
| Creeping fat | Mesenteric fat wrapping around serosal surface (pathognomonic of CD) |
"CT scan — for diagnosis & complications" [2]
| Role | Details |
|---|---|
| Diagnosis | "Diagnostic: bowel wall thickening" [14] |
| Complications | "Assess complications: fistula, abscess" [14] |
| Intervention guidance | "Aid treatment: guide percutaneous drainage of abscess" [14] — abscesses > 5 cm typically require drainage |
| Acute presentations | Preferred in emergency settings (faster than MRI); assesses for perforation, obstruction |
CT findings largely mirror MRE findings but with ionising radiation.
CXR [13]:
- "Indicated in patients presenting with fever or if perforation is suspected" — look for free gas under the diaphragm (pneumoperitoneum from perforation)
AXR [13]:
- "Indicated to evaluate for colonic calibre"
- "Toxic megacolon is defined as total or segmental non-obstructive dilatation of colon ≥ 6 cm or cecum > 9 cm and the presence of systemic toxicity" [13]
- Also look for: small bowel obstruction (dilated loops > 3 cm, valvulae conniventes), sacroiliitis (if visible)
"Perianal (CD): MRI anal canal" [10]
- Gold standard for assessment of perianal fistulae and abscesses
- Accurately maps fistula tracts (intersphincteric, transsphincteric, suprasphincteric, extrasphincteric), secondary tracts, horseshoe extensions, and undrained collections
- Essential for surgical planning (examination under anaesthesia + fistula drainage/seton placement)
- Uses the St James's University Hospital (Parks) classification of fistulae
"Small bowel series (CD)" [2]
- Largely replaced by CT/MR enterography
- Historical importance: showed the classic "string sign" (narrowed terminal ileum due to stricture/spasm)
- Still occasionally used where cross-sectional imaging is not available
Histological findings [13]:
| Feature | Crohn's Disease | Ulcerative Colitis |
|---|---|---|
| Location of inflammation | Transmural inflammation, focal patchy involvement | Mucosal and submucosal (superficial) inflammation, diffuse continuous involvement |
| Granuloma | Common (non-caseating, ~35%) | Rare |
| Goblet cells | Not depleted | Depleted (mucin depletion) |
| Crypt architecture | Distortion of crypt architecture, crypt abscess and atrophy | Crypt branching, shortening and disarray |
Additional histological features specific to CD:
- Lymphoid aggregates — transmural lymphoid aggregates, especially at the base of ulcers
- Fissuring ulcers — knife-like clefts extending deep into the submucosa or muscularis
- Submucosal fibrosis — thickened submucosa from chronic inflammation
- Neural hypertrophy — thickened nerve fibres in the submucosa (contributes to pain)
- Non-caseating granulomas — collections of epithelioid macrophages ± Langhans giant cells, WITHOUT central necrosis
Granulomas — Present in Only 35%!
A common exam pitfall: students assume granulomas must be present for CD diagnosis. In reality, non-caseating granulomas are found in only ~35% of mucosal biopsies. Their presence is highly supportive of CD (and helps distinguish from UC), but their absence does NOT exclude CD. Diagnosis rests on the overall constellation of clinical, endoscopic, radiological, and histological features.
Critical histological distinction — CD vs TB:
| Feature | Crohn's Disease | Intestinal TB |
|---|---|---|
| Granuloma type | Non-caseating | Caseating (central cheesy necrosis) |
| AFB stain | Negative | May be positive |
| Culture & sensitivity | Negative | May grow M. tuberculosis |
| Granuloma size | Usually small, scattered | Often larger, confluent |
| Granuloma location | Throughout bowel wall | Often submucosal, along lymphatics |
Once CD is diagnosed, you need to assess and quantify disease activity to guide treatment:
Clinical scores:
| Score | Components | Interpretation |
|---|---|---|
| CDAI (Crohn's Disease Activity Index) | 8 variables over 7 days: liquid stools, abdominal pain, general well-being, EIMs, anti-diarrhoeal use, abdominal mass, haematocrit, body weight | < 150 = remission; 150–220 = mild; 220–450 = moderate; > 450 = severe |
| HBI (Harvey-Bradshaw Index) | 5 variables: general well-being, abdominal pain, number of liquid stools, abdominal mass, complications | < 5 = remission; 5–7 = mild; 8–16 = moderate; > 16 = severe. Simplified version of CDAI, used more in clinical practice |
Endoscopic scores:
| Score | What It Measures |
|---|---|
| SES-CD (Simple Endoscopic Score for Crohn's Disease) | Ulcer size, ulcerated surface, affected surface, presence of narrowing across 5 ileocolonic segments |
| Rutgeerts score | Post-operative recurrence at the neo-terminal ileum after ileocaecal resection (i0–i4) |
Biochemical monitoring:
| Marker | Role |
|---|---|
| CRP | Correlates with systemic inflammation; used to track response to therapy |
| Fecal calprotectin | "Well correlated with endoscopic disease activity" [10]. "Predict disease relapse, postoperative relapse" [10]. Best non-invasive surrogate for mucosal healing. Target < 250 μg/g (some use < 150) |
| Albumin | Low albumin = severe disease / poor nutrition |
Treat-to-target concept (current standard of care): The modern approach is to treat until you achieve objective targets — not just symptom control:
- Clinical remission (symptoms resolve)
- Biochemical remission (CRP normalises, calprotectin < 250)
- Endoscopic remission / mucosal healing (SES-CD = 0, no ulcers) — the ultimate goal
- In some centres, transmural healing on MRE (resolution of wall thickening and enhancement)
| Investigation | Key Findings in CD | When to Use |
|---|---|---|
| CBP | Anaemia, leukocytosis, thrombocytosis | All patients — baseline |
| CRP / ESR | Elevated in active disease | All patients — baseline and monitoring |
| Albumin | Low = severe disease | All patients — baseline |
| Ferritin, B12, folate | Deficiencies from malabsorption | All patients — baseline |
| Fecal calprotectin | Elevated ( > 250 strongly suggestive) | Screening, monitoring, predicting relapse |
| Stool culture, O&P, C. diff | Exclude infection | All patients — at diagnosis and flares |
| ASCA / pANCA | ASCA+ supports CD | Adjunctive only — not diagnostic |
| TB screen (CXR + IGRA) | Exclude latent TB | All patients — mandatory before biologics |
| Hepatitis B/C, HIV | Baseline for immunosuppression safety | All patients — before treatment |
| Ileo-colonoscopy + biopsy | Skip lesions, deep ulcers, cobblestone, granulomas, rectal sparing | All patients — diagnostic cornerstone |
| MR enterography | Wall thickening, strictures, fistulae, abscesses, comb sign | First-line SB imaging; preferred for monitoring in young patients |
| CT enterography / CT A+P | Same as MRE; faster; emergency use; guide drainage | Acute presentations, complications |
| MRI pelvis | Fistula mapping, abscess detection | Perianal CD |
| OGD | Upper GI involvement, granulomas on duodenal biopsy | Foregut symptoms; routine in paediatric IBD |
| Capsule endoscopy | Mucosal lesions in deep small bowel | Only after excluding strictures |
| AXR | Dilated bowel, toxic megacolon | Acute presentations |
| CXR | Pneumoperitoneum, pulmonary TB | Fever, suspected perforation, TB screen |
High Yield Summary — Diagnostics of Crohn's Disease
- No single gold standard — diagnosis is multimodal: clinical + endoscopic + histological + radiological + biochemical.
- Fecal calprotectin is the key non-invasive screening and monitoring tool. Low = IBS likely. High = proceed to colonoscopy. Correlates with endoscopic activity and predicts relapse.
- Ileo-colonoscopy with segmental biopsies (min 2 from each of 6 segments) is the diagnostic cornerstone. Must include terminal ileum intubation.
