This document discusses inflammatory bowel diseases, specifically focusing on Crohn's disease. It covers the typical presentation and types of IBD, pathogenesis, epidemiology, clinical features, investigations, differential diagnosis, management and disease activity measurement of Crohn's disease. Key points include that Crohn's is a chronic inflammatory condition of the intestines characterized by periods of remission and relapse due to inappropriate immune response. Genetics and environmental factors contribute to its pathogenesis.

1. SUBJECT SEMINAR
INFLAMMATORY BOWEL
DISEASES
CHAIRPERSON: DR PRAVEEN KUSUBI
STUDENT: DR GANESH

2. GENERAL CONSIDERATIONS
Clinically, inflammatory bowel disease (IBD)
is a chronic inflammatory condition of the
intestines that is marked by remission and
relapses due to inappropriate mucosal
immune response

3. • TYPICAL IBD (2 Major Types):
– Ulcerative Colitis (Colitis Ulcerosa)
– Crohn’s Disease (Regional Enteritis)
• ATYPICAL IBD:
– Lymphocytic Colitis
– Collagenous Colitis
– Ischaemic Colitis
– Diversion Colitis
– Indeterminate Colitis
– Bachet’s Disease

4. INTERMEDIATE IBD:
In approximately 10% of cases, Crohn’s
disease cannot be distinguished from UC on
clinical grounds, although the 2 diseases are
distinct syndromes with divergent treatment
and prognosis.

5. Both diseases have a general
commonality in their pathogenesis
Derived from a deregulated mucosal
immune response to antigenic components of
the normal commensal micro biota
That reside within the intestine in a
genetically susceptible host

6. EPIDEMIOLOGY:
Reassignment of a diagnosis of Crohn’s
disease or UC may be as high as 9% in the
first 2 years after diagnosis.
Distinct and reproducible geographic and
temporal trends in incidence have been
observed.

7. This observation has been linked to
variations in exposure to sunlight, with
increasing levels of sunlight and vitamin D
exposure inversely associated.
Asia, the incidence rate has remained low,
with a mean estimated incidence of 0.54 per
100,000 person-years.

9. Studies throughout the world have shown a
small excess risk of Crohn’s disease among
women.
1.3 : 1 In the pediatric population this is
reversed.
This slight difference in risk in adult-onset
disease may be explained by hormonal or life-
style factors and stands in contrast to the
nearly equal or even slight male predominance
seen in UC.

11. Pathogenesis of IBD
American Gastroenterological Association Institute, Bethesda, MD.
Sartor RB. Nat Clin Pract Gastroenterol Hepatol. 2006;3:390-407.
Normal
Gut
Tolerance-
controlled
inflammation
Environmental
trigger
(Infection, NSAID, other)
Acute Injury
Complete Healing
Chronic Inflammation
Genetically
Susceptible
Host
Acute Inflammation
↓ Immunoregulation,
failure of repair or
bacterial clearance
Tolerance

16. CROHN’S DISEASE

17. ETIOLOGY AND PATHOGENESIS
INITIATING EVENTS
Infectious agents:
chlamydia, Listeria monocytogenes, cell-
wall–deficient Pseudomonas species &
reovirus,M Paratuberculosis..etc
Intestinal dysbiosis

18. GENETICS
Mendelian inheritance(AR)
Ashkenazi jews
NOD2 Gene
ATG16L1 Gene

19. ENVIRONMENTAL FACTORS
BREAST-FEEDING to be protective for
IBD, role in early programming Of immune
responses in the developing GI tract and in
shaping the intestinal microbiome.
HIGHER SOCIOECONOMIC STATUS,
presumably because (hygiene hypothesis).

20. ORAL CONTRACEPTIVES.
NSAIDs have been implicated not only in
exacerbations of IBD but also as a potential
precipitant of new cases, perhaps by increasing
intestinal permeability.
Increased intake of REFINED SUGARS and a
paucity of fresh fruits and vegetables in the diet

21. SMOKING is one of the more notable
environmental factors for IBD.
UC is largely a disease of ex-smokers and
non smokers,
whereas Crohn’s disease is more prevalent
among smokers.

