Inflammatory bowel disease. refers to two chronic diseases that cause inflammation of the...

Inflammatory bowel Inflammatory bowel diseasedisease

Inflammatory bowel diseaseInflammatory bowel disease

refers to two chronic diseases that cause refers to two chronic diseases that cause inflammation of the intestines: inflammation of the intestines: ulcerative ulcerative colitiscolitis and and Crohn's diseaseCrohn's disease. .

Although the diseases have some features in Although the diseases have some features in common, there are some important common, there are some important differences.differences.


Medical research hasn't determined yet what Medical research hasn't determined yet what causes inflammatory bowel disease. But causes inflammatory bowel disease. But researchers believe that a number of factors researchers believe that a number of factors may be involved, such as may be involved, such as

environment diet possibly possibly genetics


Current evidence suggests that there's likely Current evidence suggests that there's likely a genetic defect that affects how our immune a genetic defect that affects how our immune system works and how the inflammation is system works and how the inflammation is turned on and off in those people with turned on and off in those people with inflammatory bowel disease, in response to an inflammatory bowel disease, in response to an offending agent, likeoffending agent, like::

bacteria bacteria a virus a virus or a protein in foodor a protein in food

Epidemiology of IBDEpidemiology of IBD

Ulcerative colitisUlcerative colitis Crohn’s diseaseCrohn’s diseaseIncidence (US)Incidence (US) 11/100 00011/100 000 7/100 0007/100 000Age of onsetAge of onset 15-30 & 60-8015-30 & 60-80 15-30 & 60-8015-30 & 60-80Male:female ratioMale:female ratio 1:11:1 1,1-1,8:11,1-1,8:1SmokingSmoking May prevent May prevent

diseasediseaseMay cause diseaseMay cause disease

Oral contraceptiveOral contraceptive No increased riskNo increased risk Relative risk 1,9Relative risk 1,9AppendectomyAppendectomy Not protectiveNot protective ProtectiveProtectiveMonozygotic twinsMonozygotic twins 8% concordance8% concordance 67% concordance67% concordance

Genetics

Studies suggested that 1st degree relatives of an affected patient have a risk of IBD that is 4-20 times higher than that of general population.

The best replicated linkage region, IBD1, on chromosome 16q contains the CD susceptibility gene, NOD2/CARD15.

Having one copy of the risk alleles confers a 2–4-fold risk for developing CD, whereas double-dose carriage increases the risk 20–40-fold.

EtiologyEtiology

Mutations within the NOD2/ CARD15 gene contribute to CD susceptibility.

Functional studies suggest that inappropriate responses to bacterial components may alter signaling pathways of the innate immune system, leading to the development and persistence of intestinal

inflammation. Initiating pathogen?Initiating pathogen?

Infectious?Infectious? ? Possibly non-pathogenic commensal enteric flora? Possibly non-pathogenic commensal enteric flora

Pathogenesis

The mucosa of CD patients is dominated by Th1 (T helper), which produce interferon-γ and IL-2.

In contrast, UC dominated by Th2 phenotype, which produce transforming growth factor (TGF-) and IL-5.

Activation of Th1 cells produce the down-regulatory cytokines IL-10 and TGF-.

Ulcerative colitis – microscopic featuresUlcerative colitis – microscopic features

Process is limited to Process is limited to the mucosa and submucosathe mucosa and submucosa with with deeper layer unaffecteddeeper layer unaffected

Two major histologic features:Two major histologic features:

- the crypt architecture of the colon is distorted- the crypt architecture of the colon is distorted

- some patients have basal plasma cells and multiple - some patients have basal plasma cells and multiple basal lymphoid aggregatesbasal lymphoid aggregates

Ulcerative colitisUlcerative colitis

is an inflammatory disease of the large is an inflammatory disease of the large intestine, also called the colon. In ulcerative intestine, also called the colon. In ulcerative colitis, the inner lining - or colitis, the inner lining - or mucosamucosa - of the - of the intestine becomes inflamed and develops intestine becomes inflamed and develops ulcers ulcers

is often the most severe in the rectal area, is often the most severe in the rectal area, which can cause frequent which can cause frequent diarrhea. .

