Ibd

1. Inflammatory Bowel
Disease
A Aljebreen, MD, FRCPC
Jan 2010

2. Objectives
 Introduction
 Classifications
 Clinical features
 Diagnosis
 Management
 Conclusion

3. Introduction
 IBD characterized by a tendency for chronic or
relapsing immune activation and inflammation
within the gastrointestinal tract (GIT)
 Crohn’s disease (CD) and ulcerative colitis (UC)
are the 2 major forms of idiopathic IBD.

4. Less common entities
 Microscopic colitis (collagenous and
lynphocytic)
 Others
 Diversion colitis
 Radiation colitis
 Drug induced colitis
 Infectious colitis
 Ischemic colitis

5. CD and UC
 CD is a condition of
 Chronic inflammation potentially involving any
location of the GIT from mouth to anus.
 It is a lifelong disease arising from an interaction
between genetic and environmental factors
 UC is an inflammatory disorder that affects the
rectum and extends proximally to affect variable
extent of the colon.

6. Epidemiology
 CD:
 1st peak 15-30 years of age, 2nd peak around 60 y
 There is a definite incidence surge in Saudi Arabia
over the last 10 years
 UC:
 High incidence areas: US, UK, northern Europe
 Young adults, commoner in females

7. Genetics
 Studies suggested that 1st degree relatives of an
affected patient have a risk of IBD that is 4-20
times higher than that of general population.
 The best replicated linkage region, IBD1, on
chromosome 16q contains the CD susceptibility
gene, NOD2/CARD15.
 Having one copy of the risk alleles confers a 2–
4-fold risk for developing CD, whereas double-
dose carriage increases the risk 20–40-fold.

8. Etiology
 Mutations within the NOD2/ CARD15 gene
contribute to CD susceptibility.
 Functional studies suggest that inappropriate responses
to bacterial components may alter signaling pathways of
the innate immune system, leading to
 the development and persistence of intestinal inflammation.
 Initiating pathogen?
 Infectious?
 ? Possibly non-pathogenic commensal enteric flora

9. Pathogenesis
 The mucosa of CD patients is dominated by
Th1 (T helper), which produce interferon-γ and
IL-2.
 In contrast, UC dominated by Th2 phenotype,
which produce transforming growth factor
(TGF-) and IL-5.
 Activation of Th1 cells produce the down-
regulatory cytokines IL-10 and TGF-.

10. Environmental Precipitants
 Factors:
 NSAIDs use (?altered intestinal barrier), and
 Early appendectomy (increase UC incidence)
 Smoking (protects against UC but increases the risk
of CD).

11. CD: PATHOLOGY
 Early Findings:
 Aphthous ulcer.
 The presence of granulomas
 Late findings:
 Linear ulcers.
 The classic cobble stoned appearance may arise.
 Transmural inflammation
 Sinus tracts, and strictures.
 Fibrosis.

13. transmural inflammation with predominance of the
inflammation in the mucosa and submucosa.

14. UC: PATHOLOGY
 The inflammation is predominantly confined to
the mucosa.
 Non-specific (can be seen with any acute
inflammation)
 The lamina propria becomes edematous.
 Inflammatory infiltrate of neutrophils
 Neutrophils invade crypts, causing cryptitis &
ultimately crypt abscesses.
 Specific (suggest chronicity):
 Distorted crypt architecture, crypt atrophy and a
chronic inflammatory infiltrate.

16. Diagnosis
 Exclude other possibilities (need good history,
physical exam, labs, imaging and endoscopy with
biopsy)
 There are many distinguishing features of CD
and UC.
 In about 5% it is classified as indeterminate
because of overlapping features.

