Inflammatory
Bowel Disease
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IBD: ch. condition resulting from inappropriate
mucosal immune activation.
2 disorders: Crohn disease & ulcerative colitis.
Commensal bacteria normally present in
intestinal lumen probably involved in IBD
pathogenesis, distinction is based on
distribution of affected sites & morphologic
expression of disease at those sites.
UC: severe ulcerating inflam. disease limited to
colon & rectum, extends only into mucosa &
submucosa.
CD, referred to as regional enteritis (frequent
ileal involvement) may involve any area of GI
tract & is typically transmural.
Pathogenesis
Most investigators believe the 2 diseases result
from combination of defects in host interactions
with intestinal microbiota, intestinal epithelial
dysfunction, aberrant mucosal immune
responses. This supported by epidemiologic,
genetic, clinical studies & data from laboratory
models of IBD
I- Genetics: Risk of disease increased when
there is an affected family member & in
CD,concordance rate for monozygotic twins is
50%, UC only 16%
 Molecular linkage analyses of affected families
have identified NOD2 (nucleotide oligomerization
binding domain 2) as a susceptibility gene in CD.
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NOD2 encodes a protein binds to intracellular
bacterial peptidoglycans & activates NF-κB. It
has been postulated that disease-associated
NOD2 variants are less effective at recognizing
& combating luminal microbes, which enter
lamina propria & trigger inflam. reactions
II- Mucosal immune responses: immunosuppression remains mainstay of IBD therapy.
Polarization of helper T cells to e TH1 type in
CD & emerging data suggest TH17 T cells.
 Certain polymorphisms of IL-23 receptor
confer protection from CD & UC
 IL-23 is involved in development &
maintenance of TH17 cells
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Epithelial defects: variety of epithileal defects
described in both CD & UC. Ex, defects in
intestinal epith. tight junction barrier function
present in CD pt.s & subset of their healthy
first-degree relatives.
Microbiota: abundance of microbiota in GI
lumen is overwhelming, amounting 1012
organisms / ml in colon & 50% of fecal mass.
Antibodies against bacterial protein flagellin are
associated with NOD2 polymorphisms, stricture
formation, perforation, small-bowel involvement
in pt.s with CD, but uncommon in UC
Some antibiotics, e.g. metronidazole, can be helpful in
management of CD
CROHN DISEASE
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Eponym based on 1932 description by Crohn,
Ginzburg, Oppenheimer, has existed for
centuries.
Louis XIII of France (1601–1643) suffered
relapsing bloody diarrhea, fever, rectal
abscess, small intestinal and colonic ulcers and
fistulae beginning at age 20 years, most likely
due to Crohn disease.
Morphology
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CD may occur in any area of GIT, but the most
common sites involved at presentation:
terminal ileum, ileocecal valve, cecum.
Disease is limited to small intestine alone in
40% of cases; small intestine & colon both
involved in 30% of pts; remainder have only
colonic involvement.
Presence of multiple, separate, sharply
delineated areas of disease, resulting in skip
lesions characteristic of CD & may help diff.
from UC
Strictures are common
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Earliest lesion “aphthous ulcer” may progress &
multiple lesions often coalesce into elongated,
serpentine ulcers oriented along axis of bowel.
Edema & loss of normal mucosal texture
Sparing of interspersed mucosa
Patchy distribution results in a coarsely
textured, cobblestone appearance in which
diseased tissue is depressed below level of
normal mucosa.
Fissures develop between mucosal folds extend
deeply to become fistula tracts or sites of
perforation.
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Intestinal wall is thickened & rubbery as
consequence of transmural edema, inflam.,
submucosal fibrosis, hypertrophy of muscularis
propria, all of which contribute to stricture
formation.
With extensive transmural disease, mesenteric
fat frequently extends around serosal surface
(creeping fat)
Microscopic
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Active CD: abundant neutrophils infiltrate &
damage crypt epithelium.
Clusters of neutrophils within a crypt are
referred to as crypt abscesses & ass. with crypt
destruction.
Ulceration is common in CD & there may be
abrupt transition between ulcerated & adjacent
normal mucosa.
Repeated cycles of crypt destruction &
regeneration lead to distortion of mucosal
architecture
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Epith. metaplasia takes form of gastric antralappearing glands “pseudopyloric metaplasia”.
Paneth cell metaplasia may also occur in Ltcolon, where Paneth cells are normally absent
Architectural & metaplastic changes may persist
even when active inflam. has resolved.
Mucosal atrophy, with loss of crypts, may occur
after years of disease.
Non-caseating granulomas, hallmark of CD,
found in 35% of cases & may occur in areas of
active disease or uninvolved regions in any
layer of intestinal wall .
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Granulomas may also be present in mesenteric
LNs.
Cutaneous granulomas form nodules that are
referred to as metastatic Crohn disease.
The absence of granulomas does not preclude
a diagnosis of Crohn disease.
Clinical Features
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Extremely variable.
Disease begins with intermittent attacks of
relatively mild diarrhea, fever, abd pain.
20% of pt.s present acutely with Rt. lower
quadrant pain, fever, bloody diarrhea that
mimic acute appendicitis or bowel perforation.
