Fagligt Selskab for Gastroenterologiske sygeplejerkser

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1 Fagligt Selskab for Gastroenterologiske sygeplejerkser
Mikroskopisk colitis Fagligt Selskab for Gastroenterologiske sygeplejerkser Landskursus, Kolding 16. November 2012 Ole Bonderup, Medicinsk afdeling, Regionshospitalet Silkeborg

2 Mikroskopisk colitis

3 Ole Bonderup, Medicinsk afd. Regionshospitalet Silkeborg
Mikroskopisk colitis Collagenous Colitis (Lindström, 1976) Lymphocytic Colitis (Read et al.1980) (Lazenby et al., 1989) Microscopic Colitis Ole Bonderup, Medicinsk afd. Regionshospitalet Silkeborg

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5 Mikroskopisk colitis

6 Mikroskopisk colitis

7 Mucosal tears in collagenous colitis
Allende DS et al. Am J Gastroenterol 2008

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9 Mikroskopisk colitis It´s best to know what you are looking for before you look for it Normal colon mucosa Lymphocytic colitis Collagenous colitis

10 Mikroskopisk colitis MC versus non MC
Interobserver agreement 91% (kappa = 0.90) Intraobserver agreement 95% (kappa = 0.89). Tre patologer vurderer 20 lymfocytære, 20 collagene 30 normale I vort eget studie god correlation melllem to vurderinger af inflammation og tykkelse af collagent lag. Limsui D, et al Inflamm Bowel Dis. 2009

11 Epidemiologi If we now turn to the background for our studies we could ask: What is the natural history of cc. What will happen if no treatment is instituted. We have to realise that there are no prospective studies of the long term course of cc. Therefore we have only, some indications of the natural history. However this picture could indicate the answer.

12 Mikroskopisk colitis - epidemiologi
CC LC Sweden 9.0/1 --- Spain 1993–97 4.8/1 2.7/1 Sweden 7.5/1 2.1/1 US 6.7/1 1.6/1 Iceland 7.9/1 5.0/1 Female/male ratio

13 Incidence of collagenous colitis.
Annual incidence per inhabitants Örebro, Sweden Olmsted County,

14 Incidence of lymphocytic colitis
Annual incidence per inhabitants Örebro, Sweden Olmsted County,

15 Symptomer If we now turn to the background for our studies we could ask: What is the natural history of cc. What will happen if no treatment is instituted. We have to realise that there are no prospective studies of the long term course of cc. Therefore we have only, some indications of the natural history. However this picture could indicate the answer.

16 Mikroskopisk colitis F Baert et al, Gut 1999

17 Mikroskopisk colitis Hovedsymptomet ved mikroskopisk colitis er et svært diaré-problem. Hyppigt et meget langvarigt diaré-problem Afføringen beskrives som vandtynd op til gange i døgnet. Der er ofte pludselig indsættende og uimodståelig afføringstrang.

18 Mikroskopisk colitis Der er sædvanligvis ingen ”advarsels-symptomer”
Ingen blod i afføringen Intet større vægttab Ingen væsentlige smerter Er dette tilfældet skal andre sygdomme overvejes

19 Mikroskopisk colitis - symptomer
Svære afføringsgener Diaré Natlig afføring Imperiøs afføring Incontinens Lette almensymptomer Vægttab Mavesmerter Meteorisme Ole Bonderup, Regionshospitalet Silkeborg

20 Livskvalitet If we now turn to the background for our studies we could ask: What is the natural history of cc. What will happen if no treatment is instituted. We have to realise that there are no prospective studies of the long term course of cc. Therefore we have only, some indications of the natural history. However this picture could indicate the answer.

21 Mikroskopisk colitis - livskvalitet
Hjertesorg er svær at bære Mavekneb det er dog værre Piet Hein

22 Mikroskopisk colitis - livskvalitet
Kronisk diaré = Dårlig livskvalitet

23 Mikroskopisk colitis – livskvalitet
Quality of life (SF-36) in patients with collagenous and lymphocytic colitis. CC. N=38 LC. N=13 Controls Physical funct. 56.2 74.4 85.7 Role limitation – physical 35.2 83.7 Bodily pain 46.7 58.3 79.1 General health 45.4 68.1 Role limit – emotional 41.6 52.5 63.3 Vitality 79.2 88.8 Mental health 55.5 83.3 90.3 Social functioning 56.0 74.3 73.9 Miehlke et al. Ole Bonderup, Medicinsk afd.Regionshospitalet Silkeborg

24 Mikroskopisk colitis– livskvalitet
H. Hjortswang, 2005

25 Etiologi If we now turn to the background for our studies we could ask: What is the natural history of cc. What will happen if no treatment is instituted. We have to realise that there are no prospective studies of the long term course of cc. Therefore we have only, some indications of the natural history. However this picture could indicate the answer.

26 Kollagen colitis - etiologi
Importance of intraluminal agencies ?

27 Food Drugs Bile acids ? Bacte- ria

28 Behandling If we now turn to the background for our studies we could ask: What is the natural history of cc. What will happen if no treatment is instituted. We have to realise that there are no prospective studies of the long term course of cc. Therefore we have only, some indications of the natural history. However this picture could indicate the answer.

29 Mikroskopisk colitis Ubehandlet har sygdommen ofte et langvarigt kronisk forløb. Almentilstanden er relativ upåvirket, men sygdommen påvirker i svær grad livskvaliteten.