22. In addition, smokers have more surgery for
their disease and a greater risk of relapse after
resection.
The reasons for the divergent effect of
smoking on Crohn’s disease and UC are poorly
understood

23. Effects on intestinal permeability,
cytokine production, and clotting in the
microvasculature.
Carbon monoxide in stimulating
immunosuppressive effects mediated by
heme oxygenase
Whether such biologic effects contribute
to the different effects of smoking in Crohn’s
disease and UC is unknown.

24. ADAPTIVE IMMUNE RESPONSE AND
INFLAMMATION
Patients with allelic variants in NOD2 have
defective sensing of intracellular bacteria, as
well as reduced production of defensins, which
are natural antimicrobial products produced by
Paneth cells in the base of the intestinal crypts.

25. The net result is excessive activation of
adaptive immune responses to compensate for
defective innate immunity.
Hence results in inflammation related
mucosal injury

26. Similarly, variant loci of the ATG16L1 and
IRGM genes are associated with defective
autophagy,
Process that is involved in defense
against microbes and that stands at the
interface of innate and adaptive immunity in
the processing of intracellular pathogens and
presentation of antigens to T cells.

27. ANTIBODIES MUCH MORE COMMONLY
SEEN IN CD
Anti-Saccharomyces cerevisiae antibody (ASCA)
Antibodies against bacterial antigens
anti-CBir1 (antibody to flagellin from Clostridium
species)
anti-OmpC (antibody to outer membrane porin C of
E. coli),
anti-I2 (antibody to Pseudomonas-associated
sequence I2)

30. PATHOLOGY
Focal intestinal inflammation -hallmark.
Focal crypt inflammation
Focal areas of marked chronic inflammation,
Aphthae and ulcers on a background of little
or no chronic inflammation
Interspersing of segments of involved bowel
with segments of uninvolved bowel.

34. MULTINUCLEATED GIANT CELLS
MONONUCLEAR CELLS,

35. Loosely formed collection of cells,
consisting of multinucleated giant cells and
mononuclear cells, including T cells, and
epithelioid macrophages.
Central caseation is not noted
Focally enhanced gastritis
Characterized by a focal perifoveolar or
periglandular lymphomonocytic infiltrate

36. MONTREAL CLASSIFICATION OF CROHN’S DISEASE
AGE (A1, 16 years and younger; A2, 17 to 40 years;
A3, >40 years),
DISEASE LOCATION (L1, ileal: L2, colonic; L3,
ileocolonic),
DISEASE BEHAVIOR (B1, non-stricturing, non-
penetrating; B2, stricturing; B3, penetrating).
UPPER GI TRACT DISEASE location (L4) and for
PERIANAL DISEASE (P) may be added to the other
categories

37. PATHOPHYSIOLOGY OF COMMON
SYMPTOMS AND SIGNS
DIARRHEA (most common)
Alterations in mucosal function and
intestinal motility.
Altered fluid and electrolyte
Increased mucosal permeability from
mucosal inflammation
Increased production of prostaglandins,
biogenic amines, cytokines, neuropeptides, and
reactive oxygen.

38. Bile salt– induced diarrhea
Steatorrhea in the setting of ileal
dysfunction or resection
Bacterial overgrowth can occur behind
strictured bowel and contribute to
malabsorption
Disordered colonic motility
Medications used to treat Crohn’s.

39. PAIN ABDOMEN
Stretch receptors in the intestinal wall may
be stimulated as a food bolus passes through
stenotic bowel, leading to abdominal pain and
possibly vomiting.
Visceral pain can result from serosal
inflammation and local pain from abscess
formation.

