Inflammatory Bowel Disease

1. Inflammatory Bowel Disease
Hossam Ghoneim, MD

2. Definition
• A general term for a group of chronic
inflammatory disorders of unknown
etiology involving the
gastrointestinal tract.

3. IBD Epidemiology
• Whites > Blacks and Orientals
• Increased incidence (3-6 fold) in Jews
• Male=Female
• Ulcerative Colitis Incidence: 6-8/100,000
• Crohn's Incidence: 2/100,000
• Peak occurrence: Age 15-35
• Familial incidence

4. CD Vs UC

5. Causes of IBD
• Genetic predisposition?
• Infectious organisms?
• Immune mechanisms
– Immunosuppressive agents used in treatment
– Autoimmune phenomena accompany IBD
• Psychological mechanisms
– IBD may flare in association with stress
– Characteristic personality

6. Hypothesized Etiologies

7. Differential Diagnosis

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:
– Bloody diarrhea/constipation
– Abdominal pain
– Weight loss
– Fever

10. UC Manifestations/Complications
• Physical findings (nonspecific)
– Tenderness along colon
• Extracolonic manifestations
– Anemia of chronic disease + Fe deficiency
– Leukocytosis, left shift
– Electrolyte abnormalities
– 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
– toxic megacolon
– colonic perforation
– hemorrhage
– colonic carcinoma
• Crohn’s Disease
– fistulas
– sepsis
– intestinal obstruction
– 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:
– Inhibit NKC's
– Inhibit cyclooxygenase and lipoxygenase pathways
– Repair neutrophil function
– Scavenge oxygen radicals

23. Problems with sulfasalazine
• Many patients allergic or intolerant
(sulfapyridine portion)
• May be possible to "desensitize" patients
• Other adverse effects:
– fever, rash, hepatic dysfunction, agranulocytosis,
hemolytic anemia, thrombocytopenia,
pancreatitis, adverse sperm effects in males

24. • Corticosteroids:
– exact mechanism unknown
• Enemas:
– Decrease tenesmus by suppressing rectal inflammation
• IV:
– appropriate in severely ill patients to avoid uncertainty of
oral absorption
• PO:
– 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

25. Immunosuppressants
• Important in Crohn's disease
• Less well established in UC
• Azathiaprine 6-MP MTX Cyclosporine

26. • Azathiaprine-Discouraging results
• 6-Mercaptopurine-Active metabolite of azathiaprine
• Role in refractory Crohn's
– 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:
– In patients with refractory IBD, given MTX 25 mg
IM weekly x12 weeks, then oral taper:
– 5/7 with UC, 11/14 Crohn's improved allowing
decreased steroid doses

28. Cyclosporine in IBD
• Study results:
– In patients with resistant Crohn's, cyclosporine 5-
7.5 mg /kg/d x3 months
– 59% cyclosporine vs 32% placebo showed
improvement.
– No long term improvement
– Side effects need to be assessed (renal
impairment)

29. Antibiotics in IBD
• Role:
– As treatment for intercurrent infections
– As primary treatment for IBD
• Considerations:
– Infections can cause flares in IBD
– C. jejuni infections can mimic IBD
• Uncontrolled study:
– 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:
– 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:
– control of diarrhea in patients with well
established, chronic symptoms

32. Prognosis for IBD
• UC:
– 20-25% will require colectomy
– Indication for colectomy:
• failure to respond to medical management
– Long term prognosis- variable
– 10 year mortality for severe first attacks=5-10%
– 75% relapse rate

33. Prognosis for IBD
• Crohn's:
– prognosis less favorable than for UC
– disease responds less favorably to medical
therapy
– 2/3 develop complications requiring surgery
– mortality increases with duration of disease (5-
10%)
– surgery not a primary form of therapy-high rate of
recurrence

35. NBI UC

45. Thank you