Inflammatory bowel disease (IBD) includes chronic disorders like ulcerative colitis and Crohn's disease that cause inflammation in the intestines. Genetic factors contribute to IBD risk, and symptoms include abdominal pain, diarrhea, and bloody stools. Treatment involves lifestyle changes, medications like 5-aminosalicylates and immunosuppressants to reduce inflammation, and sometimes surgery for severe cases.
Inflammatory Bowel Disease Pathogenesis and Treatment
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3. Inflammatory bowel disease
It includes a group of chronic disorders that
cause inflammation or ulceration in large and
small intestines.
intestines.
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9. Genetic factors
⢠Ulcerative colitis is more common in
DR2-related genes
⢠Crohnâs disease is more common in
DR5 DQ1 alleles
⢠3-20 times higher incidence in first degree
relatives
10. Other forms of IBD
⢠Collagenous colitis
⢠Lymphocytic colitis
⢠Ischemic colitis
⢠Behcetâs syndrome
⢠Infective colitis
⢠Intermediate colitis
11. Pathogenesis of IBD
American Gastroenterological Association Institute, Bethesda, MD.
Sartor RB. Nat Clin Pract Gastroenterol Hepatol. 2006;3:390-407.
Normal
Gut
Tolerance-
controlled
inflammation
Environmental
trigger
(Infection, NSAID, other)
Acute Injury
Complete Healing
Chronic Inflammation
Genetically
Susceptible
Host
Acute Inflammation
â Immunoregulation,
failure of repair or
bacterial clearance
Tolerance
12. Pathology
Macrocopic features
⢠Ulcerative colitis
ďUsually involves rectum & extends proximally to
involve all or part of colon.
ďSpread is in continuity.
ďMay be limited colitis( proctitis &
proctosigmoiditis)
ďin total colitis there is back wash ileitis (lumpy-
bumpy appearance)
15. Macroscopic features
⢠Crohnâs disease
ďCan affect any part of GIT
ďTransmural
ďSegmental with skip lesions
ďCobblestone appearance
ďCreeping fat- adhesions & fistula
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18. Microscopic features
⢠Aphthous ulcerations
⢠Focal crypt abscesses
⢠Granuloma-pathognomic
⢠Submucosal or subserosal lymphoid
aggregates
⢠Transmural with fissure formation
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29. IBD Is Not the Same as IBS
⢠IBD is sometimes confused with irritable bowel syndrome
(IBS).
⢠The striking difference between the two diseases is that
there is no identifiable inflammation in IBS.
⢠Some symptoms may be similar - abdominal pain, diarrhea,
⢠but the other symptoms and signs of IBD are not seen -
bloody stools, fever, and weight loss.
⢠The cause of IBS is believed to be dysfunction of the
intestinal muscles, nerves, and secretions and not
inflammation.
⢠Signs of inflammation in the intestine as well as symptoms
outside of the abdomen are not seen in IBS.
44. 5-ASA Agents
â˘Sulfasalazine (5-aminosalicylic
acid and sulfapyridine as carrier
substance)
â˘Mesalazine (5-ASA), e.g. Asacol,
Pentasa
â˘Balsalazide (prodrug of 5-ASA)
⢠Olsalazine (5-ASA dimer cleaves
in colon)
45. Oral
⢠Varies by agent: may be released in the distal/terminal
ileum, or colon1
Distribution of 5-ASA Preparations
Suppositories
⢠Reach the upper rectum2,5
(15-20 cm beyond the anal verge)
Liquid Enemas
⢠May reach the splenic flexure2-4
⢠Do not frequently concentrate in the rectum3
Topical Action of 5-ASA: Extent of Disease
Impacts Formulation Choice
1. Sandborn WJ, et al. Aliment Pharmacol Ther. 2003;17:29-42; 2. Regueiro M, et al. Inflamm Bowel Dis. 2006;12:972â978; 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.
46. ⢠Use
ď In mild to moderate UC & crohnâs colitis
ď Maintaining remission
ď May reduce risk of colorectal cancer
⢠Adverse effects
ď Nausea, headache, epigastric pain, diarrhoea,
hypersensitivity, pancreatitis
ď Caution in renal impairment, pregnancy, breast feeding
47. 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
48. 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
60. Surgery
Ulcerative colitis
Indications:
⢠Fulminating disease
⢠Chronic disease with anemia, frequent stools,
urgency & tenesmus
⢠Steriod dependant disease
⢠Risk of neoplastic change
⢠Extraintestinal manifestations
⢠Severe hemorrhage or stenosis
61. Commonly observed ADR with agents
used to treat IBD
Glucocorticoids
â Hyperglycemia, hypertension, osteoporosis, fluid
retention and electrolyte, disturbances, myopathies,
psychosis, and reduced resistance to infection,
adrenocortical suppression
â Specific regimens for withdrawal of glucocorticoid
therapy have been suggested
62. Commonly observed ADR with agents
used to treat IBD
Immunosuppressants
â Bone marrow suppression, and have been
associated with lymphomas (in renal transplant
patients) and pancreatitis.
Infliximab
â Infusion reactions, serum sickness, sepsis, and
reactivation of latent tuberculosis.
63. Commonly observed ADR with agents
used to treat IBD
Sulfasalazine
â GI disturbances- nausea, vomiting, diarrhea, or
anorexia
â Patients receiving sulfasalazine should receive oral
folic acid supplementation since sulfasalazine inhibits
folic acid absorption