- AFB smear and culture on biopsy is mandatory to exclude intestinal TB — especially in Hong Kong.
- Granulomas are present in only 35% of biopsies — their absence does NOT exclude CD.
- MR enterography is first-line for small bowel assessment and preferred for monitoring in young patients (no radiation).
- TB screening (CXR + Quantiferon/T-SPOT) and hepatitis B serology are mandatory before immunosuppression/biologics.
- ASCA/pANCA are helpful but not diagnostic — "antibodies are useless in diagnosing IBD."
- Treat-to-target: Modern goal is endoscopic remission (mucosal healing), not just symptom control.
Active Recall - Diagnostics of Crohn's Disease
References
[2] Senior notes: Block A - Chronic diarrhoea_ irritable bowel syndrome and inflammatory bowel disease.pdf (pp. 13, 41) [3] Senior notes: Maksim Medicine Notes.pdf (p. 129) [5] Lecture slides: Inflammatory bowel disease.pdf (p. 10) [9] Senior notes: Block A - Gastrointestinal Data Interpretation.pdf (p. 6) [10] Lecture slides: Inflammatory bowel disease.pdf (pp. 11–12) [13] Senior notes: MBBS Final MB (Surgery) (Felix PY Lai).pdf (pp. 653–655, 666–668) [14] Senior notes: Maksim Surgery Notes.pdf (p. 95)
Management of Crohn's Disease
"To induce and maintain remission taking into account disease activity, disease site, disease behaviour and patient preference" [4][15]
This is the overarching philosophy. Every management decision in CD is individualised around four axes:
| Axis | Why It Matters |
|---|---|
| Disease activity | Mild → 5-ASA/budesonide; moderate-severe → steroids/biologics; fulminant → IV steroids/surgery |
| Disease site | Ileal → budesonide; colonic → sulfasalazine/mesalazine; extensive SB → biologics/immunomodulators |
| Disease behaviour | Inflammatory → medical; stricturing → dilatation/surgery; fistulising → antibiotics + biologics + surgery |
| Patient preference | Route of administration, fertility concerns, quality of life |
Avoidance of triggering factors: Smoking cessation [4][15]
Smoking Cessation Is Not Optional
Smoking is the single most modifiable risk factor in CD. It increases relapse rates, accelerates progression from inflammatory to stricturing/penetrating disease, increases surgical recurrence, and reduces response to medical therapy. Smoking cessation is as important as any drug.
"Traditionally, IBD management involved step-wise intensification of treatment, with assessment of response based on symptoms" [2]
"However, although symptomatic remission is essential for patients' well-being, this approach may not alter the natural course of IBD" [2]
"Because of the disconnect between symptoms and intestinal inflammation (as assessed by endoscopy), there is a risk of undertreatment in patients who are at high risk of disease progression, with continued inflammation leading to the development of bowel damage and complications" [2]
"Patients at high risk of an aggressive disease course may receive effective treatment too late" [2]
"In the biologic era, we can start using biologics much earlier, replace steroids in some situations → but in HK we kind of poor, so we still need this step up ladder" [2]
Two paradigms:
| Strategy | Description | When Used |
|---|---|---|
| Step-up (traditional) | Start with least toxic drugs (5-ASA) → escalate if needed (steroids → immunomodulators → biologics) | Low-risk patients; mild disease; resource-limited settings (current HK practice for many patients) |
| Top-down (accelerated) | Start with biologics ± immunomodulators early | High-risk patients — see adverse prognostic factors below |
"Trend towards early introduction of immunomodulator and biologics in patients with adverse prognostic factors" [4][15]:
- Young age < 40
- Extensive small bowel disease
- Perianal involvement
- Presence of strictures
- Presence of deep colonic ulcers
- Steroids required in initial treatment
The key insight: Symptoms and inflammation are disconnected. A patient can feel well but have ongoing transmural inflammation that is silently progressing towards strictures and fistulae. Modern management aims for mucosal healing (endoscopic remission), not just symptom control. The treat-to-target approach uses fecal calprotectin and endoscopy to guide escalation.
4. Medical Treatment — Drug-by-Drug Breakdown
- Indications:
- Active luminal disease (for primary or adjunctive therapy for colonic Crohn's disease but NOT isolated small intestine disease)
- Perianal diseases such as fistula
- Septic complications of IBD such as abscess and wound infections
- Mechanism of action: Efficacy may be due to treatment of an undetected pathogen, bacterial overgrowth or an unsuspected microperforation [4][15]
- Example: Ciprofloxacin / Metronidazole [4][15]
| Drug | Dose | Notes |
|---|---|---|
| Metronidazole | 400mg TDS | Also has direct immunomodulatory effects; S/E: metallic taste, peripheral neuropathy (with prolonged use), disulfiram reaction with alcohol |
| Ciprofloxacin | 500mg BD | Fluoroquinolone; S/E: tendon rupture, QT prolongation |
Why do antibiotics work in CD? CD is driven by an aberrant immune response to luminal bacteria. Reducing the bacterial load with antibiotics decreases the antigenic stimulus. In perianal disease, there is often secondary bacterial infection of fistula tracts that perpetuates the inflammatory cycle.
- Initial therapy in patients with mild to moderate Crohn disease who do not have systemic symptoms based on its relative safety to other drugs
- Mechanism of action = Anti-inflammatory effect — 5-ASA inhibits prostaglandin and leukotriene synthesis, scavenges free radicals, and inhibits NF-κB — all locally at the mucosal surface
- Clinical role = Induction agent (induction of remission)
- NO consistent evidence that is effective in maintenance of remission
- Mesalamine can be used as maintenance after surgical intervention but NOT after medically induced remission
Important 5-ASA formulations:
| Drug | Formulation | Site of Action | Key Points |
|---|---|---|---|
| Mesalamine (Pentasa / Asacol) | Controlled ileal release (CIR) / pH-dependent release | Small bowel + colon | More commonly used for both ileitis and colitis [4][15]; NOT useful in active (moderate-severe) disease [4]; S/E: nephrotoxicity |
| Sulfasalazine | Prodrug: sulfapyridine + 5-ASA linked by azo bond | Colon only | Colonic bacteria must cleave the drug to release the 5-ASA moiety [4][15][3]; no small bowel activity; S/E: nausea, headache, fever, agranulocytosis, pancreatitis, SJS [4]; reversible oligospermia [3]; pregnancy concerns: kernicterus (crosses placenta) and neural tube defect (inhibits folic acid absorption/metabolism) [4] |
Sulfasalazine is only useful in colitis (require colonic bacteria to cleave the drug to release 5-ASA moiety) [3]
5-ASA in CD — Limited Role
Unlike in UC where 5-ASA is a backbone therapy, its role in CD is controversial and limited to mild colonic disease. The major guidelines (ECCO, AGA) now de-emphasise 5-ASA for ileal CD and favour budesonide. In the HKU exam context, know the drug but understand its limitations.
Corticosteroids [16]:
- Indications: induction in mild-moderate CD or UC, NOT for long-term use [16]
| Drug | Route | Dose | Key Points |
|---|---|---|---|
| Budesonide | PO (enteric-coated) [16] | 9 mg/day, taper over 8–12 weeks | First-line for mild-moderate ileal/ileocolonic CD. Topically active corticosteroid with high first-pass hepatic metabolism → fewer systemic side effects than prednisolone. Budesonide = "bude-" from its chemical name, works locally in the ileum. |
| Prednisolone | PO | 40–60 mg/day, taper over 8–12 weeks | For moderate-severe CD or disease refractory to budesonide. Systemic steroid with full spectrum of Cushingoid side effects. |
| IV Hydrocortisone / Methylprednisolone | IV | Hydrocortisone 100mg QDS or Methylpred 60mg/day | For acute severe CD/fulminant disease (inpatient) |
| Topical | Suppository (proctitis), foam/enema (distal colitis) [16] | Variable | For isolated distal colonic/rectal disease |
Critical steroid concepts:
| Term | Definition | Implication |
|---|---|---|
| Steroid-responsive | Symptoms improve with steroids | Taper and transition to steroid-sparing maintenance |
| Steroid-dependent | Relapse when steroid dose reduced or within 3 months of stopping | Need immunomodulator or biologic for maintenance |
| Steroid-refractory | No response to adequate dose of steroids within 2–4 weeks | Escalate to biologic |
Why are steroids NOT for maintenance? Prolonged steroid use causes devastating side effects (osteoporosis, DM, adrenal suppression, cataracts, avascular necrosis, myopathy, increased infection risk) AND does NOT promote mucosal healing. Steroids suppress symptoms but do not change the underlying disease trajectory. The goal is always to get patients off steroids as fast as possible.
