GI & Hepatology JC067: Chronic Diarrhoea: Irritable Bowel Syndrome And Inflammatory Bowel Disease Flashcards
Definition of Diarrhoea
- Bowel habits vary widely between individuals
- Must first evaluate patient’s normal bowel patterns (baseline) + nature of symptoms
Diarrhoea:
- ↑ daily stool **volume, **frequency, **fluidity
- stool weight >250g / 24hr
- **>2-3 times / day or liquidity
2 types:
1. Acute
- **Inflammatory
- **Infective / Non-inflammatory
- Chronic (***記: OSMMII)
- Osmotic
- Secretory
- Malabsorptive
- Motility disorders
- Inflammatory
- Chronic infection
***Chronic diarrhoea
- Loose stools that last ***>4 weeks (sometimes >2 weeks)
- Usually means ***>=3 loose stools / day
- Osmotic
- **Lactase deficiency (i.e. Lactose intolerance)
- **Laxative abuse (for weight loss)
- Malabsorption
—> ***resolves with fasting - Secretory (uncommon)
- **Endocrine tumours (mostly)
- **Bile salt malabsorption (draw water + salt into bowel)
- Laxative abuse
—> large volume watery diarrhoea, ***persists in fasting state - Malabsorptive
- **Small bowel diseases (e.g. Crohn’s)
- **Pancreatic diseases (e.g. Pancreatitis, CA pancreas)
- Previous resection
- Bacterial overgrowth
—> weight loss, nutrient deficiency, osmotic diarrhoea, (fatty diarrhoea) - Motility disorders (**most common)
- **IBS - Inflammatory
- Crohn’s
- UC
—> **blood + **mucus in stools - Chronic infection (uncommon except in immunocompromised)
***Mechanisms of Diarrhoea
- Secretory
- e.g. Endocrine problems (VIPoma (watery diarrhoea), Carcinoid syndrome)
- persists despite fasting
- no pus, blood, no excess fat in stools
- ***watery diarrhoea - Exudative / Inflammatory
- mucus + blood in stools
- ***PMN in stools - Decreased absorption (e.g. pancreatic / small bowel diseases)
- osmotic (stop after fasting)
- **↓ in absorption surface
- **motility disorder
Drug-induced diarrhoea
- ***Antacid, Acid suppressants (Mg-containing, H2RA, PPI (∵ bacterial overgrowth))
- Alcohol
- ***Antibiotic
- Anti-HT (β blockers)
- Anti-inflammatory (NSAID, 5-aminosalicylate)
- Colchicine, Misoprostol, Theophylline
- Vitamin / Mineral supplements, Herbal products
- Coffee, Tea, Cola (caffeine / methylxanthine-induced diarrhoea)
- Dietetic foods, gums, mints (sorbitol / mannitol-related osmotic diarrhoea)
***Physical examination of Diarrhoea
- **Fluid + **Electrolyte status (i.e. extent of fluid + electrolyte depletion)
- ***Nutritional status (e.g. malabsorption, maldigestion)
- Causes of diarrhoea
- Skin rash, flushing (e.g. Carcinoid syndrome, IBD)
- **Thyrotoxicosis (thyroid masses, toxic signs)
- **Mouth ulcers (Crohn’s)
- **Arthritis (IBD)
- Hepatomegaly
- **Anorectal exam (mass, anal tone (overflow incontinence), perianal diseases (e.g. fistula, abscess —> Crohn’s)) - Signs of toxicity
- ***Fever
- Distended, rigid, tender abdomen
***Investigations / Specific testing
Directed by History + P/E
Standard investigations:
1. Blood tests
- CBC
—> Anaemia (GI blood loss, B12 folate deficiency due to malabsorption)
—> **Leukocytosis (inflammation, infection)
—> **Eosinophilia (eosinophilic GE, neoplasms, allergy, collagen vascular diseases, parasites)
- Inflammatory markers
—> **ESR (suggestive of chronic inflammation)
—> **CRP (more acute) -
**Electrolytes, RFT
—> Na, K (can be low in malabsorption)
—> Ca, PO4 (low in Vit D deficiency)
—> **Albumin (low in active IBD / other protein-losing enteropathy) - Others
—> **ANA (+ve in IBD, other autoimmune diseases), **p-ANCA (+ve in UC), serum Ig levels (immunodeficiency)
—> **HIV (immunodeficiency)
—> **TSH
—> Glucose, Sucrose (DM)
—> Metformin
—> ***B12, Folate level
- Stool examinations
- **Culture + Microbiology (rule out infection)
