Inflammatory Bowel DiseaseInflammatory Bowel Disease

Dr.CSBR.Prasad, M.D.,

May-2015-CSBRP

CaseCase

• 17yo complains of pain abdomen and h/o passage of blood and mucus in his stool since 5months

• He gives a h/o spontaneous remissions

What are your differentials?

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Case – continued….Case – continued….

• Stool examination: – Shows Mucus, RBCs & Pus cells – Negative for ova and parasites– Cultures: Repeatedly negative for pathogens

What are your differentials?

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Possible diagnosis:

• Inflammatory bowel disease

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Inflammatory Bowel DiseaseInflammatory Bowel DiseaseIBDIBD

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IBDIBD

• Def: IBD is a immune mediated chronic inflammatory condition of intestines

• Major types:– Ulcerative colitis (UC)– Crohn’s disease (CD)

Indeterminate colitis (IC):• In 15% of IBD patients it’s impossible to differentiate

UC from CD. They are designated as IC

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Epidemiology of IBD

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Pathogenesis

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Pathogenesis

Current concept:• Inappropriate immune response to the

endogenous commensal microbiota with in the intestine with / without some component of autoimmunity

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Pathogenesis – genetic factors• IBD is a polygenic disorder• More than 100 disease associated loci on

different chromosomes• 1/3rd of them overlap (UC & CD)• Genetic risk factors for IBD are also seen in

other immune mediated diseases– RA (TNF A IP3)– SLE (TNF A IP3)– Psoriasis (IL 23R, IL 12B)– Ankylosing spondilitis (IL 23R)– Type-I DM (IL 10, PTPN2)

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Pathogenesis – genetic factors

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Pathogenesis – genetic factors

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Primary genetic disorder associated with IBD

Psoriasis

Ankylosing spondylitis

Primary sclerosing cholangitis

PathogenesisOral tolerance:• Mucosal immune system is normally unreactive

to luminal contents due to “Oral tolerance”• Mechanisms:

– Deletion / anergy of Ag reactive T-cells– Induction of CD4+ T-cells that suppresses gut

inflammation– By secreting IL10 & TGF-beta

• In IBD oral tolerance is altered resulting in uncontrolled inflammation

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Pathogenesis

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Pathogenesis – Exogenous factors

1. Multiple pathogens have been implicated• Salmonella• Shigella• Campylobacter• Clostridium difficile May trigger an inflammatory response that then

goes unregulated2. Psychosocial factors

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Ulcerative colitis (UC)Ulcerative colitis (UC)

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Pathology – UC

• Always involve rectum• Extends proximally to involve all / part of

colon– 40-50% rectum / sigmoid– 30-40% beyond sigmoid– 20% total colitis– “Backwash ileitis”

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Pathology – UC• Mild inflammation: the mucosa is erythematous

with fine granular surface – sandpaper• More severe disease: the mucosa is

hemorrhagic, edematous, and ulcerated• In long-standing disease: inflammatory polyps

(pseudopolyps) • in Remission: The mucosa may appear normal• Patients with fulminant disease:

– Toxic colitis or megacolon – Ulceration– Perforation

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Ulcerative colitis

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Pan-ulcerative colitisM

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Pan-ulcerative colitis

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Pan-ulcerative colitis

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Inflamed colonic mucosa demonstrating pseudopolyps in a patient with ulcerative colitis

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Thinned out wall, ulcers, pseudopolyps

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Serpigenous ulcers, mucosal bridges and pseudopolyps

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UC - pseudopolyps

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Ulcers confined to mucosa

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Marked lymphocytic infiltration of the intestinal mucosa and architectural distortion of the crypts

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Chronic architectural changes in ulcerative colitis. Note the crypt branching and irregularity of size and shape, with an increase in chronic inflammatory cells in the lamina propria

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Crypt abscess

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UC – Clinical features• Diarrhea• Rectal bleeding• Tenesmus• Passage of mucus• Crampy abdominal pain• Anorexia, nausea, vomiting• Weight loss• o/e tender anal canal, blood on PR• Complications:

– Toxic megacolon– Perforation– Peritonitis– Strictures (mimic carcinoma)– Carcinoma

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Adenocarcinoma in UC

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Patients with ulcerative colitis can occasionally have aphthous ulcers involving the tongue, lips, palate and pharynx

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Crohn’s disease (CD)Crohn’s disease (CD)

1884-1983

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Pathology - CD• Can affect any part of the gastrointestinal tract

– 30–40% small-bowel disease (75% terminal ileum)– 40–55% both the small and large intestines, and – 15–25% have colitis alone– Rectum is often spared

• “Skip areas” in the midst of diseased intestine • Perirectal fistulas, fissures, abscesses, and • Anal stenosis are present in 1/3rd of patients• Rarely, may involve the liver and the pancreas

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Morphology

• Involved segment is rubbery and thick (due to edema, inflammation, fibrosis and hypertrophied muscularis propria)

• String sign in X-ray• Skip lesions• Cobble stone mucosa• Deep penetrating ulcers• Fistulae

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‘Cobble stone’ appearance

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‘Cobble stone’ appearance

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Creeping fat

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Stenosis of terminal ileum

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‘String sign’ – very thin luminal constrast in the terminal ileum

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Double-contrast barium enema study demonstrates marked ulceration, inflammatory changes, and narrowing of the

right colon in a patient with Crohn colitis

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Enterocolic fistula of Crohn's diseaseThe barium study outlines the fistula connecting

the small bowel to the colon

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Morphology

• Neutrophils in isolated crypts• Architectural distortion

– Villous blunting– Atophy– Metaplasia

• Transmural inflammation• Non-caseating granulomas• Submucosal fibrosis• Thickening of muscularis propria• Strictures

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Deep penetrating ulcers

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Deep knifelike, fissuring, transmural ulcer in Crohn disease

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Transmural inflammation

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Non-caseating granulomas

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CD – Clinical features

• Site of the disease influences the clinical manifestations

• Patterns:1. Fibrostenotic obstructive pattern2. Penetrating fistulous pattern

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The three most common sites of intestinal

involvement in Crohn's disease:

ileojejunalileocolic and

colonic

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CD – Clinical featuresIleocolitis:• Right lower quadrant pain• Pain releived by defecation• Weight loss• String sign in X-ray• Fistulae • Microperforations Colitis / perianal disease:• Strictures• Fistulae

Jejunoileitis:• Malabsorption

– Anemia– Hypoalbuminemia– Hypocalcemia– Coagulopathy

• Nutritional deficiency– Pellagra– Osteoporosis– Megaloblastic anemia– Neurological symptoms

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CD – Clinical features

Fistulae:• Duodenocolic (fecal vomitus)• To mid small bowel (short circuiting - malabsorption)• Rectovaginal (feculent vaginal discharge esp. after

hystrectomy)• Enterovesicle (fecaluria, pneumaturia)• Enterocutaneous • Perianal disease (fistulae, fissures)

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Complications

• Serosal adhesions• Perforations• Peritonitis• Intraabdominal / pelvic abscesses• Perianal disease• Obstruction

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Patients with Crohn’s disease can occasionally have aphthous ulcers involving the tongue, lips, palate and pharynx

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Feture Crohn’s disease Ulcerative colitis

MacroscopicMacroscopicSite Ileum +/- colon Colon only

Distribution Skip lesions Diffuse

Strictures Early Late

Wall appearance Thickened Thin

Dilatation No Yes

MicroscopicMicroscopicPseudopolyps No Marked

Ulcers Deep linear Superficial

Lymphoid reaction Marked Mild

Granulomas Present Absent

Fibrosis Marked Mild

Fistulae/sinuses Present Absent

ClinicalClinicalMalabsorptions Yes No

Malignant potential Yes Yes

Response to surgery Poor Good

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E N D

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Introduction – “Oral toleranceOral tolerance”

• Entry of pathogen is associated with production of:– Antibodies or– Activated lymphocytes

• Sites where bacteria are present normally in the body as commensals:– Skin– Oropharynx– Large intestine

• Reaction of our defences to normal commensals is inappropriate

Inflammation

No Inflammation

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