1. CROHN’S DISEASE
Gastroenterology unit

2. OUTLINE
• Introduction
• Aetiopathogenesis
• Pathology
• Clinical features
• Differential diagnosis
• complications
• Investigations
• Management
• Prognosis

3. Introduction
• IBD encompasses two distinct chronic,idiopathic
inflammatory diseases of the GI tract:Crohn’s
disease which can affect any part of the GI tract
and Ulcerative colitis which affect only the large
bowel
• There is overlap bwn these two conditions in
their clinical features,histological and radiological
abnormalities
• In 10% of cases of colitis a definitive diag of either
CD or UC is nt possible

4. CROHN’S DISEASE
• The incidence of CD varies from country to
country but is apprx 4-10/100,000 annually
• Prevalence of 27-106/100,000
• World-wide distribution but commonly found
in the west
• Incidence lower in non whites races
• Jews more prone than non-jews and
Ashkenazi jews have higher risk than
sephardic jews

5. • Slightly commoner in females(M:F=1:1.2)
• Occurs at younger age than UC(mean age
26yrs)
• In nigeria the incidence and prevalence is not
known but there are some case reports from
Zaria,Enugu etc.The writers suspect lack of
awareness of the disease,lack of adequate
diagnostic facilities to the suspected low
incidence in this part of the world

6. Aetiopathogenesis
• The etiology of CD is unknown
• Represents the interaction of 3 essential co-
factors:Genetic susceptibility,environment and
host immune response
• The environment represents both local
microenvironment (enteric microflora) and
also the nutritional environment

7. Familial
• FH is the largest independent risk factor for
the disease
• Upto 1 in 5 patients with CD and 1 in 6
patients with UC will have a first degree
relative with d disease

8. Genetic
• Increase concordance of the disease among
monozygotic twins compared to dizygotic
twins who show familial aggregation
• Both CD and UC are polygenic diseases-no
single locus identified
• Susceptibility loci identified on chromosomes
16(IBD1),12,6,14,5,19,1,16(IBD8) and 3 and
these have been renamed IBD1-9

9. • Linkage mutations have found on
CARD15(NOD2), the underlying gene on
chromosome 16(IBD1)
• The CARD15 gene is ass with CD in white
populations and has also been ass with
stricturing small bowel disease
• The autophagy genes ATG16L1 and
IRGM,which control intrcellular degradation
process(along wt CARD15),are specific for CD

10. • Modifying HLA genes on chromosome 6
• HLA DRB*0103 is linked to an aggrasive course
of UC and need for surgery and colonic
disease in CD
• DRB*0103 and MICA*010 are ass wt perianal
disease and DRB*0701 wt ilial CD

11. Environmental factors
• Good domestic hygiene has been shown to be
a risk factor for CD
• H pylori seroprevalence is reduced in CD
• A clean environment may not expose the
immune system to pathogenic or non
pathogenic micro-organisms particularly
helminthic parasites and therefore be
untrained to confront minor infections

12. lifestyle
• Breastfeeding may provide protection against IBD
in the offspring
• Nutritional:high sugar and fat intake have been
suggested to play a role in the pathogenesis of
IBD
• Smoking:pts wt CD are more likely to be smokers
and smoking has been shown to exacerbate CD
• Appendicectomy though protective against UC
may result in icrease risk of dev CD and more
aggressive dx

13. Intestinal microflora
• There is an alteration in bacterial microflora,wt
an increase in anaerobic bacteria in CD and
aerobic bacteria in UC
• Bacteria may exert their pro-inflammatory
influence by producing toll-like receptor ligands
such as PG-PS,LPS
• These interact wt intestinal surface toll-like
receptors
• The disruption in TLR signalling could prevent
mucosa withstanding bacterial insult

14. Pathogenesis
• IBD results from defective mucosal immune
system producing an inappropriate response to
luminal antigens such as bacteria
• Bacterial ligands interact wt toll-like receptors the
epithelial cell membrane which act as antigen
presenting cells to myeloid dendritic cells
• There then follows a stimulation of naïve Th 0
cells into effector T cells(Th1(IL12,INFδ),Th2(IL-
5)and Th17(IL-17),wc predominate over
regulatory T cells(T reg)

