2. • It includes a group of chronic disorders that cause
inflammation or ulceration in large and small intestines.
• 2 major types: Ulcerative colitis (UC) and Crohn’s disease
(CD)
INCIDENCE-
Highest incidence in Europe, the United Kingdom, and North
America.
Urban areas > rural areas.
high socioeconomic classes > lower socioeconomic classes.
INFLAMMATORY BOWEL DISEASE
3. • Recently two studies, both from northern India,
reported a population prevalence of ulcerative colitis
(UC) of approximately 42 per 100,000 .
• No such population based study is available for
crohn’s disease.
5. ETIOPATHOGENESIS
Exact cause is
unknown.
• Genetic factors
• Immunological factors
• Microbial factors
• Psychosocial factors
6.
7. GENETIC FACTORS
• Ulcerative colitis is more common in DR2-related genes.
• Crohn’s disease is more common is DR5 DQ1 alleles.
• 3-20 times higher incidence in first degree relatives.
8. IMMUNOLOGIC FACTORS
• Defective regulation of immunosuppression.
• 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 resulting in inflammation of mucosa
and sub mucosa.
9.
10.
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
(Infection, NSAID, other)
Complete Healing
Chronic Inflammation
Genetically
Susceptible
Host
Acute Inflammation
↓ Immunoregulation, failure of
repair or bacterial clearance
Acute injury
Environmental
triggers
12. PATHOLOGY
Macrocopic features
•Ulcerative colitis
Usually involves rectum & extends proximally to involve all
or part of colon.
Spread is in continuity.
About 40–50% of patients have disease limited to the rectum and
rectosigmoid.
30–40% have disease extending beyond the sigmoid but not
involving the whole colon, and
20% have a total colitis (10–20% patients have backwash ilietis).
13.
14. Mild disease- erythematous & sand paper appearance
(fine granular surface) of mucosa.
Moderate-marked erythema, coarse granularity, contact
bleeding & no ulceration.
Severe- spontaneous bleeding, edematous & ulcerated
(collar button ulcer) mucosal surface.
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/ perforation
19. MACROSCOPIC FEATURES
• Crohn’s disease
Can affect any part of GIT.
Transmural involvement.
Segmental with skip lesions.
Cobblestone appearance of mucosa.
Creeping fat- adhesions & fistula.
20.
21.
22. MICROSCOPIC
FEATURES
• Aphthous ulcerations.
• Focal crypt abscesses.
• Granuloma formation- pathognomic.
• Submucosal or subserosal lymphoid
aggregates.
• Transmural involvement with fissure
formation.
23.
24.
25. CLINICAL FEATURES
• Ulcerative colitis
Diarrhea
Rectal bleeding
Tenesmus
Passage of mucus
Crampy abdominal pain
Systemic symptoms fever, weight loss
Extra intestinal manifestations
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. 1. Truelove SC, et al. Br Med J. 1955;2:1041-1045.
2. Sandborn WJ. Curr Treat Options Gastroenterol.1999;2:113-118.
CLINICAL SEVERITY OF UC
Mild Moderate Severe Fulminant
Bowel movement <4/day Intermediate >6 >10
Blood in stool Intermittent moderate Frequent Continuous
Temperature Normal <37.5° >37.5° >37.5°
Pulse Normal <90bpm >90 bpm >90 bpm
Hemoglobin Normal >75% <75% Transfusion
required
ESR <30 mm/hour >30 mm/hour >30 mm/hour
Clinical signs Abdominal
tenderness
Abdominal
distension and
tenderness
34. Colonoscopy with acute ulcerative colitis: severe
colon inflammation with erythema, friability, and
exudates.
35.
36. CLINICAL FEATURES
ILEAL CROHN’S DISEASE
Abdominal pain
Diarrhea
Weight loss
Low grade fever
JEJUNOILEITIS - associated with a loss of digestive
and absorptive surface, resulting in
Malabsorption
Steatorrhea
37. Colitis and perianal disease
• Bloody diarrohea
• Passage of mucus
• Lethargy
• Malaise
• Anorexia
• Weight loss
Contd. Clinical features
38. GASTRODUODENAL DISEASE –
• Symptoms and signs of upper GI tract disease include
nausea, vomiting, and epigastric pain.
• The second portion of the duodenum is more commonly
involved than the bulb.
• Patients with advanced gastro duodenal CD may develop a
chronic gastric outlet obstruction.
43. • Endoscopic features of CD include rectal sparing,
aphthous ulcerations, fistulas, and skip lesions.
• Colonoscopy allows examination and biopsy of
mass lesions or strictures and biopsy of the
terminal ileum.
• Upper endoscopy is useful in diagnosing
gastroduodenal involvement in patients with
upper tract symptoms
53. 5-ASA AGENTS
• Sulfasalazine – combination of 5-aminosalicylic acid( anti
inflammatory ) + sulfapyradine-antibacterial).
Partially absorbed in jejunum but remainder passes in colon
Therapeutic action –inhibition of P.G.s & leukotriene
synthesis, free radical scavanging, free radical scavanging,
impairement of white cell adhesion and function, inhibition
of cytokine synthesis.
• Mesalamine group (coating 5-ASA with acrylic resins), e.g.
Asacol, Pentasa, Balsalazide (prodrug of 5-ASA).
• Olsalazine (5-ASA dimer cleaves in colon).
54.
55. Distribution of 5-ASA Preparations
Oral
•Varies by agent: may be released in the
• distal/terminal ileum, or colon1
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.
56. Use
• Mainstay of OPD treatment for mild to moderate active
UC & Crohns 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
57. GLUCOCORTICOIDS
• Anti inflammatory agents for moderate to severe
relapses (including IV treatment; enemas for
acute proctitis)
• Inhibition of inflammatory pathways.
• No role in maintenance therapy
• Prednisone-40-60mg/day
• Budesonide- 9mg/dl used for 2-3 months & then
tapered.
58. ANTIBIOTICS
• Metronidazole is effective in active inflammatory,
fistulous & perianal Crohn’s Disease.
Dose-15-20mg/kg/day in 3 divided doses.
• Ciprofloxacin 500mg BD.
• Rifaximin.
• No role of antibiotics in active/quiescent UC.
59. IMMUNOSUPPRESANTS
• Thiopurines- Azathioprine, 6-mercaptopurine.
• Methotrexate
• Cyclosporine
Reduce inflammation by suppressing immune system’s
response (which might damage digestive tissue) invading
virus or bacterium.
• Used in patients unresponsive to steroid &
amino salicylates
60. CYCLOSPORINE
Preventing clonal expansion of T cell subsets.
Use
• Steroid sparing
• Active and chronic disease
Side effects
Minor: tremor, paresthesias, malaise, headache
gingival hyperplasia, hirsutism.
Major: renal impairment, infections, neurotoxicity
61. BIOLOGICAL THERAPY
Infliximab
Anti TNF monoclonal antibody.
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 Tuberculosis
• Increased risk of Tuberculosis