Immunomodulators: Azathioprine, 6-Mercaptopurine [2][16]
- Frequently relapsing disease
- Steroid-sparing effects (steroid-dependent patients)
- Fistulating Crohn's disease
Are immunomodulators for IBD used in acute or long-term management? → Chronic management → onset of action of these drugs are very slow. Delayed onset 3 months [2]
This is a crucial point: you cannot use azathioprine to induce remission in an acute flare — it takes 3 months to work. You need a "bridge" with steroids or biologics while waiting for the immunomodulator to kick in.
Side effects: well tolerated, side effects 10% [2]:
- Bone marrow suppression
- Allergy
- Hepatotoxicity
- Pancreatitis
Azathioprine metabolism — high yield pharmacogenomics:
"Azathioprine can be broken down via three mechanisms → hence, any defect of these mechanisms can lead to excessive and toxic accumulation of the azathioprine metabolite, resulting in bone marrow suppression / neutropenic fever (6-TGTP)" [2]
Three things to check before starting azathioprine [2]:
| Check | Enzyme/Drug | Why |
|---|---|---|
| TPMT enzyme activity | Thiopurine methyltransferase | Converts active 6-MP into inactive 6-MMP. Deficiency → excessive 6-TGTP accumulation → severe myelosuppression |
| NUDT15 enzyme activity | Nudix hydrolase 15 | Helps prevent excessive accumulation of toxic 6-TGTP. More common in HK population [2] — NUDT15 variants are much more prevalent in East Asians than Caucasians. This is a key HKU exam point. |
| Xanthine oxidase inhibitor co-prescription | Allopurinol, febuxostat | XO is crucial for the conversion of active 6-MP into inactive 6-TU [2]. If XO is inhibited → 6-MP cannot be cleared → massive accumulation → life-threatening myelosuppression. Must reduce azathioprine dose by 75% if concomitant allopurinol is unavoidable. |
NUDT15 — Especially Important in Hong Kong
NUDT15 enzyme activity must be checked before starting azathioprine — more common deficiency in HK/East Asian population than TPMT deficiency (which is more relevant in Caucasians). A homozygous NUDT15 variant confers near-100% risk of severe myelosuppression on standard-dose thiopurines. This is a frequently tested pharmacogenomics point.
Methotrexate — an alternative immunomodulator:
- Used when thiopurines are not tolerated or ineffective
- Dose: 25 mg IM/SC weekly for induction → 15 mg weekly for maintenance
- Must co-prescribe folic acid 5 mg weekly (given 3 days after methotrexate) to reduce toxicity [17]
- S/E: hepatotoxicity (liver fibrosis with chronic use), myelosuppression, pneumonitis, teratogenicity (absolutely contraindicated in pregnancy — must use effective contraception)
- Better evidence in CD than UC
4.5 Biologics
"Ideally, all patients with moderate to severe disease should be on biologics → but cost is an issue. So we reserve these drugs as a second line drug, for those who do not respond to conventional therapy" [2]
Indications of biologics [2][16]:
- Standard treatment not working
- Acute severe UC not responding to steroid (for UC)
- Fistulising disease
- Extra-intestinal manifestations (pyoderma gangrenosum, uveitis, severe arthritis)
"Combination of immunomodulators + biologics → decreases immunogenicity against biologics" [3] — this is the rationale for combo therapy (biologic + thiopurine): the immunomodulator suppresses antibody formation against the biologic, maintaining its efficacy long-term.
TNF-α ("tumour necrosis factor alpha") is the master pro-inflammatory cytokine in CD. It drives macrophage activation, granuloma formation, endothelial activation, and tissue destruction. Blocking it → rapid reduction in transmural inflammation.
| Drug | Structure | Route | Dose | Key Points |
|---|---|---|---|---|
| Infliximab | Chimeric (mouse-human) monoclonal antibody | IV | 5 mg/kg at 0, 2, 6 weeks → Q8 weeks [3][17] | "Chimeric" = part mouse protein → higher immunogenicity → risk of antibodies to infliximab (ATI) [3] → loss of response. SFI (serum free infliximab) testing can detect this. |
| Adalimumab | Humanised monoclonal antibody | SC | Loading 160/80mg or 80/40mg at 0, 2 weeks → 40mg Q2 weeks [17] | Fully human → lower immunogenicity than infliximab. Self-administered subcutaneously → more convenient. |
Contraindications of anti-TNF [3][16][17]:
- Latent untreated or active TB — TNF is essential for maintaining TB granuloma integrity; anti-TNF → granuloma dissolution → disseminated TB
- NYHA Class III-IV heart failure — TNF paradoxically has cardioprotective effects in advanced HF; blocking it worsens outcomes
- History of demyelinating disease — anti-TNF can cause or worsen demyelination (MS, optic neuritis)
- Optic neuritis
- History of lymphoma
Mnemonic for anti-TNF contraindications: "STOIC" — Sepsis/TB, Tumour (lymphoma), Optic neuritis, Infusion reaction, Cardiac failure (NYHA III-IV)
| Drug | Structure | Route | Dose | Key Points |
|---|---|---|---|---|
| Vedolizumab | Humanised monoclonal antibody against α4β7 integrin | IV | 300 mg at 0, 2, 6 weeks → Q8 weeks [3][17] | Gut-selective biologic agent [3][17] |
- Mechanism: α4β7 integrin is expressed on gut-homing T lymphocytes. It binds to MAdCAM-1 on gut endothelium, allowing T cells to traffic from blood into the gut mucosa. Vedolizumab blocks this interaction → prevents inflammatory T cell infiltration into the gut
- "Gut-selective, lower risk of serious infection, onset slower than anti-TNF" [3][17]
- Because it is gut-selective, it does NOT cause systemic immunosuppression → safer profile than anti-TNF regarding TB reactivation and lymphoma
- Drawback: slower onset of action than anti-TNF
| Drug | Structure | Route | Dose | Key Points |
|---|---|---|---|---|
| Ustekinumab (Stelara) | Human monoclonal antibody against IL-12/23 p40 subunit | IV loading → SC maintenance | IV BW-based loading → SC 90mg at 8 weeks → Q12 weeks [3][17] | Blocks both IL-12 (Th1 driver) and IL-23 (Th17 driver) — hits two key pathogenic pathways simultaneously |
- "Initial IV dosing based on BW, administered over at least 1 hr; BW > 85kg: 520mg; > 55kg to < 85kg: 390mg; < 55kg: 260mg" [17]
- Then 90mg at 8 weeks and then at 12-weekly intervals, SC [17]
- Good safety profile; effective in both CD and psoriasis (shared IL-23 pathway)
- Newer selective anti-IL-23 agents (risankizumab, guselkumab) target the p19 subunit of IL-23 specifically and are increasingly used
JAK inhibitors [2]:
- "Janus Kinase" inhibitors — JAK = Janus Associated Kinase. Janus is the two-faced Roman god → JAK enzymes have two kinase domains. They sit on the intracellular side of cytokine receptors and transduce signals from multiple inflammatory cytokines.
