Inflammatory bowel disease

By
Williams E.A
 Introduction

• IBD(crohn’s disease and ulcerative colitis) are chronic

relapsing inflammatory disorder of unknown origin,
collectively known as idiopathic inflammatory bowel
disease.
• They result from an abnormal local immune response
against the normal flora of the gut, and probably
against some self antigens in genetically susceptible
individuals.
• Crohn’s disease may affect any portion of the GIT but
most often the ileum, about half of cases exhibit non
caseous granulomatous inflammation.

• Ulcerative colitis is a non granulomatous disease

limited to the colon
 Epidemiology

CROHN’S

• World wide in distribution but more prevalent in US,

Britain, Central Europe, Scandinavia but rare Asia and
Africa
• Incidence is on the increase in the US and Western
Europe.
• Global annual incidence of 3-5/100000
• It can occur at any age but peak incidence is between
2nd and 3rd decade of life and a minor peak at 6th and
7th decades
• Female are slightly more affected than male
• Whites appear to develop the disease 2-5 times
more often than blacks
• In the US it occurs 3-5 times more often in Ashkenazi
Jews than non Jews.
• A 3yr study in ABU Zaria revealed 4 cases of UC and a
case of CD and attribute the low incidence to
unavailability of diagnostic tools and low index of
suspicion
UCERATIVE COLITIS

• More commoner than CD in US, Western countries

with an incidence of 10/100000 population but
infrequent in Asia, Africa and South America.

• The disease may arise at any age with peak

incidence between ages 20 and 25

• Exhibit no particular sex predilection.

• Commoner in whites than blacks.

 IBD
Crohn’s Ulcerative Colitis
 Aetiopathogenesis

• Although the aetiology of IBD is unknown,

• it is increasingly clear that IBD represents the interaction

between several co-factors:

- Genetic susceptibility,

- Environmental,

- The intestinal microbiota

- Host immune response

• Inflammation is the common pathway for the

pathogenesis of IBD.
• Both clinical and morphological changes are

ultimately as a result of inflammatory cells

 Genetic susceptibility

• CD and UC are complex polygenic diseases and

having a positive family history is the largest

independent risk factor for development of IBD.

• Up to one in five patients with CD and one in six

patients with UC will have a 1st-degree relative with

the disease.
• The monozygotic and dizygotic twin concordance

rates for CD are 20–50% and 10%,respectively.

• The major genetic factors are the NOD2 gene

(nucleotide oligomerization domain 2), the

autophagy genes and the Th17 pathway (interleukin

23-type 17 helper T cells).

• NOD 2 is expressed in epithelial cells, macrophages,

endothelial cells.

• Individuals who are homozygote or compound

heterozygote for one of several mutations in the NOD

2 gene have a significant increased risk of developing

ileal Crohn’s disease.

• Mutations in the autophagy genes ATG16L1 and
IRGM (immunity-related GTP-ase M-protein) and IL-
23 receptor gene increase CD risk, and mutations in
genes associated with the mucosal barrier increase
UC risk.
• HLA genes on chromosome 6 also appear to have a

role in modifying the disease.

• The DRB*0103 allele, is linked to a aggressive course

of UC and the need for surgery’

• DRB*0103 and MICA*010 are associated with

perianal disease and DRB*0701 with ileal CD.

 Environmental factor

• Smoking.

• Drugs; NSAIDS, antibiotics ,contraceptive

• Hygiene: Good domestic hygiene has been shown to

be a risk factor for CD but not for UC. Poor and large

families living in crowded conditions have a lower

risk of developing CD.

• Nutritional factors: Diet high in fat and sugar, low in

fiber and vitamin D’

• Psychological factors such as chronic stress and

depression seem to increase relapses in patients with

quiescent disease.

