Fisiopatologici e Clinici

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1 18 Simposio annuale ELAS-LIGAND LIGAND ASSAY 2012 LE MALATTIE INFIAMMATORIE INTESTINALI Aspetti Fisiopatologici e Clinici Giovanni Maconi Cattedra di Gastroenterologia Dipartimento di Scienze Biomediche e Cliniche Polo Universitario Luigi Sacco Università di Milano

2 Inflammatory bowel diseases Ulcerative colitis Crohn s disease Idiopathic, Collagenous lifelong, chronic colitis intestinal Lymphocitic colitis conditions characterized by Ischaemic colitis Diversion colitis periods of REMISSION Bechet disease and Indeterminate recurrent RELAPSES. colitis

3 Inflammatory bowel diseases Epidemiology Clinical features Natural history Behaviour Extension Treatment strategies Pathogenesis

4 Inflammatory bowel diseases Epidemiology Clinical features Natural history Behaviour Extension Treatment strategies Pathogenesis

5 Incidence and Prevalence of IBD Systematic review Ulcerative colitis Crohn s disease Incidence (per 100,000 person-years) Europe North thamerica Asia and Middle East Prevalence (per 100,000 persons) Europe North America Molodecky et al. Gastroenterology 2012

6 Incidence and Prevalence of IBD Systematic review Ulcerative Crohn s disease Colitis Molodecky et al. Gastroenterology 2012

7 Inflammatory bowel diseases Epidemiology Clinical features Natural history Behaviour Extension Treatment strategies Pathogenesis

8 Inflammatory bowel diseases Clinical Features Clinical indexes Endoscopic indexes Biochemical indexes

9 Ulcerative colitis Clinical Features SEVERITA Attività clinica - Influenza il tipo di terapia (orale, topica, parenterale, chirurgica) - Remissione = < 3 scariche / die, senza sangue con mucosa normale Remissione Lieve Moderata Severa N. scariche Asintomatico 4 > Sangue Può esserci Presente Presente o Polso (bmp) Normale Segni minimi > 90 bpm o Temperatura Normale di tossicità ità > o Emoglobina Normale sistemica <10.5 g/dl o VES Normale > 30 mm/h Classificazione di Montreal dell attività clinica nella colite ulcerosa

10 Ulcerative colitis Endoscopic Features SEVERITA Attività endoscopica Scores endoscopici di attività (Baron et al., Schroder et al. Feagan et al.) Parametri endosopici: Edema, eritema, granularità, sanguinamento, erosioni, ulcere

11 Ulcerative colitis Clinical Features Mayo score SEVERITA Attività clinica ed endoscopica Remissione 0 Lieve 1 n. Scariche Normale 1-2 / die > normale Moderata / die > normale Severa 3 5 / die > normale Sangue No Tracce Evidente Abbondante Mucosa Normale Lieve friabilità Moderata friabilità Sanguinam. Spontaneo Condizioni generali Normale Lieve Moderato Severo Classificazione di Mayo dell attività clinica ed endosopica nella colite ulcerosa

12 Crohn s disease Clinical Features Crohn s Disease Activity it Index (Best) SEVERITA Attività clinica Clinical or laboratory variable Weighting g factor Number of liquid or soft stools each day for seven days x 2 Abdominal pain (graded from 0-3 on severity) each day for seven days x5 General well being, subjectively assessed from 0 (well) to 4 (terrible) each day for seven days Presence of complications * x20 Taking Loperamide or opiates for diarrhea x 30 Presence of an abdominal mass (0 as none, 2 as questionable, 5 as definite) x 10 Hematocrit of <0.47 in men and <0.42 in women x 6 Percentage deviation from standard weight x 1 x 7 Severe Active Remission disease >150 <150 >450

13 Crohn s disease and Ulcerative colitis Clinical Features - Complications Hepatobiliary Muscoloskeletal Dermatologic Ocular Genitourinary i Vascular and hematologic Cardiac Pulmonary Endocrine and metabolic Most common triad Anal fissures, fistulae or abscesses, or other fistulae Fever during previous week

14 Inflammatory bowel diseases Epidemiology Clinical features Natural history Behaviour Extension Treatment strategies Pathogenesis

15 Ulcerative colitis Clinical course during 5 years of follow up 59% 1% 9% 31% 420 patients Henriksen et al. IBD 2006

16 Ulcerative colitis Clinical course during 25 years of follow up remission i intermittent i activity i continuous activity i 100% 90% 80% 70% 60% 50% 40% 30% 20% 10 % 0% M onths after diagnosis Langholz E et al. Gastroenterology 1994

