Transcript Inflammatory Bowel Disease

‘Runs in the Family’
Sophie Cook
James Day
Sarika Deshpande
Sara Dexter
Imran Jawaid
Anna Morgan
Case Presentation
22yr old male, central heating engineer
PC (5th May 2003): Bloody diarrhoea and
abdominal pain
HPC:
Blood in stool for 1/52
Diarrhoea for 4/7 – fluid stools, 8-10 per day
Abdominal pain – cramping, relieved by defaecation
Loss of appetite
General malaise
No nausea or vomiting
No recent foreign travel, all family well
Case Presentation
PMHx:
Diagnosed with Crohn’s disease in July 2002
Initial episode (July 2002) – hospitalised
2 x relapses – increased prednisolone, resolved
without admission
This episode
Tonsillectomy – as child
R knee arthroscopy and meniscetomy
Case Presentation
 DHx: (on admission)
Prednisolone 40mg OD – increased by self for 1wk prior to
admission
Mesalazine (Pentasa) 1.5mg BD
Calcichew – 500mg OD
 FHx:
Paternal grandmother and aunt – Crohn’s disease
 SHx:
Partner
Self-employed central heating engineer
Just bought flat – worried about mortgage
Smoker – but gave up when symptoms started
Alcohol – social drinker
Case Presentation – Examination
General
Pulse – 80bpm
BP – 120/60
Afebrile
Abdomen
Soft
Mild tenderness in RIF
No organomegaly
Good bowel sounds
PR - refused
Case Presentation – Initial
Investigations
 Bloods on admission
Hb – 15.0
WCC – 11.1
Neut – 6.5
Plt – 310
Na – 136
K – 4.1
Urea – 5.0
Creat – 103
Albumin – 38
CRP – 7.9
 Other Investigations
Stool culture
C. diff toxin
Case Progress - CRP
160
140
120
CRP
100
80
60
40
20
0
5
6
7
8
9 10 11 12 14 15 17 19 22
Day of Admission
Case Progress
Day 4 - C. diff toxin +ve - started
metronidazole
Day 4 - WBC scan showed pancolitis
Failure to respond to metronidazole, and IV
steroids, started azathioprine
Day 7-10 - increase in abdo pain and vomiting
(first CRP arrow)
Day 10 - failure of medical therapy, referred to
surgeons - total colectomy and ileostomy
(second CRP arrow)
Case Progress
Day 11-15 - gradual recovery
Day 17+ - worsening of condition, abdo
pain, vomiting. AXR showed small bowel
obstruction (third CRP arrow)
Day 23+ - condition improving, eating
and drinking
Day 29 - discharged
Future plan - reversal of ileostomy
Case Presentation – Diagnosis
Initial diagnosis (July ‘02) – Crohn’s disease
Rigid sig: patchy inflammation, biopsies showed mild
inflammation confined to mucosa, no granulomata
“active proctitis”
Small bowel study: terminal ileum thickened and
ulcerated “consistent with Crohn’s”
Current diagnosis – Ulcerative colitis
Surgical specimen “..diffuse active chronic inflammation
predominantly of mucosa, superficial ulceration, no
granuloma. Terminal ileum within normal limits.
Conclusion: ulcerative colitis”
Inflammatory Bowel Disease
‘Idiopathic inflammation of the bowel,
often with relapsing and remitting course’
Presentation (colon)  Diarrhoea
 Rectal bleeding
Fresh blood - proctitis
Altered blood - proximal to rectum
 Mucus
 Abdominal pain (less common)
 Severe: anorexia, nausea, weight loss, malaise, aphthous ulcers
 Examination is often normal
Differential Diagnosis
Conditions which mimic IBD colitis include Infection - C.diff, Salmonella, Campylobacter,
Giardia, TB, Yersinia, Amoebiasis, STI’s
Ischaemia
Radiation injury
Diverticular disease
Malignancy
Differential Diagnosis
Crohn’s outside the colon may produce other
symptoms, and mimic other conditions
Mouth - ulceration (eg. Behcet’s)
Oesophagus - dysphagia
Stomach - vomiting
Small bowel - steatorrhoea
Others - failure to thrive, anorexia nervosa
IBD - Extra-Intestinal
Manifestations
 Skin - erythema nodosum, pyoderma gangrenosum
 Mouth - aphthous ulceration
 Eye - episcleritis, anterior uveitis
 Joints - ankylosing spondylitis, sacroilitis, peripheral
arthropathy
 Liver and biliary tree - fatty liver, primary sclerosing
cholangitis, cholangiocarcinoma
IBD – Severity
 Can grade the degree of inflammation by endoscopy, histology and
laboratory markers (CRP, WCC, ESR)
 Truelove and Witt developed criteria to assess the severity of a
‘flare’
PARAMETER
SEVERE
BOWEL MOVEMENTS/
>6
MODERATE
MILD
4-6
<4
37.1 - 37.8
70 - 90
None
Apyrexial
< 70
DAY
BLOOD IN STOOL
TEMPERATURE
HEART RATE
Macroscopic
> 37.8
> 90
HAEMAGLOBIN (G/DL) < 10.5
>30
ESR (MM/H)
10.5 – 11.0
> 11.0
<30
IBD - Epidemiology
Non-Specific IBD
Crohn’s Disease (CD)
Incidence: 5-6 / 100,000 annually
Prevalence: 27-106 /100,000
Ulcerative Colitis (UC)
Incidence: 6-15/100,000 annually
