IBD Sourabh

8/3/2019 IBD Sourabh

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INFLAMMATORY BOWEL DISEASE

Moderator – Dr. Poonam Nanwani

Speaker – Dr. Sourabh Mandwariya



INTRODUCTION

Group of inflammatory disorders thought to be

result of inappropriate activation of mucosal

immune system driven by the presence of normal

luminal flora.

Two disorders

1. Crohn‘s disease

2. Ulcerative colitis

Crohn‘s

Disease

INDETERMINATECOLITIS

Ulcerative

Colitis



EPIDEMIOLOGY

Common in Female

Age group – Teens and early 20s

Common in western world

Prevalence increasing in developing nations



EPIDEMIOLOGY

Improved food storage

Decreased food contamination

Reduced frequency of enteric infection

Inadequate development of mucosal immuneresponse regulatory process

Excessive response to self limited diseases

Chronic inflammatory disease

HygieneHypothes

is



EPIDEMIOLOGY

Hygiene hypothesis supported by

Low incidence of IBD in the helminthes

infection prevalent areas

IBD may precedes by an episode of acute

infectious gastroenteritis



PATHOGENESIS

Idiopathic

disorder

Defect inHost

Interactionwith

IntestinalMicrobiota

AberrantMucosal

ImmuneRespons

e

IntestinalEpithelialDysfuncti

on



PATHOGENESIS

1. Genetic factors

2. Mucosal immune responses

3. Epithelial defects

4. Microbiota



PATHOGENESIS

1. Genetic factors

More dominant in Crohn‘s disease

Concordance rate in monozygotic twinsCrohn's disease – 50 % (Similar regions and with in 2 yr of each

other)

Ulcerative colitis – 16 %

Concordance rate in Dizygotic twins – 10 % (Both)

HLA-DR associated familial predisposition

HLA-DR2 – Ulcerative colitis

- – ‘



PATHOGENESIS

1. Genetic factors

Crohn's disease

NOD2 (Nucleotide oligomerization binding domain

2) Gene; Chromosome 16q12

Regulate immune response – prevent

excessive activation by luminal microbes

Four fold increase in Crohn's disease risk

<10% individual with mutation develop disease



PATHOGENESIS

NOD2 (Nucleotide oligomerization binding domain

2) Gene

Binds to intracellular bacterial peptidoglycansActivates NF-kB

In NOD2 Mutation

Luminal microbes are less effectively

recognized

Microbes enter to lamina propria

Tri er inflammator res onses



PATHOGENESIS

ATG16L1 (Autophagy-related 16-like) and IRGM

(Immunity-related GTPase M) Gene

Involved in autophagy and clearance ofintracellular bacteria

None of these genes are associated with ulcerative

colitis



PATHOGENESIS

2. Mucosal immune responses

Activation of mucosal immunity and suppression

of immunoregulation



PATHOGENESIS



Transepithelial flux ofluminal

bacterialcomponents

Activation

of innateandadaptiveimmunity

Secretion of TNFand inflammatory

mediator (Ingenetically

susceptible Host)

Increasetight

junctionpermeabilit

y

Increaseflux ofluminalmaterial

PATHOGENESIS



PATHOGENESIS

3. Epithelial defects – Critical component

Crohn's disease

Defects in intestinal epithelial tight junction barrier

function

Associated with NOD2 Mutation

Mutation of organic cation transporter SLC22A4

Defect in secreted mucin



PATHOGENESIS

3. Epithelial defects

Ulcerative colitis

ECM1 (Extracellular matrix protein 1)

polymorphism

Inhibition of matrix metalloproteinase 9



PATHOGENESIS

4. Microbiota

Varies between individuals and modified by diet

Probiotic may combat disease

Metronidazole and other antibiotics are useful



PATHOGENESIS

4. Microbiota

Implicated causative agent

1. Mycobacterium (Particularly M.

Paratuberculosis)

2. E. Coli

3. Yersinia

4. Streptococcus

5. Viruses (Including measles)



PATHOGENESIS

6. Other Factors

An episode of appendicitis

– Reduce risk of ulcerative colitis

Smoking – Reduces risk of ulcerative colitis

- Increases risk of Crohn's's disease



CROHN'S DISEASE

In 850 AD King Alfred, "England's Darling” had a GI

illness that began at age 20 yr

At the time the illness was thought to

be due to punishment for the King's

infidelities. It is now thought to be

Crohn's disease

Louis XIII of France (1601-1643)



CROHN'S DISEASE

1913 Dr. Dalziel - Described transmural intestinal

inflammation in 13 autopsied patients.

