Inflammatory bowel diseaseInflammatory bowel disease

By:By:

Elias S.Elias S.

Maruf A.Maruf A.

IBDIBD Idiopathic and chronic intestinal inflammation.Idiopathic and chronic intestinal inflammation. Two major types: Crohn’s disease(CD)Two major types: Crohn’s disease(CD)

Ulcerative colitis(UC) Ulcerative colitis(UC) CDCD

11stst seen by the German surgeon seen by the German surgeon Wilhelm Fabry in 1623 Wilhelm Fabry in 1623

Later described and named afterLater described and named after US physician Burril B. Crohn US physician Burril B. Crohn

UCUC 11stst described by the British physician described by the British physician

Sir Samuel Wilks in 1958 Sir Samuel Wilks in 1958

Epidemiology – CD, UCEpidemiology – CD, UC Highest incidence ratesHighest incidence rates

North America, Northern Europe, UKNorth America, Northern Europe, UK Low incidence AreasLow incidence Areas

Southern Europe, Asia,Southern Europe, Asia, Most Developing countries Most Developing countries

Age of onsetAge of onset: Two peaks : Two peaks 15-30yrs, 60-80y. 15-30yrs, 60-80y. SexSex: M:F: M:F UC UC 1:1 1:1

CD CD 1.1-1.8:1 1.1-1.8:1 RaceRace: CD (N.America) : CD (N.America) per 100,000 P.per 100,000 P.

• Whites > African A. > Asian A. > Hispanic A.Whites > African A. > Asian A. > Hispanic A. 43.6 29.8 5.9 4.1 43.6 29.8 5.9 4.1

• Both more prevalent in Jewish people than anyBoth more prevalent in Jewish people than any other ethnic group other ethnic group

GeneticsGeneticsFamilial aggregation of IBD 1Familial aggregation of IBD 1stst reported in 1930 reported in 1930+ve Family Hx – the largest independent risk Factor+ve Family Hx – the largest independent risk Factor

Prevalence in 1Prevalence in 1stst degree Relatives degree Relatives

Concordance b/n P’t and 1Concordance b/n P’t and 1stst degree relative degree relative Disease type Disease type 75-80% 75-80% Disease pattern Disease pattern 64% 64% Extraintestinal manifestation Extraintestinal manifestation 70% 70%

CDCD UCUC IBD in Gen.IBD in Gen.

P’t with CDP’t with CD 2.2-16.2%2.2-16.2% 5.2-22.5%5.2-22.5%

P’t with UCP’t with UC 5.7-15.7%5.7-15.7% 6.6-15.8%6.6-15.8%

Genetics Cont…Genetics Cont… Twin studyTwin study

Pooled systematic concordance analysisPooled systematic concordance analysis Monozygotic twins: CD – 37%, UC – 10% Monozygotic twins: CD – 37%, UC – 10% Dizygotic twins: CD – 7% , UC – 3% Dizygotic twins: CD – 7% , UC – 3%

MT > DT, CD > UCMT > DT, CD > UC IBD - Polygenic diseaseIBD - Polygenic disease

So far – 12 chromosomes identifiedSo far – 12 chromosomes identified 16,12,6,14,5,19,1,7,3 16,12,6,14,5,19,1,7,3 (IBD 1-9)(IBD 1-9)

Some specific gene loci – mappedSome specific gene loci – mapped• Ch.16Ch.16 – NOD2(card15) – NOD2(card15) associated with CDassociated with CD• Ch. 5 – OCTN1,OCTN2Ch. 5 – OCTN1,OCTN2• Ch. 6Ch. 6 – encodes for MHC – encodes for MHC

mutations in HLA Alleles: HLA DRB mutations in HLA Alleles: HLA DRB*0103 / B27 / B35 / B44*0103 / B27 / B35 / B44• Mutation in IL23R gene – protective against CDMutation in IL23R gene – protective against CD

Environmental & other factorsEnvironmental & other factors Life styleLife style

• Urban > RuralUrban > Rural• Poor socioeconomic status - Poor socioeconomic status - RiskRisk• Excessive sanitation - Excessive sanitation - RiskRisk

Smoking :Smoking : Aggravate the course of CDAggravate the course of CD Risk of UCRisk of UC

Psychological stressPsychological stress Adverse life events/day to day stress Adverse life events/day to day stress activity of IBD (worsening, Relapse)activity of IBD (worsening, Relapse)

