Inflammatory Bowel Diseases (IBD) Clinical aspects Nitsan Maharshak M.D., IBD Center, Department of Gastroenterology and Liver Diseases Tel Aviv Soura

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1 Inflammatory Bowel Diseases (IBD) Clinical aspects Nitsan Maharshak M.D., IBD Center, Department of Gastroenterology and Liver Diseases Tel Aviv Sourasky Medical Center Tel Aviv, Israel

2 IBD- clinical features Chronic inflammatory diseases of the GI tract characterized by periods of exacerbations and remissions. Diarrhea Abdominal pain Rectal bleeding Fever

3 IBD History- ulcerative colitis Wilks and Moxon- were the first to identify the disease as being from a non-infectious cause.

4 IBD History- Crohn s intestinal obstruction, inflamed gut, involving jejunal, ileal and colonic areas with transmural inflammation BMJ- T. Kennedy Dalziel: 13 patients JAMA- Burril Crohn- terminal ileitis Crohn s disease.

5 IBD history Crohn s disease T. Kennedy Dalziel, reported (BMJ) treating 13 patients who had suffered from intestinal obstruction. On autopsy he found that all had inflamed gut, in the jejunal, ileal and colonic areas with transmural inflammation Burril Crohn- JAMA- terminal ileitis.

6 Global map of Crohn's disease incidence. Ng S C et al. Gut doi: /gutjnl Copyright BMJ Publishing Group Ltd & British Society of Gastroenterology. All rights reserved.

7 Crohn s disease

8 ULCERATIVE COLITIS AND CROHN S DISEASE

9 EXTRAINTESTINAL MANIFESTATIONS

10 SKIN LESIONS

11 EYE LESIONS

12 ENDOSCOPIC SPECTRUM OF SEVERITY

13 ANATOMIC DISTRIBUTION

14 INFLAMMATION

15 OBSTRUCTION

16 FISTULIZATION

17 The many faces of Crohn s disease

18 RISK OF COLORECTAL CANCER

19 More than 2 million patients around the world

20 In Israel Incidence 10/ , /year for each of the diseases Over 20, patients. 20,000000

21 Inflammatory bowel diseases: An increasing burden on patients and families, health systems, economy Admissions, surgeries, procedures Increasing incidence Symptomsfrom mild to debilitating The burden of IBD Chronic disease Young patien ts Importance Psychosocial for finding a cure Loss of school/ workdays distress Treatment, t side effects, cost Young age at diagnosis Chronic-lifelong l diseases 21

22 Genetic- IBD Risk factors Common in twins and family members. More common in Jewish people. More than 160 susceptible genes loci.

23 GWAS in IBD Total of 163 IBD loci Jostins, L. et.al. Nature 491, (01 November 2012) Anderson, C. A. et al. Nature Genet. 43, (2011) Franke, A. et al. Nature Genet. 42, (2010) Most loci contribute to both phenotypes CD 30 IBD 110 UC 23 Jostins, L. et.al. Nature 491, (01 November 2012) Many variants are associated with the immune system, however most do not have an obvious function

24 IBD- Environmental factors - Northern areas- Hygiene theory / Old friends - Industrialization- Food (refined sugars, high fat, less vegetables) - vaccination - Air pollution - Protective- Multiple siblings, rural areas

25 IBD- Environmental factors - Northern areas-

26 IBD- Environmental factors

27

28

29 Hygiene theory / Old friends

30 IBD- Environmental factors Cigarette smoke Stress (?) NSAIDs

31 ..inappropriate and ongoing activation of the mucosal immune system driven by the presence of normal luminal flora, in a genetically susceptible host. Gut microbiota Increased pro-inflammatory Decreased beneficial Genetic susceptibility Environmental triggers Barrier function Infection Bacterial killing NSAIDS Immunoregulation Smoking Stress Diet Effector immune response Increased Th1 and Th17 Defective innate responses

32 IBD Diagnosis Clinical presentation, background Laboratory studies Colonoscopy, gastroscopy CT Enterography MR Enterography Capsule endoscopy Serologies? Genetics?

33 p-anca AND ASCA IN IBD

34 DIFFERENTIAL DIAGNOSIS OF INFECTIOUS AND ULCERATIVE COLITIS

35 DIFFERENTIAL DIAGNOSIS OF IBD AND IBS

36 CONVENTIONAL DRUG THERAPIES Anti-chemokine rec.

37 Downloaded from: StudentConsult (on 24 October :39 PM) 2005 Elsevier

38 Hypersensitivity Biologics side effects: Immediate (22% vs. 9% placebo) Delayed (serum sickness-like) Infections (36% vs. 26% placebo) TB, fungal, bacterial and viral infections Abscess in fistula patients Auto antibodies ( %) /Lupus-like HACA Malignancies: Lymphoproliferative; skin cancer? Neurologic events: demyelinating i disease Cardiovascular deterioration Skin manifestations

39 UC- surgery

40 Crohn s disease- surgery

41 POSTOPERATIVE RECURRENCE RATES IN CROHN S DISEASE

42 Experimental therapies Helminths- ova of Trichuris suis Fecal transplantation

43 רבה תודה

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