Ulcerative colitis – macroscopic featuresUlcerative colitis – macroscopic features

40-50% of patients have disease limited to the rectum 40-50% of patients have disease limited to the rectum and rectosigmoidand rectosigmoid

30-40% of patients have disease extending beyond 30-40% of patients have disease extending beyond the sigmoidthe sigmoid

20% of patients have a total colitis20% of patients have a total colitis Proximal spread occurs in continuity without areas of Proximal spread occurs in continuity without areas of

uninvolved mucosauninvolved mucosa

Ulcerative colitis – macroscopic featuresUlcerative colitis – macroscopic features

Mucosa isMucosa is : :

- erythematous, has a granular surface that looks like a sand - erythematous, has a granular surface that looks like a sand paperpaper

In more severe diseasesIn more severe diseases::

- hemorrhagic, edematous and ulcerated- hemorrhagic, edematous and ulcerated

In fulminant diseaseIn fulminant disease a toxic colitis or a toxic megacolon may a toxic colitis or a toxic megacolon may develop ( wall become very thin and mucosa is severly develop ( wall become very thin and mucosa is severly ulcerated)ulcerated)

Ulcerative colitis – clinical presentationUlcerative colitis – clinical presentation

The major symptoms of UC are:The major symptoms of UC are:

- diarrhea- diarrhea

- rectal bleeding- rectal bleeding

- tenesmus- tenesmus

- passage of mucus- passage of mucus

- crampy abdominal pain- crampy abdominal pain

Ulcerative colitis – clinical presentationUlcerative colitis – clinical presentation

Patients with proctitis usually pass Patients with proctitis usually pass fresh blood or blood-fresh blood or blood-stained mucusstained mucus either mixed with stool or streaked onto the either mixed with stool or streaked onto the surfacesurface of normal or hard stool of normal or hard stool

When the disease extends beyond the rectum, blood is usually When the disease extends beyond the rectum, blood is usually mixed with stool or grossly bloody diarrhea may be notedmixed with stool or grossly bloody diarrhea may be noted

When the disease is severe, patients pass a liquid stool When the disease is severe, patients pass a liquid stool containing blood, pus, fecal mattercontaining blood, pus, fecal matter

Other symptoms in moderate to severe disease include: Other symptoms in moderate to severe disease include: anorexia, nausea, vomitting, fever, weight lossanorexia, nausea, vomitting, fever, weight loss

Ulcerative colitis - complicationUlcerative colitis - complication

HemorrhageHemorrhage PerforationPerforation StrictureStricture Toxic megacolon (transverse colon with a Toxic megacolon (transverse colon with a

diameter of more than 5,0 cm to 6,0 cm with diameter of more than 5,0 cm to 6,0 cm with loss of haustration)loss of haustration)

UC – disease presentationUC – disease presentation

MILDMILD MODERATEMODERATE SEVERESEVERE

BOWEL BOWEL MOVEMENTSMOVEMENTS

< 4 per day< 4 per day 4-6 per day4-6 per day >6 per day>6 per day

BLOOD IN BLOOD IN STOOLSTOOL

smallsmall moderatemoderate SevereSevere

FEVERFEVER nonenone <37,5<37,5°°C C > 37,5> 37,5°°C C

TACHYCARDIATACHYCARDIA nonenone <90 mean <90 mean pulsepulse

>90 mean >90 mean pulsepulse

UC – disease presentationUC – disease presentation

MILDMILD MODERATEMODERATE SEVERESEVERE

ANEMIAANEMIA mildmild >75%>75% <75%<75%

SEDIMENTATION SEDIMENTATION RATERATE

<30mm<30mm >30mm>30mm >30mm>30mm

ENDOSCOPIC ENDOSCOPIC APPEARANCEAPPEARANCE

Erythema, Erythema, decreased vascular decreased vascular pattern, fine pattern, fine granularitygranularity

Marked erythema, Marked erythema, coarse granularity, coarse granularity, contact bleeding, no contact bleeding, no ulcerationulceration

Spontaneous Spontaneous bleeding, ulcerationbleeding, ulceration

Crohn’s diseaseCrohn’s disease

Crohn's disease differs from ulcerative colitis in the Crohn's disease differs from ulcerative colitis in the areas of the bowel it involves - it most commonly areas of the bowel it involves - it most commonly affects the last part of the small intestine and parts of affects the last part of the small intestine and parts of the large intestine. the large intestine.

