GI & Hepatology JC067: Chronic Diarrhoea: Irritable Bowel Syndrome And Inflammatory Bowel Disease Flashcards

Question

***Investigations of IBD

Answer 1

1. CBC - ***anaemia (∵ bleeding, malabsorption) - ***↑ WBC 2. ***↑ CRP (+ ESR) 3. Stool (to rule out ***infection) - WBC - bacteria - parasites (ova, cysts) - ***Faecal calprotectin 4. Serology - CD: ***ASCA +ve (Anti-saccharomyces cerevisiae Ab) - UC: ***p-ANCA +ve (Perinuclear antineutrophil cytoplasmic Ab) 5. ***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 6. Small bowel series 7. CT / MR ***enteroclysis / ***enterography 8. CT scan - for diagnosis + complications (e.g. ***perforation, ***stricture, abscess)

Answer 2

1. Induce remission during acute flare up 2. Maintenance of remission 3. 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

Answer 3

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

Answer 4

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

Answer 5

New treatment for IBD Indications: - ***standard treatment not working - fistulating disease - ***extraintestinal manifestations (e.g. pyoderma gangrenosum, uveitis) 1. Anti-TNFα - ***Infliximab - Adalimumab (Humira) - Certolizumab Pegol (Cimzia) 2. Anti-adhesion molecules - Vedolizumab 3. Anti-cytokine molecules - Ustekinumab 4. 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)

Answer 6

1. ***Malnutrition - malabsorption, maldigestion - protein, calorie, vitamin deficiency - poor intake, protein losing enterography, malabsorption 2. ***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) 3. ***Stricture, ***Obstruction - mucosal thickening ∵ active inflammation, scarring, adhesions, food impaction in a long-standing stricture 4. Perianal disease - perianal abscess, perianal fistula, anal fissures (5. CRC in Colonic CD)

Answer 7

1. ***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) 2. ***CRC

Answer 8

- 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)

Answer 9

- >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 1. Resection of diseased intestine 2. ***Strictureplasty 3. ***Colectomy / Proctocolectomy

Answer 10

1. Crohn's disease (CD): ***Patchy + ***Transmural inflammation, which may affect any part of GI tract 2. Ulcerative colitis (UC): ***Diffuse + ***Mucosal inflammation limited to colon 3. Indeterminate: Fail to be classified between UC vs CD Incidence: 1. Age - CD: in the third decade - UC: between third and seventh decade 2. 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

Answer 11

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 2. Colonic (UC/CD) - ***Colonoscopy - Sigmoidoscopy (for severe active disease) 3. Small bowel (CD) - ***MR enterography (MRE) / CT enterography (CTE) - Small bowel capsule endoscopy (SBCE) - Single or double balloon enteroscopy 4. Foregut symptoms (CD) - ***OGD 5. 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)

Answer 12

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

Answer 13

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

Answer 14

- 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)

Answer 15

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 2. ***Total colectomy + ***IRA (Ileorectal anastomosis) - If rectum not inflamed - Preserve fertility in female patients (∵ proctectomy can cause adhesion / damage to nerve) 3. With permanent end ileostomy - If short mesentery, CA rectum involving sphincters

Answer 16

- Rarely curative but lead to long-lasting remissions in some patients Indications: 1. ***Complications treatment - ***Stricture - ***Abscess - ***Fistula - Perforation / bleeding 2. Severe CD ***refractory to medical treatment - ***Crohn’s disease activity index (CDAI) >450 - ***Harvey Bradshaw Index (HBI) >15 3. ***Ileocolic CD - Low threshold for surgery

Answer 17

2 types: 1. Inflammatory - ***Medical therapy 2. 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)

Answer 18

2 types: 1. ***Internal fistula - Entero-enteric: no surgery if asymptomatic - Entero-colic fistula: diarrhoea (may end up malnutrition) 2. ***External fistula - Entero-cutaneous - Entero-vesical: pneumaturia, faecaluria - Entero-vaginal Enterocutaneous fistula: Treatment ***"SNAP" 1. ***Sepsis control - Abscess drainage - Antibiotics 2. ***Nutrition support - High vs Low output (e.g. High fistula may cause malnutrition) - Nutritional assessment + support 3. ***Anatomy - CT / MR enterography 4. ***Procedure - Medication adjustment (e.g. immunosuppressant / biologics may cause surgical wound infection) - Closure with biological agents - Enbloc resection involved bowel + fistula

Answer 19

- ***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

Answer 20

- 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

Answer 21

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)

Answer 22

- 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 2. Disease - Duration - Extent - Cumulative inflammatory burden - Active inflammation endoscopically / histologically 3. 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 2. 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