Inflammatory Bowel Disease ( Pathogensis & Steps of Diagnosis and Management) For Resident at Gastroenterology and Hepatology department at Kafrelsheikh by Dr/ Mohammed Hussien ( Assistant Lecturer).

1. Dr/ Mohammed Hussien
Assistant Lecturer of Gastroentrology & Hepatology
Kafrelsheikh University
Inflammatory Bowel Disease
BY

2. What is Inflammatory Bowel Disease?
• IBD is a condition that is a recurrent and chronic immune response and inflammation of
the gastrointestinal tract
• Autoimmune disorder of the gastrointestinal tract with possible multi-organ involvement
• Recent study >8000 IBD pts – 63% had another chronic inflammatory condition

4. *Ulcerative colitis is characterised by diffuse mucosal inflammation limited to the
colon. It is classified according to the maximal extent of inflammation observed at colonoscopy
because this is most clearly related to the risk of complications, including dilatation and cancer.
The implications of limited macroscopic disease with extensive microscopic inflammation
remain unclear.
*Crohn’s disease is characterised by patchy, transmural inflammation, which may affect
any part of the gastrointestinal tract. It may be defined by: age of onset, location, or behaviour.
*About 5% of patients with IBD affecting the colon are unclassifiable after considering
clinical, radiological, endoscopic and pathological criteria, because they have some features of
both conditions. This is now termed as ‘IBD, type unclassified (IBDU)’.
*The term ‘indeterminate colitis (IC)’ should be reserved for cases where
colectomy has been performed and the pathologis tremains unable to classify the disease after
a full examination.

5. Gut Immunology and IBD

7. Genomics demonstrate common genetic
signatures between IBD and other diseases.
RA
MS
SLE AS
Psoriasis
Alopecia
Behcet’s
Asthma
Leprosy
Celiac Dz
Type II DM
IBD

8. Why does IBD matter to the us?
• Causes significant morbidity
• Causes large burden to society and health care system
• There are approximately 1-1.3 million with IBD in the U.S.
(CDC)
• The cost of care for IBD patients is up to $8 billion a year
• 10-25% of IBD patients will require surgery (CDC, AGA)
• Recent Canadian studies noted the need for nurses to play a
bigger role in the care of IBD patients

9. Clinical features and course of disease
*The cardinal symptom of ulcerative colitis is bloody diarrhoea.
Associated symptoms of colicky abdominal pain, urgency, or
tenesmus may be present.
*severe colitis is still a potentially life-threatening illness
*An appreciable minority has frequently relapsing or chronic, continuous disease and
overall, 20e30% of patients with pancolitis come to colectomy
Ulcerative colitis

10. Truelove Classification of U.C

11. Clinical features and course of disease
• Symptoms of Crohn’s disease are more heterogeneous, but typically include
abdominal pain, diarrhoea and weight loss.
• Systemic symptoms of malaise, anorexia, or fever are more common. Crohn’s
disease may cause intestinal obstruction due to strictures, fistulae (often perianal)
or abscesses.
• Surgery is not Curative and management is directed to minimising the impact of
disease. At least 50% of patients may require surgical treatment in the first 10 years
of disease
Crohn’s disease
Both ulcerative colitis and Crohn’s colitis are associated with an equivalent increased risk of colonic
carcinoma.
Smoking increases the risk of Crohn’s disease, but decreases the risk of ulcerative colitis through unknown
mechanisms

12. Extraintestinal Manifestation of IBD

13. Erythema nodosumPyoderma gangrenosum

14. Differential Diagnosis

15. Laboratory investigations
• Full blood count, urea and electrolytes, liver function tests and erythrocyte
sedimentation rate or C reactive protein, ferritin, transferrin saturation, vitamin B12
and folate.
• Serological markers such as pANCA, ASCA are present in a significant proportion of
patients with IBD but there is no evidence base to recommend their use in the
diagnosis of IBD.
• Faecal calprotectin is accurate in detecting colonic inflammation and can help
identify functional diarrhoea.
• Microbiological testing for Clostridium difficile toxin, in addition to standard
organisms, is increasingly important. C difficile infection has a higher prevalence in
patients with IBD through unknown mechanisms, may not be confined to the colon,
and is associated with increased mortality.
• Cytomegalovirus (CMV) should be considered in severe or refractory colitis

16. Endoscopy
• Colonoscopy with multiple biopsies (at least two biopsies from
five sites including the distal ileum and rectum) is the first line procedure for
diagnosing colitis.
• It allows classification of disease Based on endoscopic extent, severity of mucosal
disease and histological features
• In acute severe colitis, full colonoscopy is rarely needed and may be
contraindicated
• A rectal biopsy is best taken for histology even if there are no macroscopic
changes