—> **C. difficile toxin (pseudomembranous colitis, antibiotic-associated diarrhoea)
—> Aeromonas, Plesiomonas
—> Protozoan / Parasitic infection
—> Giardia
- ***Leukocytes —> Infective, Inflammatory cause
- ***Occult blood —> IBD, Cancers, Infective
- ***Faecal calprotectin —> IBD
- ***Fat —> Malabsorption, Maldigestion
- Na, K —> Osmotic diarrhoea (due to non-electrolytes), Secretory diarrhoea (due to electrolytes)
- pH —> <5.6 carbohydrate malabsorption
- Imaging
- **X-ray —> calcification chronic pancreatitis
- Barium meal —> non-specific diagnosis
- **SB follow through (SBFT) —> SB, ileal abnormalities in Crohn’s (e.g. **fistula, irregularities, **strictures, tumours)
- Barium enema —> colon cancer, polyp, mucosal diseases like IBD
- USG —> biliary tract obstruction, pancreatic disease
- ***CT / MRI Enterography (need to swallow contrast to distend SB) —> IBD complications - Endoscopy
- **OGD —> duodenal biopsy (Celiac, Whipple, Crohn’s)
- **Sigmoidoscopy / Colonoscopy —> obtaining mucosal biopsy —> IBD / opportunistic infections (e.g. CMV) / microscopic colitis
- SB enteroscopy / Capsule endoscopy (need to make sure patient does not have ***obstruction) - ***Biopsy
Faecal calprotectin
- 24kDa dimer of Ca binding proteins
- secreted by ***neutrophils
- indicates ***migration of neutrophils to intestinal mucosa
- ↑ in:
—> **Infective: Infectious diarrhoea
—> **Inflammatory: Crohn’s disease, UC
—> Cancer
—> some drugs (NSAIDs, PPI) - stable in room temperature
Stool fat excretion (24 hour)
rarely performed now
Normal:
- ***<9% of intake
Malabsorption / Maldigestion:
- >18g fat/day while on standard 100g fat/day diet (i.e. ***>18%)
- Malabsorptive states: <8g / 100g stool
- Maldigestive states: >8g / 100g stool (pancreatic insufficiency / biliary steatorrhoea)
Protein-losing enteropathy
Example:
- **IBD
- Tropical sprue
- Whipple’s disease
- **Allergic gastroenteropathy
- **Intestinal lymphangiectasia
- **Constrictive pericarditis (mesenteric congestion)
- Congenital hypogammaglobulinaemia
(Others:
- **Hypertrophic fold
- **Linitis plastica
- SB TB
- Lymphoma
- ***SLE (mucositis) (CL Lai))
Diagnostic workup:
1. ***Labeled human serum albumin scan
- localisation of source (see where protein is leaking from GI tract)
- ***Faecal α1-antitrypsin concentration (↑ in protein loss)
- suggestive of excessive GI protein loss - ***Serum α1-antitrypsin clearance (↑ clearance suggests excessive GI protein loss (Web))
- ***Colonoscopy
MR Enterography
- assess SB mucosal **inflammation, **fistula, *abscess, stricture (in IBD)
- advantage: radiation free (good for young patient)
Management of Chronic diarrhoea
- Specific treatment
- direct to cause of disease - Supportive treatment
- **Anti-diarrhoeals
- **Octreotide (for endocrine secreting causes e.g. VIPoma, Carcinoid syndrome) —> Octreotide/Lanreotide inhibit secretion of GI peptide e.g. gastrin, secretin, motilin etc. —> important for digestion + GI movement
- **Bile acid binding resin (bile salt-associated diarrhoea after cholecystectomy)
- **Intraluminal absorbants e.g. Charcoal
- Bismuth compounds
- Antibiotics? (sometimes useful, esp in bacterial overgrowth)
Management of Malabsorption / Maldigestion
- Dietary supplements
- Ca, Mg, Fe
- Vit A, D, K, B12, Folate - Anti-diarrhoeal agents
- **Cholestyramine (bile acid-related diarrhoea)
- **Lomotil (Diphenoxylate / Atropine), ***Imodium (Loperamide) - Pancreatic enzymes supplements
- ***Pancreatin - Enteral / Parenteral supplementation
- not common except in short bowel syndrome
***Irritable bowel syndrome
Clinical features:
1. **Abdominal pain (relieved by defaecation)
2. Change in bowel **frequency
3. Change in ***consistency