15. • The pro-inflammatory cytokines released by
these activated T cells stimulate macrophages
to secrete TNFα,IL-1 and IL-6 in large
quantities
• These mechanisms all results in leucocytes
leaving the circulation to enter the tissue and
release chemokines wc lead to tissue damage
and also atract more inflammatory cells like a
vicious circle

16. Pathology
• CD is a chronic inflammatory dx that may affect
any part of the GI system from mouth to anus bt
has a particular tendency to affect the terminal
ilium and ascending colon(iliocolonic disease)
• The disease may affect one small part of the gut
such as the terminal ilium or multiple areas wt
relatively normal bowel in between(skip lesions)
• May involve the whole colon(total colitis)
sometimes without small bowel involvement

17. Macroscopic changes
• In CD the involved small bowel is usually
thickened and narrowed
• There are deep ulcers and fissures in the mucosa
producing a cobblestone appearance
• Fistulae and absceses maybe seen in the colon
• An early feature is aphthoid ulceration,usually
seen at colonoscopy
• Later larger n deeper ulcers appear in a patchy
distribution,again producing a cobblestone
appearance

19. Microscopic changes
• In CD the inflammation extends through all
layers(transmural) of the bowel.
• There is increase in chronic inflammatory cells
and lymphoid hyperplasia
• In 50-60% of pts granulomas are seen
• These granulomas are non-caseating
epithelioid cell aggregates wt langhans giant
cells

21. Extragastrointestinal manifestations
• Eyes:uveitis,episcleritis,conjunctivitis
• Joints:Type 1 (pauci articular) arthropathy-ass wt
HLA DRB1 0103
• Type 2 (poly articular) arthropathy-HLA B44 ass
wt small joint symmetrical arthritis
• Arthralgia,ankylosing spondylitis and
inflammatory back pain
• Skin:Erythema nodosum and pyoderma
gangrenosum, Liver and biliary tree:sclerosing
cholangitis,fatty liver,gall stones etc

22. Clinical features
• The major symptoms are diarrhoea,abdominal
pain and wt loss
• Constitutional symptoms of
lethargy,anorexia,nausea,vomitting and low-
grade fever may be present and in 15% of
these pts there are no GI symptoms
• Other clinical manifestations include
bleeding,perianal disease,internal fistulae

23. • CD may present as an emergency wt right iliac
fossa pain mimicking appendicitis
• If laparotomy is perfomed an
oedematous,reddened terminal ilium is found

24. Differential diagnosis
• Ileocecal small bowel disease: infectious-acute
appendicitis,cecal diverticulitis,PID,ileocecal
tuberculosis,yersinia enterocolitica infection
• Non infectious:celiac disease,ectopic
pregnancy,lymphoma,radiation enteritis
• Colonic disease: infectious-acute bacterial
colitis(salmonella,shigella,campylobacter),amoeb
ic colitis
• Non-infectious:ulcerative colitis,radiation
colitis,ischaemic colitis

25. Complications
• Perforating disease:some group of pts have
penetrating transmural disease that may lead to
abscess or fistula formation
• Strictures:formation of recurrent strictures is the
hallmark of the fibrostenotic variant of CD and a
common complication of CD
• Perirectal disease: this may result in fistulas and
abscesses
• Cancer:there is clearly an increased risk of small
bowel adenocarcinoma in pts wt CD

26. Investigations
• FBC: normocytic,normochromic anaemia of
chronic disease,deficiency of iron/folate also
occurs
• Raised ESR and CRP and a raised white cell
count
• Hypoalbuminaemia is present in severe
disease
• Liver biochemistry may be abnormal

27. • Blood cultures are required if septicaemia is
suspected
• Serological tests: saccharomyces ceravisiae
antibody is usually present while p-ANCA is
negative.The reverse is true in UC
• Stool cultures should be performed on
presentation if diarrhoea is present

