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Inflammatory Bowel Disease Inflammatory bowel disease Dr Van de putte D Prof Dr P Pattyn Ghent, 18/12/2018 Colitis Ulcerosa Thomas Sydenham (17e eeuw) Non contagious “bloody flux” Samuel Wilks (19e eeuw) “Simple ulcerative colitis” Lockhart Mummery (1905), St. Mark’s Hospital “Electric sigmoidoscope” “Irrigation of the inflamed mucosa might heal the colonic mucosa” Colitis Ulcerosa Brown “Ileostomy to rest the bowel” (protruding ileostomy through the incision) Strauss Koenig Rutzen bag (1945) “Rubber bag cemented to the skin” Dennis (1945) “Colectomy and ileostomy” Brooke (1951)( Birmingham) and Turnbull (Cleveland) Colitis Ulcerosa Parks and Nichols (1978): Modern ileal pouch operation Crohn Burrill Bernard Crohn (1884-1983) Alfred Berg Leon Ginzburg Gordon Oppenheimer 1949 bypass operations , extended surgical resection of histological disease (short bowel) 1932 “regional ileitis” “growing realization of the increasing incidence of recurrences following all types of surgical interference” Eisenhower: 1956 bypass JFK: 1937: Mayo clinic: ‘colitis’ voor ileitis Indeterminate colitis A definitive histopathological diagnosis of UC or Crohn’s is not always possible following colectomy 10%-15% of surgical specimens diagnosis of indeterminate colitis Incidentie van IBD ? neemt toe ? neemt af ? blijft stabiel ? ↑ incidence in time and in previous low incidence regions, eg Asia –Eastern europe Molodecky et al. Increasing incidence and prevalence of inflammatory bowel diseases with time, Systematic review, Gastroenerology 2012 Invloed van geografie , demografie en tijd: IBD diagnose is duidelijk toegenomen over de laatste 4 decades Betere diagnostiek ? en/of meer blootstelling aan een ongedefinieerde trigger ? Geen verband tussen toename en in gebruik nemen van nieuwe beeldvormingstechnieken Incidentie van IBD - Risk for general population: 0,1% - Approximately 10% of patients has positive family history - Risk if 1 parent has IBD: CD: 2-3%, UC:0,5-1% - Risk if 2 parents have IBD: >30 % at 28 years of age - 20-50 fold increase in prevalence among siblings Etiopathogenesis Genetic factors Intraluminal antigens Environmental factors - Racial and ethnic differences - Increased incidence among monozygotic twins (CD) - Association with certain genetic syndromes DYSRGEGULATED IMMUNE RESPONSE GENETIC FACTORS ENVIRONMENTAL FACTORS Rookstop bij crohn: - Minder opstoten - Minder immunosuppressie nood Ponder et al. A clinical review of recent findings in the epidiology of inflammatory bowel disease, Clin Epidemiol 2013; 5:237-247 Anatomic distribution and behaviour of IBD CU Western Eastern Europe Silverberg et al. Can J Gastroenterol 2005; Burisch et al. Gut 2013 TYPES OF CROHN CROHN Silverberg et al. Can J Gastroenterol 2005 Risk for complicated disease course: L4>L1>L3>L2 LONG TERM EVOLUTION OF CROHN S DISEASE BEHAVIOUR Cosnes J et al. Inflamm Bowel Dis 2002 CROHN 20-30 % at first presentation Lehmann score Pariente et al. PEDICTORS OF POOR PROGNOSIS IN CU CHANGE IN MORTALITY in 21 COUNTRIES FROM 1951-2005 - Young age - Extensive disease - No appendectomy in childhood - Non smoking PREDICTORS OF POOR PROGNOSIS IN CD - Young age - Perianal disease - Need for steroids - Smoking - Extensive disease - Deep ulcers Sonnenberg, Int J Epidemiol 2007 RISK FOR CRC IN CU by decade Overall cancer incidence 3,7% and 5,4% in pancolitis rises with duration of disease: Castano-Milla et al. 2014 Cumulative probabilities of 2% by 10 years, 8% by 20 years and 18 % by 30 years Eaden et al. Gut 2001 Sureillance endoscopy Normally start 8 years after initial diagnosis, except PSC Symptoms UC Symptoms CD - Dependant on disease extent, location, severity, behaviour and complication - Dependant on disease extent and severity of inflammation - Onset subtle and atypical - Onset usually slow and insidious - May manifest acutely: severe pain, - Severe attack with systemic symptoms (tachycardia, fever, obstruction, hemorrhage weight loss) - More heterogeneous manifestation than UC - Rectal bleeding (up to 90%) - Abdominal pain (84%) - Diarrhea (up to 83%) - Diarrhea (57%) - Rectal urgency (up to 85%) - Weight loss (43%) - Nocturnal defecation - Blood/mucus in the stool (up to 50%) - Tenesmen - Systemic symptoms (fever) - Crampy abdominal pain - Anemia - Passage of mucopurulent exudates - Failure to grow - Anorexie, weight loss, fever, nausea, vomiting - Bowel obstruction - Extraintestinal manifestations - Nausea, vomiting, abdominal distention → disease activity: Truelove and Witts score - Symptoms of perianal/RV/enterocutaneaous/entero- enteric fistulae or abcesses Diagnosis ENDOSCOPY Ileal involvement Skip lesions Lee et al. Clinical Endoscopy 2016 Diagnosis ENDOSCOPY UC ENDOSCOPY CD Simple endoscopy scores Crohn disease vs Crohn’s endoscopic index of severity Diagnosis