Week 4: inflammatory bowel disease

Question 1

Definition of inflammatory bowel disease

Answer 1

• chronic inflammatory condition of the GI tract characterized by relapsing course
• two subtypes: Crohn’s disease and ulcerative colitis

Question 2

Epidemiology of IBD

Answer 2

• peak age onset 15-30 yo and 50-60 yo

- Caucasians in industrialized countries

Question 3

Pathogenesis of IBD

Answer 3

1. genetic predispositions: familial risk and genes identified by GWAS involved in innate immunity, epithelial barrier, t-cell regulation
2. environment
3. immune dysregulation
   - persistent infection with pathogen
   - defective innate immunity w/ loss of mucosal barrier
   - dysregulated response to normal luminal antigens

Question 4

Distribution of disease: UC vs Crohn’s

Answer 4

1. UC
   - colon only, rectum almost always involved
   - inflammation limited to mucosa
2. Crohn’s
   - anywhere from mouth to anus, with terminal ileum most common
   - transmural: cobblestoning, deep ulcers
   - complications: strictures, perforation, fistulas

Question 5

Common symptoms of IBD: UC vs crohns

Answer 5

1. Crohns
   - ab pain, diarrhea, weight loss, perianal fistula, growth failure in children
   - mouth ulcers, perianal abnormalities such as fistulas, abscesses, anal tags, fissures
2. UC
   - diarrhea, rectal bleeding and mucus in stools, tenesmus (feeling of incomplete defecation), weight loss
   - Always have BLOODY Diarrhea

Question 6

Extraintestinal manifestations of IBD

Answer 6

1. MSK: common
   - peripheral arthritis
   - sacroilitis
   - ankylosing spondylitis
2. Derm
   - erythema nudism
   - pyoderma gangrenosum
3. Ocular
   - uveitis, scleritis, episcleritis
4. biliary
   - cholelithiasis (CD only)
   - primary sclerosing cholangitis
5. Misc
   - nephrolithiasis (CD only)
   - anemia, thromboembolism
   - -Parallels IBD activity: peripheral arthritis type 1, sacroilitis, Ankylosing spondylitis
   - -Indep.: peripheral arthritis type II, pyoderma

Question 7

Evaluation of IBD

Answer 7

1. Lab tests
   -CBC, ESR, Crp, albumin, stools for Oand P, C difficil
2. Radiology
   -not necessary if diagnosis is clear from endoscopy
   may be useful for complication or small bowel
3. Endoscopy
   -UC: continuous pattern, rectal involvement
   -crohns: rectal sparing, patchy colitis, cobblestoning, deep ulcers, ileal ulcers

Question 8

Toxic megacolon

Answer 8

• dilation of colon> 6cm
• 3 of: fever, tachycardia, high wbc, anemia
• any 1 of: dehydration, electrolyte abn., hypotension, altered mental status
• surgical emergency

Question 9

Complications of IBD

Answer 9

1. UC
   - massive hemorrhage, toxic megacolon, colonic perforation, malignant stricture
   - colorectal cancer
   - cholangiocarcinoma
   - anemia
2. CD
   - stenosing type obstruction
   - perforating: fistula, abscesses
   - inflammatory: malabsorption, cancer

Question 10

Treatment for UC

Answer 10

1. mild: mesalamine, sulfasalazine (mechanism: possible inhibition of COX/lipoxygenase pathways and disruption of transcription of inflammatory mediators)
2. moderate: steroids, 6MP/AZA. Patients generally respond to first dose of steroids, but 1 year later, some become dependent and others need surgery. Only good for short term.
   - azathioprine and 6-MP are purine analogs that affect rapidly proliferating cells.
3. severe: surgery, biologics
   - monoclonal antibodies against TNFa
   - vedolizumab: targets intern
   - total protocolectomy with end ileostomy or illegal J pouch

Question 11

Treatment for Crohn’s disease

Answer 11

Opposite of approach to UC. Aggressive treatment initially is beneficial

1. early: mesalamine, budesonide (locally active steroid in distal ileum and right colon)
2. combo therapy: Biologics, 6MP/AZA
   - side effects: opportunistic infection with Hep B and Tb
   - early use of this combo therapy is increasingly recommended
3. Late: steroids, surgery

Question 12

Ulcerative colitis- pathology

Answer 12

1. site of involvement: rectum (95%)/rectosigmoid. diffuse involvement, total colon involvement less frequent that Crohns. Ileum not involved, though there may be backwash ileitis.
2. Gross
   - acute: diffuse hyperemia with superficial ulcers
   - inflammatory pseudopolyps
   - chronic: mucosa is flat and atrophic. No thickening of wall.
   - complications: toxic megacolon, perforation
3. Micro
   - inflammation restricted to mucosa. No granulomas
   - acute: crypt architecture distortion, cryptitis, crypt abscess, ulceration
   - chronic: crypt atrophy, distorted architecture with branching, mild inflammation
4. increased risk for colon acne

Question 13

Crohn’s disease- pathology

Answer 13

1. site of involvement
   - combined ileal+ colon most common
   - may involve any part of GI tract
   - peri-anal lesions
2. Gross
   - segmental involvement with skip lesions
   - acute: hyperemia, ulceration
   - mesenteric fat wraps bowel wall “creeping fat”
   - cobblestoning: longitudinal ulcers separated by irregular islands of edematous mucosa
   - chronic: affected segment thickened and rigid “lead pipe”
   - narrowed lumen with strictures
3. Micro
   - transmural inflammation
   - cryptitis, crypt abscess and normal appearing mucosa (skip areas)
   - deep fissure ulcer, +/- fistula
   - epithelioid granulomas
   - regional lymph nodes enlargement
4. increased risk for adenocarcinoma