2. Inflammatory bowel disease
intestines.
It includes a group of chronic disorders that
cause inflammation or ulceration in large and
small intestines.
3. TYPES
Crohn’s disease Ulcerative colitis
• Extends into the deeper
layers of the intestinal wall, • causes ulceration and
and may affect the mouth, inflammation of the inner
esophagus, stomach, and lining of the colon and
small intestine. rectum.
• Transmural inflammation
and skip lesions. • It is usually in the form of
• In 50% cases -ileocolic,30% characteristic ulcers or open
ileal and 20% -colic region. sores.
• Regional enteritis
4.
5. Other forms of IBD
• Collagenous colitis
• Lymphocytic colitis
• Ischemic colitis
• Behcet’s syndrome
• Infective colitis
• Intermediate colitis
6. Epidemiology
Ulcerative colitis Crohn’s
Incidence / 1 lac. 2.2-14.3 3.1-14.6
Age of onset 15-30, 60-80
Ethnicity Jewish
Male: Female 1:1 1.1-1.8 : 1
Smoking May prevent Causative
Oral contraceptives No risk 1.4 odds ratio
Appedicectomy Protective Not
Monozygotic 6% 58%
Dizygotic 0% 4%
7. Etiopathogenesis
• Exact cause is unknown.
• Genetic factors
• Immunological factors
• Microbial factors
• Psychosocial factors
8. Genetic factors
• Ulcerative colitis is more common in
DR2-related genes
• Crohn’s disease is more common in
DR5 DQ1 alleles
• 3-20 times higher incidence in first degree
relatives
9. Immunologic factors
• Defective regulation of immunesuppresion
• Activated CD+4 cells activate other
inflammatory cells like macrophages & B-cells
or recruit more inflammatory cells by
stimulation of homing receptor on leucocytes
& vascular epithelium.
10.
11. Pathogenesis of IBD
Tolerance
Acute Injury
Environmental
trigger
Normal Complete Healing
Gut (Infection, NSAID, other)
Genetically
Tolerance- Acute Inflammation Susceptible
controlled Host
↓ Immunoregulation,
inflammation
failure of repair or
bacterial clearance
Chronic Inflammation
American Gastroenterological Association Institute, Bethesda, MD.
Sartor RB. Nat Clin Pract Gastroenterol Hepatol. 2006;3:390-407.
12. Pathology
Macrocopic features
• Ulcerative colitis
Usually involves rectum & extends proximally to
involve all or part of colon.
Spread is in continuity.
May be limited colitis( proctitis &
proctosigmoiditis)
in total colitis there is back wash ileitis (lumpy-
bumpy appearance)
13.
14. • Mild disease- erythema & sand paper
appearance(fine granularity)
• Moderate-marked erythema,coarse
granularity,contact bleeding & no ulceration
• Severe- spontaneous bleeding, edematous &
ulcerated(collar button ulcer).
• Long standing-epithelial regeneration so
pseudopolyps , mucosal atrophy &
disorientation leads to a precancerous
condition.
• Eventually can lead to shortening and
narrowing of colon.
• Fulminant disease-Toxic colitis/megacolon
19. Macroscopic features
• Crohn’s disease
Can affect any part of GIT
Transmural
Segmental with skip lesions
Cobblestone appearance
Creeping fat- adhesions & fistula
20.
21.
22. Microscopic features
• Aphthous ulcerations
• Focal crypt abscesses
• Granuloma-pathognomic
• Submucosal or subserosal lymphoid
aggregates
• Transmural with fissure formation
25. • Diarrhea & bleeding blood-intermittent &mild.
do not seek medical attention.
• Patient with proctatis-pass fresh or blood
stained mucus with formed or semi formed
stool. They also have tenesmus , urgency with
feeling of incomplete evacuation.
• With proctosigmoiditis-constipation
• Severe disease-liquid stools with blood , pus &
fecal matter.
26. • Physical signs
Proctitis – Tender anal canal & blood on rectal
examination
Extensive disease-tenderness on palpation of
colon
Toxic colitis-severe pain &bleeding
If perforation-signs of peritonitis
27. Clinical Severity of UC
Mild Moderate Severe Fulminant
Bowel movement <4 >6 >10
Blood in stool Intermittent Frequent Continuous
Temperature Normal >37.5° >37.5°
Pulse Normal >90 bpm >90 bpm
Intermediate
<75% normal Transfusion
Hemoglobin Normal
rate required
ESR <30 mm/hour >30 mm/hour >30 mm/hour
Abdominal
Abdominal
Clinical signs distension and
tenderness
tenderness
1. Truelove SC, et al. Br Med J. 1955;2:1041-1045.
2. Sandborn WJ. Curr Treat Options Gastroenterol.1999;2:113-118.
52. 5-ASA Agents
•Sulfasalazine (5-aminosalicylic
acid and sulfapyridine as carrier
substance)
•Mesalazine (5-ASA), e.g. Asacol,
Pentasa
•Balsalazide (prodrug of 5-ASA)
• Olsalazine (5-ASA dimer cleaves
in colon)
53. Topical Action of 5-ASA: Extent of Disease
Impacts Formulation Choice
Distribution of 5-ASA Preparations
Oral
• Varies by agent: may be released in the distal/terminal
ileum, or colon1
Liquid Enemas
• May reach the splenic flexure2-4
• Do not frequently concentrate in the rectum3
Suppositories
• Reach the upper rectum2,5
(15-20 cm beyond the anal verge)
1. Sandborn WJ, et al. Aliment Pharmacol Ther. 2003;17:29-42; 2. Regueiro M, et al. Inflamm Bowel Dis. 2006;12:972–978; 3. Van Bodegraven AA,
et al. Aliment Pharmacol Ther. 1996; 10:327-332; 4. Chapman NJ, et al. Mayo Clin Proc. 1992;62:245-248; 5. Williams CN, et al. Dig Dis Sci. 1987;32:71S-75S.
54. • Use
In mild to moderate UC & crohn’s colitis
Maintaining remission
May reduce risk of colorectal cancer
• Adverse effects
Nausea, headache, epigastric pain, diarrhoea,
hypersensitivity, pancreatitis
Caution in renal impairment, pregnancy, breast feeding
55. Glucocorticoids
• Anti inflammatory agents for moderate to
severe relapses.
• Inhibition of inflammatory pathways
• Budesonide- 9mg/dl used for 2-3 months &
then tapered.
• Prednisone-40-60mg/day
• No role in maintainence therapy
56. Antibiotics
• No role in active/quienscent UC
• Metronidazole is effective in active
inflammatory,fistulous & perianal CD.
• Dose-15-20mg/kg/day in 3 divided doses.
• Ciprofloxacin
• Rifaximin
58. Cyclosporine
• Preventing clonal expansion of T cell subsets
• Use
Steroid sparing
Active and chronic disease
• Side effects
Tremor, paraesthesiae, malaise, headache, gingival
hyperplasia, hirsutism Major: renal impairment,
infections, neurotoxicity
59. Biological therapy
• Infliximab
Anti TNF monoclonal antibody
Infliximab binds to TNF trimers with high affinity, preventing cytokine
from binding to its receptors
It also binds to membrane-bound TNF- a and neutralizes its activity &
also reduces serum TNF levels.
• Use
Fistulizing CD
Severe active CD
Refractory/intolerant of steroids or immunosuppression
• Side effects
Infusion reactions, Sepsis, Reactivation of Tb, Increased risk of Tb