Functional disease: no gold standard of diagnosis (no endoscopy / blood test can make diagnosis, only based on ***clinical symptoms)
**Rome IV criteria:
- Recurrent abdominal pain, on average **>=1 day per week in last ***3 months
- Associated with >=2 of following:
1. Related to defaecation
2. Change in frequency of stool
3. Change in form (appearance) of stool
(- For last 3 months with symptom onset >=6 months before diagnosis)
Epidemiology:
- 25% population (Rome 1, 2 criteria)
- 4-5% population (Rome 4 criteria)
Pathophysiological features:
1. Brain-gut axis
2. Autonomic nervous system problem
3. Altered bowel motility (motor)
4. Visceral hypersensitivity (sensory)
5. Psychosocial factors
6. Neurotransmitter imbalance (serotonin)
IBS subtypes
- IBS with diarrhoea (IBS-D)
- ***loose / watery stool >=25%
- hard stool <25% - IBS with constipation (IBS-C)
- loose / watery stool <25%
- ***hard stool >=25% - Mixed IBS (IBS-M)
- hard stool >=25%
- loose / watery stool >=25%
- ***alternating - Unsubtyped IBS
- insufficient abnormality of stool consistency to meet criteria for IBS-C, D, M
Features ***against IBS
History
1. **Weight loss
2. Rectal **bleeding
3. Onset in ***older patients
4. Family history of CA colon / IBD
Investigations
1. Positive faecal occult blood
2. Anaemia
3. **↑ WBC
4. **↑ ESR, CRP
5. Abnormal biochemistry (HypoK, HypoCa)
***Management of IBS
Multi-faceted approach
1. Education
2. Reassurance
3. Dietary modifications
4. Pharmacotherapy (for refractory case)
5. Psychological treatments
Medical treatment: Targets predominant symptoms of IBS
Abdominal pain
1. **Smooth muscle antispasmodics: Otilonium, Mebeverine
2. Peppermint oil
3. TCA: Amitriptyline, Desipramine
4. **SSRI: Citalopram, Paroxetine, Sertraline (slow onset, symptoms may worsen initially)
5. Chloride channel activator (Lubiprostone)
6. Guanylate cyclase C agonists (Linaclotide)
- Tend not to give Anticholinergic (Hyoscine) (∵ many SE)
Diarrhoea
1. **Opioid agonists (loperamide)
2. **Diet (Low FODMAP (fermentable oligo-, di-, mono- saccharides and polyols))
- FODMAP: ↑ osmotic pressure in gut + cause bacterial overgrowth + bloating + distension + diarrhoea
- avoid excessive fructose, fructans, sorbitol, raffinose
3. ***Bile salt sequestrants (Cholestyramine)
4. Probiotics
5. Antibiotics (Rifaximin) (oral, non-systemic, broad-spectrum antibiotic that targets gut and associated with low risk of bacterial resistance)
Constipation
1. **Psyllium
2. **PEG
3. Chloride channel activators (Lubiprostone)
4. Guanylate cyclase C agonists (Linaclotide)
***Inflammatory bowel diseases
- Ulcerative colitis (UC)
- Colon only (start from rectum)
—> **Proctitis (33%)
—> **Left-sided colitis (33%) (higher chance of malignancy)
—> **Extensive / Pan-colitis (33%) (higher chance of malignancy)
(- **Backwash ileitis (BWI): Inflammation in distal terminal ileum: caused by reflux of colonic contents where the entire colon is involved (web))
- **Continuous lesion
- **Mucosa + Submucosa confined (no deep penetration) - Crohn’s disease (CD)
- Whole GI tract (mouth to anus)
—> Ileocolonic (40-55%) (SB disease (SpC Medicine))
—> Colon only (20%)
—> Anoreactal (30-40%) (anal fistula, anal fissure, periproctitic and other abscesses)
—> Esophagus, stomach, duodenum (3-5%)
- **Skipped lesion
- **Mucosa to Serosa (full thickness)
(3. Indeterminate colitis (does not fit in UC / CD))
Epidemiology:
- ↑ worldwide incidence
- ↑ CD incidence
- ***unknown reason
—> NSAIDs, Infection, Antibiotics (depend on dose + timing), Western diet, Stress, Smoking (SpC Medicine)
Disease course:
Ongoing inflammatory activity —> Accumulation of ***bowel damage (stricture, abscess etc.)
