Inflammatory Bowel Disease

Question 1

Notes on thiopurine metabolism (azathioprine)

Answer 1

• Before starting should check TPMT → identifies rare poor metabolisers; gives a guide to starting dose but even normal activity does not preclude leucopaenia
• Target ranges:
  
  • TGN → 235- 450 (>235 = steroid free remission in 65%, >450 = myelotoxicity risk but can occur at any concentration)
  • 6MMP >5700: increased risk hepatic/myelotoxicity

Question 2

Notes on therapeutic drug monitoring for azathioprine

Answer 2

Shunters:

• 6MMP/6TGN ratio >20: therapeutic 6TGN unlikely to be achieved with dose increase
• Reduce thiopurine dose to 25-50% and add allopurinol 50-100mg (xathine oxidase inhibitor); reverses shunting with preference for 6TGN production
• Also potential use in reducing side effects

Question 3

Side effects of azathioprine

Answer 3

• 25% intolerance - mostly nausea
• Cytopaenias and hepatitis
• Non-melanoma skin cancer (even after discontinuation)
• Cervical dysplasia
• Lymphoma - higher with combo therapy with TNF inhibitor
• Serious infections (particularly in combo with anti TNF → combo reduces IBD related infections but increases opportunistic infections)

Question 4

Notes on microscopic colitis

Answer 4

• Female predominance
• Symptoms can be aggravated by medications - aspirin, PPIs, NSAIDs,
• 3 subtypes based on histological features
  
  • Collagenous
  • Lymphocytic
  • Incomplete
• Subendothelial bands of collagen on biopsy
• Treatment → budesonide

Question 5

Extra-intestinal manifestations of inflammatory bowel disease associated with disease activity

Answer 5

1. Large joint arthritis
2. Oral ulcers
3. Erythema nodosum
4. Episcleritis

Question 6

Extra-intestinal manifestations of inflammatory bowel disease independent of disease activity

Answer 6

1. Ankylosing spondylitis
2. Uveitis
3. PSC
4. Pyoderma gangrenosum
5. Kidney stones
6. Gallstones

Question 7

Notes on aminosalicylates

Answer 7

• Topical anti-inflammatory
• Used in the induction and maintainence of ulcerative colitis
• Potential benefit in reducing risk of colorectal cancer
• Sulphasalazine
  
  • 5-ASA linked to sulfapyridine via an azo bond (cleaved by colonic bacteria). Sulfapyridine functions as a carrier molecule to achieve colonic delivery → also largely responsible for dose dependent adverse events (10-45%)
• New 5ASA delivery systems → sulfa moiety done away with
  
  • Mesalazine
    
    • Pentasa → released in distal ileum/right colon
    • Asacol → more released in distal colon