First fully described and published by

– Crohn's, Ginzburg, Oppenheimer (1932)

Regional enteritis or Granulomatous colitis



CROHN'S DISEASE

Equal frequency in both sexes

Common in twenties to thirties

Can manifest in any age from childhood to old age

May occur in any area of GI tract

Most common sites – Terminal ileum

- Iliocecal valve

- Cecum



CROHN'S DISEASE Crohn's’s Disease:

Anatomic Distribution

Small bowelalone(33%)

Colon alone(20%)

Ileocolic

(45%)

LeastMost

Freq of involvement



CROHN'S DISEASE

Gross features

Earliest Crohn's disease lesion – Aphthoid ulcers

Pinpoint reddish

purple erosions

of mucosa

Progress to elongated

serpentine ulcers



CROHN'S DISEASE

Gross features

- Sharp demarcation between

normal and abnormal areas



CROHN'S DISEASE

Skip lesions – multiple, separate sharply delineated

areas of disease



CROHN'S DISEASE

Occasionally entire length of small bowel will be

evolved ( Diffuse jejunoileitis)

Soggy feeling of small bowel

Edema, fibrosis and loss of normal mucosal

architecture Intramural abscess formation



Transmural involvement

CROHN'S DISEASE



CROHN'S DISEASE

Cobblestone appearance – Diseased tissue is

depressed below the level of normal mucosa



CROHN'S DISEASE

Gross features

Cobblestone appearance



CROHN'S DISEASE

Gross features

Fissures Fistula tracts Perforation



CROHN'S DISEASE

Gross features

Perforation



CROHN'S DISEASE

Gross features

Creeping fat – In extensive

transmural disease

extension of mesenteric

fat around the serosal

surface



CROHN'S DISEASE

Gross features

Thickened and rubbery

intestinal wall

– Due to transmural edema,

inflammation, submucosal

fibrosis, hypertrophy of

muscularis propria



CROHN'S DISEASE

Strictures are common

– Marked narrowing of

lumen along with

dilatation and

hypertrophy of

proximal segment



Microscopic features

Submucosal lymphedema – Earliest change

Active disease – Marked infiltration of neutrophilsand destruction of crypt epithelium

Mucosal ulceration, necrosis and atrophy with loss

of crypts

CROHN'S DISEASE




Distortion of mucosal

architecture

– By repeated cycles

of destruction and

regeneration

CROHN'S DISEASE




Lymphoid hyperplasia – Lamina propria and

submucosa

Chronic inflammatory cell infiltrate

Edema, lymphatic dilation, hyperemia along with

hyperplasia of muscularis mucosa

CROHN'S DISEASE





CROHN'S DISEASE




Noncaseating granulomas

Hallmark of Crohn's disease (60% cases)

Sarcoid – like – with in center of lymphoid follicle

Composed of epithelioid cells and multinucleatedgiant cells with absent or minimal necrosis

CROHN'S DISEASE



Microscopic featuresCROHN'S DISEASE



CROHN'S DISEASE


Noncaseating granulomas

– May present anywhere in the wall of bowel, lymph

node, blood vessels (Granulomatous vasculitis)




Fissures – Slit like spaces with sharp edges and

narrow lumina, arranged perpendicularly to the

mucosa and extending

deeply into the

submucosa or even upto

the muscularis externa

CROHN'S DISEASE




Obliterative muscularization

Increase in number of smooth muscle fibers in

submucosa

Stricture formation

Tenascin – Involved in morphogenesis of muscle

tissue and wound healing

Enteritis cystica profunda – Cystically dilated

CROHN'S DISEASE




Disproportionate inflammation – Well defined focus

of inflammatory cells surrounded by noninflamed

and histologically normal mucosa

Mesenteric lymph nodes – May show granuloma

formation

Metastatic Crohn's disease – Formation of

cutaneous granuloma

CROHN'S DISEASE



Clinical features

Intermittent attacks of abdominal pain, fever and

mild bloody diarrhea

Mimic acute appendicitis or bowel perforation

Active disease period is interrupted byasymptomatic periods for weeks to many months