***UC vs CD
UC:
1. Radiological
- Diffuse + Continuous
- **Rectosigmoid always involved (*start from rectum)
- No small bowel involved
- No skip lesion
- No stricture / fistula
- Endoscopic
- Hyperaemic mucosa
- ***Shallow ulcers
- Diffusely granular appearance - Histology
- Superficial inflammation
- Continuous involvement
- **Granuloma rarely seen
- **Goblet cell depletion
CD:
1. Radiological
- Patchy
- Rectosigmoid involved in 50%
- Usually SB, Terminal ileum involved
- Skip lesion (Regional enteritis (SpC Medicine))
- ***Stricture + Fistula (∵ deep penetration)
- Endoscopic
- Aphthous lesions
- **Solitary + Deep ulcers
- **Cobblestone appearance (scattered) - Histology
- **Transmural inflammation
- Patchy involvement
- **Granuloma common (DDx: ***TB small bowel)
- Goblet cells present
IBD patient characteristics
UC:
- ***older patients
- M:F = 1:1
- 3% family history
- longer duration of disease since diagnosis (117 months)
CD:
- **younger patients (at least 10 years younger)
- **more male (2:1)
- 3% family history
- shorter duration of disease since diagnosis (84 months)
***Causes of IBD
Generally unknown
1. Family aggregation of both UC, CD —> suggesting genetic basis in both diseases and partially sharing genetic basis
- cannot identify single gene accounting for IBD
- MHC genes (complicated for UC, CD)
- **NOD2 gene SNP8, 12, 13 (no effect for UC, **↑ for CD)
- other genes by linkage analysis (complicated for UC, CD)
- Environmental (diet, infection, antibiotics)
- smoking (protective for UC, ***↑ for CD (more severe as well))
- early appendicectomy in childhood (protective for UC, no effect for CD) - Immunological
- Gut microbiota (early change in gut microbiota)
CD: ***Vienna and Montreal classification
Location:
L1: Ileal
L2: Colonic
L3: Ileocolonic
L4: Isolated upper disease
Behaviour:
B1: Non-stricturing, non-penetrating
B2: **Stricturing
B3: **Penetrating (i.e. fistula formation)
p: perianal disease modifier
Clinical features of IBD (SpC Surg Interactive tutorial: IBD, SpC Medicine)
SpC Medicine:
Inflammation:
1. Abdominal pain, tenderness
2. Diarrhoea
3. Weight loss
Obstruction:
1. Cramps
2. Distension
3. Vomiting
Fistula (Enteroenteric, Enterovesical, Retroperitoneal, Enterocutaneous):
1. Diarrhoea
2. Pain
3. Air / Faeces in urine
SpC Surg:
Related to inflammatory damage in GI tract
1. Diarrhoea
2. Constipation (i.e. UC limited to rectum)
3. Pain / Rectal bleeding with bowel movement
4. Tenesmus
5. Abdominal cramps and pain
Extraintestinal manifestations
記: Joint, Skin, Eye
- **Arthritis, Peripheral arthropathy, **Spondylitis mimicking ankylosing spondylitis
- Biliary tract complications
- **Gallstones (∵ impaired bile salt reabsorption —> easier for cholesterol to precipitate)
- **Primary sclerosing cholangitis (PSC) (rare) (if concurrent UC + PSC —> much higher chance of ***malignancy) - Renal complications
- Kidney stones - Skin complications
- **Pyoderma gangrenosum (inflammatory skin disease where painful pustules or nodules become ulcers that progressively grow)
- **Erythema nodosum (inflammation of fat cells under the skin —> tender red nodules)
- ***Aphthous ulcers of mouth - Eye complications
- ***Uveitis
- Iritis
- Episcleritis
- Scleritis
Diagnosis of IBD
No single test / gold standard (no single endoscopy / blood test / biopsy) —> need combination
Diagnosed by
1. **Endoscopic
+
2. **Radiological
+
3. ***Pathological
+/-
4. Biochemical findings
- including focal, asymmetric, transmural, ***non-caseating granulomatous features
- have to rule out infection esp. **TB!!! (∵ can mimic CD; **CMV colitis can mimic UC; HIV can present with colitis features)