Periods of active disease are typically
interrupted by asymptomatic periods last for
weeks to many months.
Disease re-activation can be ass. with variety
of external triggers “physical or emotional
stress, specific dietary items, cigarette
smoking”.
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The latter is a strong exogenous risk factor for
development of CD, in some cases, disease
onset is associated with initiation of smoking.
Unfortunately, smoking cessation does not
result in disease remission.
ULCERATIVE COLITIS
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Closely related to CD but intestinal disease in
UC is limited to colon & rectum.
Common extra-intestinal manifestations of UC
overlap with those of CD & include migratory
polyarthritis, sacroiliitis, ankylosing
spondylitis, uveitis, skin lesions,
pericholangitis, primary sclerosing cholangitis.
Long-term for UC pt.s depends on severity of
active disease & disease duration
Morphology
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Always involves rectum & extends proximally in
continuous fashion to involve part or all of
colon.
Skip lesions are not seen
Disease of entire colon is termed “pancolitis”
while Lt-sided disease extends to only
transverse colon
Limited distal disease “ulcerative proctitis” or
“ulcerative proctosigmoiditis”
Small intestine: normal, although mild mucosal
inflam. of distal ileum, backwash ileitis, may be
present in severe cases of pancolitis.
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Involved colonic mucosa: red & granular or
have extensive, broad-based ulcers
There can be abrupt transition between
diseased & uninvolved colon
Ulcers are aligned along long axis of colon but
do not typically replicate the serpentine ulcers
of CD
Isolated islands of regenerating mucosa often
bulge into lumen to create pseudopolyps & tips
of polyps may fuse to create mucosal bridges
Ch. disease may lead to mucosal atrophy with
flat & smooth mucosal surface that lacks
normal folds.
Unlike CD, mural thickening is not present,
serosal surface is normal, no strictures.
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Inflammation & inflam. mediators can damage
muscularis propria & disturb neuromuscular
function leading to colonic dilation & toxic
megacolon, which carries significant risk of
perforation
Microscopically
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Mucosal disease in UC are similar to colonic CD
Include inflam. infiltrates, crypt abscesses,
architectural crypt distortion, epith. metaplasia
Inflam. process is diffuse & limited to mucosa
& superficial submucosa
Severe cases: extensive mucosal destruction
may be accompanied by ulcers that extend
more deeply into submucosa
Submucosal fibrosis, mucosal atrophy,
distorted mucosal architecture remain as
residua of healed disease but histology may
also revert to near normal after prolonged
remission.
Granulomas are not present in UC
Clinical Features
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Is relapsing disorder characterized by attacks
of bloody diarrhea with stringy, mucoid
material, lower abd. pain, cramps that are
temporarily relieved by defecation.
Symptoms may persist for days, weeks or
months before they subside
Colectomy effectively cures intestinal disease in
UC but extra-intestinal manifestations may
persist
Trigger may be infectious, psychologic stress,
shortly after smoking cessation in some pt.s
Feature
Crohn Disease
Ulcerative
Colitis
MACROSCOPIC
Bowel region
Ileum ± colon
Colon only
Distribution
Skip lesions
Diffuse
Stricture
Yes
Rare
Wall appearance Thick
Thin
MICROSCOPIC
Crohn Disease
Ulcerative Colitis
Inflammation
Transmural
Limited to mucosa
Pseudopolyps
Moderate
Marked
Ulcers
Deep, knife-like
Lymphoid reaction
Marked
Superficial, broadbased
Moderate
Fibrosis
Marked
Mild to none
Serositis
Marked
Mild to none
Granulomas
Yes (∼35%)
No
Fistulae/sinuses
Yes
No
CLINICAL
Crohn Disease
Perianal fistula
Yes (in colonic
disease)
Yes
Fat/vitamin
malabsorption
Malignant
potential
Recurrence after
surgery
Toxic megacolon
Ulcerative
Colitis
No
No
With colonic
involvement
Common
Yes
No
Yes
No
Note: All features may not be present in a single case
Idiopathic inflammatory bowel disease
Crohn disease
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Small bowel and colon
(mostly right side)
Patchy involvement
Transmural inflammation,
fistulas, strictures, serositis
Non-caseating granulomas
Poor response to surgery
Increased risk for cancer
Ulcerative colitis
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Colon only
Continuous involvement
Superficial inflammation
No granulomas
Good response to surgery
Increased risk for cancer
IBD DIFFERENCES
 CROHN
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TRANSMURAL, THICK WALL
NOT LIMITED to COLON
GRANULOMAS
FISTULAE COMMON
TERMINAL ILEUM OFTEN
SKIP AREAS
“CRYPT” ABSCESSES NOT
COMMON
– NO PSEUDOPOLYPS
– MALABSORPTION
 ULCERATIVE
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MUCOSAL, THICK MUCOSA
LIMITED to COLON
NO GRANULOMAS
FISTULAE RARE
TERMINAL ILEUM NEVER
NO SKIP AREAS
“CRYPT” ABSCESSES COMMON
PSEUDOPOLYPS
NO MALABSORPTION