40. WEIGHT LOSS AND MALNUTRITION
Decreased absorption
Catabolic state secondary to inflammation
Poor intake
Cachexia
Drugs

41. Fever
Easy fatigability
Malnutrition

44. EPISCLERITIS,

45. ERYTHEMA NODOSUM

46. FACIAL PG. THIS CAN BE A VERY DESTRUCTIVE LESION
REQUIRING AGGRESSIVE AND MULTIFACTORIAL TREATMENT
APPROACHES

48. DIFFERENTIAL DIAGNOSIS OF ILEITIS
Backwash ileitis in UC
Drug-related
Ectopic pregnancy,Endometriosis…etc
Ileitis associated with spondyloarthropathy
Infiltrative disorders

49. Amyloidosis
Eosinophilic gastroenteritis
Lymphoid nodular hyperplasia
Neoplasms
Carcinoid tumor, Cecal or ileal
adenocarcinoma
Lymphoma,Metastatic cancer

50. DIFFERENTIAL DIAGNOSIS OF COLITIS
Acute self-limited colitis
Behçet’s disease
Chronic granulomatous disease
Diversion colitis,Diverticulitis

51. Drug-induced colitis (NSAIDs, gold,
penicillamine)
Eosinophilic gastroenteritis
Graft-versus-host disease
Indeterminate colitis Infections

53. TB CROHN’S
Involvement of
terminal ileum
shorter longer
Features Narrowed,
thickened, rigid
terminal ileum with
pulled up ceacum
Asymmetry and
cobble stoning
Longitudinal
Ulceration
absent present
TUBERCULOSIS VS CHRON’S

55. MANAGEMENT

56. ESTABLISHING THE DIAGNOSIS AND
EVALUATING DISEASE ACTIVITY
No single symptom, sign, or diagnostic test
establishes the diagnosis of Crohn’s disease.
Rather the diagnosis is established
through a total assessment of the clinical
presentation with confirmatory evidence from
radiologic, endoscopic, and in most cases,
pathologic findings.

57. Initial evaluation includes a thorough
history-taking, physical examination, and basic
laboratory tests.
Fever may be associated with the
underlying disease or a suppurative
complication.
A careful examination of the abdomen for
signs of obstruction, tenderness, or a mass
should be undertaken.

58. History taking focuses on the key symptoms
and their severity and duration.
Specific points to be covered should include
recent travel history, use of antibiotics and other
medications, diet, and sexual preference and
activity.

59. A family history of IBD can raise the level of
suspicion but does not guarantee the diagnosis.
The review of systems should focus on eliciting
EIMs and weight loss

60. Thorough inspection of the perineum and
a rectal examination might disclose findings
highly suggestive of the underlying diagnosis
or gross or occult blood.
Laboratory data may be normal. Anemic
patients should undergo further evaluation to
define the contributions of iron,
folate, or vitamin B12 deficiencies.

61. INVESTIGATIONS
ESR,CRP,StoolC/S
Clonoscopy and biopsy
CT/MRI Enterography
EUS
Barium study
Video Capsule Endoscopy

62. MULTIPLE AREAS OF NARROWED SMALL
BOWEL ARE EVIDENT, WITH A CLASSIC
COBBLESTONED APPEARANCE OF THE
MUCOSA.
STRING SIGN OF A MARKEDLY NARROWED
BOWEL SEGMENT AMIDST WIDELY SPACED
BOWEL LOOPS IS A RESULT OF SPASM AND
EDEMA

64. APHTHOUS ULCERS
COBBLESTONED APPEARANCE
STELLATE ULCERS DISCRETE ULCERS

65. MEASURING DISEASE ACTIVITY
Most commonly the Crohn’s Disease Activity Index
(CDAI) are used in an attempt to integrate the many
possible features of the disease.
Other-
van Hees index,133,Cape Town index,134 the Harvey-
Bradshaw index,135 the International Organization of IBD
(or Oxford) index,136 the St. Marks Crohn’s index,137 De
Dombal’s index,138 the Talstad index,139 and a Crohn’s
disease activity index for survey
research.

67. CDAI < 150 implies remission.
150 -250 Mild
251 -450 moderate
> 450 imply severe disease
CDAI improvements exceeding 70 to 100
points are considered clinically important.