***Investigations of IBD
- CBC
- **anaemia (∵ bleeding, malabsorption)
- **↑ WBC - ***↑ CRP (+ ESR)
- Stool (to rule out **infection)
- WBC
- bacteria
- parasites (ova, cysts)
- **Faecal calprotectin - Serology
- CD: **ASCA +ve (Anti-saccharomyces cerevisiae Ab)
- UC: **p-ANCA +ve (Perinuclear antineutrophil cytoplasmic Ab) -
**Colonoscopy / Sigmoidoscopy + **Biopsy
- CD: **Granuloma
- UC: **Mucosal inflammation
—> involvement of GI tract, pattern, severity of inflammation, histology (to rule out infection)
—> chronic changes like glandular distortion + atrophy - Small bowel series
- CT / MR **enteroclysis / **enterography
- CT scan
- for diagnosis + complications (e.g. **perforation, **stricture, abscess)
***Treatment of IBD
- Induce remission during acute flare up
- Maintenance of remission
- Modification of clinical course
- ↓ Complications
- ↓ Surgery
- Improve nutritional status
- Cancer prevention (UC)
- Improve QOL
Medications:
1. **5-ASA (5-aminosalicylic acid) (Mesalazine, Sulfasalazine)
2. **Steroid
3. **Immunomodulators (Azathioprine)
4. **Biologics (e.g. Infliximab)
Traditional **Pyramid approach to therapy
Mild:
1. **Aminosalicylate (ASA) (e.g. Mesalazine, Sulfasalazine)
2. **Corticosteroid (Budesonide (suppository))
3. *Antibiotics (Metronidazole (SpC Medicine))
Moderate:
1. Corticosteroids
2. **TNF inhibitors
3. **AZA / 6-MP / *MTX
Severe
1. **TNF inhibitors
2. **Cyclosporine
3. Bowel rest
4. ***Surgery (CD for complications, for refractory UC who developed cancers)
*: CD only
Early intervention to prevent disease progression
- 5-aminosalicylic acid (5-ASA)
Indications:
- mild - moderately severe UC / colonic CD
- maintenance of remission
MOA:
- Local anti-inflammatory action
- NOT absorbed —> Topically active anti-inflammatory agent for inflamed intestinal mucosa (SpC Medicine)
**Sulfasalazine (now rarely used)
- Sulfapyridine + 5-ASA
- break down by colonic bacteria —> active ingredient 5-ASA
- SE (Sulfapyridine): **skin rash, haemolysis, **neutropenia, **male infertility, pancreatitis
5-ASA analogues:
- ***Mesalazine, Olsalazine
- oral / enema / suppository
- Immunomodulators / Immunosuppressants
Azathioprine, 6-Mercaptopurine
Indications
- frequently relapsing disease
- ***steroid sparing effects
- fistulating CD
PK:
- delayed onset 3 months —> **NOT good for induce remission
- well tolerated
- SE 10%: **BM suppression, allergy, ***hepatotoxicity, pancreatitis
- Biologics
New treatment for IBD
Indications:
- **standard treatment not working
- fistulating disease
- **extraintestinal manifestations (e.g. pyoderma gangrenosum, uveitis)
- Anti-TNFα
- ***Infliximab
- Adalimumab (Humira)
- Certolizumab Pegol (Cimzia) - Anti-adhesion molecules
- Vedolizumab - Anti-cytokine molecules
- Ustekinumab - Blockade of downstream signaling (JAK pathway)
- ***Tofacitinib (SE: DVT (SpC PP))
Risks of Biologics:
- Infections: reactivation of **latent **TB / viral infection e.g. **Hep B flare
- Malignancy: **lymphoma
- ***Autoimmunity: haemolytic anaemia, lupus-like, anti-dsDNA, anti-ANA
(SpC Medicine:
Infusion Reactions:
- Usually can continue treatment and infuse at slower rate
- Cover with hydrocortisone 100mg iv before infusion
- Less common with Humira and Cimzia
- More injection site pain with Humira)
SE:
- Infection, multiple sclerosis, lupus-like reactions (common to all ant-TNFs)
- Higher risk of common bacterial infections, TB, Fungal infections
- Before commencement check:
1. **HBsAg
2. **QuantiFERON-TB Gold
3. ***CXR
- Treat abscess (antibiotics + drainage), withhold anti-TNF)
***Complications of CD
- ***Malnutrition
- malabsorption, maldigestion
