8Truelove & Witts Criteria Defines severe Ulcerative ColitisBowels open > 6 times per 24 hoursPlus any one or more of the systemic manifestationsHaemoglobin < 10.5ESR > 30Pulse rate > 90Temperature > 37.5
9Differential Diagnoses Bacterial infectionC. diff, Campylobacter, Salmonella, Shigella, E. coli 0157Viral infection if immuno-compromised (CMV)Amoeba especially if travel historyCrohn’s colitis and ischaemiaDiverticulitis can occasionally mimic
10Investigations on Admission BloodsFBCESR & CRPU&E, creatLFT (albumin)Blood cultures (if temp > 38°)Glucose(Mg+ and Cholesterol)
11Investigations on Admission Stool Culture and MicroscopyC. Diff (3 separate samples)AXR: look for stool-free colon (indicates extent involved); severe disease indicated by mucosal oedema (thickened wall), mucosal islands, dilated small bowel loops, colonic dilatation (diameter > 6cm)Inform the surgeons on call if the colon is dilated
12Colectomy more likely if: -Mucosal islands present-Dilated small bowel loops
13Investigations on Admission Arrange a sigmoidoscopy and rectal biopsy. DO NOT prescribe bowel prepshould be done within hours of admissionAvoid colonoscopy and barium enema in patients with acute, severe colitis
14Daily Investigations Bloods FBC U&E, creat (particularly watch the potassium)LFTCRP (a vital prognostic guide)AXR for severe extensive colitis (any of fever, tachycardia, tenderness, dilatation on initial films) – in absence of these criteria less frequent AXR is OKResults must be reviewed the same day (esp potassium) particularly if abdominal X-ray is requested.
15Extra InvestigationsIn appropriate patients, send Amoebic Fluorescent Antibody testCheck CMV titre if patient is not responding after 3 days (EDTA sample)
16Daily Monitoring Temperature and pulse Stool chart FrequencyColour / blood contentEstimate of volume (record even if only passed blood or mucus)Abdo examination findingstenderness, bowel soundsNote increasing pulse / temp / abdominal pain or tenderness may indicate deterioration or frank perforation and requires appropriate urgent investigation and d/w SpR / consultant.
17Management Rehydrate with IV fluids Correct electrolyte imbalance (in particular potassium)Nutrition : Low residue diet (IV fluids if vomiting)Inform colorectal surgeons & IBD nurse
18ManagementCorticosteroids: Hydrocortisone 100mg QDS IV until remission achieved. May use Predsol/Predfoam PR once or twice per day (mainly for distal disease)Antibiotics (if febrile / toxic dilatation)Severely anaemic patients (Hb < 9g / dl) should be considered for transfusionDVT prophylaxis e.g enoxaparin 40mg od
19Management Look for and treat proximal constipation If stop 5-ASA, restart on dischargeDO NOTUse opiates / codeine phosphate/ loperamide (may precipitate paralytic ileus, megacolon and proximal constipation)Use anti-cholinergics
20Travis CriteriaAfter three days of intravenous hydrocortisone, the presence ofeitherStool frequency > 8 times per 24 hoursorStool frequency > 3 times + CRP > 45gives an 85% likelihood of requiring colectomy on the same admission
21The Management of Acute Severe UC: options for rescue....... If no improvement by day 3 make plans for day 5!SurgeryorCyclosporineInfliximabMUST be discussed with a Consultant Gastroenterologist
22Indications for colectomy Toxic dilatation with failure to improve clinically / radiologically within 24 hrsPerforationUncontrolled lower GI haemorrhageFailure to respond after 3 days IV steroidsDeterioration at any stage
23Acute severe UC: the role of cyclosporine Only use if stool cultures negativeToxic drug – safety is paramountIV hydrocortisone is continuedCheck Mg+ and ensure cholesterol >3Be aware of side effects (seizures)Care in elderly / hypertensive / impaired renal function
24Acute severe UC: the role of cyclosporine What dose?2mg/kg as IV infusion in 500mls glucose over 2-6 hrsMonitor levels ( mcg/l trough)Levels monitored at UHCW Mon-FriRapid steroid wean once clinical responseIf responded switch to oral after 3-5 days:5mg/kg/day in 2 divided doses
26Acute severe UC: the role of cyclosporine – long term outcome Clinical experience from Oxford76 pts from followed 2.9 yrs54 received 4mg/kg, 22 oral 5mg/kg74% entered clinical remission and left hospitalBUT 65% relapse at 1 yr, 90% at 3 yrs58% of those came to colectomy at 7 yrs