Undulating yet progressive course

CROHN'S DISEASE



Clinical features

Reactivation is associated with

– Emotional stress

- Specific dietary items

- Smoking

CROHN'S DISEASE



Other associated clinical features

Small bowel disease – Malabsorption

- Sever protein loss

- Hypoalbuminemia

- Vit. B12 deficiency,

Colonic disease - Iron deficiency anemia

CROHN'S DISEASE



Clinical features

Extra intestinal manifestation (25%) –

Ocular manifestation – Uveitis

Musculoskeletal system - Migratory polyarthritis

- Osteoporosis

- Ankylosing spondylitis

Skin involvement - Hidradenitis suppurativa

- Clubbing of finger tips

CROHN'S DISEASE



Clinical features


Skin involvement - Erythema nodosum

- Perianal abscess and fistula

formation

- Erythema multiforme

- Aphthous ulcer

- Cutaneous vasculitis

CROHN'S DISEASE

http://162.129.70.33/images/erythema_nodosum_1_041024.jpg

http://162.129.70.33/images/erythema_nodosum_1_041024.jpg



Clinical features


Hepatobiliary system – Pericolangitis

- Primary sclerosing cholangitis

CROHN'S DISEASE



Differential diagnosis

Tuberculosis – Multiple circumferential ulcers

- Caseous necrosis

Sarcidosis - Rarely involve small intestine

- Associated with other systemic features

CROHN'S DISEASE




Yersiniosis – Colonies of gram negative bacteria

beneath the ulcers

- Identification of organism in stool,

lymphnode, blood and peritoneal fluid

Eosinophilic enteritis – Peripheral eosinophilia with

CROHN'S DISEASE



Greek physician Soranus - 130 AD

First officially described by Wilks and Moxon in

1875

Before this discovery, all diarrheal diseases were

believed to be caused by infectious agents and

bacteria

ULCERATIVE COLITIS



Severe ulcerating inflammatory disease limited to

colon and rectum

Involves only mucosa and submucosa

Common age group – 20 to 30 yr and 70 to 80 yr

ULCERATIVE COLITIS



Gross features Always involves rectum

Extends proximally in continuous fashion to involve

colon

Limited disease – Ulcerative proctitis

- Ulcerative proctosigmoiditis

- Left sided colitis

- Pancolitis

ULCERATIVE COLITIS



Gross features

- Backwash ileitis – Involvement of distal ileum

ULCERATIVE COLITIS

Farmer RG, Easley KA, Ranking GB. Dig DisSci 1993;38(6):1137-1146.



37%

17%

46%

Farmer RG, Easley KA, Ranking GB. Dig Dis Sci 1993;38(6):1137-1146

ULCERATIVE COLITIS



Gross features

Mucosa – Red and granular with petechial

hemorrhages

ULCERATIVE COLITIS



Gross features

Active disease (left)

atrophic changes(Right)