Crohn's disease isn't limited to these areas and can Crohn's disease isn't limited to these areas and can attack any part of the digestive tractattack any part of the digestive tract

Crohn's disease generally tends to involve the entire Crohn's disease generally tends to involve the entire bowel wallbowel wall

Crohn’s disease – macroscopic featuresCrohn’s disease – macroscopic features

Can affect any part of GI tract from the mouth to the anusCan affect any part of GI tract from the mouth to the anus

30-40% of patients have small bowel disease alone30-40% of patients have small bowel disease alone

40-55% of patients have both small and large intestines disease40-55% of patients have both small and large intestines disease

15-25% of patients have colitis alone15-25% of patients have colitis alone

In 75% of patients with small intestinal disease the terminal In 75% of patients with small intestinal disease the terminal ileum in involved in 90%ileum in involved in 90%

Distribution of gastrointestinal Crohn's disease. Based on data from American Gastroenterological Association.


CD is a transmural processCD is a transmural process

CD is segmental with skip areas in the midst of CD is segmental with skip areas in the midst of diseased intestinediseased intestine

In one –third of patients with CD perirectal fistulas, In one –third of patients with CD perirectal fistulas, fissures, abscesses, anal stenosis are presentfissures, abscesses, anal stenosis are present


mild diseasemild disease is characterized by: is characterized by: aphtous or small superficial ulcerationsaphtous or small superficial ulcerations

In more In more active diseaseactive disease:: stellate ulcerations fuse longitudinally and stellate ulcerations fuse longitudinally and

transversely to demarcate island of mucosa that are transversely to demarcate island of mucosa that are histologically normalhistologically normal

Cobblestone appearanceCobblestone appearance is characteristic of CD (both is characteristic of CD (both endoscopically and by barium radiography)endoscopically and by barium radiography)


Active CD is characterized by focal Active CD is characterized by focal inflammation and formation of fistula tractsinflammation and formation of fistula tracts

The bowel wall thickens and becomes The bowel wall thickens and becomes narrowed and fibrotic, leading to chronic, narrowed and fibrotic, leading to chronic, recurrent bowel obstructionrecurrent bowel obstruction


Aphtoid ulceration and focal crypt abscesses with Aphtoid ulceration and focal crypt abscesses with loose aggregation of macrophages which form loose aggregation of macrophages which form granulomasgranulomas

Transmural inflammation that is accompanied by Transmural inflammation that is accompanied by fissures that penetrate deeply into the bowel wallfissures that penetrate deeply into the bowel wall

Crohn’s disease – sign and symptomsCrohn’s disease – sign and symptoms

IleocolitisIleocolitis - right lower quadrant pain and diarhhea- right lower quadrant pain and diarhhea - palpable mass, fever and leucocytosis- palpable mass, fever and leucocytosis - pain is colickly and relieved by defecation- pain is colickly and relieved by defecation

JejunoileitisJejunoileitis - inflammatory disease is associated with loss of - inflammatory disease is associated with loss of

digestive and absorptive surfacedigestive and absorptive surface

Crohn’s disease – sign and symptomsCrohn’s disease – sign and symptoms

Colitis and perianal diseaseColitis and perianal disease - low grade fever, malaise, diarrhea, crampy abdominal pain, - low grade fever, malaise, diarrhea, crampy abdominal pain,

sometimes hematocheziasometimes hematochezia - pain is caused by passage of fecal material through narrowed - pain is caused by passage of fecal material through narrowed

and inflamed segments of large boweland inflamed segments of large bowel

Gastroduodenal diseaseGastroduodenal disease - - nusea, vomiting, epigastric painnusea, vomiting, epigastric pain - second portion of duodenum is more commonly involved than - second portion of duodenum is more commonly involved than

the bulbthe bulb

IBD is associated with variety of extraintestinal menifestation.

