1. Inflammatory Bowel Disease
Dr. WM Simmonds
Internal Medicine
Gastroenterology
29/08/2011

2. Inflammatory Bowel Disease Objectives
Understand the pathogenesis of inflammatory bowel disease
Know the differences between Crohn`s disease and ulcerative colitis
Have an approach to the new patient with bloody diarrhoea
Know the differential diagnosis of IBD
Know the exta-intestinal manifestations of IBD
Know the principles of therapy of inflammatory bowel disease

3. Inflammatory Bowel Disease Introduction
Inflammatory bowel disease (IBD) is an immune mediated, heterogeneous syndrome which is divided into 2 major phenotypes:
Crohn`s disease (CD)
Ulcerative Colitis(UC).
There is no pathognomomic test for either CD or UC.
Diagnosis is made on a combination of clinical, radiological, endoscopic and histological grounds.

4. Inflammatory Bowel Disease Epidemiology
IBD is a condition of developed countries and outside of Europe, the United Kingdom and North America, is seen in Australia, South-Africa, and Israel at an appreciable frequency.
IBD is more common in urban areas and in high socioeconomic settings.
It is more common in caucasians, and especially those of Jewish extraction.
It occurs less frequently in other race groups.
Smokers have double the risk of developing CD as opposed to non-smokers. In contrast to this, smoking protects against UC.
First degree relatives of those with IBD have an increased risk of developing IBD.

5. Inflammatory Bowel Disease Etiology and pathogenesis
IBD is currently thought to be due to a dysregulated immune response to an as yet unidentified environmental antigen (possibly enteric microbes).
As such the abnormal immune response develops in those with a genetic predisposition, and is modified by certain factors (smoking).
The current hypothesis holds that the immune response in patients with IBD is against normal bowel flora which is erroneously perceived as being pathogenic.

6. Inflammatory Bowel Disease Etiology and pathogenesis
Numerous genetic polymorphisms have been identified to date which confer a certain risk, and in certain cases predict disease behaviour (e.g. NOD2/CARD15 on chromosome 16, which is associated with CD of the terminal ileum).
Some genetic polymorphisms are specific for CD or UC and some are shared. Genes implicated are involved in regulation of the innate immune system, the adaptive immune system and autophagy.
An alternative hypothesis that patients with IBD have an abnormalities in mucosal defence (defensin production).

7. Ulcerative Colitis
Disease is confined to the large bowel (that is apart from extra-intestinal manifestations).
The disease is characterised by mucosal inflammation of the large bowel.
Perianal disease, fistulas and small bowel strictures are NOT part of the clinical picture and are suggestive of CD.

8. Ulcerative Colitis Clinical picture
Blood per rectum
Bloody diarrhoea (including nocturnally). Blood macroscopically visible in 95% of active disease.
Cramps (especially before bowel movements)
Urgency and at times incontinence
Tenesmus
Tenderness over inflamed colon
Extra intestinal manifestations

9. Ulcerative Colitis Endoscopic characteristics
Rectum almost always involved
Extends continuously for varying distances proximally
20% have pan-colitis
Pan-colitics may have “backwash ileitis”
Longstanding colitis may manifest as a featureless colon, which is narrow and shortened
Pseudopolyps are a manifestation of prior severe inflammation

10. Ulcerative Colitis

11. Ulcerative Colitis Severity: Truelove en Witts Classification
Mild
Severe
<4 stools per day
>6 liquid stools per day
Minimal or no bleeding
Bloody
No fever
T⁰>37.5⁰C
No tachycardia
Pulse > 90bpm
Mild anaemia at most
Hb <10.5(<75%)
ESR <30mm/H
ESR >30mm/H

12. Ulcerative Colitis Endoscopic grading of UC
Mayo grade:
Loss of vascular pattern
Friability
Spontaneous haemorrhage

13. Ulcerative Colitis Microscopic characteristics
Inflammation is limited to mucosa and superficial sub mucosa, except with fulminant colitis when it may become transmural
Features of chronicity
Crypt architectural distortion (branching and fallout)
Basal plasma cells and lymphoid aggregates
Active disease
Neutrophyl infiltration of epithelium and crypt abscesses

14. Ulcerative Colitis

15. Ulcerative Colitis Radiological Characteristics
Plain abdominal x-ray
Collapse of involved segment
Haustral thickening (“thumb printing”)
Dilated colon (>6 cm dilatation of caecum or transverse implies megacolon)
Ba enema (not used much now)
Ulceration
Featureless, shortened colon (chronicity features) “lead pipe”
CT scan
Dilated loops of colon
Enhancement of colonic wall

16. Ulcerative Colitis

17. Ulcerative Colitis Complications
Colonic haemorrhage
Toxic megacolon
Perforation
Longstanding disease (> 10 years) increases the risk of colon Ca.

18. Crohn’s Disease
Transmural inflammation of bowel, which may affect any part of the GI tract from the mouth to the anus, but tends to affect individual patients in a particular location, which remains stable over time.
It follows that resected Crohn`s disease tends to recur at the site of resection.

19. Crohn’s Disease
Disease behaviour may follow one of 3 patterns or combinations there of, i.e.
Luminal inflammatory disease
Stricturing disease
Fistulating /penetrating disease.

20. Crohn’s Disease Disease pattern/behaviour /ultimate
phenotype may not be apparent
initially and develops over a period
of years.
30% of patients have isolated ileal disease
30% have ileo-colitis
30% have isolated colitis.
Peri-anal disease with
fisures and fistulas is common.
Upper gastrointestinal
involvement occurs less frequently.

