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Inflammatory bowel disease
It includes a group of chronic disorders that
cause inflammation or ulceration in large and
small intestines.
intestines.
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
Other forms of IBD
• Collagenous colitis
• Lymphocytic colitis
• Ischemic colitis
• Behcet’s syndrome
• Infective colitis
• Intermediate colitis
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
↓ Immunoregulation,
failure of repair or
bacterial clearance
Tolerance
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)
Microscopic features
 Crypts atrophy & irregularity
 Superficial erosion
 Diffuse mixed inflammation
 Basal lymphoplasmacytosis
Macroscopic features
• Crohn’s disease
Can affect any part of GIT
Transmural
Segmental with skip lesions
Cobblestone appearance
Creeping fat- adhesions & fistula
Microscopic features
• Aphthous ulcerations
• Focal crypt abscesses
• Granuloma-pathognomic
• Submucosal or subserosal lymphoid
aggregates
• Transmural with fissure formation
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.
D/D of IBD?
Diagnosis
• Laboratory tests
• Endoscopy
• Radiography
• Biopsy
• CT enterography
Laboratory tests
• CRP-elevated
• ESR-elevated
• Anemia
• Leukocytosis
• hypoalbuminemia
Barium enema
String
sign
Colonoscopy
CT enterography
• Mural hyperenhancement
• Stratification
• Engorged vasa recta
• Perienteric inflammatory
changes
Treatment
Treatment
Lifestyle changes
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)
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;12:972–978; 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.
• 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
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
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
Immunosuppresants
• Thiopurines
Azathioprine
6-mercaptopurin
• Methotrexate
• Cyclosporine
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
Other medications
Anti- diarrheals - Loperamide (Imodium)
Laxatives - senna, bisacodyl
Pain relievers. acetaminophen (Tylenol).
Iron supplements
 Nutrition
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
Commonly observed ADR with agents
used to treat IBD
Glucocorticoids
– Hyperglycemia, hypertension, osteoporosis, fluid
retention and electrolyte, disturbances, myopathies,
psychosis, and reduced resistance to infection,
adrenocortical suppression
– Specific regimens for withdrawal of glucocorticoid
therapy have been suggested
Commonly observed ADR with agents
used to treat IBD
Immunosuppressants
– Bone marrow suppression, and have been
associated with lymphomas (in renal transplant
patients) and pancreatitis.
Infliximab
– Infusion reactions, serum sickness, sepsis, and
reactivation of latent tuberculosis.
Commonly observed ADR with agents
used to treat IBD
Sulfasalazine
– GI disturbances- nausea, vomiting, diarrhea, or
anorexia
– Patients receiving sulfasalazine should receive oral
folic acid supplementation since sulfasalazine inhibits
folic acid absorption
References
• http://demystifyingmedicine.od.nih.gov/DM1
2/2012-03-27/2012-03-27-Yao.htm
• http://www.slideshare.net/ParichiBuch/inflam
matory-bowel-disease-10728466
• http://www.medicinenet.com/inflammatory_
bowel_disease_ibd_pictures_slideshow/articl
e.htm
Inflammatory Bowel Disease

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Inflammatory Bowel Disease

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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 • Crohn’s 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 • Behcet’s 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 ↓ Immunoregulation, failure of repair or bacterial clearance Tolerance
  • 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)
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  • 14. Microscopic features  Crypts atrophy & irregularity  Superficial erosion  Diffuse mixed inflammation  Basal lymphoplasmacytosis
  • 15. Macroscopic features • Crohn’s disease Can affect any part of GIT Transmural Segmental with skip lesions Cobblestone appearance Creeping 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.
  • 31. Diagnosis • Laboratory tests • Endoscopy • Radiography • Biopsy • CT enterography
  • 32. Laboratory tests • CRP-elevated • ESR-elevated • Anemia • Leukocytosis • hypoalbuminemia
  • 35. CT enterography • Mural hyperenhancement • Stratification • Engorged vasa recta • Perienteric inflammatory changes
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  • 44. 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)
  • 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;12:972–978; 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.
  • 46. • 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
  • 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
  • 50. 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
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  • 59. Other medications Anti- diarrheals - Loperamide (Imodium) Laxatives - senna, bisacodyl Pain relievers. acetaminophen (Tylenol). Iron supplements  Nutrition
  • 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 – Hyperglycemia, hypertension, osteoporosis, fluid retention and electrolyte, disturbances, myopathies, psychosis, and reduced resistance to infection, adrenocortical suppression – Specific regimens for withdrawal of glucocorticoid therapy have been suggested
  • 62. Commonly observed ADR with agents used to treat IBD Immunosuppressants – Bone marrow suppression, and have been associated with lymphomas (in renal transplant patients) and pancreatitis. Infliximab – Infusion reactions, serum sickness, sepsis, and reactivation of latent tuberculosis.
  • 63. Commonly observed ADR with agents used to treat IBD Sulfasalazine – GI disturbances- nausea, vomiting, diarrhea, or anorexia – Patients receiving sulfasalazine should receive oral folic acid supplementation since sulfasalazine inhibits folic acid absorption

Editor's Notes

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