17 Crohn s disease Clinical course during 10 years of follow up 43% 3% 19% 32% 197 patients Solberg C et al. CGH 2007

18 Crohn s disease Clinical course during 25 years of follow up 100% 90% 80% 70% 60% 50% 40% 30% 20% 10 % 0% High activity Low activity Remission years from diagnosis 373 patients Copenhagen Munkholm P et al. Scand J Gastroenterol 1995

19 Crohn s disease Natural history Symptoms Complications Lesions Surgery

20 Crohn s disease Natural history Behaviour over time inflammatory stenosant penetrating Louis E et al. Gut 2001

21 Crohn s disease Natural history Behaviour over time Cosnes Acta Gastroenterol Belg 2008

22 Crohn s disease Natural history Strictures and Fistulae Stenosi Fistola Ulcere profonde Riepitelizzazione

23 Crohn s disease Natural history Cumulative surgery rate ±2 SD Probabilit ty % Years Munkholm et al. Gastroenterology 1993

24 Crohn s disease Natural history Number of operations Years after diagnosis 1 surgery 2 surgery >3surgery No surgery 5 37 % 7% 5% 51 % % 11 % 12 % 39 % % 14 % 22 % 30 % Munkholm P et al. Gastroenterology 1983

25 Crohn s disease Natural history Use of immunosuppressant and Surgery rate Cosnes J et al. Gut 2005

26 Crohn s disease Natural history Recurrence and symptoms after operation Rutgeerts P. et al. Gastroenterology 1990

27 Inflammatory bowel diseases Treatment Conventional approach INDUCTION OF REMISSION Infliximab? Other biologics? MAINTAINANCE OF REMISSION Infliximab? Other biologics? CyA 6MP/AZA Corticosteroids 5-ASA/SASP severe moderate mild 6MP/AZA 5-ASA/SASP

28 Inflammatory bowel diseases Treatment Reversing the therapeutic pyramid? Early Biologics Steroids AZA / 6-MP / MTX Surgery Late 5-ASA +/- Antibiotics

29 Inflammatory bowel diseases Epidemiology Clinical features Natural history Behaviour Extension Treatment strategies Pathogenesis

30 Inflammatory Bowel Diseases Disease extension Ulcerative colitis Crohn s disease

31 Inflammatory Bowel Diseases Disease extension a dynamic state Influence on: Therapeutic and monitoring i approach Disease complications Delayed time to diagnosis from symptoms onset Cancer risk and timing of surveillance programs

32 Ulcerative Colitis Disease extension - Progression Extent at diagnosis Extent at follow-up Proctitis Left-sided colitis Pancolitis Pancolitis 34,0 % 70,4 % 98,3 % Lef-sided colitis 11,9 % 25,7 % 0,8 % Proctitis 54,1 % 3,9 % 0,8 % 1116 Cleveland pts Farmer RG et al. Dig Dis Sci 1993

33 Ulcerative Colitis Disease extension - Risk Factors of Progression Distal colitis Colitis with progression Extraintestinal manifestations 15.5% 5% 42.9% Steroid-refractory course 2.2% 28.0% Requirement of thiopurines 17.3% 44.3% Cyclosporine 1.9% 25.4% Infliximab 1.2% 9.5% Surgery 0.6% 20.6% Neoplasia 0% 6.3% 420 UC patients Etchevers M et al. IBD 2009

34 Ulcerative Colitis Disease extension and Cancer Risk Extensive colitis Left-sided colitis Cumula ative risk % Years

35 Crohn s disease Disease extension over time ileal colonic ileocolonic upper Louis E et al. Gut 2001

36 Crohn s disease Disease extension and cancer Site Relative risk 95% CI Ileal 1,0 0,1-3,4 Ileocolonic 32 3, ,7-9,2 Colonic 5,6 2,1-12,2 Other 1,2 1,3-4,3 Total 2,5 1,3-4,3 Ekbom et al. Lancet 1990

37 Inflammatory bowel diseases Pathogenesis Why?

38 Inflammatory bowel diseases Pathogenesis Genetics NOD2 Crohn s disease

39 Inflammatory bowel diseases Pathogenesis Immunity

40

41 Immune system in IBD

42 Inflammatory bowel diseases Biochemical, molecular and fecal biomarkers Challenges in IBD Diagnosis Differential diagnosis Assessment of disease activity Assessment of risk of complications Prediction of relapse Monitoring the effect of therapy

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