Prevalence: 80-150/100,000
Any part of the GI tract
Only large bowel affected
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More common in the West
Lower incidence in non-Caucasians
Jews more prone to IBD than non-Jews
CD more common in females ( F : M = 1.2 : 1), mean age =26 yrs
UC more common in males ( F : M = 1 : 1.2 ), mean age =34 years
Any age affected, but most commonly occurs in those aged 20-40
IBD - Aetiology
 Familial – UC and CD more common in patients with
family members affected by IBD (6-10% of Pts with
UC/CD have 1+ relative with the disease)
 CD risk in 1st degree relatives of Pt with CD = 10-14 x
 UC risk in 1st degree relatives of Pt with UC = 8 x
 Studies in monozygotic twins show higher concordance
in CD than UC, suggesting that CD has a larger genetic
component than UC
 Chromosome 16 - a susceptibility gene has been
demonstrated, its contribution is greater in UC than it is
in CD
 Nob-2 gene in Crohn’s disease
IBD - Aetiology
 Diet - ?butyric acid ?sulphides ?glutamine
 Smoking
Increase CD, and exacerbates the condition
Increase UC in non/ex smokers, nicotine could be
considered an effective treatment in UC!!
 Infective agents - controversial, Mycobacterium, measles
virus, Listeria monocytogenes, Helicobacter hepaticus, H.
cinaedi, H. fenelliae and Saccharomyces cerevisiae
 Endogenous bacteria - bacteriods and E.coli, ?probiotics
 Immunopathogenesis - upregulation of macrophages and
TH1 lymphocytes in CD
IBD - Problems in Diagnosis
Overlap between Crohn’s colitis and UC occurs
in their clinical presentation, and in their
histological and radiological abnormalities, thus
making diagnosis difficult
10% of cases of colitis – ?diagnosis
Other forms of non-specific IBD exist
Differences Between CD and UC
- Histology
Crohn’s Disease Ulcerative Colitis
Bowel Affected
Any part from mouth
to anus
Inflammation
Granulomas
Deep - transmural
Patchy distribution –
‘skip lesions’
++
Colon
Terminal ileum may
experience reflux
ileitis
Mucosal - superficical
Continuous
distribution
Rare
Goblet Cells
Present
Depleted
Crypt abscesses
+
++
Differences Between CD and
UC - Histology
Crohn’s
UC
Images from: Allison MC, Dhillon AP, Lewis WG, Pounder RE.
Inflammatory Bowel Disease. London; Mosby: 1998
Differences Between CD and
UC - Radiology
 Crohn’s - deep ‘rose thorn’ fissures (Left)
 UC - smooth featureless colon (Right)
 Images from: Grainger RG, Allison DJ, Adam A, Dixon AK (eds).
Diagnostic Radiology (4th ed). London: Churchill Livingstone; 2001
IBD – Management
Principles of Management
Accurate diagnosis - may be difficult
Multi-dimensional - acute vs. chronic, medical
vs. surgical, complications, age-related
problems
Acute management - stepped approach
Chronic management - aim to keep in
remission
Medications: steroids, 5-ASA,
immunosuppressive drugs, novel therapies
IBD – Management: 5-ASA
5-ASA splits into sulphonamide and
amino-salicylic compounds
Preparation selected on basis of disease
location
Distal colonic disease - suppository, enema
Widespread colonic disease - oral conjugated
(eg. Mesalazine)
LHS colonic disease - oral and topical combo
Proximal small bowel - slow release oral
formulations
IBD - Management: Steroids
Topical in distal UC / proctitis
Oral - moderately severe UC or Crohn’s
IV - severe disease in hospitalised
patients - usually respond in 7-10 days.
Should only be used to control acute
activity, no maintenance benefit proven
Minimise steroid use to reduce side effects
IBD - Management:
Immunosuppressive Drugs
Eg. Azathioprine, methotrexate, cyclosporin
Use acutely if poor response to steroids
Allow decrease in steroid dose (chronic
management), and increase in remission
Toxic effects - may need monitoring
according to drug type
Azathioprine - WCC - risk of agranulocytosis
Methotrexate - LFT
IBD - Management: Other
Therapies
Anti-TNF drugs
Infliximab - trials show good efficacy in Crohn’s,
quick onset, ?response may reduce over time,
cost
Antibiotics
May be useful in Crohn’s, due to the possibility
of Mycobacterium as causative agent
Others: nicotine patches, thalidomide,
growth hormone, heparin, fish oil, elemental
diet
IBD - Management: Role of
Surgery
 Indications for surgery
Severe inflammation unresponsive to medical
therapy
Toxic megacolon +/- perforation
Chronic active disease
Prevention of cancer in UC
Risk of colon Ca increased by duration and extent of
UC, and FHx