- Oral formulation (unlike biologics which are IV/SC) → "not strictly a biologic — the small molecules, oral formulations, unlike the injections" [2]
- Example: tofacitinib (JAK1/3 inhibitor, primarily for UC), upadacitinib (JAK1 selective, approved for CD)
Side effects of JAK inhibitors [2]:
- Herpes zoster — JAK signalling is important for IFN-mediated antiviral immunity; blocking it → reactivation of VZV
- Thromboembolic risk — mechanism not fully understood; possibly related to altered haematopoiesis
Proton pump inhibitors: for upper GI involvement [17] — if CD affects the oesophagus, stomach, or duodenum, PPI is added for acid suppression.
Nutritional support is a critical but often underappreciated component of CD management:
| Approach | Indication | Details |
|---|---|---|
| Exclusive enteral nutrition (EEN) | First-line induction therapy in paediatric CD (equivalent efficacy to steroids without steroid side effects); adjunctive in adults | Polymeric or elemental formula for 6–8 weeks, replacing all oral food. Works by altering gut microbiome, reducing antigenic exposure, and providing nutritional repletion |
| Supplementary enteral nutrition | Malnourished patients, high-output fistulae | Peptamen (elemental diet for malabsorption) [18] |
| Parenteral nutrition (TPN) | Refractory IBD [18]; proximal SB fistula (to facilitate closure) [18]; short bowel syndrome post-resection; perioperative optimisation | Via central venous catheter; provides complete nutrition IV; TPN aids closure of fistula [4] |
| Micronutrient replacement | All patients as needed | Iron, B12, folate, calcium, vitamin D, zinc, vitamin K [19] |
6. Surgical Management
"More common in Crohn's disease than ulcerative colitis. Greater than 50% of CD patients will require surgery during their lifetime, compared to 20% of UC patients" [2]
"Surgical treatment is NOT curative in Crohn's disease and is mainly used to treat complications only" [4][15]
"Bowel preserving surgery should be performed as repeated bowel resections can lead to short gut syndrome. Conservative and minimal resection as possible. Extended resection does not decrease recurrence." [4][15]
Emergency:
- Perforation / bleeding
- Fulminant colitis / toxic megacolon
- Life-threatening haemorrhage
Elective:
- Stricture (intestinal obstruction)
- Abscess
- Fistula
- Failed medical treatment / refractory to medical treatment
- Crohn's Disease Activity Index (CDAI) > 450
- Harvey-Bradshaw Index (HBI) > 15 [20]
- Risk of cancer / malignancy (high-grade dysplasia, adenocarcinoma)
- Debilitating EIM, except those independent of colitis activity (sacroiliitis, hepatobiliary) [14]
- Severe perianal disease [3]
"Rarely curative but lead to long-lasting remissions in some patients. Low threshold for ileocolic CD" [20]
6.2 Surgical Procedures
Surgical principle: preservation of bowel length (should document residual SB length) [14]
| Procedure | Indication | Details |
|---|---|---|
| Small bowel resection with primary anastomosis [4][15] | Long-segment SB disease, failed medical therapy | Remove diseased segment, join healthy ends. Minimal margins — wide margins do not reduce recurrence. |
| Strictureplasty | Short-segment strictures (bowel preservation) | Short stricture < 10 cm = Heineke-Mikulicz strictureplasty (incise longitudinally, close transversely — widens the lumen without removing bowel). Long stricture 10–20 cm = Finney strictureplasty (side-to-side anastomosis configuration) [4][15] |
| Endoscopic balloon dilatation | Distal ileal strictures are sometimes amenable to balloon dilatation [4][15] | Non-surgical alternative for short, accessible, non-fistulising strictures |
"Bypass is NOT recommended since there is risk of malignant transformation in the bypassed segment" [4][15]
| Procedure | Indication |
|---|---|
| Right hemicolectomy | Most commonly performed for ileocaecal CD [4][15] |
| Total colectomy with ileorectal anastomosis (IRA) | Extensive colonic CD if rectum spared [4][15] |
| Total proctocolectomy with IPAA | Limited perianal disease [4][15] — risky in CD due to high pouch failure rate from recurrence |
| Total proctocolectomy with end ileostomy | If rectum affected [4][15] — definitive procedure for Crohn's colitis with rectal disease |
"NO role for strictureplasty in Crohn's colitis since there is a 7% risk of malignancy over 20 years" [4][15]
Strictureplasty — SB Only!
Strictureplasty is only for small bowel strictures. In colonic CD, strictures carry a significant malignancy risk (~7% over 20 years), so the strictured segment should be resected and sent for histology, not simply widened.
"Perianal disease: examination under anaesthesia (EUA) to assess extent of disease, drain collections, seton drainage, advancement flaps, fistula plugs" [17]
| Procedure | Purpose |
|---|---|
| EUA + abscess drainage | Drain perianal sepsis, assess fistula anatomy |
| Seton insertion | Loose non-cutting seton through fistula tract → maintains drainage, prevents recurrent abscess, allows tract to mature → then definitive therapy with biologics or advancement flap |
| Fistulotomy | Only for simple, low intersphincteric fistulae (risk of incontinence if high trans-sphincteric) |
| Advancement flap | Covers internal opening of fistula with a flap of rectal mucosa |
| Fistula plug | Biologic plug inserted into tract to promote closure |
Fistula management: SNAP [4][15]:
| Letter | Principle | Action |
|---|---|---|
| S | Sepsis control | Antibiotics + Percutaneous abscess drainage (CT-guided) |
| N | Nutrition support | TPN aids closure of fistula — bowel rest reduces output through fistula |
| A | Anatomical location | Imaging to locate fistula (MRI pelvis, CT, fistulography) |
| P | Plan | Definitive surgery once sepsis controlled + nutrition optimised |
"Disease will recur close to the anastomosis" [2]
After ileocaecal resection, the recurrence rate is high:
- ~50% endoscopic recurrence within 1 year
- ~20–25% clinical recurrence within 5 years
Post-operative prophylaxis:
- Smoking cessation — most important modifiable factor
- Mesalamine — can be used as maintenance after surgical intervention but NOT after medically induced remission [4][15]
- Immunomodulators (azathioprine) or biologics (anti-TNF) in high-risk patients
- Surveillance ileo-colonoscopy at 6–12 months post-op → Rutgeerts score to assess neo-terminal ileal recurrence → guides escalation
- Fecal calprotectin — "Predict disease relapse, postoperative relapse" [10] — non-invasive monitoring between endoscopies
| Drug Class | Examples | Role | Key Side Effects / Cautions |
|---|---|---|---|
| Antibiotics | Metronidazole, Ciprofloxacin | Perianal disease, colonic CD, septic complications | Peripheral neuropathy (metro), tendon rupture (cipro) |
| 5-ASA | Mesalazine, Sulfasalazine | Mild colonic CD induction; post-surgical maintenance | Nephrotoxicity (mesalazine); oligospermia, agranulocytosis (sulfasalazine) |
| Corticosteroids | Budesonide, Prednisolone, IV Hydrocortisone | Induction (NOT maintenance) | Cushingoid features, osteoporosis, DM, adrenal suppression |
| Immunomodulators | Azathioprine, 6-MP, Methotrexate | Steroid-sparing maintenance; fistulating CD | BM suppression (check TPMT + NUDT15), hepatotoxicity, pancreatitis |
| Anti-TNF | Infliximab (IV), Adalimumab (SC) | Moderate-severe CD; fistulising CD; EIMs | TB reactivation, lymphoma, demyelination, HF |
| Anti-integrin | Vedolizumab (IV) | Gut-selective; lower infection risk | Slower onset; less effective for EIMs |
| Anti-IL-12/23 | Ustekinumab (IV → SC) | Moderate-severe CD | Good safety profile |
| JAK inhibitors | Tofacitinib, Upadacitinib (PO) | Oral option; moderate-severe disease | Herpes zoster, thromboembolic risk |
| PPI | Omeprazole etc. | Upper GI CD | Standard PPI side effects |
High Yield Summary — Management of Crohn's Disease
- Principles: Induce and maintain remission; individualise by activity, site, behaviour; treat-to-target (mucosal healing, not just symptoms); smoking cessation is essential.