68. Treatment

69. Lifestyle changes

74. Numerous studies with a variety of
preparations have failed to demonstrate
prevention of relapses of Crohn’s disease with
5-ASA compounds.
Therefore, although maintenance therapy with
mesalamine often is prescribed in Crohn’s
disease, little data justify the
expense and inconvenience of this practice,
AMINOSALICYLATES

75. In summary, sulfasalazine 4 to 6 g/day may
be useful for inducing remission of mild to
moderate colonic Crohn’s disease, whereas the
role of mesalamine is uncertain.
The small margin of benefit and relatively slow
onset of effect (4 to 8 weeks) must be weighed
against the excellent safety profile of these
agents

77. ANTIBIOTICS
INDICATIONS; Pyogenic complications
and perineal diseases and post operative
propylaxis
Ciprofloxacin 500mg bd for 6 months
Metronidazole 20mg/kg/day for 3 months
other antibiotics;
clarithromycin,refaximin

78. STEROIDS
There are several principles of glucocorticoid
Use an effective dose
Do not overdose.
Do not treat for excessively short periods.
Do not treat for excessively long periods.
Anticipate side effects.

79. INDICATIONS FOR STEROIDS
Mild to moderate disease that does not
respond to primary therapy
Severely active disease
A Cochrane review of the use of
corticosteroids for the induction of
remission of Crohn’s disease supports this
efficacy of traditional steroids over ASA and
placebo

80. PREDNISONE 0.5 to 0.75 mg/kg/day for
initial treatment of active disease, with the
dose adjusted according to CDAI
6-METHYLPREDNISOLONE 48 mg/ day in
the first week, tapered to 12 mg by week 6,
and held at 8 mg for remission up to 2 years

81. Patients with severely active disease
usually respond to IV administration of
glucocorticoids.
HYDROCORTISONE (100 mg IV every 8
hours), prednisolone (30 mg IV twice daily)
or methylprednisolone (16 to 20 mg IV every
8 hours).

82. BUDESONIDE
Possesses glucocorticoid receptor affinity superior to
that of traditional glucocorticoids
Enhanced first-pass metabolism by the liver to limit
systemic exposure.
A controlled ileal-release formulation of budesonide
targets the terminal ileum and right colon.
Studies have demonstrated that 9 mg/day of this
preparation are superior to placebo and mesalamine
about 15% less effective than prednisolone in
achieving remission

83. Glucocorticoids are effective for the shortterm
control of symptoms of Crohn’s
But they are neither effective nor safe for
long-term maintenance of response.
In patients with disease that is refractory to or
dependent on glucocorticoids,
steroid-sparing strategies should be
considered,
including immune modulators or surgery.

84. THIOPURINE AGENTS
AZA generally is used in doses of 2 to 2.5
mg/kg/day
6-MP is given in doses of 1 to 1.5 mg/kg/day.

85. METHOTREXATE (MTX)
Chronically active Crohn’s disease despite at
least 3 months of prednisone (at least 12.5
mg/day)
With at least 1 failed attempt to taper off
treatment
Weekly injections of MTX 25 mg IM or placebo
while executing a tapering prednisone regimen
over 16 weeks to be continued till 1 year

86. ANTI TNF AGENTS
INFLIXIMAB
Maintenance dosing every 8 weeks at 5
mg/kg IV after a 0-, 2- and 6-week
induction regimen.
ADALIMUMAB
160mg SC at week 0, 80mg at week
2,and then 40mg every other week

87. CERTOLIZUMAB PEGOL
400 mg, administered subcutaneously at
weeks 0, 2, and 4 weeks and then every 4
weeks till 26 weeks.
other: NATALIZUMAB,VEDOLIZUMAB and
TOFACITINIB

88. NUTRITIONAL THERAPY IN CROHN’S DISEASE
To repletion of nutrients and treatment of the
primary disease
Specific deficits should be identified and
corrected.
Protein-calorie malnutrition should beaddressed,
preferably with enteral supplementation.
Many, but not all, patients with Crohn’s disease
are lactose intolerant and may need increased
calcium supplementation.

89. TPN may be considered for patients with severe
malnutrition before surgery or for selected
patients with severe Crohn’s disease as a primary
therapy in combination with bowel rest.
Patients with short bowel syndrome from
numerous small bowel resections can require
enteral nutrition with defined diets; rarely,
patients with severe short bowel syndrome
require lifelong TPN.

