Ulcerative Colitis (UC)

Question 1

List some DDx for a presentation of:

• bloody and mucous diarrhoea (6/52)
• prev episode 1 yr ago

Answer 1

PDx. IBD (most likely UC)
DDx.
- AI- CD, coeliac
- Vascular- ischaemic colitis 
- Infective: bacterial (shigella, salmonella, E coli), viral (norovirus, rotavirus)
- Inflammatory: pseudomembranous colitis (C diff from abx), diverticulitis 
- Neoplastic: CRC (L sided)
- Psych: laxative abuse, IBS

Question 2

What investigations would you do?

Answer 2

Diagnostic:
- Endoscopy/colonoscopy and biopsy
Bedside
- PR
- ECG (electrolytes, arrhythmia)
- Stool MCS, OCP, C diff toxin test, faecal calprotein (indicate neutrophil migration)
Labs:
- CRP/ESR
- FBC
- EUC
- Nutritional markers: Fe, Ca, Mg, folate, vit A, vit E, vit B12, zinc
- LFTs: primary sclerosing cholangitis
- blood culture
- coag panel: INR/aPTT
- AI panel: P-ANCA (70% UC), ASCA (CD +ve)
- Coeliac Abs (anti-endomesial, anti-transglutaminase Abs)
Imaging:
- AXR: loss of haustra, toxic megacolon, no faecal shadows, colonic dilation

Question 3

If she just took antibiotics recently, how might that affect you Dx?

Answer 3

Consider pseudomembranous colitis secondary to Clostridum difficile infection

• C diff: GP rods, anaerobic, spore-forming, releases toxins (enterotoxin and cytotoxin to damage large bowel tight gap junctions)
• clinical: abdo pain, fever, secretory diarrhoea, perforation
• abx disrupt normal bowel flora
• causative abx: cephalosporin, penicillin, clindamycin
• Rx. Metronidazole or Vancomycin

Question 4

Compare UC and CD?

Answer 4

UC:
Location: continuous inflammation from rectum of colon, possible ileitis backwash
Invasion: mucosal and submucosal
Histo: crypt abscesses (more), pseudopolyps (regenerating mucosal bulge), granulation tissue in ulcer craters, fibrosis, inflam cells (neutrophils, lymphocytes, macrophages)
Complications: toxic megacolon -> perforation CRC (more), bleed, perianal abscess, malnutrition, electrolyte imbalance, medication SE

CD:
Location: skin lesions, non-continuous ulceration from mouth to gut (esp ileum and caecum)
Invasion: transmural
Histo: non-caseating granulomas, cobble-stone appearance (healthy tissue becoming stones rising above longitudinal/ transverse ulceration), distinct margin between inflamed and normal, crypt abscesses, fat creeping around serosa, thickened bowel wall, strictures (healing fibrosis), villus blunting, mucosal metaplasia, inflam cells
Complications: strictures, obstruction, fistula (enterocutaneous, enterovesical, etc), perforation, CRC, malabsorption (B12, folate, Fe, bile acids), malnutrition, electrolyte imbalance, medication SE

Question 5

List some extra-intestinal SE of IBD?

Answer 5

• Skin/nails: erythema nodosum, clubbing, perianal skin tags, psoriasis
• Ocular: conjunctivitis, iritis, uveitis, scleritis
• Mouth: apthous ulcer
• Joints: peripheral arthritis (seronegative), ankylosing spondylitis, osteoporosis (low Ca due to fat malabsorption)
• Hepatobilary: cholesterol stones, primary sclerosing cholangitis
• Renal: kidney stones (oxalate precipitate)
• Vascular: PE, DVT, vasculitis
• Haem: vit deficiency (B12), AI haemolytic anaemia

Question 6

Compare the X-ray findings of UC and CD?

Answer 6

UC:
- no faecal shadows
- colonic dilation
- toxic megacolon (dilation >6cm)
- mucosal thickening
- lead pipe appearance (loss of haustra)
- colon shortened
CD:
- fat stranding
- strictures -> string sign (terminal ileum)

Question 7

How would you manage UC?

Answer 7

Active colitis: Sulfasalazine
- add rectal corticosteroids
Mild/mod UC: add oral corticosteroids
Severe UC: Aziathioprine
- if cannot tolerate: Methotrexate, Infliximab
Severe acute UC: IV hydrocortisone 

Surgical bowel resection- not CD (skin lesion)

Question 8

Describe the MA and SE of Methotrexate?

Answer 8

Methotrexate: DMARD
MA:
- cytotoxic: inhibits hydrofolate reductase -> inhibits DNA
- immunosuppressive: inhibits purine metabolism -> adenosine accumulation -> inhibits T cell activation, B cell down regulation, IL1 inhibition

Question 9

Describe the MA and SE of Aziothoprine?

Answer 9

Aziothoprine: immunosuppressant
MA: alters purine synthesis -> decreased cellular proliferation -> impaired cellular immunity -> reduced inflammation
SE: pancreatitis, myelosuppression, alopecia, diarrhoea, mouth ulcers, oesophagitis

Question 10

Describe the MA and SE of Infliximab?

Answer 10

Infliximab (TNFa inhibitor)
MA: binds to TNF alpha receptors -> inhibition of overall inflammatory response
SE: delayed hypersensivity, serum sickness (type 3 hypersensitivity to foreign protein)