ULCERATIVE COLITIS



Gross features

Sharp demarcation between active ulcerative colitis

and normal area

ULCERATIVE COLITIS



Gross features

Broad based ulcer

with various size

ULCERATIVE COLITIS



Gross features

Pseudopolyps – Elevated small

multiple sessile reddish noduledue to isolated islands of

mucosal ulceration

ULCERATIVE COLITIS



Gross features

Pseudopolyps

ULCERATIVE COLITIS

http://en.wikipedia.org/wiki/Image:Chronic_Ulcerative_Colitis_1.jpg



Gross features

Pseudopolyps and cobblestone appearance

ULCERATIVE COLITIS



Gross features

Mucosal bridges

– Fusion of tips of

Pseudopolyps

ULCERATIVE COLITIS



Gross features

Chronic disease – Mucosal atrophy (Flat and

smooth

ULCERATIVE COLITIS



Gross features

Submucosal fat deposition

Fibrotic, narrowed and shortened bowel

ULCERATIVE COLITIS



Gross features

Toxic megacolon – Due to destruction of muscularis

propria and disturbed

neuromuscular

function due to

inflammation and

inflammatory

mediators - Significant risk of perforation

ULCERATIVE COLITIS



Gross features

No stricture formation

No mural thickening

Normal serosal surface

ULCERATIVE COLITIS




Mucosal and submucosal

involvement

ULCERATIVE COLITIS




Acute phase – Inflammatory cell infiltrate in lamina

propria

Progressive destruction of glands

ULCERATIVE COLITIS




Crypt abscess – Collection of neutrophils in

glandular lumen

ULCERATIVE COLITIS



Microscopic features - Crypt abscess

ULCERATIVE COLITIS




Atrophic and regenerative changes present

together

Stromal inflammatory cell infiltrate

ULCERATIVE COLITIS




Pseudopolyps formation - Composed of granulation

tissue mixed with inflamed and hyperemic mucosa

Duplication of muscularis mucosa

Obliterative endarteritis with dilation and

thrombosis of blood vessels

Accumulation of mast cells at the line of

demarcation between normal and abnormal

ULCERATIVE COLITIS




Pseudo pyloric metaplasia

- Presence of gastric antral

appearing glands

ULCERATIVE COLITIS



Clinical features

Relapsing and remitting course

Episode of Mucoid bloody diarrhea, lower

abdominal pain and cramp may last for days to

months

Relived by defecation

Triggering factors – Infectious enteritis,

ULCERATIVE COLITIS



Clinical features

Extra intestinal manifestations

– Ocular manifestation – Uveitis

- Musculoskeletal system - Migratory polyarthritis

- Ankylosing spondylitis

- Skin lesions - Pyoderma gangrenosus

- Perianal abscess

ULCERATIVE COLITIS



Clinical features

Extra intestinal manifestations

– Hepatobiliary system - Fatty infiltration

- Liver abscess

- Cirrhosis

- Pericolangitis

- Primary sclerosing cholangitis

- Carcinoma of biliary tract

ULCERATIVE COLITIS




Nonspecific bacterial colitis – Acute inflammation

out

of proportion of chronic inflammation

- Absence of crypt distortion

Allergic colitis and proctitis – Mucosal edema and

eosinophilic infiltration

- Common in infants and children

ULCERATIVE COLITIS




Pseudomembranous colitis – Presence of yellow

white

mucosal plaques

- Focal explosive mucosal lesion

Cytomegalovirus colitis – inclusion bodies

- Common in immunocompromised patient

ULCERATIVE COLITIS



LABORATORY INVESTIGATIONS



Anti - neutrophil cytoplasmic antibodies

– Ulcerative colitis (75% cases)

- Crohn's disease (11% cases)

Anti Saccharomyces cerevisiae antibodies

- IgA and IgG against cell wall of Sac.cerevisiae – Crohn's disease (60% cases)

SEROLOGICAL STUDIES



Anti-OmpC*

Anti-Cbir1

Anti-I2

Anti-Glycan Abs

Anti pancreatic Ab (PAB)

Anti-laminaribocide Ab (ALCA)

Anti-chitobioside (ACCA)

SEROLOGICAL STUDIES



Definitive diagnosis is not possible in 10 % of cases

Pathological and clinical overlap between

Ulcerative colitis and Crohn's disease

Colonic disease in contentious pattern –

Suggestive of ulcerative colitis

Patchy histological disease, fissure, family history

of Crohn's disease, onset after initiating use of

cigarette – Against Ulcerative colitis

INDETERMINATE COLITIS



Long term complication Risk factors

Risk increase after 8 to 10 years of disease

initiation

Patient with Pancolitis are at greater risk

Greater frequency and severity of active

inflammation – increase risk (presence of

neutrophils)

IBD ASSOCIATED NEOPLASM



Begins with dysplasia and develop into invasive

carcinomas

Categories for dysplasia

1. Negative for dysplasia

2. Indefinite for dysplasia, probably negative

3. Indefinite for dysplasia, unknown

4. Indefinite for dysplasia, probably positive




Indefinite for dysplasia




5. Positive for dysplasia, low grade




6. Positive for dysplasia, high grade




Adenocarcinoma

Carcinoid tumor

Anaplastic carcinomas

Carcinosarcomas

Malignant lymphomas Colonic adenomas may also occur

Regular follow-up with mucosal biopsy


TREATMENT



TREATMENT

Medical – Immunosuppression

- Elemental diet

- Total parenteral nutrition

Surgical management – Resection of involved

bowel segment



Features Crohn's disease Ulcerative colitis

Clinical

Rectal bleeding Inconspicuous Common

Perforation 4 % 12%Colon carcinoma Very rare 5%-10%

Analcomplications

75 %; Fissure,Fistulas,

Ulceration

Rare; Minor

Abdominal mass 10%-15% Practically never

Abdominal pain Usually right-sided

Usually left side

CROHN'S DISEASE V/S ULCERATIVE COLITIS




Radiographic

Sparing ofrectum

90 % Exceptional

Involvement ofileum

Common;Constricted

Rare; Dilated(Backwash ileitis)

Strictures Often present Absent

Skip areas Common AbsentInternal fistulas May be present Absent

Longitudinal andtransverse ulcer

Common Exceptional





Morphologic

Distribution ofinvolvement

Transmural Mucosal andsubmucosal

Mucosal atrophyand regeneration

Minimal Marked

Cytoplasmicmucin

Preserved Diminish

Lymphoidaggregates

Common Rare

Edema Marked Minimal




Features Crohn's disease Ulcerative colitisMorphologic

Hyperemia Minimal May be extreme

Crypt abscesses Rare Common

Rectalinvolvement

50 % Practicallyalways

Granulomas Present in 60% Absent

Fissuring Present Absent

Lymph nodes May containgranulomas

Reactivehyperplasia




REFERENCES

Rosai and Ackerman’s; surgical pathology

Robbins and Cotran: pathological Basis of Disease

An atlas of gross pathology; C D M Fletcher & P H

McKee New Concepts in the Pathophysiology of Inflammatory

Bowel Disease ; Annals of Internal Medicine

Harsh Mohan ; Textbook of Pathology

Various internet link




Fissures

CROHN'S DISEASE



THANK YOU

THANKS



THANKS

IBD Sourabh

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