- Step-up vs Top-down: Traditional step-up still used in HK due to cost, but early biologic use (top-down) is indicated for adverse prognostic factors (young age, extensive SB, perianal, deep ulcers, strictures, steroid requirement).
- Steroids induce but do NOT maintain — always transition to steroid-sparing agents (immunomodulators or biologics).
- Before azathioprine: Check TPMT, NUDT15 (especially important in HK/East Asian population), and concomitant xanthine oxidase inhibitor (allopurinol) use.
- Before anti-TNF: Screen for latent TB (CXR + IGRA), HBV, HIV. Anti-TNF C/I: active TB, NYHA III-IV HF, demyelination, lymphoma history.
- Biologics: Anti-TNF (infliximab, adalimumab), Anti-α4β7 (vedolizumab — gut-selective, safer), Anti-IL-12/23 (ustekinumab), JAK inhibitors (oral, herpes zoster risk).
- Surgery: > 50% of CD patients need surgery in their lifetime. NOT curative — disease recurs at anastomosis. Bowel-preserving principle: minimal resection, strictureplasty for SB (not colon — 7% malignancy risk). Fistula: SNAP (Sepsis, Nutrition, Anatomy, Plan).
- Post-op: Surveillance colonoscopy at 6-12 months (Rutgeerts score); fecal calprotectin for monitoring; mesalazine or immunomodulator/biologic for prophylaxis.
Active Recall - Management of Crohn's Disease
References
[2] Senior notes: Block A - Chronic diarrhoea_ irritable bowel syndrome and inflammatory bowel disease.pdf (pp. 17, 43, 45, 47, 48) [3] Senior notes: Maksim Medicine Notes.pdf (pp. 129, 131) [4] Senior notes: MBBS Final MB (Medicine) (Felix PY Lai).pdf (pp. 860–863); MBBS Final MB (Surgery) (Felix PY Lai).pdf (pp. 655–660) [10] Lecture slides: Inflammatory bowel disease.pdf (p. 11) [14] Senior notes: Maksim Surgery Notes.pdf (pp. 93–94) [15] Senior notes: MBBS Final MB (Surgery) (Felix PY Lai).pdf (pp. 655–660) [16] Senior notes: Ryan Ho GI.pdf (p. 125) [17] Lecture slides: Handbook of Internal Medicine 2024.pdf (p. 112); Inflammatory bowel disease.pdf (p. 27) [18] Senior notes: Ryan Ho Fluids and Nutrition.pdf (pp. 9, 11) [19] Senior notes: Ryan Ho Fundamentals.pdf (p. 292) [20] Lecture slides: Inflammatory bowel disease.pdf (p. 27)
Complications of Crohn's Disease
The complications of Crohn's disease flow directly from its fundamental pathological nature: transmural, skip-lesion, granulomatous inflammation that can affect any part of the GIT. Because the inflammation penetrates the full thickness of the bowel wall — unlike UC which stays mucosal — CD produces a unique and devastating set of structural complications (fistulae, abscesses, strictures) on top of the metabolic and systemic consequences of chronic inflammation and malabsorption.
Complications of CD [21]:
- Malnutrition
- Abscesses and fistula
- Stricture / obstruction
- Perianal disease
These are the four cardinal complications emphasised in the GC lecture slides. Below we dissect each in exhaustive detail, then cover additional complications including toxic megacolon, perforation, malignancy, extraintestinal manifestations, treatment-related complications, and others.
"Protein, calorie and vitamin deficiencies. Poor intake, protein-losing enteropathy, malabsorption" [2][21]
Malnutrition is one of the most pervasive complications of CD and is present in up to 75% of patients at some point in their disease course. It is multifactorial:
| Mechanism | Explanation |
|---|---|
| Reduced oral intake | "Food fear" — eating triggers crampy pain and diarrhoea (especially with stricturing disease), so patients consciously restrict intake. Anorexia from pro-inflammatory cytokines (TNF-α, IL-1, IL-6 suppress appetite via hypothalamic pathways) |
| Malabsorption | Terminal ileal disease → bile acid malabsorption → fat malabsorption (steatorrhoea) → fat-soluble vitamin deficiency (A, D, E, K). Terminal ileal disease/resection → B12 deficiency. Proximal SB disease → folate, iron, calcium malabsorption. Bacterial overgrowth in strictured bowel deconjugates bile salts → further fat malabsorption |
| Protein-losing enteropathy | Transmural inflammation → damaged lymphatics → albumin and protein leak into the bowel lumen → hypoalbuminaemia → peripheral oedema |
| Increased metabolic demand | Chronic inflammation raises basal metabolic rate by 10–30% |
| Iatrogenic | Repeated bowel resections → short bowel syndrome; corticosteroids → muscle wasting, osteoporosis, hyperglycaemia |
Specific nutritional deficiencies and their consequences:
| Deficiency | Why It Occurs | Clinical Consequence |
|---|---|---|
| Iron | Chronic blood loss + malabsorption (duodenal/jejunal disease) | Microcytic anaemia, koilonychia, angular stomatitis |
| Vitamin B12 | Terminal ileal disease or resection | Megaloblastic anaemia, subacute combined degeneration of the cord, peripheral neuropathy, glossitis |
| Folate | Proximal SB disease; methotrexate; sulfasalazine | Megaloblastic anaemia |
| Vitamin D | Fat malabsorption (bile salt depletion) | Osteoporosis (fat malabsorption → ↓ fat-soluble Ca) [3], osteomalacia, hypocalcaemia, tetany |
| Vitamin K | Fat malabsorption | Coagulopathy, easy bruising |
| Vitamin A | Fat malabsorption | Night blindness, xerophthalmia |
| Zinc | Chronic diarrhoea, malabsorption | Acrodermatitis, poor wound healing, impaired immunity |
| Protein / Albumin | Protein-losing enteropathy + poor intake + ↓ hepatic synthesis | Peripheral oedema, poor wound healing, immunodeficiency |
Anaemia in IBD [3]: Can result from active IBD (anaemia of chronic disease — hepcidin-mediated iron sequestration), Fe/B12 malabsorption, sepsis (suppressed erythropoiesis), or azathioprine-induced myelosuppression. Always consider multiple concurrent causes.
Short Bowel Syndrome
Repeated resections for strictures, fistulae, and abscesses can cumulatively reduce the functional small bowel length below the threshold needed for adequate absorption ( < 200 cm without colon, < 100 cm with colon in continuity). This leads to short bowel syndrome — dependence on parenteral nutrition for survival. This is why the surgical principle in CD is always bowel preservation and why residual SB length should be documented after every operation [14].
