1. Management of Acute Severe Colitis
Dr Jayne Eaden
Consultant Gastroenterologist, UHCW

2. Symptoms Bloody diarrhoea (urgency & tenesmus) Abdominal pain
Weight loss
Obstructive symptoms
Abdominal mass (esp RIF)

3. Warning Signs Fever > 37.8 oC Dehydration
Tachycardia (P>90), Hypotension
Abdominal pain and tenderness (beware toxic dilatation and perforation)
Patients can look well if been on steroids - beware

4. Other Signs Mouth ulcers Perianal disease Erythema nodosum
Pyoderma gangrenosum
Eye disease
Arthropathy (large joints, asymmetrical and non-deforming)

8. Truelove & Witts Criteria
Defines severe Ulcerative Colitis
Bowels open > 6 times per 24 hours
Plus any one or more of the systemic manifestations
Haemoglobin < 10.5
ESR > 30
Pulse rate > 90
Temperature > 37.5

9. Differential Diagnoses
Bacterial infection
C. diff, Campylobacter, Salmonella, Shigella, E. coli 0157
Viral infection if immuno-compromised (CMV)
Amoeba especially if travel history
Crohn’s colitis and ischaemia
Diverticulitis can occasionally mimic

10. Investigations on Admission
Bloods
FBC
ESR & CRP
U&E, creat
LFT (albumin)
Blood cultures (if temp > 38°)
Glucose
(Mg+ and Cholesterol)

11. Investigations on Admission
Stool Culture and Microscopy
C. 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

12. Colectomy more likely if:
-Mucosal islands present
-Dilated small bowel loops

13. Investigations on Admission
Arrange a sigmoidoscopy and rectal biopsy. DO NOT prescribe bowel prep
should be done within hours of admission
Avoid colonoscopy and barium enema in patients with acute, severe colitis

14. Daily Investigations Bloods FBC
U&E, creat (particularly watch the potassium)
LFT
CRP (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 OK
Results must be reviewed the same day (esp potassium) particularly if abdominal X-ray is requested.

15. Extra Investigations
In appropriate patients, send Amoebic Fluorescent Antibody test
Check CMV titre if patient is not responding after 3 days (EDTA sample)

16. Daily Monitoring Temperature and pulse Stool chart
Frequency
Colour / blood content
Estimate of volume (record even if only passed blood or mucus)
Abdo examination findings
tenderness, bowel sounds
Note increasing pulse / temp / abdominal pain or tenderness may indicate deterioration or frank perforation and requires appropriate urgent investigation and d/w SpR / consultant.

17. Management Rehydrate with IV fluids
Correct electrolyte imbalance (in particular potassium)
Nutrition : Low residue diet (IV fluids if vomiting)
Inform colorectal surgeons & IBD nurse

18. Management
Corticosteroids: 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 transfusion
DVT prophylaxis e.g enoxaparin 40mg od

19. Management Look for and treat proximal constipation
If stop 5-ASA, restart on discharge
DO NOT
Use opiates / codeine phosphate/ loperamide (may precipitate paralytic ileus, megacolon and proximal constipation)
Use anti-cholinergics

20. Travis Criteria
After three days of intravenous hydrocortisone, the presence of
either
Stool frequency > 8 times per 24 hours or
Stool frequency > 3 times + CRP > 45
gives an 85% likelihood of requiring colectomy on the same admission

21. The Management of Acute Severe UC: options for rescue.......
If no improvement by day 3 make plans for day 5!
Surgery or
Cyclosporine
Infliximab
MUST be discussed with a Consultant Gastroenterologist

22. Indications for colectomy
Toxic dilatation with failure to improve clinically / radiologically within 24 hrs
Perforation
Uncontrolled lower GI haemorrhage
Failure to respond after 3 days IV steroids
Deterioration at any stage

23. Acute severe UC: the role of cyclosporine
Only use if stool cultures negative
Toxic drug – safety is paramount
IV hydrocortisone is continued
Check Mg+ and ensure cholesterol >3
Be aware of side effects (seizures)
Care in elderly / hypertensive / impaired renal function

24. Acute severe UC: the role of cyclosporine
What dose?
2mg/kg as IV infusion in 500mls glucose over 2-6 hrs
Monitor levels ( mcg/l trough)
Levels monitored at UHCW Mon-Fri
Rapid steroid wean once clinical response
If responded switch to oral after 3-5 days:
5mg/kg/day in 2 divided doses

26. Acute severe UC: the role of cyclosporine – long term outcome
Clinical experience from Oxford
76 pts from followed 2.9 yrs
54 received 4mg/kg, 22 oral 5mg/kg
74% entered clinical remission and left hospital
BUT 65% relapse at 1 yr, 90% at 3 yrs
58% of those came to colectomy at 7 yrs

28. Acute severe UC: the role of cyclosporine – exit strategy
Azathioprine naive vs refractory
Ideally check TPMT levels on admission
Commence Azathioprine at discharge
Wean off Cyclosporine after 6-8 weeks
Septrin 960mg alt days – prophylaxis against opportunistic infection
Early follow up to check remission and bloods

34. Three 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:

37. Acute severe UC: the role of infliximab – safety issues
Possible risk of lymphoma & malignancy
Increased if pt on other immunosuppressants
Infectious complications (VZV, candida)
Serious in 3%
TB reactivation (PPD & CXR required prior to treatment)
Interactions tacrolimus / live vaccines

38. Acute severe UC: the role of infliximab – safety issues
Contraindications:
Sepsis
Significantly raised LFTs (x3),
Hypersensitivity to infliximab
Active TB
Pregnancy } avoid for 6 months after
Breast Feeding } stopping treatment
Cautions:
Previous TB
Hepatic Impairment
Renal Impairment
Heart Failure
Mouse allergies
> 14 weeks since last infusion
Several patients have died of sepsis following use, so it is contraindicated when uncontrolled bacterial infection is present.

40. The 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.

41. An 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.

42. Infliximab 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

43. Management of acute severe UC: summary of evidence
Acute severe UC requires specialist care within an experienced MDT
Confirm diagnosis and exclude infection
Non responders should be identified early and salvage therapy considered
Controlled trials of cyclosporine vs infliximab are awaited

44. Management of acute severe UC: a multi disciplinary model
Physicians
Surgeons
The
Patient
Combined approach
Nurses
Dieticians
Pharmacists
Radiologists
Pathologists