90. A meta-analysis has found defined enteral diets to
be inferior to glucocorticoids in achieving clinical
response
But defined enteral or polymeric diets still may be
useful in some children for whom glucocorticoids
are undesirable
Elemental diets do not appear to be superior to
polymeric diets

91. Children may be taught to receive nocturnal
feedings after self-intubation with an NG tube.
Long-term tolerance may be poor, however, and
disease tends to recur when the patient’s
usual diet is reintroduced.
A number of dietary interventions have been
evaluated.
Most of the focus has been on elimination diets,
dietary fiber including prebiotics, glutamine, fish
oil, and carbohydrates.

93. SURGERIES
• Ileocaecal resection
• Segmental resection
• Colectomy & ileorectal anastamosis
• Temporary loop ileostomy
• Proctocolectomy
• Stricturoplasty

94. STRICTUROPLASTY FOR CROHN DISEASE

95. ULCERATIVE COLITIS
UC is a chronic idiopathic inflammatory
disease of the GI tract that affects the large
bowel and is a major disorder under the
broad group of conditions termed
inflammatory bowel disease,

96. Incidence rates of 0.3 to 5.8 per 100,000 and
prevalence rate of 7 to 30% person-years in
other parts of the world, including Asia and
Africa.
Industrialization has been postulated to lead
to IBD, possibly owing to changes
in microbial exposures, sanitation, pollution,
diet, and medication exposures

97. UC can occur at any age, although diagnosis
before the age of 5 years or after 75 years is
uncommon.
The peak incidence of UC occurs in the
second and third decades of life.
Studies have reported a second, smaller
peak in older adults, between the ages of 60
and 70 years.

98. This second peak of disease incidence is
less pronounced than that for CD.
Studies have not shown any gender
difference in the occurrence of UC, and a
male-to-female ratio of nearly 1 : 1 applies
to all age groups.

99. SMOKING AND UC
A recent met analysis of 10 studies examining this issue
found no association between passive smoking and future
development of UC.
Several mechanisms have been postulated for the
apparent protective effect of active smoking.
modulation of cellular and humoral immunity,
changes in cytokine levels,
increased generation of free oxygen radicals, and
modification of eicosanoid-mediated inflammation.

100. Smoking also might have an effect on
mucus production by the colonic mucosa,
and might alter colonic mucosal blood flow
and intestinal motility.
No single mechanism, however, can
explain the clinical observation of the
beneficial influence of smoking on UC and
its adverse effect
on CD

101. PATHOGENESIS
The best-characterized intestinal auto
antigen is a 40-kd epithelial antigen found in
normal colonic epithelium.
This auto antigen is recognized by IgG eluted
from the inflamed colonic mucosa of patients
with UC and is a component of the tropomyosin
family of cytoskeletal proteins
Genetic factors – NOD2, ATG16L1 and IRGM
gene mutations

102. The antibody response to this 40-kd
protein appears to be unique to UC and
is not found in CD or in other
inflammatory conditions.
This auto antigen shares an epitope
with antigens found in the skin, bile
duct, eyes, and joints, sites often
involved in the extra intestinal
manifestations of UC.

103. HISTORICALLY, THE OVERSIMPLIFIED VIEW OF
ADAPTIVE IMMUNITY IN IBD IS THAT CD IS
MEDIATED BY TH1 CELLS, WHEREAS UC IS
MEDIATED BY TH2 CELLS;

104. DIFFUSE CHRONIC INFLAMMATION OF THE
LAMINA PROPRIA AND CRYPT.
SINGLE DISTORTED COLONIC CRYPT WITH
PLASMA CELLS BETWEEN THE CRYPT AND THE
MUSCULARIS MUCOSAE,
CRYPT ABSCESS, BOTTOM OF THIS DISTORTED
CRYPT HAS BEEN DESTROYED BY AN
AGGREGATE OF POLYMORPHONUCLEAR
NEUTROPHILS

105. A, SMALL INTESTINAL STRICTURE. B, LINEAR MUCOSAL ULCERS AND
THICKENED INTESTINAL WALL. C, CREEPING FAT.

106. PSUEDOPOLYPS

107. CLINICAL FEATURES
SYMPTOMS
Diarrhea
Rectal bleeding
Passage of mucus
Tenesmus
Urgency
Abdominal pain
Fever
Weight loss
Extra intestinal manifestations

109. SIGNS
Bowel sounds are normal.
Digital rectal examination also is often
normal
Rectal mucosa might feel velvety and
oedematous,
Anal canal may be tender, and blood may be
seen on withdrawal of the examining
finger.