17. Distinguishing characteristics of CD and UC
UC
CD
Feature
Only colon (rarely
“backwash ileitis”
SB or colon
Location
Continuous,
begins distally
Skip lesions
Anatomic
distribution
Involved in >90%
Rectal spare
Rectal
involvement
Universal
Only 25%
Gross bleeding
Rare
75%
Peri-anal disease
No
Yes
Fistulization
No
50-75%
Granulomas

18. Endoscopic features of CD and UC
UC
CD
Feature
Continuous
Discontinuous
Mucosal
involvement
Rare
Common
Aphthous ulcers
Abnormal
Relatively
normal
Surrounding
mucosa
Rare
Common
Longitudinal ulcer
No
In severe cases
Cobble stoning
Common
Uncommon
Mucosal friability
distorted
Normal
Vascular pattern

19. Pathologic features of CD and UC
UC
CD
Feature
Uncommon
Yes
Transmural inflammation
No
50-75%
Granulomas
Rare
Common
Fissures
No
Common
Fibrosis
Uncommon
Common
Submucosal inflammation

20. Radiologic features of CD and UC
UC
CD
Feature
Collar button
ulcers
Nodularity
granularity
cobble stoning
string sign of SB

25. UC: Presentation
 Must exclude infectious cause before making Dx.
 Rectal Bleeding
 Diarrhea:
 frequent passage of loose or liquid stool, often associated
with passing large quantities of mucus.
 Abdominal Pain:
 it is not a prominent symptom.
 Anorexia, nausea, fever…

26. DDX of UC
 Infectious
 Drug induced
 Microscopic colitis

27. UC: Presentation
 Mild attack:
 Most common form, mainly left sided colitis, <4
BM/day with no blood
 Moderate attack:
 25% of all patients, 4-6 BM/day with blood.
 Severe or fulminant colitis:
 ~ 15% of cases, >6BM/day, bloody, fever, weight
loss, diffuse abd tenderness, elevated WBC, most
refractory to medical therapy

28. CD
 Anatomic
distribution
 CD activity index
 DDx (lymphoma,
Yersinea
Enterocolitis, TB)

29. CD: clinical presentations
 Disease of the ileum:
 May present initially with a small bowel obstruction.
 Patients with an active disease often present with anorexia,
loose stools, and weight loss.
 Perianal disease
 In 24% of patients with CD.
 Skin lesions include superficial ulcers, and abscesses.
 Anal canal lesions include fissures, ulcers, and stenosis.

30. CD ilitis: DDx
 Lymphoma
 Yersinea Enterocolitis and
 TB

31. CD: clinical presentations
 colonic disease
 The typical presenting symptom is diarrhea, occasionally with
passage of obvious blood.
 proctitis
 May be the initial presentation in some cases of CD

32. Extra-intestinal manifestations of IBD
 Arthritis:
 Peripheral arthritis, usu paralels the disease activity
 Ankylosing Spondylitis, 1-6%, sacroiliitis
 Ocular lesions:
 Iritis (uvietis) (0.5-3%), episcleritis, keratitis,
 Skin and oral cavity:
 Erythema nodosum 1-3%
 Pyoderma Gangrenosum 0.6%
 Aphthus stomatitis, metastatic CD.

35. Extra-intestinal manifestations of IBD
 Liver and Biliary tract disease:
 Pericholangitis, fatty infiltration, PSC (1-4%, more
with UC), cholangiocarcinoma, gallstones
 Thromboembolic disease, vasculitis, Renal
disease (urolithiasis, GN), clubbing, amyloidosis.

37. Complications of IBD
 Bleeding
 Stricture
 Fistula
 Toxic megacolon
 Cancer

40. How to diagnose IBD
 History
 Physical examinations
 Labs
 Radiology
 Endoscopy
 Histopathology

41. Case scenario 1
 17 year old female presented with 1 year history of
intermittent abdominal cramps and increasing
abdominal gases and bloating.
 What other history you want?

42. Case scenario 2
 65 year old male presented with 6 months history of
bleeding per rectum.
 What other history you want?
 What else you need?

