Diarrhoea & Inflammatory Bowel Disease on the Medical Take

Reena Sidhu FRCP MD Consultant Gastroenterologist Royal Hallamshire

Hospital, Hon Professor University of Sheffield

Next 25min- Case Based

• Case history

• Inflammatory Bowel Disease -a quick revision

• Management of IBD in the acute setting

• Escalation therapy

• Case 2 & 3

• Summary

Case 1: RH • 23 year old female

• 8 week history of left iliac fossa pain and bloody diarrhoea, opening bowels 7/ day

• Drug history: trimethoprim 2 weeks ago for UTI

• Past history: asthma as a child

• Smoking history: stopped smoking 6 months ago

• Work history: teaching assistant

• Family history: nil

Clinical Examination

• Temp 37.2 C

• Normotensive, pulse 96 bts/min

• Abdomen- tenderness LIF, no guarding. Bowel sounds normal.PR normal

• Bloods: Hb 109, WCC 10.1, platelets 435, MCV 81, ESR 17, CRP 25, albumin 35, urea 7.5, creatinine 99, PT 11

• Was given trimethoprim but Urine culture 2/52 –wcc on microscopy-culture negative

Abdominal Xray Image

A No toxic dilatation of colon

B Toxic Dilatation of Colon

What is the Definition of Toxic Megacolon

A) Transverse Colon diameter > 4.5cm

B) Transverse Colon diameter > 5.5cm

C) Transverse Colon diameter >6.5cm

D) Transverse Colon diameter > 7.5cm

E) Transverse Colon diameter >8.5cm

AXR: Toxic megacolon

Definition of Toxic

megacolon

5.5cm,

caecum >9cm

Differential diagnosis

• Infective diarrhoea-exclude C-difficile

• Inflammatory bowel disease

Triage to gastroenterology

Management- Pick all correct answers

A) Further stool culture, stool chart B) Antibiotics C) Prophylactic low molecular weight heparin D) Faecal calprotectin E) Flexible sigmoidoscopy • Risk of VTE 2-3x with acute flare/ does not

increase risk of bleeding • Role of Faecal calprotectin – infection &

inflammation • Flexi sigi?

Ulcerative colitis Vs Crohn’s ds

• Diffuse, continuous inflammation proximal to anal canal, granularity, loss of vascular pattern, friability, superficial ulceration

• Clear demarcation of disease extent & Stricturing is rare

Manes G, et al. Inflammatory Bowel Dis 2008;14:1133–8. Magro, et al. J Crohn’s Colitis 2013;7(10):827–51. Odze R, et al. Am J Surg Pathol 1993;17:869–75.

Endoscopy images courtesy of Dr Reena Sidhu

UC CD

Distribution Continuous; proctitis, left sided,

pancolitis

Patchy;

TI, colon, upper GI tract

Mucosal inflammation

Superficial, continuous,

denuded

Transmural, patchy,

cobblestoning

Histology Cryptitis, crypt abscesses

Granulomas

Fistula - Perianal, enteric

How do you define Severe Ulcerative Colitis?

Criteria for Acute severe ulcerative colitis

• Truelove and Witts criteria1

– >6 bloody stools/day, and

– tachycardia > 90 bpm, or

– pyrexia > 37.8C, or

– Hb < 10.5 g/dL, or

– ESR > 30 mm/h, or

• Stool chart, day 3 CRP/ESR, consider repeating AXR

• Flexible sigmoidoscopy-is it safe? Yes/ No

1Truelove, Witts. Br Med J 1954; 2: 375-378. 2CONSTRUCT. Williams et al. Lancet Gastroenterol Hepatol 2016; 1: 15-24.

Flexible Sigmoidoscopy: Images of UC

Normal

mucosa

Loss of vascular pattern, granularity

Mucosal granularity, exudate,

superficial ulceration,

Pseudo-membrane colitis

The modified Mayo score (0–3) is a commonly used endoscopic score

Comparison of mild vs severe disease

• Vascular pattern

• Bleeding

• Erosions/ulcers- Presence of deep ulcers associated with higher rates of

colectomy

Feagan BG, et al. N Engl J Med 2005;352:2499–507. Travis SP, et al. Gut 2012:61:535–42.

Ulcerative colitis

Classification Definition Maximal endoscopic involvement

E1 Proctitis Limited to rectum

E2 Left-sided Limited to colonic distal to splenic flexure

E3 Extensive Extends proximal to splenic flexure

Colectomy rate higher with more extensive ds

Images of Crohn’s disease

Ulceration, erythema

Severe ulceration with exudate

Pseudopolyp

Images from www.endoatlas.com

Crohn’s disease

A: Age of onset L: Location B: Behaviour

A1 = ≤16 y L1 = ileal B1 = non-structuring, non-penetrating

A2 = 17–40 y L2 = colonic B2 = stricturing

A3 = >40 y L3 = ileocolonic B3 = penetrating

L4* = isolated upper GI + p = perianal disease is present

Silverberg MS, et al. Can J Gastroenterol 2005;19 Suppl A:5A-36A.

Antibiotics cover Required?

If c-difficile strongly suspected/ detected- concomitant steroids and oral vancomycin Trimethoprim –low risk for C-difficile compared to ciprofloxacin etc

Lamb C et al Gut 2019

Day 3 –Sunday

• Day 3 Iv steroids

• Bowels 6/day

• CRP 15

• Stool cultures negative

• How long should steroids be continued before escalation?

How long should steroids be continued • In the CONSTRUCT cohort, response rate to intravenous

steroids was 49%.

