INFLAMMATORY BOWEL DISEASE - Definition,Epidemiology, Etiology & Pathogenesis, Clinical features, Extra Intestinal manifestations, Diagnosis and D/D

1. INFLAMMATORY
BOWEL DISEASE
Dr. Ansuman Dash

2. IBD
Inflammatory bowel disease is an idiopathic
inflammatory intestinal disease resulting from an
inappropriate immune activation to host intestinal
microflora.
Types of IBD are
 Ulcerative colitis
 Crohn’s disease
 Indeterminate colitis

3. ■ Ulcerative colitis - nonspecific inflammatory bowel disease of
unknown etiology that effects the mucosa and submucosa of the
colon and rectum
■ Crohn’s disease - nonspecific inflammatory bowel disease that may
affect any segment of the gastrointestinal tract
■ Indeterminate colitis
– 15% patients with IBD impossible to differentiate

4. History
 Morgagni provided a description of intestinal inflammation
characteristic of Crohn's disease in 1761.
 In 1932, the landmark publication of Crohn, Ginzburg, and
Oppenheimer called attention to “terminal ileitis” as a
distinct entity and chronic disease.
 The name “Crohn's disease” has been adopted to encompass
the many clinical presentations of this pathologic entity. But
for the alphabetic priority these authors chose Crohn's
disease.

5. EPIDEMIOLOGY
■ Incidence and prevalence highest in westernized nations.
■ Prevalence rates are
■ 4.9-505 /1 lakh in Europe
■ 37.5 – 248 /1 lakh in north America
■ 4.9 – 168.3 in Asia
■ Peak incidence in 2nd to 4th decade with a 2nd peak in 7th – 9th
decade.

6. EPIDEMIOLOGY
■ A house to house survey of 4796 houses including 21921 persons (>
14 years age) in Haryana state revealed 10 cases (5 each in both
sexes) which gave a prevalence of 45.5/105 population (42.8/105 for
males and 48.6/105 for females).
■ In a later study from the neighbouring state of Punjab where
cluster sampling method was employed the crude incidence and
prevalence of UC was found to be 6.02/105 and 44.8/105 population
which was the highest in Asia but still less than that of North
America and Europe.

7. Etiopathogenisis
Genetic
susceptibility
Environmental
factors
Host immunity

8. etiology
• DIET:
• Fat intake
• Fast food ingestion
• Milk and fibre consumption
• Total protein and energy intake
• DRUGS:
• NSAIDS: DICLOFENAC
• Antibiotics: may precipitate the relapse
• Oral contraceptives increase the risk of developing CD
• Smoking is protective against UC but increases the risk of CD
8

9. GENETICS:
• If a patient has IBD, the lifetime risk that a first-degree
relative will be affected is ~15%.
• If two parents have IBD, each child has a 36% chance of
being affected.
• In twin studies , 58% of monozygotic twins are concordant
for CD and 6% are concordant for UC, whereas 4% of
dizygotic twins are concordant for CD and none are
concordant for UC.
• Mutations of gene CARD15/NOD2 on chromosome 16 is
associated with SI CD 2 other genes – OCTN1, DLG5
■ ETHNIC: Jews are more prone to IBD than non jews.
■ STRESS: Increase the relapse of IBD
9

10. CONTD..
■ INFECTION:
– Mycobacterium paratuberculosis : CD
– Diarrhoea :Ulcerative colitis
IBD is currently considered an inappropriate immune
response to endogenous commensal microbiota within
the intestines, with or without some component of
autoimmunity.
10

11. PATHOPHYSIOLOGY
11

12. 12

13. Genetics
Crohn’s disease Ulcerative colitis
1. NOD2/CARD15
2. Autophagy-related
genes
3. Interleukin (IL)-23
1. MDR 1
2. HLA-DR1
3. HLA-DR3,DQ2

14. Anatomical classification of ulcerative colitis and
CROHN’s disease
ULCERATIVE
COLITIS CROHNS DISEASE
– Proctitis
– Proctosigmoiditi
s
– Left sided colitis
– Pancolitis
– Backwash ileitis
– Gastro duodenal
Crohn’s disease(
gastroduodenitis)
– Jejunoileitis
– Ileitis
– Ileocolitis
– Crohn’s
(granulomatous) colitis14