43. Treatment
 Goals of therapy
 Induce and maintain remission.
 Ameliorate symptoms
 Improve pts quality of life
 Adequate nutrition
 Prevent complication of both the disease and
medications

44. 5-Aminosalicylic Acids
 The mainstay treatment of mild to moderately
active UC and CD (induction).
 5-ASA may act by
 blocking the production of prostaglandins and
leukotrienes,
 inhibiting bacterial peptide–induced neutrophil
chemotaxis and adenosine-induced secretion,
 scavenging reactive oxygen metabolites

45. 5-Aminosalicylic Acids
 For patients with distal colonic disease, a
suppository or enema form will be most
appropriate.
 Maintenance treatment with a 5-aminosalicylic
acid can be effective for sustaining remission in
ulcerative colitis but is of questionable value in
Crohn's disease.

47. Corticosteroids
 Topical corticosteroids can be used as an
alternative to 5-ASA in ulcerative proctitis or
distal UC.
 Oral prednisone or prednisolone is used for
moderately severe UC or CD, in doses ranging
up to 60 mg per day.
 IV is warranted for patients who are sufficiently
ill to require hospitalization; the majority will
have a response within 7 to 10 days.

48. Corticosteroids
 No proven maintenance benefit in the treatment
of either UC or CD.
 Many and serious side effects.
 Budesonide:
 less side effects,
 its use is limited to patients with distal ileal and right-
sided colonic disease

50. Immunosuppressive Agents
 These agents are generally appropriate for patients in
whom the dose of corticosteroids cannot be tapered or
discontinued.
 Azathioprine & 6-MP
 The most extensively used immunosuppressive agents.
 The mechanisms of action unknown but may include
 suppressing the generation of a specific subgroup of T cells.
 The onset of benefit takes several weeks up to six months.
 Dose-related BM suppression is uniformly observed

51. Immunosuppressive Agents
 Methotrexate
 Effective in steroid-dependent active CD and in
maintaining remission.
 Cyclosporine
 Severe UC not responding to IV steroid &need
urgent proctocolectomy.
 50% of the responders will need surgery within a
year.

52. Anti-TNF Therapy
 It is a chimeric monoclonal antibody, binds soluble
TNF.
 Infleximab, Adalimumab (Humira) and Certolizumab
 Prompt onset, effects takes 6weeks to max of 6m.
 Indicated in fistulising crohns, moderate to severe CD
 Infleximab also indicated in severe ulcerative colitis

53. Side effects
 They are safe and usually tolerable
 Acute infusion reactions, which may include chest tightness,
dyspnea, rash, and hypotension.
 Delayed hypersensitivity reactions, consisting of
 severe polyarthralgia,
 myalgia,
 facial edema,
 urticaria, or rash,
are an unusual complication occurring from 3 to 12 days after an infusion.

54. Side effects
 Increase risk of infections including
exacerbations of abdominal abscess or
increasing upper respiratory infections.
 Reactivation of tuberculosis has been observed
and has resulted in disseminated disease and
death.

55. INDICATIONS FOR SURGERY
 In patients with UC:
 Severe attacks that fail to respond to medical therapy.
 Complications of a severe attack (e.g., perforation, acute
dilatation).
 Chronic continuous disease with an impaired quality of life.
 Dysplasia or carcinoma.
 In patients with CD
 Obstruction, severe perianal disease unresponsive to medical
therapy, difficult fistulas, major bleeding, severe disability
 30 % relapse rate

56. IBD Sequelae
 UC:
 Risk of cancer begins after 8 years, risk of pancolitis
7% at 20 years and 17% at 30 years.
 Increased risk: early age of onset, pancolitis.
 Need for colonoscopic screening after 8 years
 CD:
 True incidence of cancer is uncertain, but could be
as high as UC
 Need the same screening policy.

57. IBD conclusion
 It is a chronic disorders
 Need to exclude other possibilities
 Need to differentiate between the two
 Need long term management with primary goal
to induce then maintain remission and prevent
complications of both the disease and drugs.