1. Inflammatory bowel diseases (I.B.D)

2. IBD TWO MAIN FORMS: ULCERATIVE COLITIS- AFFECTS LARGE BOWEL ONLY
CROHN’S DISEASE- AFFECTS ANY PART OF GIT

4. Epidemiology of IBD Ulcerative colitis Crohn’s disease 11/100 000
Incidence (US)
11/ 7/
Age of onset
15-30 & 60-80
Male:female ratio
1:1
1,1-1,8:1
Smoking
May prevent disease
May cause disease
Oral contraceptive
No increased risk
Relative risk 1,9
Appendectomy
Not protective
Protective
Monozygotic twins
8% concordance
67% concordance

5. High
Medium
Low

6. Epidemiology UC
Highest incidence in Europe, United Kingdom, North America
Incidence per person-years
2.2–14.3/100,000
Age of onset
15–30 & 60–80
Male:female ratio
1:1
Smoking
May prevent disease
Oral contraceptives
No increased risk
Appendectomy
Protective
Monozygotic twins
6% concordance
Dizygotic twins
0% concordance

7. Epidemiology Crohn,s disease
Incidence: 7/ pop/yr
World wide distribution but more common in the West.
The incidence is lower in
non-white races.
Females are affected more than males 1.2:1
Epidemiology
Jews are more affected
than non-Jews
Bimodal age distribution:
20-40 yrs/60-80 yrs
The incidence is rising
Prevalence: 100/ pop/yr

8. Etiology
Genetic
Defective immune regulation
Exogenous factors

9. Etiology & Pathogenesis
The aetiology of IBD disease is unknown. There are many proposed
pathogenic mechanisms, some of which are represented in this diagram.
As there is no one cause, it is likely that IBD disease is an outcome of
interactions between genetic predisposition, environmental factors and the
subsequent reaction of the host immune system.
Genetic susceptibility
Environmental factors
Host
Immune
Response
IBD

10. Genetic:
IBD patients have disease-associated foci on chromosome 16, 12,7,5,3,1 (gene NOD-2)
Ulcerative colitis express HLA DR2 and CD express DR5 DQ1, DRB0301.
IBD patients with HLA DRB10130, have extensive disease and extraintestinal manifestation such as : mouth ulcers,arthritis,uveitis

11. Immune dysregulation in IBD
NORMAL
IBD
normal
IBD
Antigen and flora
Antigen and flora
Dysregulation ?
CD4+ T
Inhibitory cytokines
IL-10,TGF-b
CD -TH2
CD-TH1
IL-4,IL5,IL13
ING- ,TNF
Inflammatory cytokines
Oral tolerance
Ulcerative colitis
Crohn,s colitis

13. Pathology Ulcerative colitis : (1)Is a mucosal disease of colon
(2) 40-50% involve rectum ,30-40% rectosigmoid ,20% pancolitis
(3) Backwash ileitis :10-2%%
(4) Mucosa is erythematous , hemorrhage ,ulcerations , pseudopolyps

14. Pathology( crohn,s): Affect any part of GI from mouth to anus
30-40% small bowel
40-55% small and large bowel
15-25% alone colitis,” cobblestone”
90% terminal ileum is involved
is a transmural disease with skip area , rectum is spared ,preanal lesion like fistula ,fissures , abcesses,anal stenosis in see in 30%.

15. Normal colon

16. ULCERATIVE COLITIS CONTINUOUS INVOLVEMENT

17. CROHNS vs PM COLITIS

18. Clinical:
Intestinal
Extraintestinal

19. Ulcerative colitis

20. Disease distribution Ulcerative Colitis Left sided cloitis
Proctosigmoiditis
Proctitis

22. Disease distribution
The disease typically is most severe distally and progressively less severe more proximally.
In contrast to Crohn's disease, continuous and symmetrical involvement is the hallmark of UC, with sharp transition between diseased and uninvolved segments of bowel

23. Clinical Features diarrhea rectal bleeding passage of mucus tenesmus
urgency
abdominal pain

24. The onset of UC typically is slow and insidious.
Clinical Features
The onset of UC typically is slow and insidious.
Symptoms have usually been present for weeks or months by the time the patient seeks medical attention.
The median interval between the onset of symptoms and diagnosis of UC is approximately 9 months.
Some patients with UC may present much more acutely, with symptoms mimicking infectious colitis.

25. Intestinal symptoms of UC
Diarrhea, rectal bleeding ,tenesmus, passage of mucus crampy pain, incomplete evacuation.
Intestinal complications : bleeding, toxic colon, perforations , obstructions

34. Intestinal symptoms of CD :
Ileocolitis : diarrhea and chronic RLQ pain
Jejunoileitis :malabsorption
Colitis :diarrhea, low grade fever,pain, some times hematochezia
Gastroduodenal : G.O.O
Intestinal complications :fistula, perforation, intestinal obstruction, hemorrhage, preanal diseases.