15. Ulcerative Colitis

16. 16

17. UC Pathology
Macroscopic Appearance
■ Involves rectum and extends proximally to involve entire colon.
40 – 50 % - disease limited to rectum and rectosigmoid
30 – 40 % - extends beyond sigmoid but not involving whole colon
20 % - Pancolitis
 No skip lesions.
 Backwash ileitis – Inflammation extends 2 – 3 cm into terminal ileum in
10 -20 %

18. ■ Mild Inflammation – Mucosa is erythematous and has granular
surface. (Sandpaper appearance)
■ Severe inflammation – Mucosa hemorrhagic, edematous and
ulcerated.
■ Long standing disease – Pseudopolyps
■ Toxic megacolon –Transverse or right colon with diameter >
6cm with loss of haustrations in severe UC.

19. Microscopic Appearance
■ Limited to mucosa and submucosa.
■ Deeper layers may be affected in fulminant disease.
■ Distortion of crypt architecture
■ Basal plasma cells and lymphoid aggregates.
■ Mucosal vascular congestion with edema and focal hemorrhage.
■ Cryptitis and Crypt abscess – Neutrophils invade the epithelium in the
crypts
■ Mucosal infiltration by Neutrophils, Lymphocytes, Plasma cells and
Macrophages.

21. Crypt
distortion
Diffuse
inflammation

22. CLINICAL FEATURES of UC
■ Diarrhoea
■ Rectal bleeding
■ Tenesmus
■ Passage of mucus
■ Crampy abdominal pain
Proctitis –
■ Fresh blood and blood stained mucus, either with stool or streaked onto
the surface of normal or hard stool. Sense of incomplete evacuation and
urgency
■ Proctosigmoiditis – May have constipation

23. Severe Colitis
■ Grossly bloody diarrhea
■ Liquid stool containing blood, pus and fecal matter
■ Anorexia
■ Nausea
■ Vomiting
SIGNS –
■ Tender anal canal
■ Blood on DRE
■ Tenderness on palpation over colon in severe disease

24. Ulcerative Colitis: Disease Presentation
Mild Moderate Severe
Bowel movements <4/day 4-6/day >6/day
Blood in stools Small Moderate Severe
Tachycardia None <90/min >90/min
Fever None <99.5F >99.5F
Anemia Mild Moderate Severe
ESR <30 >30
Endoscopy Erythema,
decreased vascular
pattern, fine
granularity
Marked erythema,
coarse granularity,
absent vascular
markings, contact
bleeding, no
ulcerations
Spontaneous
bleeding,
ulcerations

25. INVESTIGATIONS
■ Elevated acute phase reactants like CRP and elevated ESR
■ Low Hemoglobin
■ Leukocytosis may be seen
■ Fecal lactoferrin and fecal Calprotectin levels – Correlate with histologic
inflammation and predict relapses
■ Stool examination for bacteria, C. difficile toxin and ova and parasites
■ P-ANCA is positive in 60 -70 %. ASCA positive in 10 – 15 %.
■ SIGMOIDOSCOPY and COLONOSCOPY with biopsy – to assess disease activity and
confirm diagnosis
■ Mild disease – Mild erythema and friability
■ Severe disease – spontaneous bleeding and ulcerations

26. RADIOLOGY
■ Earliest radiologic change with single-contrast barium enema is fine
mucosal granularity.
■ Deep ulcers appear as collar – button ulcer
■ Loss of haustrations in long standing disease.
■ Colon becomes shortened and narrowed
CT and MRI
■ Mild mural thickening
■ Absence of small bowel thickening
■ Target appearance of rectum
■ Adenopathy

27. Etiology
■ Three prevalent theories include:
– response to a specific infectious agent
– a defective mucosal barrier allowing an increased exposure to antigens
– an abnormal host response to dietary antigens
■ One infectious agent that has generated some interest is Mycobacterium
paratuberculosis, isolated in up to 65% of tissue samples from Crohn's patients
■ A statistically significant association between the onset of Crohn's disease and
prior use of antibiotics has also been observed
■ Smoking appears to be a risk factor for Crohn's disease, and after intestinal
resection, the risk of recurrence is greatly increased in smokers