• Appendicectomy.
 Intestinal microbiota

• Intestinal dysbiosis.
• Specific pathogenic organisms. e.g increased E.coli
adherence.
• Bacterial antigens.
• Defective chemical barrier or intestinal defensins.
• Impaired mucosal barrier function
 Host immune response

• IBD occurs when the mucosal immune system exerts

an inappropriate response to luminal antigens, such

as bacteria, which may enter the mucosa via a leaky

epithelium
• pro-inflammatory cytokines are released by

activated effector T cells stimulate macrophages to

secrete proinflammatory cytokines such as tumour

necrosis factor α(TNF-α), IL-1 and IL-6 in large

quantities.
• Increased adhesion molecule expression on the

intestinal vascular endothelium, which facilitates the

recruitment of leucocytes from the circulation and

the release of chemokines all of which lead to tissue

damage
 Pan-
Colitis

leftsided
Colitis
Backwash
Ileitis

Proctitis

Progression from rectum to cecum

 Pathology
Crohn’s Ulcerative Colitis

Rectum and extends

Mouth to anus!
proximally!
• Terminal illeum • Proctitis
• Ileocolonic disease • Left sided colitis
– Ascending colon – Sigmoid and descending
• Skip lesions • Pancolitis
• Pancolitis • Backwash ileitis
– Can be large bowel only – Distal terminal illem
 Crohn’s
Macroscopic
changes
o Bowel is
thickened
o Lumen is
narrowed
o Deep ulcers
o Mucusal fissures
o Cobblestone
o Fistulae
o Abscess
o Apthoid
ulceration
 Macroscopic Ulcerative Colitis
changes
• Reddened Ulcerative Colitis
mucosa
• Shallow ulcers
• Inflamed and
easily bleeds
 Microscopic Changes
Crohn’s Ulcerative Coltis

Transmural! Mucosal!

• Chronic inflammatory cells: • Chronic inflammatory cells:

transmural lamina propria

• Lymphoid hyperplasia • Goblet cell depletion

• Granulomas • Crypt abscess
– Langhan’s cells
 Clinical Features
Crohn’s Ulcerative Colitis

• Presenting complaint • Presenting complaint

– Diarrhoea – Bloody diarrhoea
– Abdominal pain – Lower abdominal pain
– Weight loss – +/- mucus
– Malaise/lethagy – Malaise/lethargy
– Nausea/vomiting – Weight loss
– Low grade fever – Apthous ulces in mouth
– Anorexia
 History

• What to ask?
– Rashes

– Mouth ulcers

– Joint/back pain

– Eye problems

– Family history

– Smoking status
 History

• What else to ask?

– Previous diagnosed?
• How many flares do they get?
• Are they well managed?
• Do they have any concerns about their
treatment?
– Do they see a specialist?
 Physical signs

General Exam

- Weight loss

- Apthous ulcer of mouth

- Anaemia

- Clubbing
Abdominal Exam

- Colostomy bag

- May be some abdominal tenderness, may not.

- May find a RIF mass

 Abscess

 Inflamed loops of bowel

 Extraintestinal Manifestations

EYES Crohn’s UC
Uveitis 5% 2%
Episcleririts 7% 6%
Conjunctivitis 7% 6%
 Extraintestinal Manifestations

JOINTS Crohn’s UC
Type 1 Arthropaty 6% 4%
(Pauci)
Type 2 Arthropathy 4% 2.5%
(Poly)
Arthralgia 14% 5%
Ankylosing Spondylitis 1.2% 1%
Inflammatory back pain 9% 3.5%
 Extraintestinal Manifestations

SKIN Crohn’s UC
Erythema Nodosum 4% 1%
Pyoderma Gangrenosum 2% 1%
 Extraintestinal Manifestations
LIVER/BILLARY Crohn’s UC
Sclerosing cholangitis 1% 5%
Gall stones Increased Normal
Fatty liver Common Common
Hepatitis/ Cirrhosis Uncommon Uncommon

 Kidney stones in Crohn’s (oxalate stones post resection)

 Anaemia (B12 deficiency in Crohn’s)

 Venous thrombosis

 Other autoimmune diseases

 Investigations

• Stool culture: exclude infection

• Colonoscopy
• FBC : anaemia and likely raised WCC
• LFT: hypoalbuminaemia is present in severe disease,
hepatic manifestations
• Blood cultures: if septicaemia is suspected in the acute
presentation
• Serological: pANCA (UC)
Colonoscopy
• But never in severe attacks of UC due to high risk of
perforation
• May be painful in Crohn’s due to anal fissures
• Diagnostic
• Surveillance
 UC of more than 10 years duration increased risk of
dysplasia and carcinoma
 Investigations