2. Abscesses and Fistulae
"Extension of the mucosal fissure and ulcer through the bowel wall into the extra-intestinal tissue. Abscess: peritoneal cavity. Fistula: adjacent viscera, bladder, vagina and abdominal wall" [2][21]
This is the hallmark complication that distinguishes CD from UC. Here is why it happens:
- Deep fissuring ulcers (driven by Th1/macrophage transmural inflammation) penetrate through the mucosa → submucosa → muscularis → serosa
- Once the ulcer breaches the serosa, two things can happen:
- Abscess: The inflammatory material is walled off by omentum, mesentery, or adjacent bowel loops → creates a contained collection of pus (phlegmon → abscess)
- Fistula: The inflammatory tract finds a path of least resistance and burrows into an adjacent structure, creating an abnormal epithelialised connection
| Type | Pathway | Clinical Features |
|---|---|---|
| Entero-enteric | Bowel → bowel | Diarrhoea (bypasses absorptive surface), malabsorption; bacterial overgrowth in bypassed segment |
| Enterovesical | Bowel → bladder | Fistula can be entero-vesical → feces in urine [2]; pneumaturia (air in urine), faecaluria, recurrent polymicrobial UTIs |
| Enterovaginal | Bowel → vagina | Can be entero-vaginal → feces in vaginal discharge [2]; passage of flatus/stool per vagina |
| Enterocutaneous | Bowel → skin (abdominal wall) | Can be entero-cutaneous → feces coming out from abdominal wall [2]; often post-surgical |
| Perianal | Anorectal → perianal skin | See perianal disease section below |
| Entero-peritoneal | Bowel → peritoneal cavity (free) | Peritonitis — surgical emergency |
- Occurs in ~15–30% of CD patients
- Presents with fever, localised abdominal pain/tenderness, a palpable mass, leukocytosis, and elevated CRP
- Diagnosed by CT abdomen with contrast (rim-enhancing fluid collection)
- Management: Antibiotics + percutaneous CT-guided drainage (if ≥ 3–5 cm) + subsequent definitive surgery if needed. Small abscesses ( < 3 cm) may resolve with antibiotics alone
3. Stricture and Intestinal Obstruction
"Mucosal thickening due to active inflammation, scarring, adhesions, food impaction in a long-standing stricture" [2][21]
Strictures in CD arise from two distinct processes — and the distinction is clinically critical:
| Type | Mechanism | Response to Treatment |
|---|---|---|
| Inflammatory stricture | Active transmural inflammation → bowel wall oedema and thickening → luminal narrowing | Responds to anti-inflammatory/biologic therapy (reversible) |
| Fibrotic stricture | Repeated cycles of inflammation → healing by fibrosis (collagen deposition in all bowel wall layers) → permanent luminal narrowing | Does NOT respond to medical therapy — requires endoscopic dilatation, strictureplasty, or resection |
In practice, most strictures are mixed (inflammatory + fibrotic). MR enterography helps distinguish the two components (enhancement/oedema = inflammatory; no enhancement = fibrotic).
- Partial obstruction (most common): Colicky abdominal pain (especially post-prandial), abdominal distension, nausea/vomiting, borborygmi, visible peristalsis
- Complete obstruction: Absolute constipation (no flatus or stool), progressive distension, vomiting (bilious if distal to ampulla)
- Food impaction can precipitate acute-on-chronic obstruction in a long-standing stricture — a food bolus gets stuck in an already narrowed lumen
- Inflammatory component: Optimise medical therapy (steroids, biologics)
- Fibrotic stricture:
- Endoscopic balloon dilatation — for short ( < 4–5 cm), accessible, non-fistulising strictures
- Strictureplasty — for small bowel strictures (Heineke-Mikulicz for < 10 cm; Finney for 10–20 cm)
- Resection with primary anastomosis — for long, complex, or multiple strictures not amenable to strictureplasty
- "NO role for strictureplasty in Crohn's colitis since there is a 7% risk of malignancy over 20 years" [4] — colonic strictures must be resected and sent for histology
"Perianal abscess or fistula, anal fissures" [2][21]
Perianal disease affects 30–40% of CD patients and is one of the most debilitating manifestations. It can be the presenting feature, preceding any bowel symptoms by years.
| Manifestation | Details |
|---|---|
| Perianal fistula | Abnormal tracts from the anal canal to perianal skin; can be simple (single, low) or complex (multiple, high, with secondary tracts/horseshoe extensions) |
| Perianal abscess | Walled-off collection in the perianal/ischiorectal space; presents with acute pain, swelling, fever; requires surgical drainage |
| Anal fissure | Often atypical (lateral, deep, multiple, painless) — unlike simple idiopathic posterior midline fissures |
| Anal/rectal stricture | Chronic inflammation → fibrosis → narrowing of the anal canal/rectum → obstructed defecation |
| Skin tags | Large, oedematous "elephant ear" tags — characteristic of CD |
Management of perianal CD (multimodal):
- MRI pelvis to map fistula anatomy
- EUA (examination under anaesthesia) — drain abscesses, place seton through fistula tract
- Antibiotics (ciprofloxacin + metronidazole) — reduce sepsis
- Anti-TNF biologics (infliximab/adalimumab) — best evidence for fistula healing
- Definitive procedures: advancement flap, LIFT procedure, fistula plug — once sepsis controlled and inflammation treated
- Proctectomy with permanent stoma — last resort for severe, refractory, destructive perianal CD
5. Toxic Megacolon
While more commonly associated with UC, toxic megacolon can occur in Crohn's colitis.
"Which form of inflammatory bowel disease more commonly causes toxic megacolon? — Ulcerative colitis. Can happen with Crohn's, but UC more common" [2]
"Total or segmental non-obstructive dilatation of colon ≥ 6 cm or cecum > 9 cm and the presence of systemic toxicity" [22]
Severe transmural inflammation → destruction of the muscularis propria and myenteric (Auerbach's) plexus → loss of smooth muscle tone → massive colonic dilatation. The thinned, necrotic bowel wall is at extremely high risk of perforation.
"Presents with fever, tachycardia, hypotension, dehydration, electrolyte disturbances, anaemia, hypoalbuminaemia and mental changes" [22]
Clinical features of severe toxic megacolon [2]:
- Fever > 38°C
- Heart rate > 120/min
- Anaemia
- Low albumin
- Abdominal distension, tenderness, absent bowel sounds (paralytic ileus)
- Reduced or absent flatus/stool
Diagnosis: Plain abdominal X-ray [2]
"Must exclude coexisting infection: C. difficile, CMV infection" [2] — both can precipitate or exacerbate toxic megacolon in IBD patients, especially those on immunosuppression.
Treatment [2]:
- Bowel rest and total parenteral nutrition
- Fluid and electrolyte replacement
- Corticosteroids (IV hydrocortisone or methylprednisolone)
- Close monitoring (serial AXR, clinical reassessment Q12h)
- Broad-spectrum antibiotics (cover for perforation/translocation)
- Nasogastric decompression
- Stop all medications that slow motility (opioids, anticholinergics, antidiarrhoeals)
Prognosis [2]:
- Around 50% will respond to medical treatment
- Around 50% will go to urgent colectomy if not responding within 3–7 days
If there is no improvement within 24–72 hours, or if perforation/clinical deterioration occurs → emergency subtotal colectomy with end ileostomy.
"Perforation / bleeding" [20]
- Free perforation into the peritoneal cavity → generalised peritonitis (rigid abdomen, absent bowel sounds, septic shock) → surgical emergency with high mortality
- Contained perforation → phlegmon or abscess formation (more common in CD, as omentum and adjacent loops tend to wall off the perforation)
- Most commonly occurs as a consequence of toxic megacolon, but can also result from deep fissuring ulcers perforating through a thinned bowel wall
- "Perforation with peritonitis is associated with high mortality" [22]
- Diagnosis: erect CXR (free gas under diaphragm — Rigler's sign on AXR); CT abdomen if equivocal
- Management: emergency laparotomy with resection of perforated segment
"Life-threatening haemorrhage" [14]
- Massive GI haemorrhage occurs in ~1–6% of CD patients
- Usually from deep ulceration eroding into a mesenteric vessel
- Presents with haematochezia, haemodynamic instability
- Management: resuscitation (IV fluids, blood products) → angiographic embolisation or emergency surgery (resection of the bleeding segment)
"Malignancy (CRC, SB cancer, cholangiocarcinoma): higher risk in UC; surveillance colonoscopy Q3 years" [3]
While CRC risk is more prominently associated with UC, patients with colonic CD (Crohn's colitis) also have an increased CRC risk, particularly with:
- Long-standing disease ( > 8–10 years)
- Extensive colonic involvement
- Concurrent PSC
- Family history of CRC
- Presence of strictures (any colonic stricture should be biopsied to exclude malignancy)
Small bowel cancer is also increased in CD (small bowel adenocarcinoma in areas of chronic inflammation) — though absolute risk remains low.