28. COMPLICATIONS
■ Massive hemorrhage
■ Toxic Megacolon
■ Perforation and Peritonitis
■ Stricture in 5 – 10 % of patients. A stricture that is
impassable to colonoscope should be presumed
malignant unless proven otherwise.
■ Malignant transformation

29. Risk for carcinoma in UC
■ Disease duration
– 25% at 25 yrs, 35% at 30 yrs, 45% at 35 yrs, and 65% at 40 yrs
■ Pancolonic disease
– Left-sided only pts less likely to develop cancer than pancolitis pts
■ Continuously active disease
■ Severity of Inflammation
– Colonic stricture must be considered to be cancer until proven
otherwise

30. CROHN’S DISEASE

31. Pathology
MACROSCOPIC FEATURES
■ Can affect any part of the GI tract from mouth to anus.
■ 30 – 40 % - small bowel ds alone
■ 40 – 55 % - both small and large intestine affected
■ 15 – 25 % - colitis alone
■ Terminal ileum is involved in 90 % of small intestinal ds
■ Skip Lesions
■ Perirectal fistulas, fissures, abscesses and anal stenosis seen in one
third of CD patients.
■ Mild disease – small aphthous ulcers

33. ■ Linear serpiginous ulcers seen
■ Cobblestone appearance
■ Pseudopolyps may be seen
■ Fistula tracts may be seen
■ Fibrosis and stricture of bowel
■ Creeping fat

34. ■ Histologic
– transmural inflammation, submucosal edema,
loose macrophage aggregation, and ultimately
fibrosis
– Pathognomonic: the noncaseating granuloma, a
localized, well-formed aggregate of epithelioid
histocytes surrounded by lymphocytes and giant
cells; found in 50% of resected specimens.
– Focal crypt abscess may be seen

35. 35

36. Clinical Presentation
ILEOCOLITIS –
 Recurrent right lower quadrant pain and diarrhea
 Palpable mass in right lower quadrant
 Mimics acute appendicitis
 May present as bowel obstruction.
JEJUNOILEITIS –
 Malabsorption and steatorrhoea
 Anemia, hypoalbuminemia, hypocalcemia, hyperoxaluria

37. COLITIS
■ Malaise
■ Diarrhoea
■ Crampy abdominal pain
■ Hematochezia
■ Incontinence, hemorrhoidal tags, anorectal tags,
perirectal abscess in perianal disease

38. Unusual Presentations of CD
■ Gastroduodenal - H-pylori-negative peptic ulcer disease,
dyspepsia or epigastric pain as the primary symptoms
■ Esophageal - < 2% of patients.
– Dysphagia, odynophagia, substernal chest pain, and
heartburn
– Mouth ulcers
– Esophageal stricture and esophagobronchial fistula
■ acute granulommatous appendicitis -

39. Perianal disease of CD
1. Skin lesions- include maceration, superficial ulcers,
abscesses, and skin tags
 type 1 (elephant ears) are typically soft and painless and
large
 type 2 are typically edematous, hard, and tender.
2. Anal canal lesions - fissures, ulcers, and stenosis
3. Perianal fistulas.

40. Aggressive fistulizing disease
 Fistulas are manifestations of the transmural nature of CD
 Perianal fistulas are common and occur in 15% to 35% of
patients.
 Enterovaginal fistulas occur in women
 Enterovesicular - recurrent polymicrobial UTI or as frank
pneumaturia and fecaluria.
 Enterocutaneous fistula after appendectomy
 Other types- enteroenteric, enterocolonic, and colocolonic
fistulas

42. Stricture
 Stricture is another characteristic complication of long-
standing inflammation
 Symptoms can include colicky, postprandial abdominal pain
and bloating, punctuated by more-severe episodes, and often
culminating in complete obstruction.
 String sign - markedly narrowed bowel segment amid widely
spaced bowel loops

44. EXTRAINTESTINAL MANIFESTATIONS

45. Musculoskeletal
 Clubbing
 Arthritic manifestations
Peripheral arthropathy - 16% to 20%
 Pauciarticular arthropathy (type I, affecting four or fewer joints)
 Polyarticular arthropathy (type II, with five or more joints
affected)
Axial arthropathies - 3% to 10%
Metabolic bone disease
Granulomatous vasculitis, periostitis and amyloidosis.