17. Endoscopic Features :

18. Histopathology of IBD

19. Diagnosing IBD and discerning between CD
vs UC.
• Crohn’s - Endoscopic = 3 Major findings, Apthi (early) are
transmural, Cobblestoning (ulcers are the ‘cracks’), and
Discontinuous lesions (skip areas). Proximal to Distal.
• Ulcerative Colitis – Endoscopic = Edema, Erythema, Erosions,
Friability, Granularity, Pseudopolyps, and Ulcers. Distal to Proximal.
• UC Mayo Clinic Scores – 0-12

20. CD – Endoscopic views

21. UC – Endoscopic views

23. Pill Cam for visualizing the small bowel

24. Enteroscopes-Role in diagnosis
• Double Balloon (Fujinon)
• Single Balloon (Olympus)
• Single Balloon Smart system (Smart System w/ Pentax)
• Spiral (EndoEase Discovery SBE)
• SpyGlass ? (Boston Scientific)

26. Imaging modalities
• Imaging can be helpful in diagnosis, assessment of disease extent and severity and for
investigation of suspected complications.
• Ultrasound
• Ultrasound cannot comprehensively assess the gut when used in isolation.
Magnetic resonance imaging
• Modern MRI hardware and software facilitate rapid and accurate assessment of the small
bowel.
• Computed tomography scanning
• CT imaging of the bowel (either CT enteroclysis or CT enterography) provides similar
information to MRI, although tissue characterisation capability is less. It is traditionally the ‘gold
standard’ for the detection of extraluminal complications, notably abscess formation.
Intravenous contrast administration is usually
• performed during CT. Advantages over MRI include widespread availability, rapid image
acquisition (few seconds) and superior spatial resolution.

27. Radiologic evaluation: CT, CT-E, and CT-C
• Because of the transmural nature of the Crohn’s disease, mesenteric and perianal
manifestations are fairly common. Because of the inflammation, strictures resulting
from edema, inflammation, and, ultimately fibrosis and scaring, are frequent. Crohn
disease is pervasive. The basic pathologic process of disease can occur at any
segment of the alimentary tract.
• In ulcerative colitis, hemorrhagic and ulcerative inflammation is mostly limited to
the mucosa, with recurrence leading to atrophic mucosa. Ulcers often have irregular
borders, giving rise to a collar-stud effect.

29. Newer methods upcoming

30. Lower radiation dose PET/CTE for fistulas

31. Pelvic MRI of IBD perianal disease. Representative axial T2 fat suppressed (a, b) and post-contrast T1 fat-suppressed (c, d)
images demonstrating an intersphincteric perianal fistula (a, c) and presacral abscess (b, d) in two patients with known
Crohn’s disease. Arrows indicate sites of disease.

32. Barium fluoroscopy
• High-quality barium studies have superior sensitivity over crosssectional
techniques for subtle early mucosal disease, although in those with established
and/or more advanced disease, both
• CT and MR may be equivalent and also provide information on submucosal
disease
• Isotope-labelled scans
A variety of nuclear medical techniques can be used in the assessment of IBD,
although they have no role in the primary diagnosis of IBD.47 Technetium-99m
labelling of white blood cells remain a widely acceptable scintigraphic method
for the evaluation of disease extension and severity

33. THERAPEUTIC OPTIONS IN THE MANAGEMENT OF
IBD
Nutrition
Specific attention should be paid to nutrient deficits such as calcium, vitamin D, other fat
soluble vitamins, zinc, iron and (after ileal resection especially) vitamin B12 status. Serum
vitamin B12 is best measured annually in patients with ileal Crohn’s disease
Macronutrients
In specific circumstances, protein and caloric support is indicated, such as when the gut is
reduced in short bowel syndrome or in the perioperative care .This may mean total
parenteral nutrition (TPN) including home TPN in a minority of Crohn’s disease patients
with intestinal failure.

34. TPN in IBD
• Six trials noted TPN has no greater advantage over enteral nutrition in low risk IBD
• However in moderate/severe cases w/ gut rest (77% remission) vs continuing
enteral route.
• Multiple small bowel resections (+/- short gut syndrome)
• Corrects nutritional micronutrient deficiency

35. Elimination Diet
• Remove food from the diet for a period of time and see if symptoms
improve/resolve.
• If on enteral nutrition/elemental diet then introduce 1 new food at a time
over a week each.
• Comparison of steroids vs elimination diet alone noted that relapse rate in 2
years was slightly lower in elimination diet (69%) vs steroids (72%).
• Food intolerance was common with cereals, lactose, and yeast products.
• Elimination diet vs unrefined carbs diet. Relapse at 6 months after remission
was 30% for elimination dieters vs 100% unrefined carbs diet

36. Prebiotics & Probiotics
•Prebiotics
•Prebiotics are non-digestible dietary carbohydrates,such as fructo-
oligosaccharides which are fermented by the gut microflora to produce short-
chain fatty acids. Their role is unproven to date.
Probiotics
Bacteria or yeast generally ingested orally as therapy are termed probiotics. They
may be administered as a single organism or a defined mixture, aiming to
beneficially alter the microbial ecology of the gut.