Infectios agentsInfectios agents Normal flora Normal flora ?M.paratuberculosis, Paramyxovirus, Helicobactor H.?M.paratuberculosis, Paramyxovirus, Helicobactor H. ?others – Salmonella,Shigella, Campylobactor?others – Salmonella,Shigella, Campylobactor

Drugs:Drugs: OCP – weak association with CD OCP – weak association with CD NSAID NSAID

Breast feedingBreast feeding – protective against IBD – protective against IBD Appendectomy :Appendectomy : ?protective for UC, ? ?protective for UC, ?complications of CDcomplications of CD

ImmunopathologyImmunopathology

GI mucosal surfaceGI mucosal surface A physical interface of immune system withA physical interface of immune system with

outside world : rich in lymphoid tissue outside world : rich in lymphoid tissue• Bombarded with high Ag loadBombarded with high Ag load• Harbors >500 sp. of micro floraHarbors >500 sp. of micro flora

Normal state - Immune toleranceNormal state - Immune tolerance• Non-Responsiveness (inhibited immune function)Non-Responsiveness (inhibited immune function)• Mechanism- not clearly understoodMechanism- not clearly understood

Dysregulated immune function - IBD Dysregulated immune function - IBD

Healthy GutHealthy Gut A complex network ofA complex network of

Lymphoid, non-Lymphoid Lymphoid, non-Lymphoid cells, Humoral factorscells, Humoral factors

Balanced differentiation of Balanced differentiation of T-helper cellsT-helper cells Effecter c.Effecter c.(Th1,Th2,Th17)(Th1,Th2,Th17) Regulatory c. Regulatory c. (Tr, Th3)(Tr, Th3)

Tightly regulated cytokine Tightly regulated cytokine network network

Tightly regulatedTightly regulated immunity immunity

IBD – IBD – Dysregulated immune responseDysregulated immune response Leaky barrier – luminalLeaky barrier – luminal

Ag gain access Ag gain access Commensals recognized as Commensals recognized as

pathogenspathogens Expression of differentExpression of different

profile & pattern of receptorsprofile & pattern of receptors Imbalanced T-helper cellImbalanced T-helper cell

differentiation differentiation effector cellseffector cellsCD: Th0CD: Th0Th1 (INFTh1 (INF∂∂,IL12),IL12)UC: Th0UC: Th0Th2 (IL5)Th2 (IL5)

NK cellsNK cells Cyclic activation of Cyclic activation of

macrophagesmacrophages Continious inappropriate Continious inappropriate

inflammatory responseinflammatory response

Ulcerative ColitisUlcerative Colitis A mucosal diseaseA mucosal disease (non-transmural) (non-transmural) RelapsingRelapsing Involve rectum and colonInvolve rectum and colon

• 40-45% - rectum & recto sigmoid40-45% - rectum & recto sigmoid• 30-40% - extend beyond sigmoid30-40% - extend beyond sigmoid• 20% - total colitis20% - total colitis

10-20% - backwash ileitis10-20% - backwash ileitis continuous spreadcontinuous spread

• Mild inflammation – Erythema with fine granularMild inflammation – Erythema with fine granular surface surface

• More sever disease – ulceration with hemmge and edemaMore sever disease – ulceration with hemmge and edema• Long standing disease – inflammatory polypsLong standing disease – inflammatory polyps

Major histologic featureMajor histologic feature• Distorted crypt architectureDistorted crypt architecture• Cyptitis, crypt abscessCyptitis, crypt abscess

UC cont…UC cont… Typical presentationTypical presentation

• Diarrhea,tenesmus,passage of pus,mucusDiarrhea,tenesmus,passage of pus,mucuscrampy abdominal paincrampy abdominal pain

Site specific presentationSite specific presentation• Distal disease (proctitis): Distal disease (proctitis):

Passage of fresh blood, constipation Passage of fresh blood, constipation Abdominal pain – Rare Abdominal pain – Rare

• Proximal disease (colon)Proximal disease (colon) gross bloody diarrhea, abd. Pain gross bloody diarrhea, abd. Pain nausea, vomiting, W’t loss nausea, vomiting, W’t loss

Imading studiesImading studies• Plain abd. Film: colon thickning, dilatationPlain abd. Film: colon thickning, dilatation• Barium: thickned mucosa with superficial ulcerBarium: thickned mucosa with superficial ulcer

Deep ulcer – “collar button” Deep ulcer – “collar button” loss of haustration loss of haustration

• CT – mild mural thickning (<1.5cm)CT – mild mural thickning (<1.5cm) with inhomogenous wall density with inhomogenous wall density

UC cont…..UC cont…..