- protein, calorie, vitamin deficiency
- poor intake, protein losing enterography, malabsorption -
Abscess, **Fistula
- extension of mucosal fissure and ulcer through bowel wall into extra-intestinal tissue
- abscess: peritoneal cavity
- fistula: adjacent viscera, bladder, vagina, abdominal wall (*enterocutaneous fistula) -
**Stricture, **Obstruction
- mucosal thickening ∵ active inflammation, scarring, adhesions, food impaction in a long-standing stricture - Perianal disease
- perianal abscess, perianal fistula, anal fissures
(5. CRC in Colonic CD)
***Complications of UC
-
**Toxic megacolon
- Acute UC
- Diagnosed by plain AXR: **thumb printing (large bowel wall thickening)
- Clinical features of severe UC
—> **Fever >38oC
—> **HR >120
—> **Anaemia
—> **Low albumin
—> **Abdominal pain
—> **Diarrhoea
- Exclude co-existing **C. difficile / **CMV infection
- Treatment:
—> **Bowel rest
—> **TPN
—> **Fluid + electrolyte replacement
—> **IV corticosteroid
—> Close monitoring
- Outcome: ~50% respond to medical treatment, 50% go to urgent colectomy if not respond in 3-7 days
(Pathophysiology (Web + Davidson):
- NO released by neutrophils paralyse GI tract muscle —> dilatation —> bacterial toxins pass freely across diseased mucosa into portal then systemic circulation)
- ***CRC
Malignancy
- Moderately ↑ risk of colon cancer in patients with **UC (+ **Colonic CD)
- Extensive UC: ***8-10 years after onset
- Limited / Left side UC: ***10-15 years
- Need regular **endoscopic surveillance in long-standing disease
—> **NOT polypoid in appearance
—> Inflammatory cancers - Higher risk in patients with concurrent ***primary sclerosing cholangitis (PSC) (require annual surveillance colonoscopy)
Surgical therapy
- > 50% of CD require surgery during life time (e.g. ***abscess drainage, bowel resection)
- Not curative for CD, disease recurs close to the anastomosis
- Try to preserve as much gut as possible (to avoid short bowel syndrome)
- Much lower colectomy rate for UC (4-5% at 10 years, mainly for **toxic megacolon / **CRC)
Indications:
- severe bleed, perforation, stricture, fistula, abscess, failed medical treatment, risk of cancer
- Resection of diseased intestine
- ***Strictureplasty
- ***Colectomy / Proctocolectomy
SpC Interactive tutorial (Surg): IBD
Epidemiology of IBD
- Crohn’s disease (CD): **Patchy + **Transmural inflammation, which may affect any part of GI tract
- Ulcerative colitis (UC): **Diffuse + **Mucosal inflammation limited to colon
- Indeterminate: Fail to be classified between UC vs CD
Incidence:
1. Age
- CD: in the third decade
- UC: between third and seventh decade
- Gender
- CD: F>M (M>F in East Asia)
- UC: F=M
Prevalence:
- CD: urban > rural areas, higher socioeconomic classes
East vs West:
- More male prevalence with CD, ileocolonic CD
- Less family clustering
- Lower rates of surgery (5-8%)
- Fewer extraintestinal manifestations
- Less primary sclerosing cholangitis with UC
- Higher rates of penetrating and perianal disease CD
History taking, P/E, Investigation in IBD
History:
- Bowel symptoms
- **Medications
- **Surgery (esp. in CD)
- Immunization status (e.g. TB, HBV —> for future initiation of immunosuppressants)
P/E:
- General and abdomen
- Perianal region: skin tags, fissures, fistulas, abscess, PR exam (e.g. rectal stricture)
- Extraintestinal inspections: mouth, eyes, skin, joints
Investigations:
Laboratory tests
1. Blood tests: CBP, **CRP, **ESR, albumin, ferritin
2. **p-ANCA (UC)
3. **ASCA (CD)
4. Hepatitis serology, HIV, TB testing (for future initiation of immunosuppressants)
5. Stool examination: culture, **Cl. difficile toxin, **calprotectin
Imaging and endoscopy