37. Smoking cessation
• Smoking is an important environmental factor in the pathogenesis of IBD, though the
mechanisms remain under investigation. Current smokers are more likely to develop
Crohn’s disease and, following diagnosis, have a poorer prognosis with a significantly
higher chance of surgical resection.
• and (if smoking still continues) a greater chance of recurrence at the surgical
anastomosis.
• Smoking cessation is associated with a 65% reduction in the risk of a relapse as
compared with continued smokers,
• a similar magnitude to that obtained with immunosuppressive therapy

38. Non-steroidal anti-inflammatory drugs
• There are many publications claiming an adverse effect of non-steroidal anti-
inflammatory drugs (NSAIDs) in precipiating de novo IBD or exacerbating pre-
existing disease, although the evidence remains contradictory and confusing
• Selective inhibition with COX-2 inhibitors or COX-1 inhibition with low dose
aspirin seems to be safe, at least in the short term

39. Drugs For IBD & its side effects

40. Types of Aminosalicylic acid

41. Approach To Management Of Ulcerative Colitis
• Goals of treatment : are induction and maintenance of
remission of symptoms to provide an improved quality of life,
reduction in need for long-term corticosteroids, and minimization
of cancer risk.

42. • Patients with mild to moderate distal colitis may be treated with oral
aminosalicylates, topical mesalamine, or topical steroids
(Topical mesalamine agents are superior to topical steroids or oral aminosalicylates)
• The combination of oral and topical aminosalicylates is more eff ective than
either alone In patients refractory to oral aminosalicylates or topical corticosteroids,
mesalamine enemas or suppositories may still be effective
• The unusual patient who is refractory to all of the above agents in maximal doses,
or whose systemically ill, may require treatment with oral prednisone in doses up to
40– 60 mg per day, or infl iximab with an induction regimen of 5 mg / kg at weeks 0, 2,
and 6,.
ACG Recommendations For Ulcerative
Colitis

43. RECOMMENDATIONS FOR MAINTENANCE OF
REMISSION IN DISTAL DISEASE
• Mesalamine suppositories are effective in the maintenance of remission in
patients with proctitis, whereas mesalamine enemas are effective in patients with
distal colitis when dosed even as infrequently as every third night
• Sulfasalazine, mesalamine compounds, and balsalazide are also effective in
maintaining remission; the combination of oral and topical mesalamine is more
effective than either one alone
• Topical corticosteroids including budesonide, however, have not proven effective for
maintaining remission in distal colitis
• When all of these measures fail to maintain remission in distal disease, thiopurines
(6-mercaptopurine (6-MP) or azathioprine) and infliximab (, but not corticosteroids,
may prove effective

44. RECOMMENDATIONS FOR MANAGEMENT OF MILD –
MODERATE EXTENSIVE COLITIS: ACTIVE DISEASE
• Patients with mild to moderate extensive colitis should begin therapy with oral
sulfasalazine in daily doses titrated up to 4 – 6 g per day, or an alternate
aminosalicylate in doses up to 4.8 g per day of the active 5-aminosalicylate acid (5-
ASA) .
• Oral steroids are generally reserved for patients who are refractory to oral
aminosalicylates in combination with topical therapy, or for patients whose symptoms
are so troubling as to demand rapid improvement
• 6-MP and azathioprine are effective for patients who do not respond to oral steroids,
and continue to have moderate disease, and are not so acutely ill as to require
intravenous therapy
• Infliximab is an effective treatment for patients who are steroid refractory or steroid
dependent despite adequate doses of a thiopurine, or who are intolerant of these
medications

45. • The infliximab induction dose is 5 mg / kg intravenously at weeks 0, 2, and 6
weeks.
• Infliximab is contraindicated in patients with active infection, untreated latent
TB, preexisting demyelinating disorder or optic neuritis, moderate to severe
congestive heart failure, or current orrecent malignancies.