Natural courseNatural course 50% of the P’ts – clinical remission at any50% of the P’ts – clinical remission at any

given time given time 90% - intermittent course90% - intermittent course

Complications Complications Massive hemorrhage (1%)Massive hemorrhage (1%) Toxic megacolon (5%)Toxic megacolon (5%) PerforationPerforation ?Rarely – colonic obstruction?Rarely – colonic obstruction Long term - malignancyLong term - malignancy

Croh’ns diseaseCroh’ns disease TransmuralTransmural, Relapsing, Relapsing Affect any part of GI – from mouth to anusAffect any part of GI – from mouth to anus

• Location: Location: Terminal ileumTerminal ileum – 47% – 47% colon – 28%, ileocolon – 21% colon – 28%, ileocolon – 21% upper GI – 3% upper GI – 3%

• Rectum- sparedRectum- spared Segmental involvementSegmental involvement with skip areas with skip areas Disease behaviourDisease behaviour

• Non-stricturing/non-penetrating – 70%Non-stricturing/non-penetrating – 70%• Stricturing – 17%, Penetrating – 13%Stricturing – 17%, Penetrating – 13%

Mild disease: aphtous ulcerationsMild disease: aphtous ulcerations More active disease: More active disease: “cobble stone”“cobble stone” appearance appearance

May involve liver & pancreas May involve liver & pancreas Major histologic finding: Major histologic finding: noncaseating Granulomasnoncaseating Granulomas

CD cont……CD cont…… Clinical presentation – Clinical presentation – depends on the sitedepends on the site

Ileocolitis : common site - terminal ileumIleocolitis : common site - terminal ileum RLQ pain, diarrhea, palpable massRLQ pain, diarrhea, palpable mass low grade fever, w’t loss low grade fever, w’t loss edema / bowel wall thickeningedema / bowel wall thickening fibrosis fibrosis narrowing of the lumennarrowing of the lumen ( ( radiographic “string” signradiographic “string” sign))

Jejunoileitis : Jejunoileitis : loss of digestive/absorptive surfaceloss of digestive/absorptive surface Malabsorption, steatorrheaMalabsorption, steatorrhea

ColitisColitis: : Bloody diarrhea, abd cramp, tenesmus Bloody diarrhea, abd cramp, tenesmus Massive bleeding (1-2%) Massive bleeding (1-2%)

Perianal diseasePerianal disease (1/3 of p’ts) : incontinence, anal stricture, (1/3 of p’ts) : incontinence, anal stricture, anorectal fistula, abscess anorectal fistula, abscess

Gastro duodenalGastro duodenal: Nausea, vomiting, epigastric pain: Nausea, vomiting, epigastric pain

CD cont….CD cont….

Natural courseNatural course 67-73% - chronic intermittent course67-73% - chronic intermittent course 10-13% - remain in remission for several yrs10-13% - remain in remission for several yrs After 20 yrs – most require surgeryAfter 20 yrs – most require surgery

ComplicationComplication Strictures - Strictures - Bowel obstruction (40% of cases)Bowel obstruction (40% of cases) Fistula, AbscessFistula, Abscess Malabsorbtion syndromeMalabsorbtion syndrome rarely – massive hemmorhagerarely – massive hemmorhage

UC CDUC CD

UC CDUC CD

UC CDUC CD

Extra intestinal manifestationsExtra intestinal manifestations In 25% of IBD casesIn 25% of IBD cases Usually seen with Usually seen with

colonic involvementcolonic involvement Involve any organ Involve any organ

systemsystem Skin, joints, eyes,Skin, joints, eyes,

biliary tract commonlybiliary tract commonlyaffectedaffected

Mainly immune Mainly immune mediatedmediated

Most respond to Rx ofMost respond to Rx ofthe underlying diseasethe underlying disease

The common onesThe common ones SkinSkin : : Erythema nodosum, Pyoderma gangrenosumErythema nodosum, Pyoderma gangrenosum

JointsJoints : Peripheral arthritis, Ankylosing spondylitis : Peripheral arthritis, Ankylosing spondylitis Sacroliitis Sacroliitis

OcularOcular : conjunctivitis, anterior uveitis / iritis, episcleritis : conjunctivitis, anterior uveitis / iritis, episcleritis

HepatobiliaryHepatobiliary : Hepatic steatosis, Cholelithiasis : Hepatic steatosis, Cholelithiasis P. sclerosing cholangitis P. sclerosing cholangitis

UrologicUrologic : Nephrolithiasis, ureteral obstruction, Fistulas : Nephrolithiasis, ureteral obstruction, Fistulas

THANK YOUTHANK YOU