28. Radiology and imaging
• Barium follow-through: the findings include an
assymetrical alteration in the mucosal pattern
wt deep ulceration,and areas of narrowing or
stricturing
• Although commonly confined to the terminal
ilium,other areas of small bowel can be
involved and skip lesions can also be seen
btwn affected sites

30. • Colonoscopy: is performed if colonic involvement
is suspected except in pts presenting wt severe
acute disease
• High-resolution ultrasound and spiral CT scanning
are both helpful techniques in defining thickness
of the bowel wall and mesentry as well as intra-
abdominal and paraintestinal abscesses
• Rectal uss and MRI are used to evaluate perianal
disease

31. Disease activity
• This can be assesed using simple parameters
such as HB,white cell count,inflammatory
markers(raised ESR,CRP and platelet count)
and serum albumin
• Fecal calprotectin has the potential as a
cheap,simple non invasive marker of disease
activity in IBD and may be of value in
predicting response to and failure of
treatment

32. Medical management
• The aim of management is to induce and
maintain remission
• Pts with mild symptoms may require only
symptomatic treatment
• Cigarette should be stopped,diarrhoea can be
controlled with loperamide,codeine sulphate or
co-phenotrope
• Diarrhoea in long standing disease may be due to
bile acid malabsorbtion and should be treated wt
cholestyramine

33. • Anaemia if due to vit B12,folic acid or iron def
should be treated wt appropriate hematinics
• Anaemia of chronic disease will usually
improve as the pt gets better
• Pts wt active moderate/severe attack may
have to be admitted

34. Remission induction
• Glucocorticoids are commonly used to induce
remission in moderate and severe attack of CD
• Oral prednisolone 30-60mg/day
• In pts wt ileocaecal,but not colonic CD,slow
release formulations of budesonide are as
efficatious as prednisolone
• Enteral nutrition: is an underutilised means of
inducing remission in moderate/severe attacks of
CD and efficacy is independent of nutritional
status

35. • Enteral diets wt a low fat(1.3% of total calories)
and a low linoleic acid content are administered
as the sole source of nutrition for 28 days,rates of
induction of remission are similar to those
obtained wt steroids
• Relapse rates are high particularly in those wt
colonic involvement
• In unresponsive pts remission is sometimes and
maintained by raising the dose of azathioprine to
levels that make pts leucopaenic

36. Maintainance of remission
• Remission can be maintained in crohn’s colitis
but not in those wt small bowel involvement
with aminosalicylates
• Remission in other pts can be maintained wt
azathioprine(AZT,2.5mg/kg/day),6-
mercaptopurine(6MP,1.5mg/kg/day),methotr
exate(25mg i.m/week) and mycophenolate
mofetil(1g/day)
• These drugs have steroid sparing properties

37. Biologic agents
• In pts in whom remission could not be induced or
maintained wt corticosteroid/immunosupressive
therapy,treatment with a biologic agent will be
indicated
• Infliximab: a chimeric anti TNF-α monoclonal
antibody,is the most widely used biologic agent
• Succesful at inducing remission in
corticosteroid/immunosuppressive resistant
patients,remission can be maintained(5mg/kg
iv.weeks 0,2,6 and 8-weekly until week 46)

38. • Further courses of treatment can be given to
reinduce and maintain remission
• Two other anti TNF-α antibodies inhibitors are
now widely used:Adalimumab and
certolizumab pegol
• New anti TNF-α antibody therapies include
CDP571,etanercept and onercept

39. Surgical management
• Apprx 80% of pts will require surgery during the
course of their illness
• Nevertheless surgery should be avoided if
possible or minimal resections undertaken as
recurrence(15%/year) is almost inevitable
• Indications for surgery include:failure of medical
therapy with acute or chronic symptoms
producing ill-health,complications( eg toxic
dilatation,obstruction,perforation etc),failure to
grow in children despite medical therapy

40. Prognosis
• The course of CD is highly variable.majority of pts
lead a productive ,satisfying life punctuated by
intermittent episodes of disease relapse
• Over the course of their disease 80% will require
surgery and another 50% will subsequent surgery
at some point
• Currently mortality rates appear to be only
slightly higher than in age marched controls,this
maybe due to cancer ass wt CD