21. Crohn’s Disease Clinical features
Weight loss
Diarrhoea (only bloody in 50% of patients with colonic disease)
Abdominal pain
Symptoms of obstruction (if stricturing disease)
Peri-anal symptoms and disease
Palpable abdominal mass
High fever suggests abscess formation (intra-abdominal, ischio-rectal)
General features of chronic inflammation with pallor, cachexia if severe uncontrolled disease.

22. Crohn’s Disease Endoscopic characteristics
Depends on distribution
Ileitis
Colitis
Rectum involved in 50% of patients with colitis
Ulceration:
Aphthous
Stellate
Serpigenous
Skip lesions

23. Crohn’s Disease

24. Crohn’s Disease Microscopic characteristics
Transmural inflammation
Granulomas (non-caseating)
Only seen in 20% of mucosal biopsies and 50% of full thickness biopsies

25. Crohn’s Disease Radiological characteristics
Ba small bowel enemas
Strictures (“string sign”)
Separation of loops (inflammation with thickening of the bowel wall)
Mucosal ulceration
Fistulous tracts
CT scan
Abscesses/fluid collections
Thickened bowel
MRI
Especially good for perianal disease
Fistulas

26. Crohn’s Disease

27. Crohn’s Disease Complications
Strictures
Fistulas
Entero-enteric
Entero-vaginal (usually only after hysterectomy)
Entero-cutaneous
Recto-vaginal
Peri-anal
Abscess formation
Gallstones
Kidney stones (oxalate)

28. Extra-intestinal manifestations
Associated with
disease activity
Independant of
Arthropathy
Pauciarticular (type 1) large peripheral joints
Small joint peripheral arthropathy (type 2)
Axial arthropathy (HLA B27)
Sacro-ileitis
Ankylosing spondylitis
Ocular manifestations
-Episcleritis
-Uveitis
Skin
-Erythema nodosum
-Pyoderma gangrenosum
Hepato-biliary
-PSC

29. Uveitis

30. Erythema nodosum

31. Pyoderma gangrenosum

32. Differential diagnosis of IBD
Infectious
Non-infectious
-Bacteria
Salmonella
Shigella
Campylobacter
Yersinia (Ileitis)
E.coli (enteroadherent, enteroinvasive, enterohemorrhagic)
Clostridium difficile
-Inflammatory
Diverticular colitis
Ischaemic colitis
Radiation colitis
Solitary rectal ulceration
Appendicitis
Behcet’s disease
-Mycobacateria
Tuberculosis (Ileo-caecal disease)
-Parasites
Entamoeba histolytica
Trichuris trichura (whipwurm)
Necator americanus (hakwurm)
Strongyloides stercoralis
-Neoplastic
Lymphoma (terminale ileum)
Carcinoma
Viruses
CMV
HSV
HIV
-Medication
NSAID’s
Chemotherapy
Bowel preparation
-Fungi
Histoplasmosis (ileitis)

33. Clinical approach to a patient with bloody diarrhoea
History and clinical examination
Stool sample
Microscopy, Culture and sensitivity
Clostridium difficile toxin assay
Sigmoidoscopy and biopsy (if biopsy available)
Full length colonoscopy in the absence of a diagnosis and persistent disease or alarm features
weight loss
anaemia,
age >50 years)

34. Truelove en Witt’s Classification
Mild
Severe
<4 stools per day
>6 liquid stools per day
Minimal or no bleeding
Bloody
No fever
T⁰>37.5⁰C
No tachycardia
Pulse > 90bpm
Mild anaemia at most
Hb <10.5(<75%)
ESR <30mm/H
ESR >30mm/H

35. Therapy Induction of remission with corticosteroids Then: Stop.
Hydrocortisone 100 mg q 6 hourly IVI for 3 days
Then:
Prednisolone 40 mg per day po 1 week
Prednisolone 30 mg per day po 1 week
Prednisolone 20 mg per day po 1 month (Initiation of maintenance therapy)
Prednisolone 15 mg per day po 1 week
Prednisolone 10 mg per day po 1 week
Prednisolone 5 mg per day po 1 week
Stop.

36. Therapy Maintenance of remission (UC) Mild to moderate UC
5-ASA preparations
Sulphasalazine
Mesalazine
Balsalazide
Severe or steroid dependant UC
Thiopurines
Azathioprine mg per kg per day
6 mercaptopurine mg per kg per day
Steroid refractory UC
Cyclosporine
Anti-TNFα
Colectomy

37. Therapy Maintenance of remission (CD)
Crohn`s disease(5 ASA probably does NOT work)
Very mild disease (nothing)
Moderate to severe disease
Azathioprine or 6 MP
Methotrexate
Primary prophylaxis
Severe disease unresponsive to immunomodulators
Biological agents/antibodies
Infliximab (Anti-TNF)
Adalimumab
Vedolizumab
?“Top down” therapy – Biologic agents first.

38. General measures Stop smoking (especially CD patients) Avoid NSAID`s
Drug compliance
Remember complications of therapy
Steroids: osteoporosis, diabetes, cataracts, osteonecrosis, Cushingoid habitus, hypertension, mood changes
5-ASA: bone marrow suppression (rare), and male infertility
Thiopurines hepatitis, pancreatitis, bone marrow suppression
Methotrexate: teratogenic, liver fibrosis
All drugs may be used in pregnancy & before conception (according to indication) except Methotrexate which is absolutely contraindicated.
If you are a GP, remember initial correct diagnosis and therapy should be followed by timely referral to a specialist.

39. Indications for surgeryUC
Treatment refractory disease
Toxic megacolon
Colonic haemorrhage
Dysplasia/cancer CD
Strictures/obstruction
Treatment refractory fistulae
Abscesses
Massive haemorrhage(rare)

40. Thank you