Almost one-third of the patients have at least one.

Extraintestinal manifestationExtraintestinal manifestation

Dermatologic

1. Erythema nodosum occurs in up to 15% of CD patients and 10% of UC patients

The lesions of EN are hot, red, tender nodules measuring to 5cm in diameter and are found on the anterior surface of the legs, ankles, calves, thighs and arms

2. Pyoderma gangrenosum (PG) is seen in 1 to 12% of UC patients and is less common in CD colitis. PG may occur years before the onset of bowel symptoms.

Lesions are common on the dorsal surface of the feet and legs but may occur on the arms, chest and even face.


RheumatologicRheumatologic Peripherial arthritisPeripherial arthritis developes in 15 to 20% of IBD patients, is more developes in 15 to 20% of IBD patients, is more

common in CD.common in CD.

It is asymmetric, polyarticular and migratory.It is asymmetric, polyarticular and migratory.

Most often affects large joints of the upper and lower extremitiesMost often affects large joints of the upper and lower extremities

Ankylosing spondylosisAnkylosing spondylosis (AS) occurs in 10% of IBD. (AS) occurs in 10% of IBD.

SacroilitisSacroilitis is symetrical, occurs equally in UC and CD, often asymptomatic is symetrical, occurs equally in UC and CD, often asymptomatic


OcularOcular

The incidence of ocular complications in IBM patients is 1 to The incidence of ocular complications in IBM patients is 1 to 10%10%

The most common is The most common is conjunctivitis, anterior uveitis, conjunctivitis, anterior uveitis, episcleritisepiscleritis

Symptoms includeSymptoms include: ocular pain, photophobia, blurred vision, : ocular pain, photophobia, blurred vision, headacheheadache


UrologicUrologic

The most frequent genitourinary complications are: The most frequent genitourinary complications are: calculi, ureteral obstruction, fistulascalculi, ureteral obstruction, fistulas

The highest frequency of nephrolithiasis (10-20%) The highest frequency of nephrolithiasis (10-20%) occurs in patients with CD.occurs in patients with CD.

Patients with IBD have an increased prevelance of osteoporosis secondary to vitamin D deficiency, calcium malabsorbtion, malnutrition, corticosteroid use

More common cardiopulmonary manifestations include endocarditis, myocarditis, pleuropericarditis and interstitial lung disease.

Different clinical featuresDifferent clinical features

UCUC Crohn’s diseaseCrohn’s disease

Blood in stoolBlood in stool YesYes OccasionallyOccasionally

MucusMucus YesYes OccasionallyOccasionally

Systemic Systemic symptomssymptoms

OccasionallyOccasionally FrequentlyFrequently

PainPain OccasionallyOccasionally FrequentlyFrequently

Abdominal massAbdominal mass RarelyRarely YesYes

Perineal diseasePerineal disease NoNo FrequentlyFrequently

Different clinical featuresDifferent clinical features


FistulasFistulas NoNo YesYes

Small intestine Small intestine obstructionobstruction

NoNo FrequentlyFrequently

Colonic Colonic obstructionobstruction

RarelyRarely FrequentlyFrequently

Response to Response to antibioticantibiotic

NoNo YesYes

Recurrence after Recurrence after surgerysurgery

NoNo YesYes

Different endoscopic featuresDifferent endoscopic features


Rectal sparingRectal sparing RarelyRarely FrequentlyFrequently

Continuous Continuous diseasedisease

YesYes OccasionallyOccasionally

„„cobblestoning”cobblestoning” NoNo YesYes

Granuloma on Granuloma on biopsybiopsy

NoNo OccasionallyOccasionally

Inflammatory bowel disease. refers to two chronic diseases that cause inflammation of the...

Documents

Transcript of Inflammatory bowel disease. refers to two chronic diseases that cause inflammation of the...