28Acute severe UC: the role of cyclosporine – exit strategy Azathioprine naive vs refractoryIdeally check TPMT levels on admissionCommence Azathioprine at dischargeWean off Cyclosporine after 6-8 weeksSeptrin 960mg alt days – prophylaxis against opportunistic infectionEarly follow up to check remission and bloods
34Three intervention possibilities may prevent CRC: 1) surveillance by colonoscopy, 2) surgical removal of the ‘target’ and 3) cancer chemoprevention. However, despite the use of colonoscopic surveillance programmes for UC Dukes’ A, B, C and metastatic cancers still occur. Therefore, surveillance offers little help in early recognition of CRC. To increase the effectiveness of preventative measures for CRC, patients should be assessed with regard to: 1) family risk of CRC; 2) the genes underlying the inherited syndromes of CRC – which have been identified and 3) improved screening tests – which are now validated9. Whether these approaches offer any advantage in identifying patients at the pre-cancer/dysplastic stage in UC and CD has not been elucidated to date.Cancer prevalence rates of 3–22% have been reported in association with low-grade dysplasia10. In one study, 590 UC patients after proctocolectomy had the histological findings of their preoperative colonoscopy assessed. The odds ratio for synchronous cancer was 43 for low-grade dysplasia and 15 for high-grade dysplasia.1Rosenstock et al. Gastroenterol 1985; 89:2Connell et al. Gastroenterol 1994; 107:3Jones et al. Gut 1988; 29:4Lennard-Jones et al. The Lancet 1983; 2:5Brostrom et al. Gut 1986; 27:6Nugent et al. Gastroenterol 1993; 100:7Lashner et al. Dig Dis Sci 1989; 34:8Rozen et al. gastroenterol 1995; 108:9Burt. Gastroenterology 2000; 119:10Gorfine et al. Dis Col Rec 2000; 43:
37Acute severe UC: the role of infliximab – safety issues Possible risk of lymphoma & malignancyIncreased if pt on other immunosuppressantsInfectious complications (VZV, candida)Serious in 3%TB reactivation (PPD & CXR required prior to treatment)Interactions tacrolimus / live vaccines
38Acute severe UC: the role of infliximab – safety issues Contraindications:SepsisSignificantly raised LFTs (x3),Hypersensitivity to infliximabActive TBPregnancy } avoid for 6 months afterBreast Feeding } stopping treatmentCautions:Previous TBHepatic ImpairmentRenal ImpairmentHeart FailureMouse allergies> 14 weeks since last infusionSeveral patients have died of sepsis following use, so it is contraindicated when uncontrolled bacterial infection is present.
40The 5-aminosalicylates have a lower risk of inducing GI tract bleeding than NSAIDs. Indeed, the risk of developing GI bleeding from 5-ASA is 1% compared with 18% for aspirin (ASA) and 2.6% for ibuprofen-based treatments1. Furthermore, NSAIDs are relatively contraindicated in IBD patients due to intestinal re-bleeding and reactivation of terminal ileitis2.1Skeith KJ, Wright M et al. Differences in NSAID tolerability profiles. Fact or fiction? Drug Safety :183–195.2Bjarnason I, Williams P et al. Intestinal permeability and inflammation in rheumatoid arthritis: effects of non-steroidal anti-inflammatory drugs. Lancet :1171–1174.
41An epidemiological cohort study of 373 CD patients and 1161 UC patients, followed from 1962–1987, recommended maintenance treatment with sulphasalazine (and later 5-ASA, mesalazine)1,2 . In this study, approximately 42% of the patients, monitoring maintenance treatment with sulphasalazine or 5-ASA was continuous, and in 23% was intermittent.It was speculated that this high level of medical therapy with 5-ASA combined with early surgical treatment was responsible for the low occurrence of cancers in this cohort.1Langholz E. Ulcerative colitis. An epidemiological study based on a regional inception cohort, with special reference to disease course and prognosis. Dan Med Bull :400–415.2Munkholm P. Crohn's disease--occurrence, course and prognosis. An epidemiologic cohort-study. Dan Med Bull :287–302.
42Infliximab for chronic active UC: can we predict who will respond? Serum albumin <30g/l: 67% vs 23% colectomy OR 6.86 ( ) p=0.05 (Lees et al APT 2007)No effect of smoking status, age, stool frequency or disease extent
43Management of acute severe UC: summary of evidence Acute severe UC requires specialist care within an experienced MDTConfirm diagnosis and exclude infectionNon responders should be identified early and salvage therapy consideredControlled trials of cyclosporine vs infliximab are awaited
44Management of acute severe UC: a multi disciplinary model PhysiciansSurgeonsThePatientCombined approachNursesDieticiansPharmacistsRadiologistsPathologists