• Extending therapy> 7-10 days: no additional benefit & increases toxicity

Rescue therapy

• Cyclosporin 2mg/kg IV infusion followed by oral – success rate 80% but reviews suggest colectomy rates 26-47%

• Side effects infection (5%)nephrotoxicity, seizures, anaphylaxis. Measuring levels at the weekend

• Anti TNF – single dose colectomy rates 50% versus 76%

controls at 2 years. • Azathioprine reduces Ab formation • Similar outcomes with anti TNF and cyclosporin but

easier administration of anti TNF in acute setting • Ensure screening for TB, hepatitis, EBV etc done prior to

rescue therapy ( best practice –done on admission)

Surgical Review

Lamb C Gut 2019

Case 1- Progress

• Patient settled and discharged home

14 weeks later

• Telephone from GP to medical Spr: over weekend –patient now travelling abroad- what advise to be given?

Travel Advise

Risk of DVT advise Lamb C Gut 2019

Readmission

• 11 months stable on anti TNF monotherapy

• Readmission

• Worsening diarrhoea- bowels 5-7/day.

• Examination normal.

• CRP 12. FBC- HB 12. neutrophilia. AXR non specific bowel gas pattern

• Flare of disease ?

• What next?

Management

• Steroids

• Flexi sigi- mild erythema only. Biopsies including for CMV

• Stool culture- campylobacter!

• Antibiotics as not self limiting

• UK study showed 10.5% readmission in IBD related to enteric infection

Lamb C Gut 2019

Summary of Case 1

• Recognising IBD and markers of severity

• Don’t delay steroids

• Markers of severity at flexible sigmoidoscopy

• Reassess Day 3- Consider rescue therapy/ surgical input when steroids are failing

• Consider infection during flare ups

Case 2: EM

• 28 year old diarrhoea 6/day

• Urgency, morning rush

• Abdo cramps, severe bloating

• Medical hx- depression

• Medication- nil

• Examination normal

Blood parameters

• Hb 130, Wcc 8, Plts 245. CRP <5 ESR 5

• Faecal calprotectin by GP <5.

• AXR –nad

• What is differential dx

• IBS positive diagnosis on Rome Criteria- abdo discomfort 1/day per week for 3 months associated with change in frequency/ consistency of stool

Alterations in gut flora

Altered brain-gut

interaction

GI dysmotility

Psychological stress

Neurotransmitter dysfunction

Visceral hypersensitivity

IBS

Irritable Bowel Syndrome versus IBD

Faecal Calprotectin : A calcium- and zinc-binding neutrophilic cytosolic

protein

Expressed by activated neutrophils.

Inflammation in the bowel results in acute phase reaction & migration of

leukocytes to the gut.

Production of large number of proteins detectable in serum and stool.

IBS versus IBD using Faecal Calprotectin

Abraham Gastro Clin N Am 2012

Investigations: Baseline

• TSH

• Coeliac serology, Ig,ca , haematinics

• Faecal elastase

• Loperamide, anti spasmodics

• Discharge and refer to gastro as OPD

Learning points Case 2

• Differentiating IBS & IBD clinically

• Tests that are helpful at baseline

• Safe to discharge

Case 3- SH

Acute physician on call Saturday 26 female with ulcerative colitis on azathioprine & anti TNF presents with bloody diarrhoea for 2 weeks and abdominal pain past 24 hours. She says she has not had a period for the past 3 months • What investigations would I request? AXR –Y/N • What treatments would I want to start or stop? Stop

anti TNF/ azathioprine? • Who do I inform? • Should I admit her?

Investigations Case 3

• Pregnancy test, Bloods, Stool culture and chart, LMWH

• Radiology / Endoscopy?

• In pregnant women with suspected IBD or IBD flare, we

recommend limiting radiologic investigations to the use

of sonography and magnetic resonance imaging where

possible in 2nd trimester

• Flexi sigi- considered to be safe in pregnancy; however,

these procedures should only be done when there is a

strong indication and should be preferably performed in

the second trimester

Ecco Guidelines

General advice in pregnancy • Combined care with an interested Obstetrician

• Vast majority of IBD drug treatment is safe except methotrexate and thalidomide

• 5ASA, prednisolone, azathioprine and anti-TNF are safe in pregnancy

• Current advice is to continue immunosuppression & biologics through pregnancy on discussion with pregnant mother with avoidance of live vaccination in the newborn for 6 months

• Breast-feeding on the vast majority of treatment is safe

Case 3 management

Exclude infection/ stool cultures

Consider steroids IV , continue other medications

Imaging vs endoscopy

Combined Care with Obstetrician/ monitoring of fetal growth

General advice in pregnancy

• Flares of UC and CD can occur in pregnancy

• Encourage conception when IBD is well controlled

• Better controlled the chronic illness i.e. IBD prior to conception, lower the risk of a flare

• Better the IBD during pregnancy better the outcomes of the pregnancy

• Active IBD is associated with complications such as small for gestational age and premature delivery

Summary of all 3 cases

• Recognising IBD and markers of severity

• Don’t delay steroids

• Markers of severity at flexible sigmoidoscopy

• Reassess Day 3- Consider rescue therapy/ surgical input when steroids are failing

• Recognising difference between IBD & IBS and when safe to discharge

• Vast majority drugs safe in pregnancy except MTX/ thalidomide

Thank You Fancy gastroenterology research in Sheffield?

Clinical Fellow/Post CCT fellow

ReenaSidhu@nhs.net