37. Extraintestinal Manifestations of IBD
Skin
Erythema nodosum
Pyoderma gangrenosum
Joints
Peripheral arthritis
Sacroileitis
Ankylosing spondylitis
Eye
Uveitis
Episcleritis
Iritis
Hepatobiliary complications
Gallstones
PSC
Renal complications
Nephrolithiasis
Recurrent UTIs

39. Extraintestinal complications of I.B.D
Oral :
Dermatologic :
(1)Erythema nodosum, CD, 15%
(2)Pyoderma gangrenosum , UC ,1-12%

40. Extraintestinal complications of I.B.D
Rheumatologic :
(1)Peripheral arthritis, CD,15-20%
(2)Ankylosing spondylitis : CD, 10%, and 2/3 have positive test fir HLA-B27,no relation to activity
(3)Sacroiliitis :CD=UC, No relation to activity

43. Extraintestinal complications of I.B.D
Ocular :1-10%
(1)Conjuntivitis
(2)Anterior uveitis/iritis
(3)Episcleritis

46. Extraintestinal complications of I.B.D
Hepatobiliary:
(1)Hepatic steatosis :50%
(2)Cholelithiasis : CD>UC is seen in 10-35% patients with ileitis
(3) Primary sclerosing cholangitis :1-5%of I.B.D patients have PSC
50%-75 of patients with PSC have I.B.D
(4)Peicholangitis :

48. Extraintestinal complications of I.B.D
Urologic :
(1)Calculi :CD, 10-20%
(2)Ureteral obstruction
(3)fistula

53. Lab in IBD
In ESR,CRP, Hb
PANCA :Is positive in 5% population, 5-10% in first degree relatives 5-10% in CD , 60-70% in UC
ASCA : 5% Population ,10-15% in UC, 60-70% in CD
ANCA positivity is more associated with pancolitis, early surgery, pouchitis, PSC.

59. Medical treatment
(1)Sulfasalazine

60. Adverse Effects of Sulfasazine
Dose related
nausea
vomiting
anorexia
folate mal-ab.
Headache
alopecia
Not dose related
skin rash
hemolytic anemia
agrannulocytosis
fibrosing alveolitis
hepatitis
male infertility
colitis

61. Newer therapy: (2) 5-ASA a-azo-band : olsalazine
b-5-ASA dimer(resin) :delayed release, pH dependent , Asacol
c: sustained released: ethylcellulose microgranules , PENTASA

62. Treatment (continuous):
(3)Glucocorticoids :
a-oral
b-Iv
c-suppository and enema
(4) Antibiotics : metronidazole, ciprofloxacin.
fistula , preanal lesions
(5)Azthioprine,,methotrexate,cyclosporine(iv dose2-4mg/kg 82% effective in UC refractory to therapy )
6-MP
(6)Anti-TNF antibody (infliximab) : dose 5mg/kg ,65% of refractory CD respond,repeat every 8 weeks.

63. Treatment protocol is based in two factors:
Colonic involvement extent
DAI

64. Disease distribution Ulcerative Colitis Left sided cloitis
Proctosigmoiditis
Proctitis

72. FACTORS MODIFYING RISK OF COLITIS-ASSOCIATED CANCER
Cancer risk in IBD:
41. FACTORS MODIFYING RISK OF COLITIS-ASSOCIATED CANCER
It has long been recognized that long duration and wide anatomical extent of colitis are the two principal factors contributing to increased risk of colitis-associated colorectal cancer. More recently, a positive family history of colorectal cancer has been identified as an additive risk factor, much as it is in the non-colitis population. The co-existence of colitis with primary sclerosing cholangitis also sharply increases the likelihood of dysplasia and carcinoma of the colon. Although it is not entirely clear whether the reasons for this observation are primarily biological or artifactual, the fact remains that colorectal cancer surveillance needs to start soon after the diagnosis of PSC-associated colitis. (See Fig. 38)
On the other side of the coin, there is also some evidence suggesting that aminosalicylate treatment, folate supplementation, and “tight” medical control of the inflammatory process might lower the long-term risks of colorectal cancer in ulcerative colitis.
• Shetty K, Rybicki L, Brzezinski A et al. The risk of cancer or dysplasia in ulcerative colitis patients with primary sclerosing cholangitis. Am J Gastroenterol 1999;94:1643-9
• Itzkowitz SH. Inflammatory bowel disease and cancer. Gastroenterol Clin North Am 1997;26:
• Askling J, Dickman PW, Karlen P et al. Family history as a risk factor for colorectal cancer in IBD. Gastroenterology 2001;120:
Primary sclerosing
cholangitis
Family history of
colorectal cancer
pseudopolyp

73. Cancer in I.B.D
Sporadic colonic cancer (SCC) arise from adenomatous polyp; colitis associated colonic cancer(CACs ) arise from flat dysplasia or dysplasia-associated lesion or mass (DALM)
Multiple synchronous cancers occurs in3-5% SCC and in 12% CAC
Mean age SCC is 60 and CAC 30 years
SCC exhibits a left- sided predominance ,CAC distribute uniformly
Mucinous and anaplastic cancers are more common in CAC than SCS

74. Inflammatory bowel diseases & pregnancy
Patients with quiescent UC and CD have normal fertility rates
With increased activity patients have chance of abortion , stillbirths and developmental defects, but not due to medications
Antibiotics like ampicillin, cephalosporin,ormetronidazole for short courses are safe
Methotrexate and ciprofloxacin are contraindicated
Sulfasalazine , 5-ASA and Glucocorticoids are safe

75. Indications for surgery:
Ulcerative colitis
Crohn,s disease
Intractable disease
Fulminant disease
Toxic megacolon
Colonic perforation
Massive colonic hemorrhage
Extracolonic disease
Colonic obstruction
Colonic cancer
CD of small intestine:
Stricture,obstruction,fistula
Refractory to medical therapy
Abscess
CD of colon and rectum:
Intractable
Preanal disease,fistula, obstruction refractory to therapy
cancer