46. Mucocutaneous
Pyoderma gangrenosum
Erythema nodosum
Granulomatous inflammation of the skin
Aphthous ulcers of the mouth
Angular cheilitis

47. Pyoderma Gangrenosum

48. Erythema
Nodosum

49. Ocular
 Occur in 6% of patients .
 Episcleritis
 Scleritis
 Uveitis - the anterior segment
 Keratopathy and night blindness

51. Hepatobiliary
Gallstones
Asymptomatic and mild elevations of liver biochemical
tests
 PSC more often is associated with UC
 Autoimmune hepatitis.
Vascular
 venous thromboembolism
 arterial thrombosis.

52. Renal and Genitourinary
Inflammatory entrapment of the ureter
 Uric acid and oxalate stones.
 Membranous nephropathy &Glomerulonephritis
 Renal amyloidosis.
. Penile and vulvar edema

53. Investigations
 CBC
 Nutritional evaluation: Vitamin B12 , iron studies, folate & other
nutritional markers
 ESR and CRP levels
 Fecal calprotectin level
 Serologic studies: pANCA, ASCA, anti-CBir1
 Stool studies: Stool R/M, C/S, evaluation for Clostridium difficile toxin

54. DISTINGUISHING CHARACTERISTICS OF CROHN’s disease AND Ulcerative
colitis
Characteristic Feature Ulcerative Colitis Crohn’s Disease
Abdominal tenderness May be present Common
Abdominal wall and internal fistulas Common Absent
Abdominal pain Uncommon Common
Fever , Malaise Uncommon Common
Bloody Diarrheoa Frequent Occasional
Location Only colon GIT
Anatomic distribution Continuous, begins distally Skip lesions
Weight loss Occasional Frequent
54

55. Characteristic Feature Ulcerative colitis Crohn’s disease
Palpable mass Rare Common
Intra-abdominal abscess Rare Common
Bowel Obstruction Rare Common
Antibiotic response Rare Frequent
Skip lesions Rare Frequent
Effect of smoking Often improves Often worsens
Serologic markers
ASCA +
P-ANCA +
15%
70%
65%
20%
Iron deficiency anaemia, raised CPR/
ESR, hypoalbuminaemia
Common Common
Recto vaginal fistula Rare Frequent
Perianal Fistula Rare Frequent
55

56. PATHOLOGIC FEATURES OF CD AND UC
Characteristic feature Crohn’s disease Ulcerative colitis
Transmural Inflammation Common Uncommon
Granulomas Common Rare
Fissures Common Rare
Fibrosis Common No
Sub mucosal inflammation Common Uncommon
Rectal involvement Rare Common
Ileal involvement Very Common Rare
Strictures Common Rare
Crypt abcess Rare Very common
Linear clefts Common Rare
Cobblestone appearance Common Absent
ComprEhensive pharmacy review –LEON shargel, CLINICAL PHARMACY AND THERAPEUTICS- ROGER WALKER, pHARMACOTHERAPY a pathophysiologic
appraochjosepht. dipiro
56

57. Imaging studies
 Upright chest and abdominal radiography
 Barium double-contrast enema radiographic studies
 Abdominal ultrasonography
 Abdominal/pelvic computed tomography scanning/magnetic
resonance imaging with enterography
 Colonoscopy, with biopsies of tissue/lesions
 Upper gastrointestinal endoscopy
 Capsule enteroscopy/double balloon enteroscopy

58. Plain radiograph
In severe disease, the luminal margin of the colon
becomes edematous and irregular.
Thickening of the colonic wall often is apparent on a
plain film
Plain films also are useful for detecting the presence of
fecal material.
 The presence of marked colonic dilatation suggests
fulminant colitis or toxic megacolon.

