Inflammatory Bowel Disease

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)
• Crohns 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
  24-fold risk for developing CD, whereas
  double-dose carriage increases the risk
  2040-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-? 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.

12
(No Transcript)
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.

15
(No Transcript)
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 gt90 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
21
(No Transcript)
22
(No Transcript)
23
(No Transcript)
24
(No Transcript)
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, lt4
  BM/day with no blood
• Moderate attack
• 25 of all patients, 4-6 BM/day with blood.
• Severe or fulminant colitis
• 15 of cases, gt6BM/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.

33
(No Transcript)
34
(No Transcript)
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.

36
(No Transcript)
37
Complications of IBD

• Bleeding
• Stricture
• Fistula
• Toxic megacolon
• Cancer

38
(No Transcript)
39
(No Transcript)
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 peptideinduced 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.

46
(No Transcript)
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

49
(No Transcript)
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.