HISTOLOGY UC HISTOLOGY CD - Only mucosal layer involved - Transmural inflammation - Epithelial erosions - Mixed infiltrate - Crypt distortion - Discontinuous inflammation - Crypt abcesesses - Granuloma’s - Globlet cell deletion Extra-intestinal manifestations IBD - Musculoskeletal (peripheral and axial arthropathy, osteoporosis) - Cutaneous (pyoderma gangrenosum, erythema nodosum) - Ocular (episcleritis, uveitis) - Hepatobiliary (primary sclerosing cholangitis) - Thromboembolism - Anemia THERAPY 1998 1998 1998 Introductie van Infliximab Monoclonaal Al ↔ TNF alfa THERAPY IBD: Step up strategy Combi IFX +thiopurine is superior in CD and UC ANTI-TNF: Infliximab (Remicade) (UC-CD) – Adalimumab (Humira) – Golimumab (Simponi) (RA) VEDOLIZUMAB (Entyvio) (UC-CD) USTIKINUMAB (Stellara) Azathioprine (Imuran) of Mercaptopurine (Purinethol) – Thioguanine (Lanvis) (THIOPURINES ) Methylprednisolone (Medrol) bij matige tot ernstige CU en Crohn (ileo)colitis Blokkeert pro-inflammtoire genen + promoot anti- Lokaal: Budesonide (Entocort-Budenofalk lokaal bij proctitis) of inflammatoire genen per os bij milde of matige ileitis– of beclomethasone diproprionaat po (Clipper) bij links CU niet responsief op 5ASA Anti-inflammatoir en anti- Indicatie : milde CU: Mesalazine (Pentasa- Colitofalk) – tumoraal in CU Sulfasalazine (Salazopyrine) Goal of treatment - Change the course of the disease Hit inflammation to avoid structural damage Top down strategies - Deep disease remission - Symptoms control - Avoid complications and surgery Colitis ulcerosa en heelkunde 15 en 40% colectomie Hoogste kans eerste jaar na diagnose Voornamelijk pancolitis en ernstige ziekte bij diagnose ziekte Selby W. Baillieres Clin Gastroenterol 1997;11:53-64 Crohn en heelkunde 60% heelkunde binnen 10 jaar na diagnose ± 20-40% zullen binnen de 5 jaar na heelkunde opnieuw heelkunde ± 40-70% zullen binnen de 15 jaar na heelkunde opnieuw heelkunde nodig hebben 2/3 van de crohn patiënten zullen minstens 1 * heelkunde nodig hebben gedurende hun leven Sales DJ, Arch Inter Med 1983;143:249-299 Operaties voor IBD ? Nemen af in aantal ? Blijven status quo ? Nemen toe ? Trends in Surgery for Crohn's Disease in the Era of Infliximab. Jones, Douglas; Finlayson, Samuel; MD, MPH Annals of Surgery. 252(2):307-312, August 2010. DOI: 10.1097/SLA.0b013e3181e61df5 Jaarlijkse database (NIS) in USA : aantal chirurgische procedures + hospitalisaties voor ziekte van Crohn Trends in surgery for Crohn’s Disease (1993-2004) Results 38% toename van opnames voor Crohn tussen 1993 en 2004 Lichte daling van de gemiddelde leeftijd Daling van de hospitalisatieduur van 8 naar 5,7 dagen 59% ♀ FIGURE 1. Colorectal resections. Trends in population-based rates of colorectal resections in patients with Crohn's disease from 1993 FIGURE 2. Fistula repairs. Trends in population-based FIGURE 3. Incision of perianal abscess. Trends in population-based rates of to 2004 using classification in Table 1. rates of fistula repairs in patients with Crohn's disease incision of perianal abscess in patients with Crohn's disease from 1993 to 2004 from 1993 to 2004 using classification in Table 1. using classification in Table 1. Meest frekwente ingreep : rechter hemicolectomie Op de 15 meest frequente type ingrepen: Colorectaal (9) fistel herstel (3) dundarm (2) drainage een anaal abces (1) Surgery, Crohn's Disease, and the Biological Era: Has There Been an Impact?. Slattery, Eoin; MD, MRCPI; Keegan, Denise; Hyland, John; MCh, FRCSI; ODonoghue, Diarmuid; MD, FRCPI; Mulcahy, Hugh; MD, FRCPI Journal of Clinical Gastroenterology. 45(8):691-693, September 2011. DOI: 10.1097/MCG.0b013e318201ff96 IBD database of St. Vincent’s University Hospital, Dublin, Ireland: 722 patients 20 jaar periode (1986-2005): onderverdeeld in 4 periodes (quartiles) en resecties waren gerapporteerd 1 en 3 jaar na diagnose Introduction of biologicals (infliximab): multiple RCT: response rates of more than 60% Effect on intestinal resection ? FIGURE =1 . Surgical rates at 1 and= 3 years from diagnosis *P=0.03, [yen]P=0.963. = = Geen invloed van Infliximab op vroege darmresectie Type heelkunde veranderde niet over de jaren: 60% ileocolische resecties 25% colectomieën 20% geïsoleerde dundarmresecties 2 Laparoscopic ileocaecal resection versus infliximab for terminal ileitis in Crohn's disease: a randomised controlled, open-label, multicentre trial (LIRIC trial) Ponsioen et al. Lancet gastroenterology and hepatology, 2017 4 y follow up: Resection (N=72): 26% received IFX Infliximab (N=70): 37 % needed surgery Ulcerative colitis Definition and evolution Ulcerative colitis: a chronic inflammatory disorder of the colonic mucosa, usually beginning in the rectum and extending proximally to a variable extent. Management General principles • Majority controlled by medical
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