46. RECOMMENDATIONS FOR MILD – MODERATE
EXTENSIVE COLITIS: MAINTENANCE OF REMISSION
*Once the acute attack is controlled, a maintenance regimen is usually required,
especially in patients with extensive or relapsing disease. Sulfasalazine, olsalazine,
mesalamine, and balsalazide are all effective in reducing relapses
*Patients should not be treated chronically with steroids. Azathioprine or 6-MP may
be useful as steroid-sparing agents for steroid-dependent patients and for
maintenance of remission not adequately sustained by aminosalicylates, and
occasionally for patients who are steroid depend ent but not acutely ill
*Infliximab is effective in maintaining improvement and remission in the patients
responding to the infl iximab induction regimen

47. RECOMMENDATIONS FOR MANAGEMENT OF SEVERE
COLITIS
• The patient with severe colitis refractory to maximal oral treatment with prednisone,
oral aminosalicylate drugs, and topical medications may be treated with infliximab
5 mg / kg if urgent hospitalization is not necessary.
• The patient who presents with toxicity should be admitted to hospital for a course of
intravenous steroids
• Failure to show significant improvement within 3 – 5 days is an indication for either
colectomy or treatment with intravenous cyclosporine in the patient with severe
colitis. Long-term remission in these patients is significantly enhanced with the
addition of maintenance 6-MP
• Infliximab may also be effective in avoiding colectomy in patients failing intravenous
steroids but its long-term efficacy is unknown in this setting

48. RECOMMENDATIONS FOR SURGERY
*Absolute indications for surgery are exsanguinating hemorrhage, perforation, and
documented or strongly suspected carcinoma
*Other indications for surgery are severe colitis with or without toxic megacolon
unresponsive to conventional maximal medical therapy, and less severe but medically
intractable symptoms or intolerable medication side effects
*Patients who develop typical symptoms and signs of pouchitis after the IPAA should be treated with a short
course of antibiotics
*Controlled trial studies show efficacy for metronidazole in a dose of 400 mg three times daily, or 20 mg / kg daily,
or ciprofl oxacin 500 mg twice daily
Other etiologies mimicking pouchitis include irritable pouch syndrome, cuffitis, CD of the pouch, and postoperative
complications such as anastomotic leak or stricture. Inadequate evidence exists to recommend routine
surveillance of the pouch for dysplasia or adenocarcinoma
RECOMMENDATIONS FOR THE MANAGEMENT OF
POUCHITIS

49. RECOMMENDATIONS FOR CANCER SURVEILLANCE
*Aft er 8 – 10 years of colitis, annual or biannual surveillance colonoscopy with
multiple biopsies at regular intervals should be performed
*The finding of HGD in flat mucosa, confirmed by expert pathologists ’ review, is an
indication for colectomy, whereas the fi nding of LGD in fl at mucosa may also be an
indication for colectomy to prevent progression to a higher grade of neoplasia

50. Approach To Management Of Crhons Disease
• Goals of treatment : are induction and maintenance of
remission of symptoms to provide an improved quality of life,
reduction in need for long-term corticosteroids, and minimization
of cancer risk.

51. Recommendations for Induction of Remission
*ACG Against Using Thiopurine Monotherapy to Induce Remission in Patients With
Moderately Severe CD.
*Using Methotrexate to Induce Remission in Patients With Moderately Severe CD Using
Anti–TNF-a Drugs in Combination With Thiopurines Over Thiopurine
Monotherapy to Induce Remission in Patients Who Have Moderately Severe CD.
* Using Anti–TNF-a Monotherapy Over Thiopurine Monotherapy to Induce Remission
in Patients Who Have Moderately Severe CD.
*Using Anti–TNF-a Drugs in Combination With Thiopurines Over Thiopurine
Monotherapy to Induce Remission in Patients Who Have Moderately Severe CD

52. Recommendations for Maintenance
of Remission
• Using Thiopurines Over No Immunomodulator Therapy to Maintain a
Corticosteroid-Induced Remission in Patients With CD
• Using Anti–TNF-a Drugs Over No Anti–TNF-a Drugs to Maintain Corticosteroid- or
Anti–TNF-a—Induced Remission in Patients With CD
• Make No Recommendation for or Against the Combination of an Anti–TNF-a Drug
and a Thiopurine Versus an Anti–TNF-a Drug Alone to Maintain Remission Induced
by a Combination of These Drugs in Patients With CD

54. Summary

61. Recent Options for treatment
• Anti-Integrin antibodies
• Natlizumab (Tysabri) – anti-alpha-4 integrin
• Vedolizumab (Entyvio) –anti-alpha-4-beta-7 integrin
• Anti-IL-12 and IL-23 – inhibit their receptors on Tc, NKc, and APC
• Ustekinumab blocks IL-12 and IL-23 receptors
• Anti-IL-17 antibodies inhibit TH17 activation
• TPN and gut rest
• Antibiotics – Cipro and Metroniazole, ? Xifaxan, ?Alinia