5. Causes of IBD
• Genetic predisposition?
• Infectious organisms?
• Immune mechanisms
o Immunosuppressive agents used in treatment
o Autoimmune phenomena accompany IBD
• Psychological mechanisms
o IBD may flare in association with stress
o Characteristic personality
8. Ulcerative Colitis
• Inflammatory reaction involving primarily
colonic mucosa
• Colon appears ulcerated, hyperemic
• Inflammation is uniform and continuous, with
no intervening areas of normal mucosa.
• Rectum usually involved (95%) and extends
proximally
9. UC Clinical Features
• Major symptoms:
o Bloody diarrhea/constipation
o Abdominal pain
o Weight loss
o Fever
10. UC Manifestations/Complications
• Physical findings (nonspecific)
o Tenderness along colon
• Extracolonic manifestations
o Anemia of chronic disease + Fe deficiency
o Leukocytosis, left shift
o Electrolyte abnormalities
o Hypoalbuminemia
• Colon CA
• Toxic megacolon
• Hemorrhage
11. UC Clinical Course
• > 50% will relapse within 1 year (may be
prolonged remissions)
• Severity of symptoms reflects intensity of
inflammation
• Rectal involvement-major symptoms rectal
bleeding, tenesmus
• 85% have mild to moderate disease
• 15% disease involves entire colon
12. UC Characteristic Appearance of
Colon
• Smooth “lead pipe” appearance
radiographically
• “Pseudopolyps”: Inflammatory, not neoplastic
resulting from regenerating mucosa
surrounded by ulceration
• Dysplasia may influence decision for
colectomy
13. Crohn's Disease
• Inflammation extending through all layers of
intestinal wall
• Involves entire digestive tract, especially distal
ileum, colon, anorectal area
14. Crohn's Disease Clinical
Presentation
• (Depends on anatomic location of disease)
• Fever
• Abdominal pain (with colonic involvement)
• Diarrhea often w/blood (with colonic
involvement)
• Generalized fatigability
• Weight loss
15. Crohn's Disease Bowel Appearance
• Bowel appears greatly thickened, lumen
narrows (associated with varying degrees of
obstruction.)
• Mucosa appearance variable; may appear
normal, in contrast to UC
• "Cobblestone" appearance of mucosa
• Discontinuous "skip lesions" present
• Rectum spared in 50% of cases (never in UC)
16. Crohn's Disease Complications
• Severe complications include fistulas, fissures,
abscesses
• Toxic megacolon: less than with UC
• Colonic cancer: less than with UC
17. Systemic Complications of IBD
• Joint manifestations (25% incidence)
• Arthralgias to acute arthritis
• Skin manifestations (15% incidence)
• Severity reflects activity of bowel disease
• More common with colonic disease
• Erythema nodosum: and eruption of painful red
nodules of legs
• Pyoderma gangrenosum: ulcerating lesion often
occurring on the trunk
• Aphthous ulcers: resemble canker sores of mouth
• Treat symptomatically only
18. Systemic Complications of IBD
• Ocular manifestations (5% incidence)
• May represent severe manifestation of disease
• Episcleritis, recurrent iritis may occur
• Activity parallels course of bowel disease
• Lesion may respond when colectomy
performed
19. Local complications of IBD
• UC
o toxic megacolon
o colonic perforation
o hemorrhage
o colonic carcinoma
• Crohn’s Disease
o fistulas
o sepsis
o intestinal obstruction
o B12 malabsorption
20. Treatment of UC and Crohn's
Disease
• Similarities: Initial treatment is medical
• Surgery reserved for specific complications,
intractable disease
• Differences: Response to drug therapy may
differ
• Complications often different
• Prognosis following surgery different
21. Goals of Pharmacotherapy for IBD
• Control inflammatory process
• Replace nutritional losses
• Improvements following IV fluid and
electrolyte replacement
• Blood transfusions may be necessary
• Agents to control diarrhea should be used with
caution
22. Drug Therapy in IBD
• Aminosalicylates
• Sulfasalazine-reaches colon intact where diazo
bond is cleaved by flora to mesalamine
(active) and sulfapyridine.
• Proposed mechanisms of action:
o Inhibit NKC's
o Inhibit cyclooxygenase and lipoxygenase
pathways
o Repair neutrophil function
o Scavenge oxygen radicals
23. Problems with sulfasalazine
• Many patients allergic or intolerant
(sulfapyridine portion)
• May be possible to "desensitize" patients
• Other adverse effects:
o fever, rash, hepatic dysfunction, agranulocytosis,
hemolytic anemia, thrombocytopenia, pancreatitis,
adverse sperm effects in males
24. • Corticosteroids:
o exact mechanism unknown
• Enemas:
o Decrease tenesmus by suppressing rectal inflammation
• IV:
o appropriate in severely ill patients to avoid uncertainty of
oral absorption
• PO:
o After 7-10 days, if improvement (dec. fever, diarrhea,
increased appetite), start oral feedings and taper steroids
• To decrease side effects: Use rapid tapering
schedules
• Every other day schedules
• AM dosing
26. • Azathiaprine-Discouraging results
• 6-Mercaptopurine-Active metabolite of azathiaprine
• Role in refractory Crohn's
o Studies have shown reductions in steroid use, healing of
fistulas and abscesses.
• Toxicities: pancreatitis 3.3%
• BM suppression 2%
• Allergy 2%
• Hepatitis 0.3%
• Should be considered in treatment of patients with
refractory Crohn's, or in patients intolerant of steroids
or sulfasalazine
27. Methotrexate in IBD
• Interferes with IL-1's inflammatory actions
• Study results:
o In patients with refractory IBD, given MTX 25 mg
IM weekly x12 weeks, then oral taper:
o 5/7 with UC, 11/14 Crohn's improved allowing
decreased steroid doses
28. Cyclosporine in IBD
• Study results:
o In patients with resistant Crohn's, cyclosporine 5-
7.5 mg /kg/d x3 months
o 59% cyclosporine vs 32% placebo showed
improvement.
o No long term improvement
o Side effects need to be assessed (renal impairment)
29. Antibiotics in IBD
• Role:
o As treatment for intercurrent infections
o As primary treatment for IBD
• Considerations:
o Infections can cause flares in IBD
o C. jejuni infections can mimic IBD
• Uncontrolled study:
o Continuous treatment with ATB's resulted in
symptomatic improvement in 41/44 patients with
Crohn's
30. Metronidazole in IBD
• Only antimicrobial with firm rationale for use
in Crohn's
• May work through mechanism independent of
antimicrobial properties
• No evidence in UC, except in treating C.dif
infections
• Study results:
o Patients with unremitting Crohn's, 21/21 had
improvements in drainage, erythema, induration.
10/18 had complete healing.
31. Anticholinergics/Antispasmodics
• Symptomatic treatment
• Use should be discouraged in acute symptoms;
• May ppt. ileus, toxic megacolon
• Major usefulness:
o control of diarrhea in patients with well
established, chronic symptoms
32. Prognosis for IBD
• UC:
o 20-25% will require colectomy
o Indication for colectomy:
• failure to respond to medical management
o Long term prognosis- variable
o 10 year mortality for severe first attacks=5-10%
o 75% relapse rate
33. Prognosis for IBD
• Crohn's:
o prognosis less favorable than for UC
o disease responds less favorably to medical therapy
o 2/3 develop complications requiring surgery
o mortality increases with duration of disease (5-
10%)
o surgery not a primary form of therapy-high rate of
recurrence