110. Tachycardia, fever, orthostasis, and weight loss.
The abdomen typically is soft, with only mild
tenderness over the diseased segment.
Abdominal tenderness may become diffuse
and moderate with more severe disease.
Bowel sounds may be normal or hyperactive
but diminish with disease progression.

111. In fulminant colitis, the abdomen often
becomes distended and firm, with absent
bowel sounds and signs of peritoneal
inflammation.
There may be aphthous ulceration of the
oral mucosa.
Clubbing of the fingernails is a
manifestation of chronic
disease.

113. NATURAL HISTORY & PROGNOSIS
Approximately 50% of all patients in
remission at any time point during follow-
up.
The fraction of patients with active disease
gradually decreases to about 30%,
Approximately 20% of patients undergo
colectomy within 25 years after diagnosis.

115. INVESTIGATIONS
ESR, CRP, Stool C/S and faecal calponectin
Colonoscopy and biopsy
CT/MRI Enterography
EUS
Barium study
Video Capsule Endoscopy

117. TOXIC MEGACOLON THE COLON (TYPICALLY TRANSVERSE COLON) BECOMES DILATED
TO ATLEAST 6 CM (USUALLY GREATER).
THERE IS ADDITIONAL LOSS OF HAUSTRAL MARKINGS WITH PSEUDOPOLYPS
EXTENDING INTO LUMEN.

118. Barium enema
• Fine mucosal granularity
• Superficial ulcers seen
• Collar button ulcers
• Pipe stem appearance-
loss of haustrations
• Narrow & short colon-
ribbon contour colon

119. LOSS OF VASCULARITY, AND PATCHY
SUBEPITHELIAL HEMORRHAGE.
LOSS OF VASCULARITY, HEMORRHAGE, AND
MUCOPUS

120. SIGMOID COLON SHOWS ACTIVE
INFLAMMATION

121. TRANSVERSE COLON IS DILATED THE COLON
WALL IS THICKENED, AND MUCOSAL ISLANDS
ARE VISIBLE. DISTENDED LOOPS OF SMALL
BOWEL ARE APPARENT

122. Ulcerative Colitis with lead pipe colon.

126. ASSESSMENT OF DISEASEACTIVITY
Truelove and Witts( most commonly)
Purely clinical classification categorizes
disease as mild, moderate, or severe based on a
combination of clinical findings and laboratory
parameters
Is reliable and simple to use in clinical practice,
most applicable for patients with extensive
colitis
Not adequately reflect disease severity in
patients with limited colitis.

128. MAYOS SCORE
Disease activity index ranges from 0 to 12
Higher total scores representing more
severe disease.
Patient is considered to be in remission if
the Mayo score is 2 or below
severe disease if the score is above 10.
Clinical response is generally accepted when
the score decreases 3 points from the
patient’s initial baseline score.

133. Oral
• Varies by agent: may be released in the distal/terminal
ileum, or colon1
Distribution of 5-ASA Preparations
Suppositories
• Reach the upper rectum2,5
(15-20 cm beyond the anal verge)
Liquid Enemas
• May reach the splenic flexure2-4
• Do not frequently concentrate in the rectum3
TOPICAL ACTION OF 5-ASA: EXTENT OF
DISEASE IMPACTS FORMULATION CHOICE

139. CONCLUSION
• Inflammatory bowel diseases are chronic group of disorders
which have a long course of disease with intermittent periods of
active disease and remission.
• They can be easily diagnosed by multimodality approach
combining clinical symptoms , colonoscopy, and radiology.
• Conventional radiological investigations like barium studies are
still necessary for diagnosis of characteristic intramural changes.
• However the CT and MRI investigations are nowadays frequent
and less invasive, useful for detection of extraintestinal
manifestations of IBD.

140. REFERENCE
• SLEISENGER AND FORDTRANS
GASTROENTEROLOGY
• ROBINS PATHOLOGY
• HARRISONS ILLUSTRATED CLINICAL MEDICINE
• CMDT GASTROENTEROLOGY

141. •THANK YOU…..