30 Collagenous colitis - background
Retrospective evaluation of treatment in collagenous colitis. No. of pts. Effect No effect Adv. effect Sulphasalazine Mesalazine Olsalazine Prednisolone Budesonide Metronidazole Erythromycin Penicillin Cholestyramin Loperamide What have been the previous treatment options for these patients? This is a retrospective analysis of treatment provided for 163 patients with cc. Some patients were treated on the basis of the experience from chronic inflammatory bowel diseases, some patients were treated with antibiotics and some with simple anti-diarrhoeals. However, none of the treatment options seemed fully effective. Bohr et al. Gut, 1996

31 Kollagen colitis Dobbelt-blind undersøgelse
Budesonide treatment of collagenous colitis Long-term budesonide treatment of collagenous colitis

32 Budesonide Chemical structure of budesonide
This is the chemical formula for budesonide. Budesonide is a modified glucocorticosteroid. The effect of budesonide is - similar to other glucocorticosteroids - mediated by a binding to intracytoplasmatic steroid receptors. The activation of the steroid receptors primarily results in a well known potent antiinflammatory response. Chemical structure of budesonide

33 Ole Bonderup, Medicinsk afd. Regionshospitalet Silkeborg
Kollagen kolitis Budesonide Steroid med lokal virkning Frigøres i terminale ileum Høj affinitet for steroid receptore High first-pass metabolisme i leveren Ole Bonderup, Medicinsk afd. Regionshospitalet Silkeborg

34 Double-blind treatmente phase Double-blind follow-up (off treatment)
Kollagen colitis Budesonide treatment of collagenous colitis. Study design of the 8 week randomised, double-blind, placebo-controlled trial. Budesonide n = 10 R Placebo n = 10 Double-blind treatmente phase Double-blind follow-up (off treatment) 8 weeks 8 weeks R, randomisation

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36 Budesonide treatment of collagenous colitis.
Results of the 8 week randomised, double-blind, placebo-controlled trial. Clinical effect + effect - effect Budesonide (n=10) 10 Placebo (n=10) 2 8 P<0.001

37 Ole Bonderup, Medicinsk afd. Regionshospitalet Silkeborg
Kollagen colitis Budesonide Ole Bonderup, Medicinsk afd. Regionshospitalet Silkeborg

38 Ole Bonderup, Medicinsk afd. Regionshospitalet Silkeborg
Kollagen colitis Kaplan-Meier curve of the risk of relapse after 8 weeks budesonide treatment . Ole Bonderup, Medicinsk afd. Regionshospitalet Silkeborg

39 Ole Bonderup, Medicinsk afd. Regionshospitalet Silkeborg
Kollagen colitis Long-term budesonide treatment of collagenous colitis. Study design of the 54 week randomised, double-blind, placebo-controlled trial. Ole Bonderup, Medicinsk afd. Regionshospitalet Silkeborg

40 Kollagen colitis Double-blind maintenance phase
Double-blind follow-up (off treatment) 6 30 54 weeks Budesonide mg once daily 4/17 (23.5%) 17 13/17 (76.5%)*** Placebo 17 2/17 (12%) 2/17 (12%) ***p<0.001 versus placebo (Fisher’s exact test)

41 Ole Bonderup, Medicinsk afd. Regionshospitalet Silkeborg
Kollagen colitis Ole Bonderup, Medicinsk afd. Regionshospitalet Silkeborg

42 Kollagen colitis

43 Budesonide 10% 100% Pharmacokinetic of budesonide
This figure illustrates the pharmacokinetic properties of budesonide. After oral ingestion budesonide – protected in capsules - is transported through the stomach and the proximal part of the small intestine. In the terminal ileum the capsule is released and the drug is almost completely absorbed in the terminal ileum and ascending colon. However, after absorption about 90% of budesonide is metabolised in the liver and only about 10% is released to the systemic circulation. These pharmacokinetic properties favour the balance between the desired clinical effect and the risk of side effects. Pharmacokinetic of budesonide

44 Ækvieffektive forhold budesonid versus prednisolon
Budesonid (Entocort) Prednisolon Klinisk effekt ved aktiv Crohn’s sygdom mg p.o mg p.o. Påvirkning af binyrebarkfunktionen mg p.o mg p.o.

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46 Kollagen colitis - behandling
NSAID NSAID seponeres. Kost Nedsætte kaffe forbrug Anti-diaré behandling. HUSK Imodium Questran Ole Bonderup, Medicinsk afd. M1, Regionshospitalet Silkeborg

47 Kollagen colitis -behandling
Budesonide First-line behandling i uger 9 mg 1x dgl i uger 6 mg 1x dgl i uger 3 mg 1x dgl i uger Ved recidiv behandling i 24 uger Omkring 30% har behov for langtidsbehandling Ole Bonderup, Medicinsk afd. Regionshospitalet Silkeborg

48 EMCC Consensus Treatment of Microscopic Colitis
MC established Drug-induced colitis ?Consider drug withdrawel* asymptomtatic  no Tx Dietary recommendations* quit smoking mild symptoms moderate/severe symptoms* i.e. antidiarrheals +/- cholestyramine* Budesonid 9 mg/ for 6-8 weeks failure failure relapse mild/moderate symptoms Alternative drugs Aminosalicylates +/- Cholestyramin Bismuth Probiotics Retreatment with Budesonide*(intermittend, continous) + Calcium/Vitamin D severe symptoms Immunomodulators i.e. AZT, MTX failure relapse, intolerance failure Surgery