IBD

Clinical Features

• Abdominal pain and diarrhea (75%) and recurrent fever (50%).
• Usually more indolent onset than UC.
• Other symptoms depend on area of involement.
  • Small Bowel - Malabsorption, malnutrition
  • Colon - Colonic Bleeding, Diarrhea
  • Peri-anal Disease - Abscesses, Fistulas, Fissures - 25%
• Complications

  • Intestinal Obstruction	Malabsorption, malnutrition
    Fistulas	- Peri-anal Fistulas, enteral-enteral, entero-vesicular,   entero-vaginal, entero-cutaneous - Painless --> to abscess formation.
    Perforation	Uncommon
    Abscesses	Pain, fevers
    Polyps	Can have clusters

•  
• Defining Features:
  • Transmural Inflammatory Disease
    • Involves all layers of the bowel wall. (Thickened bowel).
  • Discontinuous Involvement
    • Inflammation areas are separated by areas of normal bowel.
  • Other Features:
    • Mesenteric lymph nodes are frequently enlarged
    • Intestinal lumen is narrowed by inflammation and fibrosis.
    • Nodular swelling, firbosis, and mucosal ulceration lead to "cobblestone" apperance. 
    • Since inflammation is transmural, fustulas can form, and can fistulize with blatter, bowel, uterus, vagina, skin.   Lesions at distal rectum and anus can form perianal fistulas. 
    • Noncaceating granulomas often form in submucosa.  
           (Presence of granulomas = strong predictor for CD, but half of CD doesn't have it.)
• Involement:
  • Anywhere mouth to rectum.

  • Location
    Ileum and Cecum	50%
    Only Small intestine	15%
    Only Colon	20%
    Mainly Anorectal Region	15%
    Upper GI	<10%

• Increases small bowel cancer 3-fold, and predisposes to colorectal cancer.
• Complications:
  • Liver disease (Scerosing Cholangitis)
  • Cholelithiasis
  • Renal oxalate stones
  • Amyloidosis.
  • Eye (episcleritis, uveitis)
  • Medium-sized joints (Arthritis)
  • Skin (erythema nodosum)

Treatment

• Remission

1. Symptomatic Therapy (loperamide, acetaminophen)
2. Diet
   • Some role , need to be highly motivated.  Can help stunt growth, and puberty.
3. 5-ASA (mesalamine)
   • 5-ASA usually no role... maybe if really really mild case, can work. 
   • More helpful in UC (only affects mucosa, not transmural inflammation)
   • Most Crohn's is terminal ilium
4. Corticosteroids (budesonide, prednisone)
   • Only for remission (acute setting)
   • Usually steroid + immunomodulator, then taper steroid. 
5. Thiopurines
   • Azathioprine, 6-MP
   • Methotrexate + 1mg folic acid
     • If cannot tolerate thiopurines (i.e. pancreatitis, etc..)
     • Only effective in CD
6. Biologics
   • TNF-antagonists (infliximab, adalimumab)
     • Big push to start Anti-TNF therapy early (alone or with thiopurines) for flares [SONIC Study]
       • Classically usually started if steroids and immunomodulators aren't effective.
     • For flares and maintenance
   • Natalizumab (blocks lymphocyte recruitment to bowel)
     • If Anti-TNF therapy unsuccessful (or contraindicated).
     •  (not used often due to fear of progressive multifocal leukoencephalopathy due to JC virus infection).
     • Considered more aggressive than TNF-alpha
7. Experimental/ Surgery
8. Cipro+Flagyl  (Adjunctive Therapy)
   • Usually only if abscess or wound infection. (In past used very often)
   • Especially for colonic and peri-anal disease.
9. Surgery (last resort)
   • For refractory disease to resect diseased segment of bowel.
   • Consider if very focal area of bowel involved.
   • Peri-anal disease -> surgical drainage, and seton placement (rubber band through fistula orifice and out through anus to prevent further abscesses and heal fistula).
     • Anti-TNF very effective for peri-anal disease

• Remission Maintenance
  • Biologics (TNF-alpha inhibitors)
    • Excellent for remission maintenance
    • SONIC study --> clinical outcomes were better with mod-to-severe Crohn's treated aggressively with anti-TNF therapy (+/- azathioprine or 6MP) vs. azathiprine/6MP alone.
  • Aminosalicylates
  • Antibiotics (for fistulizing disease)
• Treatments:

  • Treatment	Notes
    Lifestyle/Diet	Smoking cessation - Enteral diet (aids in remission, but no change in natural hx) If excessive small bowel resection/involvement replace VitD, Ca, Mg, Zinc, Fe, B12 Loperamide (Immodium) > diphenoxylate (Lomotil) > codeine (cheap, works additive) avoid during flare-ups of colitis (toxic megacolon risk)
    5-ASA	Most evidence for mild colonic disease (controversial) Sulfasalazine (Salazopyrin): 5-ASA bound to sulfapyridine             (Intestinal bacterial hydrolyzes, releases 5-ASA -- efficady dose dependent) Mesalamine (Pentasa): coated 5-ASA releases 5-ASA in ileum and colon
    Antibiotics	For perianal Crohn's (metronidazole, cipro), relapses when stopped.
    Corticosteroids	Prednisone: 40mg OD for acute exacerbations, IV methylpred for severe            (No evidence for maintaining remission, masks intra-abdo sepsis)
    Immunosuppression	Most common: 6-mercaptopurine Azathioprine (Imuran) Methotrexate (less often) For maintenance (steroid sparing) Not for active flare Response in ~3mo Helps heal fistula (only simple ones), decrease disease activity.
    Biologics	Infliximab IV (Remicade) Adalimumab SC (Humira) Effective in fistulae and refractory CD. STUDY: first line infliximab+azathioprine more effective for remission than either alone.
    Surgery	For fistulae, obstruction, abscess, performation, bleeding, refactory. If <50% or <200cm of intestine --> short gut syndrome. Complications: <100cm resected --> watery diarrhea (impared bile salt absorption Tx: cholestyramine, andi-diarrheals (loperamide) >100cm resected --> steatorrhea (cannot absorb, bile salt deficiency) Tx: fat restriction, medium chain TGs

Evidence Base

• Starting with immunosuppressives + immunomodulators ("bottom-up approach") is more popular
  • Lancet 2008; 371;660-667
• Azathioprine + infliximab --> highest remission rate (NEJM 2010;362; 1383-1395)