Inflammatory bowel disease

1. Inflammatory bowel disease By: Elias S. Maruf A.

2. IBD • Idiopathic and chronic intestinal inflammation. • Two major types: Crohn’s disease(CD) Ulcerative colitis(UC) • CD • 1st seen by the German surgeon Wilhelm Fabry in 1623 • Later described and named after US physician Burril B. Crohn • UC • 1st described by the British physician Sir Samuel Wilks in 1958

3. Epidemiology – CD, UC • Highest incidence ratesNorth America, Northern Europe, UK • Low incidence Areas Southern Europe, Asia, Most Developing countries • Age of onset: Two peaks  15-30yrs, 60-80y. • Sex: M:F UC  1:1 CD  1.1-1.8:1 • Race: CD (N.America) per 100,000 P. • Whites > African A. > Asian A. > Hispanic A. 43.6 29.8 5.9 4.1 • Both more prevalent in Jewish people than any other ethnic group

4. GeneticsFamilial aggregation of IBD 1st reported in 1930+ve Family Hx – the largest independent risk FactorPrevalence in 1st degree Relatives • Concordance b/n P’t and 1st degree relative • Disease type  75-80% • Disease pattern  64% • Extraintestinal manifestation  70%

5. Genetics Cont… • Twin study • Pooled systematic concordance analysis Monozygotic twins: CD – 37%, UC – 10% Dizygotic twins: CD – 7% , UC – 3% • MT > DT, CD > UC • IBD - Polygenic disease • So far – 12 chromosomes identified 16,12,6,14,5,19,1,7,3 (IBD 1-9) • Some specific gene loci – mapped • Ch.16 – NOD2(card15) associated with CD • Ch. 5 – OCTN1,OCTN2 • Ch. 6 – encodes for MHC mutations in HLA Alleles: HLA DRB*0103 / B27 / B35 / B44 • Mutation in IL23R gene – protective against CD

7. Environmental & other factors • Life style • Urban > Rural • Poor socioeconomic status - Risk • Excessive sanitation - Risk • Smoking :Aggravate the course of CD Risk of UC • Psychological stress Adverse life events/day to day stress activity of IBD (worsening, Relapse) • Infectios agents Normal flora ?M.paratuberculosis, Paramyxovirus, Helicobactor H.?others – Salmonella,Shigella, Campylobactor • Drugs: OCP – weak association with CD NSAID • Breast feeding – protective against IBD • Appendectomy : ?protective for UC, ?complications of CD

8. Immunopathology • GI mucosal surface • A physical interface of immune system with outside world : rich in lymphoid tissue • Bombarded with high Ag load • Harbors >500 sp. of micro flora • Normal state - Immune tolerance • Non-Responsiveness (inhibited immune function) • Mechanism- not clearly understood • Dysregulated immune function - IBD

9. Healthy Gut • A complex network ofLymphoid, non-Lymphoid cells, Humoral factors • Balanced differentiation of T-helper cellsEffecter c.(Th1,Th2,Th17) Regulatory c. (Tr, Th3) • Tightly regulated cytokine network • Tightly regulated immunity

10. IBD – Dysregulated immune response • Leaky barrier – luminal Ag gain access • Commensals recognized as pathogens • Expression of differentprofile & pattern of receptors • Imbalanced T-helper cell differentiationeffector cellsCD: Th0Th1 (INF∂,IL12)UC: Th0Th2 (IL5) • NK cells • Cyclic activation of macrophages • Continious inappropriate inflammatory response

11. Ulcerative Colitis • A mucosal disease (non-transmural) • Relapsing • Involve rectum and colon • 40-45% - rectum & recto sigmoid • 30-40% - extend beyond sigmoid • 20% - total colitis • 10-20% - backwash ileitis • continuous spread • Mild inflammation – Erythema with fine granular surface • More sever disease – ulceration with hemmge and edema • Long standing disease – inflammatory polyps • Major histologic feature • Distorted crypt architecture • Cyptitis, crypt abscess

12. UC cont… • Typical presentation • Diarrhea,tenesmus,passage of pus,mucuscrampy abdominal pain • Site specific presentation • Distal disease (proctitis): Passage of fresh blood, constipation Abdominal pain – Rare • Proximal disease (colon) gross bloody diarrhea, abd. Pain nausea, vomiting, W’t loss • Imading studies • Plain abd. Film: colon thickning, dilatation • Barium: thickned mucosa with superficial ulcer Deep ulcer – “collar button” loss of haustration • CT – mild mural thickning (<1.5cm) with inhomogenous wall density

13. UC cont….. • Natural course • 50% of the P’ts – clinical remission at any given time • 90% - intermittent course • Complications • Massive hemorrhage (1%) • Toxic megacolon (5%) • Perforation • ?Rarely – colonic obstruction • Long term - malignancy

14. Croh’ns disease • Transmural, Relapsing • Affect any part of GI – from mouth to anus • Location: Terminal ileum – 47% colon – 28%, ileocolon – 21% upper GI – 3% • Rectum- spared • Segmental involvement with skip areas • Disease behaviour • Non-stricturing/non-penetrating – 70% • Stricturing – 17%, Penetrating – 13% • Mild disease: aphtous ulcerations • More active disease: “cobble stone” appearance May involve liver & pancreas • Major histologic finding: noncaseating Granulomas

15. CD cont…… • Clinical presentation – depends on the site • Ileocolitis : common site - terminal ileumRLQ pain, diarrhea, palpable mass low grade fever, w’t loss edema / bowel wall thickening fibrosis narrowing of the lumen ( radiographic “string” sign) • Jejunoileitis : loss of digestive/absorptive surface Malabsorption, steatorrhea • Colitis: Bloody diarrhea, abd cramp, tenesmus Massive bleeding (1-2%) • Perianal disease (1/3 of p’ts) : incontinence, anal stricture, anorectal fistula, abscess • Gastro duodenal: Nausea, vomiting, epigastric pain

16. CD cont…. • Natural course • 67-73% - chronic intermittent course • 10-13% - remain in remission for several yrs • After 20 yrs – most require surgery • Complication • Strictures - Bowel obstruction (40% of cases) • Fistula, Abscess • Malabsorbtion syndrome • rarely – massive hemmorhage

17. UC CD

18. UC CD

19. UC CD

20. Extra intestinal manifestations • In 25% of IBD cases • Usually seen with colonic involvement • Involve any organ system • Skin, joints, eyes,biliary tract commonlyaffected • Mainly immune mediated • Most respond to Rx ofthe underlying disease

21. The common ones • Skin: Erythema nodosum, Pyoderma gangrenosum • Joints : Peripheral arthritis, Ankylosing spondylitis Sacroliitis • Ocular : conjunctivitis, anterior uveitis / iritis, episcleritis • Hepatobiliary : Hepatic steatosis, Cholelithiasis P. sclerosing cholangitis • Urologic : Nephrolithiasis, ureteral obstruction, Fistulas

22. THANK YOU