Cholangiocarcinoma risk is increased in patients with concurrent PSC.
Surveillance protocol:
- Begin colonoscopic surveillance 8–10 years after symptom onset in patients with colonic CD
- Frequency: approximately every 1–3 years (guided by risk factors — more frequently if PSC, extensive disease, family history)
- Chromoendoscopy or high-definition endoscopy with targeted biopsies improves dysplasia detection
- If low-grade dysplasia → intensified surveillance or consider colectomy; if high-grade dysplasia or dysplasia-associated lesion/mass (DALM) → colectomy
Extra-intestinal manifestations of IBD — more common in CD in general [3]:
These have been discussed in detail in the clinical features section; here we frame them as complications:
| System | Complication | Course |
|---|---|---|
| Skin | Clubbing, oral aphthous ulcer (), stomatitis, perianal skin tag, erythema nodosum (), pyoderma gangrenosum (a/w sterile abscess), psoriasis, Sweet syndrome (), hidradenitis suppurativa* [3] | (*) = parallel course; others = independent |
| MSK | Peripheral arthropathy (Types 1 & 2^), axial SpA^, osteoporosis* [3] | Osteoporosis: fat malabsorption → ↓ Vit D → ↓ Ca; corticosteroid use; inflammatory cytokines |
| Blood | Anaemia (active IBD, Fe/B12 malabsorption, sepsis, azathioprine-induced myelosuppression) [3] | |
| Ocular | Uveitis, episcleritis () (painless), scleritis (painful & vision-threatening)* [3] | |
| Hepatobiliary | Fatty liver, liver abscess, gallstones (↓ reabsorption of bile salt), PSC (a/w UC but can occur in CD) [3] | Gallstones: terminal ileal disease → bile salt malabsorption → depleted bile salt pool → cholesterol supersaturation → cholesterol gallstones |
| Urologic | Kidney stones (fat malabsorption → ↓ fat-soluble Ca in blood → ↑ oxalate absorption & excretion → oxalate stone) [3] | Free fatty acids bind Ca²⁺ in gut lumen → oxalate (normally bound to Ca²⁺) remains free → absorbed in colon → hyperoxaluria → calcium oxalate renal stones |
| Vascular | Arterial and venous thromboembolism (portal and mesenteric thrombosis, DVT) [22] | Chronic inflammation → ↑ procoagulant factors (fibrinogen, factor VIII, vWF), ↑ platelet count, endothelial activation, ↓ antithrombin. IBD patients have 2–3× increased VTE risk, especially during flares |
Why do IBD patients get gallstones AND kidney stones? Both are consequences of terminal ileal dysfunction:
- Gallstones: Bile salts are normally reabsorbed in the terminal ileum and recycled (enterohepatic circulation). If the TI is inflamed/resected → bile salts are lost in stool → bile becomes supersaturated with cholesterol → cholesterol gallstone formation
- Kidney stones: Fat malabsorption → free fatty acids in the colonic lumen bind calcium → calcium is unavailable to bind oxalate → free oxalate is absorbed → hyperoxaluria → calcium oxalate stones in the kidney
These are important to recognise as they can mimic disease flare or cause independent morbidity:
| Drug | Complication | Mechanism |
|---|---|---|
| Corticosteroids | Osteoporosis, DM, adrenal suppression, cataracts, AVN, psychosis, Cushingoid features, myopathy | Systemic glucocorticoid effects |
| Azathioprine / 6-MP | Myelosuppression, hepatotoxicity, pancreatitis, lymphoma (rare) | TPMT/NUDT15 pharmacogenomics; purine analogue toxicity |
| Methotrexate | Hepatic fibrosis, pneumonitis, myelosuppression, teratogenicity | Folate antagonism |
| Anti-TNF | TB reactivation, lymphoma (particularly in young male patients), paradoxical psoriasis, demyelination, heart failure exacerbation [2][3] | Immunosuppression; disruption of granuloma maintenance |
| JAK inhibitors | Herpes zoster, thromboembolic risk [2] | Impaired IFN-mediated antiviral immunity; altered haematopoiesis |
| 5-ASA (mesalazine) | Nephrotoxicity (interstitial nephritis) | Idiosyncratic |
| Sulfasalazine | Agranulocytosis, reversible oligospermia, pancreatitis | Sulphonamide moiety |
"Reactivation of latent TB & latent viral infection e.g. HBV (anti-TNFs)" [2] "Herpes zoster (JAKi)" [2]
| Complication | Details |
|---|---|
| Disease recurrence | The most common post-surgical complication. ~50% endoscopic recurrence at the neo-terminal ileum within 1 year; ~20–25% clinical recurrence within 5 years. Recurrence is almost always at the anastomosis, on the proximal (small bowel) side |
| Short bowel syndrome | After repeated resections; functional SB < 200 cm → malabsorption of macronutrients, fluids, electrolytes → dependence on TPN |
| Anastomotic leak | Early post-operative complication → peritonitis, sepsis |
| Adhesions | Post-surgical adhesions → small bowel obstruction (adhesive SBO is the most common cause of SBO in the developed world) |
| Stoma-related complications | Prolapse, retraction, parastomal hernia, skin irritation, high output |
High Yield Summary — Complications of Crohn's Disease
Four cardinal complications (GC slide): Malnutrition, abscesses/fistulae, stricture/obstruction, perianal disease.
Malnutrition: Multifactorial — poor intake (food fear), malabsorption (bile salt, B12, fat-soluble vitamins), protein-losing enteropathy, increased metabolic demand. Key deficiencies: iron, B12, folate, Vit D, Vit K, zinc, albumin.
Fistulae: Result from transmural fissuring ulcers penetrating through serosa → adjacent structures. Types: entero-enteric, enterovesical (pneumaturia, faecaluria), enterovaginal, enterocutaneous, perianal.
Strictures: Inflammatory (reversible with medical Rx) vs fibrotic (irreversible — needs dilatation/strictureplasty/resection). No strictureplasty for colonic strictures (7% malignancy risk). Bypass NOT recommended (malignant transformation in bypassed segment).
Perianal disease: 30–40% of CD. Fistulae, abscesses, fissures, skin tags, strictures. Managed with EUA, seton drainage, antibiotics, anti-TNF, definitive surgery.
Toxic megacolon: Colonic dilatation ≥ 6 cm with systemic toxicity. More common in UC but can occur in CD. Exclude C. diff and CMV. 50% respond to medical Rx; 50% need emergency colectomy.
Malignancy: CRC risk increased in colonic CD (especially > 8–10 years, PSC, extensive disease). SB adenocarcinoma. Surveillance colonoscopy every 1–3 years. Any colonic stricture must be biopsied.
Metabolic: Gallstones (bile salt malabsorption → cholesterol supersaturation) and renal stones (fat malabsorption → free oxalate absorption → calcium oxalate stones).
Treatment-related: Steroid toxicity; thiopurine myelosuppression (TPMT, NUDT15); anti-TNF: TB reactivation, lymphoma; JAKi: herpes zoster, VTE.
Active Recall - Complications of Crohn's Disease
References
[2] Senior notes: Block A - Chronic diarrhoea_ irritable bowel syndrome and inflammatory bowel disease.pdf (pp. 37–38) [3] Senior notes: Maksim Medicine Notes.pdf (pp. 128, 130) [4] Senior notes: MBBS Final MB (Surgery) (Felix PY Lai).pdf (pp. 660) [14] Senior notes: Maksim Surgery Notes.pdf (pp. 93–94) [20] Lecture slides: Inflammatory bowel disease.pdf (p. 27) [21] Lecture slides: GC 033. Chronic diarrhea_irritable bowel syndrome and inflammatory bowel disease.pdf (p. 58) [22] Senior notes: MBBS Final MB (Medicine) (Felix PY Lai).pdf (p. 878); MBBS Final MB (Surgery) (Felix PY Lai).pdf (p. 675)
High Yield Summary
Definition: Crohn's disease is a chronic, relapsing-remitting, transmural, granulomatous inflammatory disorder affecting any part of the GIT (mouth to anus), most commonly the terminal ileum and ileocaecal region.