1. Contrast study
- Follow through (Serial X-ray): check any obstruction
- Enema: check mucosa appearance
- Colonic (UC/CD)
- ***Colonoscopy
- Sigmoidoscopy (for severe active disease) - Small bowel (CD)
- ***MR enterography (MRE) / CT enterography (CTE)
- Small bowel capsule endoscopy (SBCE)
- Single or double balloon enteroscopy - Foregut symptoms (CD)
- ***OGD - Perianal (CD)
- ***MRI anal canal
(Calprotectin:
- Neutrophil-derived protein, 60% of neutrophil cytosol
- Most sensitive marker of intestinal inflammation in IBD
- Well correlated well with endoscopic disease activity
- Predict disease relapse, postop relapse)
Treatment of IBD
Medical treatment (Main treatment):
- Induce clinical **remission
- **Prevent complications
- Maintain medically + surgically remission
Surgery for UC:
- ***Cure for disease (∵ UC confined to colon)
- Laparoscopic surgery feasible
Surgery for CD:
- **NOT a cure
- To deal with **complication only
- Conservative + minimum resection
- Extended resection do NOT reduce recurrence
Surgery for UC
Emergency surgery indications:
1. **Acute severe colitis failing medical treatment
2. **Toxic megacolon >6cm
3. Perforation
4. Severe bleeding
Elective surgery indications:
1. Chronic colitis with severe symptoms
2. Steroid dependent
3. Recurrent attacks
4. ***Dysplasia / Cancer
5. Extra-intestinal manifestation
Acute severe colitis in UC / CD
- 20% UC, 5-10% Crohn’s colitis
ECCO and ACG guidelines:
- ***>=6 Bloody stools/day + at least one of the followings:
—> Fever (37.8℃)
—> Tachycardia
—> Anaemia (<10.5g/dl)
—> Raised CRP
Investigation:
- AXR
- CT abdomen + pelvis
Treatment:
1. Steroid +/- anti-TNF (≥ D5)
2. Colectomy (if medical treatment fail)
***Colectomy
Indication:
1. Failure of toxic dilation to respond to 48 hours therapy
2. Deterioration despite optimal treatment
3. Patient choice
Risk for need of colectomy (w/o 2nd line therapy):
- 24 h stool frequency > 8
- stool frequency 3-8 + CRP > 45 mg/L
Emergency surgery:
1. **Total abdominal colectomy + **End ileostomy
—> Rectum left untouched
—> **2nd stage operation when patients are stable
—> Completion **proctectomy +/- ***IPAA (Ileal pouch-anal anastomosis) (join ileum to anal canal)
Elective surgery:
1. Restorative **proctocolectomy + **IPAA (Ileal pouch-anal anastomosis)
- Laparoscopic / Conventional
- Suitable candidate for laparoscopic surgery
- Need temporary + protective ileostomy (to rest the bowel after surgery)
- Stapled / Hand-sewn
- Pouch complications
-
**Total colectomy + **IRA (Ileorectal anastomosis)
- If rectum not inflamed
- Preserve fertility in female patients (∵ proctectomy can cause adhesion / damage to nerve) - With permanent end ileostomy
- If short mesentery, CA rectum involving sphincters
Surgery for CD
- Rarely curative but lead to long-lasting remissions in some patients
Indications:
1. **Complications treatment
- **Stricture
- **Abscess
- **Fistula
- Perforation / bleeding
- Severe CD **refractory to medical treatment
- **Crohn’s disease activity index (CDAI) >450
- ***Harvey Bradshaw Index (HBI) >15 - ***Ileocolic CD
- Low threshold for surgery
Small bowel stricture
2 types:
1. Inflammatory
- ***Medical therapy
- Fibrostenosing (after repeated attacks of inflammation):
- ***Strictureplasty preferred
—> Heineke–Mikulicz strictureplasty (for short strictures <10cm)
—> Finney strictureplasty (intermediate stricture 10-20cm)
—> Michelassi (side-to-side) strictureplasty (long stricture 20-25cm)
- Resection (only if suspect malignancy / isolated stricture)
- Endoscopic dilatation (if can access stricture through enteroscopy)
Abdominal fistula
2 types:
1. ***Internal fistula
- Entero-enteric: no surgery if asymptomatic
- Entero-colic fistula: diarrhoea (may end up malnutrition)
- ***External fistula
- Entero-cutaneous
- Entero-vesical: pneumaturia, faecaluria
- Entero-vaginal
Enterocutaneous fistula: Treatment
**“SNAP”
1. **Sepsis control
- Abscess drainage
- Antibiotics
- ***Nutrition support
- High vs Low output (e.g. High fistula may cause malnutrition)
- Nutritional assessment + support - ***Anatomy
- CT / MR enterography - ***Procedure
- Medication adjustment (e.g. immunosuppressant / biologics may cause surgical wound infection)
- Closure with biological agents
- Enbloc resection involved bowel + fistula
Ileocaecal CD
- ***80% ileocaecal CD require surgery
- An alternative to medical Tx in the early disease course
Treatment:
1. Laparoscopic ileocaecal resection
- Technically more difficult
—> adhesion due to inflammation
—> phlegmon (localised inflamed soft tissue)
—> shortened mesentery
- Reduction of adhesive bowel obstruction
- Can consider to stop medical Tx after one year of remission
Perianal CD
- 24.5% of patients with Crohn’s disease
- ***83% required surgery
- ***More complicated courses of fistula tract (∵ most are extra / suprasphincter fistula)
- **MRI pelvis + **EAUS (Endoanal Ultrasound) necessary to document before the definite treatment
Treatment:
1. **Anti-TNF (Infliximab) +/- **AZA
Abscess:
2. **Antibiotics
- **Metronidazole/ciprofloxacin
3. ***Abscess drainage
Fistula:
4. Simple fistula (Inter / Low transphincteric) —> **Fistulotomy
5. Complex fistula
- **Seton insertion for drainage
- Azathioprine
- Biologics
6. ***Colostomy / Proctectomy
Algorithm:
Antibiotics + AZA
—> EUA +/- Abscess drainage +/- Seton
—> Infliximab 5mg/kg at 0, 2, 6 weeks
—> Remove Seton at 6 weeks
—> Continue Infliximab 8-weekly
—> MRI pelvis
—> Complete response: Stop Infliximab + Continue AZA
—> Partial response: Continue Infliximab, reassess 6-monthly
—> No response: Surgical intervention
Biologics for CD
Anti-TNF (may develop resistance after prolonged use —> need to switch to other class):
1. Infliximab (1st gen) (IV)
2. Adalimumab (2nd geb) (SC (i.e. can do at home by patient))
3. Certolizumab pegol (SC)
Anti-integrin:
1. Vedolizumab (IV)
Anti-IL12/23 Ab:
1. Ustekinumab (IV then SC)
IBD-associated CRC
- Incidence of CRC in IBD: 18% after 30 years of colitis
Pathogenesis:
- Colitis —> Dysplasia —> Carcinoma
Risk factors:
1. Patient
- History of **PSC
- History of **colorectal neoplasia
- Family history of CRC
- Smoking
- Disease
- Duration
- Extent
- Cumulative inflammatory burden
- Active inflammation endoscopically / histologically - Endoscopic features
- Stricture
- Shortened tubular colon
- Pseudopolyps
∵ The cancer do not develop from polyp —> only develop from flat lesion —> need dye to coat dysplastic mucosa
***Chromoendoscopy:
- SCENIC endoscopic classification of superficial colorectal dysplasia in IBD
- Visible dysplasia 90%
- Invisible dysplasia 10%
(Even if no visible dysplasia —> still take biopsy to rule out Invisible dysplasia)
Management of dysplasia:
1. Endoscopically visible dysplasia
- Polypoid: **polypectomy
- Non-polypoid: **endoscopic resection (EMR / ESD) if complete resection possible
- ***Surgery should be considered if not endoscopically feasible
- Endoscopically invisible dysplasia
- Associated with high rate of CRC
- Referred to an experienced endoscopist
- If Low grade dysplasia / No dysplasia
—> 5% LGD changed to HGD or CRC
—> Surveillance or surgery?
- If invisible HGD or multifocal LGD —> surgery should be offered
Guideline for surveillance colonscopy:
1. AGA guideline 2010
2. BSG guideline 2010