• Imaging
– Plain AXR: helpful in acute attacks
• Thumb printing

• Lead pipe sign

– Barium follow-through in Crohn’s

– CT

– CXR
• Perforation

–
 UC CD

features Bloody diarrhea, Left lower quadrant Non bloody diarrhea, wt loss
abdominal pain, tenesmus mouth ulcers, perianal dx, RIF
mass
extraintestinal Primary sclerosing cholangitis

complications More Risk of colorectal cancer Obstruction, fistula, colorectal

cancer
pathology Inflamation always start at rectum, not Lesion seen anywhere from
beyond ileocecal area, asso with pANCA mouth to anus, skip lesion
present, asso with ASCA

histology No inflammation beyond submucosa Inflamation is mural, non

unless fuminant dx, depletion of goblet caseating granuloma formation
cells
endoscopy Widespread ulcers with preservation of Deep ulcres, skip lesions
adjacent mucosa, appearance of
pseudopolyps

radiology Loss of haustrations , pseudopolyps Stricture, fitulae, proximal

bowel dilatation
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 Definition of severe case

• Stool frequency >6 stools/day with blood +++

• Fever >37.5°C
• Tachycardia >90/min
• ESR >30 mm/h
• Anaemia <100 g/L haemoglobin
• Albumin <30 g/L
 MGT

• Admit to hospital
• i.v. fluids
• Give prophylactic anticoagulation
• Monitor daily:
• stool frequency
• abdominal X-ray
• FBC, CRP, albumin
 Treating IBD

• Induce remission
– Steroids – oral or IV
– Enteral nutrition
– Azathioprine / 6MP (Crohns)
• Maintain remission
– Aminosalicylates (UC)

– Azathipreine/ 6MP

– Methorexate

• Biologicals generally for Crohn’s only

– Infliximab,

– Adalimumab

Note: Test for TB first!

 Treating IBD

Crohn’s Ulcerative Colitis

1. Azathioprine 1. Aminosalicylates
- Mesalazie
2. Methotrexate
2. Steroids
3. Cyclosporin
- Foam/PR
4. Humera
- Oral
- Adalimumab/anti TNF
- IV

3. Azathiorprine
• Steroids for flares
 Surgical Management

Surgery can be curative for ulcerative colitis

80% of Crohn’s have resections but generally little help

Indications for surgery in Ulcerative Colitis

Acute:
 Failure of medical treatment for 3 days
 Toxic dilatation
 Haemorrhage I CHOP
 Perforation Infection
Chronic Carcinoma
Haemorrhage
 Poor response to medical treatment Obstruction
 Excessive steroid use Perforation
 Non compliance with medication
 Risk of cancer
 Prognosis

• UC
– 1/3 Single attack

– 1/3 Relapsing attacks

– 1/3 Progressively worsen requiring colectomy within 20 years

• Crohn’s
– Varied prognosis, new biological agents improving

• Cancer
– Both have increased risk of colon cancer, though UC>Crohn’s

– Screening colonoscopy done every 2 years after 10 years disease

 COMPLICATIONS

• Carcinoma

• Toxic dilatation of the colon (toxic megacolon)

• Malabsorption syndrome.

• Severe hemorrhage

• Electrolyte imbalance

• Perforation

• Fistula

• Stricture
 CANCERS IN IBD
• Patients with IBD have an increased incidence of developing

dysplasia and subsequent colon cancer.

• The risk of dysplasia is related to the extent and duration of

disease as well as the presence of untreated mucosal

inflammation.

• A family history of colorectal cancer and the presence of

primary sclerosing cholangitis also increase the risk.

• Patients with CD of the small intestine have a small increase in

the incidence of small bowel carcinoma

 FACTORS INCREASING RISK OF CANCER

• Disease duration > 10yrs

• Patient with pancolitis

• Onset on before 15yrs old

• Unremitting disease

• Poor adherence to treatment

 PREGNANCY AND UC
• Women with inactive UC have normal fertility.

• Fertility, may be reduced in those with active disease, and patients

with active disease are twice more likely to suffer spontaneous
abortion than those with inactive disease.

• The rate of relapse of UC in pregnant patients is similar to non-

pregnant patients and is often due to inappropriate
discontinuation of maintenance therapy.

• Patients with CD, like those with UC, do not have an increased
risk of flare-up during pregnancy.
•THANK YOU

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