Epidemiology (HK): Incidence ~1/100,000 (rising), M ≥ F in Chinese populations, earlier onset than UC (peak 15–35y).
Risk Factors: Smoking (↑ risk — opposite for UC), FHx IBD, prior appendicectomy (↑ risk — opposite for UC), infectious GE in past year, NSAIDs, OCP, antibiotics, Western diet, NOD2 mutations (rare in Chinese).
Pathophysiology: Genetically susceptible host + environmental trigger → mucosal barrier defect → luminal antigens cross epithelium → exaggerated Th1/Th17 immune response → TNF-α, IL-12, IL-23 → transmural granulomatous inflammation → ulceration, fibrosis, fistulae.
Key Locations: Ileocolonic (40–55%) > SB only / colon only (~20–30% each); anorectal disease 30–40%.
Phenotypes: Inflammatory (30%), fibrostenotic (50%), fistulising (20%).
Clinical Features:
- Symptoms: RLQ crampy abdominal pain (stricturing/obstruction), watery non-bloody diarrhoea ± steatorrhoea (bile acid malabsorption), constitutional symptoms (fever, weight loss, fatigue), oral ulcers, perianal symptoms (fissure, fistula, abscess), anaemic symptoms.
- Signs: Palpable RLQ mass (25%), perianal disease (skin tags, fissures, fistulae, abscess), cachexia, pallor, clubbing, nutritional deficiency signs.
- Extraintestinal: Arthritis, erythema nodosum, pyoderma gangrenosum, uveitis/episcleritis, PSC, gallstones, renal stones, osteoporosis, thromboembolic disease.
Pathology: Transmural inflammation, non-caseating granulomas (35%), skip lesions, cobblestone appearance, creeping fat. DDx TB colitis (caseating granulomas — must rule out before biologics).
Fecal calprotectin: Differentiates IBD from IBS (high = IBD likely); ASCA associated with CD, pANCA with UC — but serology is not diagnostic.
High Yield Summary — DDx of Crohn's Disease
- Always rule out TB before starting biologics — especially in Hong Kong. Caseating granulomas + AFB stain + C/ST + Quantiferon/T-SPOT. Anti-TNF can reactivate latent TB.
- UC vs CD: Continuous vs skip, mucosal vs transmural, rectal involvement vs sparing, bloody diarrhoea vs non-bloody, no granulomas vs non-caseating granulomas.
- IBS vs IBD: Fecal calprotectin is the key discriminator — low favours IBS, high favours IBD. Serology (ASCA/pANCA) is not diagnostic.
- Infectious colitis: Exclude with stool culture, O&P, C. diff toxin. Yersinia can closely mimic CD (terminal ileitis + granulomas).
- Colorectal cancer: Any colonic stricture in IBD must be biopsied. CRC can complicate long-standing colonic CD.
- No single gold standard — diagnosis is multimodal: clinical + endoscopic + radiological + pathological + biochemical.
High Yield Summary — Diagnostics of Crohn's Disease
- No single gold standard — diagnosis is multimodal: clinical + endoscopic + histological + radiological + biochemical.
- Fecal calprotectin is the key non-invasive screening and monitoring tool. Low = IBS likely. High = proceed to colonoscopy. Correlates with endoscopic activity and predicts relapse.
- Ileo-colonoscopy with segmental biopsies (min 2 from each of 6 segments) is the diagnostic cornerstone. Must include terminal ileum intubation.
- AFB smear and culture on biopsy is mandatory to exclude intestinal TB — especially in Hong Kong.
- Granulomas are present in only 35% of biopsies — their absence does NOT exclude CD.
- MR enterography is first-line for small bowel assessment and preferred for monitoring in young patients (no radiation).
- TB screening (CXR + Quantiferon/T-SPOT) and hepatitis B serology are mandatory before immunosuppression/biologics.
- ASCA/pANCA are helpful but not diagnostic — "antibodies are useless in diagnosing IBD."
- Treat-to-target: Modern goal is endoscopic remission (mucosal healing), not just symptom control.
High Yield Summary — Management of Crohn's Disease
- Principles: Induce and maintain remission; individualise by activity, site, behaviour; treat-to-target (mucosal healing, not just symptoms); smoking cessation is essential.
- Step-up vs Top-down: Traditional step-up still used in HK due to cost, but early biologic use (top-down) is indicated for adverse prognostic factors (young age, extensive SB, perianal, deep ulcers, strictures, steroid requirement).
- Steroids induce but do NOT maintain — always transition to steroid-sparing agents (immunomodulators or biologics).
- Before azathioprine: Check TPMT, NUDT15 (especially important in HK/East Asian population), and concomitant xanthine oxidase inhibitor (allopurinol) use.
- Before anti-TNF: Screen for latent TB (CXR + IGRA), HBV, HIV. Anti-TNF C/I: active TB, NYHA III-IV HF, demyelination, lymphoma history.
- Biologics: Anti-TNF (infliximab, adalimumab), Anti-α4β7 (vedolizumab — gut-selective, safer), Anti-IL-12/23 (ustekinumab), JAK inhibitors (oral, herpes zoster risk).
- Surgery: > 50% of CD patients need surgery in their lifetime. NOT curative — disease recurs at anastomosis. Bowel-preserving principle: minimal resection, strictureplasty for SB (not colon — 7% malignancy risk). Fistula: SNAP (Sepsis, Nutrition, Anatomy, Plan).
- Post-op: Surveillance colonoscopy at 6-12 months (Rutgeerts score); fecal calprotectin for monitoring; mesalazine or immunomodulator/biologic for prophylaxis.
High Yield Summary — Complications of Crohn's Disease
Four cardinal complications (GC slide): Malnutrition, abscesses/fistulae, stricture/obstruction, perianal disease.
Malnutrition: Multifactorial — poor intake (food fear), malabsorption (bile salt, B12, fat-soluble vitamins), protein-losing enteropathy, increased metabolic demand. Key deficiencies: iron, B12, folate, Vit D, Vit K, zinc, albumin.
Fistulae: Result from transmural fissuring ulcers penetrating through serosa → adjacent structures. Types: entero-enteric, enterovesical (pneumaturia, faecaluria), enterovaginal, enterocutaneous, perianal.
Strictures: Inflammatory (reversible with medical Rx) vs fibrotic (irreversible — needs dilatation/strictureplasty/resection). No strictureplasty for colonic strictures (7% malignancy risk). Bypass NOT recommended (malignant transformation in bypassed segment).
Perianal disease: 30–40% of CD. Fistulae, abscesses, fissures, skin tags, strictures. Managed with EUA, seton drainage, antibiotics, anti-TNF, definitive surgery.
Toxic megacolon: Colonic dilatation ≥ 6 cm with systemic toxicity. More common in UC but can occur in CD. Exclude C. diff and CMV. 50% respond to medical Rx; 50% need emergency colectomy.
Malignancy: CRC risk increased in colonic CD (especially > 8–10 years, PSC, extensive disease). SB adenocarcinoma. Surveillance colonoscopy every 1–3 years. Any colonic stricture must be biopsied.
Metabolic: Gallstones (bile salt malabsorption → cholesterol supersaturation) and renal stones (fat malabsorption → free oxalate absorption → calcium oxalate stones).
Treatment-related: Steroid toxicity; thiopurine myelosuppression (TPMT, NUDT15); anti-TNF: TB reactivation, lymphoma; JAKi: herpes zoster, VTE.