59. Barium studies
Aphthous ulcers, a coarse villus mucosal pattern, and
thickened folds.
Pseudo sacculation of the antimesenteric border
Cobblestone appearance
Fistulas, sinus tracts, and fixed strictures
The earliest radiologic change of UC seen is fine
mucosal granularity

61. String sign

62. lead-pipe or stove-pipe appearance

65. MR enterography
Intestinal wall thickening, submucosal edema, vasa recta
engorgement, and lymphadenopathy are signs of active
diseas
FIESTA images can add information regarding the
functional status of fibrotic segment
 MRI images yield a diagnostic accuracy of 91%.

66. Colonoscopy
 The hallmark of UC is continuous inflammation that begins in
the rectum.
 The earliest endoscopic sign of UC is a mucosal erythema and
edema
 As disease progresses, the mucosa becomes granular and
friable.
 In severe inflammation, the mucosa may be covered by yellow-
brown mucopurulent exudates associated with mucosal
ulcerations.

67. Ulcerative Colitis

70. Uses of colonoscopy
Determine the extent and severity of colitis
Provide tissue to assist in the diagnosis.
Therapeutic use is stricture dilation

71. Capsule Enteroscopy
Swallows encapsulated video camera
Transmits an image to a receiver outside the pt.
It is most commonly used for finding obscure sources
of GI blood loss,
The images can find ulcerations associated with CD if
endoscopy and colonoscopy are unrevealing
 The major risk is the potential to get lodged at the
point of a stricture

72. Complications of CD
 Perforation
 Abscess formation
 Stricture & small bowel obstruction
 Nutritional deficiencies
 Cancer: small bowel adenocarinoma
 Cancer: colon???

73. Complications of UC
Toxic Megacolon:
 Defined as a transverse or right colon with a diameter of >6 cm,
with loss of haustration in patients with severe attacks of UC.
 It occurs in about 5% of attacks and
 It can be triggered by electrolyte abnormalities and narcotics.
 About 50% of acute dilations will resolve with medical therapy
alone
 Urgent colectomy is required for those that do not improve

74. Complicatins of UC
 Colon adenocarcinoma
 After 8–10 years of colitis, annual or biannual surveillance colonoscopy with multiple
biopsies at regular intervals should be performed
 extensive mucosal involvement (pancolitis)
 family history of carcinoma of the colon.
 Perforation
 Massive hemorrhage

75. DIFFERENTIAL DIAGNOSIS

76. SUMMERY

77. INVESTIGATIONS
Crohn’s disease Ulcerative colitis
BloodTest
•CP with morphology: Normocytic normocromic
anemia of CHRONIC disease
•Serum B12 level may be low.
•Raised ESR, CRP and raisedWBC count.
•Hypo albuminaemia.
•Blood culture in septicaemia.
•Fe deficiency anemia
•Raised white cell and platelet count
•Raised ESR, CRP
•Hypo albuminaemia
SerologicalTest
• Saccharomyces cerevisiae antibody is usually
present
•P-ANCA positive in 5 – 10 %
•P-ANCA positive in 60 – 70 %
•ASCA positive in 10 – 15 %
Stool culture
•Should always be performed in both to rule out infective cause

78. CONTD..
Crohn’s Disease Ulcerative Colitis
Radiography
PlainABD. X-ray:
•Loss of haustral markings and shortening of bowel
Is seen in sever lession.
•Narrowing of bowel lumen is seen
Ultrasound:
•Thickened small bowel loops and mesentery or
abscess
•Thickening of colonic wall and presence of free
fluid in abdominal cavity
Barium Enema (contraindicated in toxic
megacolon)
•Skip lesions
•Rose thorn appearance
•String appearance
•Cobble stone appearance
•Omega sign are also seen
•Ulcerations
•Pseudopolyps
•Loss of haustration
•Shortening of bowel is seen

79. CONTD..
Crohns disease Ulcerative colitis
Instant Barium enema
•Patchy sup. Ulceration to wide spread deep
•Cobble stone appearance and narrowing
•Superficial ulcers
•Shortened and narrowed colon in long standing
disease
Colonoscopy
•Fissures and fistulae •Pseudopolyps
•Mucosal granularity and hyperemia
High resolution USG. And spiral CT
•Radionuclide scan with gallium labeled
polymorphs or indium or technetium labeled
leucocytes
•Capsule imaging of the gut.
•Radionuclide scan used to assess colonic
inflammation
Stricture evaluation and dilation
complicated Lesser complicated