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CROHNS DISEASE

RAHUL R MENONI MSc MB & GE

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INTRODUCTION

Inflammatory bowel disease (IBD) is a group

of inflammatory conditions of the colon and the

small intestine.

The major types of IBDs are Crohns disease andUlcerative colitis.

Other IBDs

Collagenous colitis.Lymphocyte colitis.

Ischemic colitis.

Infective colitis.

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CROHNS DISEASE

Crohns Disease is an idiopathic, chronic,

transmural inflammatory process of the bowel

that often leads to fibrosis and obstructive

symptoms that can affect any part of the GI

tract from the mouth to the anus.

It involves inflammation of the

intestine,especially the smallintestine(terminal ileum).

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HISTORY

1806 : First reported by Combe andSanders to the Royal College of Physicians

in London, England.

1932 :Described by Crohn,

Ginsburg, and Oppenheimer

of Mount Sinai Hospital inNew York.

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CLASSIFICATION

ILETIS - affects ileum only. ILEOCOLIC - affects both the ileum and the large

intestine.

COLITIS - affects large intestine only.

GASTRODUODENAL - affects stomach and first

part of the small intestine, called the duodenum.

JEJUNOILEITIS - affects top half of the small

intestine, called thejejunum and marked by

spotty patches of inflammation.

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CLASSIFICATION BASED ON THE

BEHAVIOUR OF DISEASE PROGRESSION

Stricturing disease - causes narrowing of the

bowel that may lead to bowel obstruction.

Penetrating disease - creates abnormal

passageways (fistulae) between the bowel and

other structures such as the skin.

Inflammatory disease -causes inflammation

without causing strictures or fistulae.

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PATHOGENESIS

CD

Other factors

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GENETIC SUSCEPTIBILITY

CARD 15(caspase recruitment domain family

member 15, formerly known as NOD2) gene.

Located on chromosome 16.

Three mutationscausing amino-acid

substitutions Arg702Trp and Gly908Arg and

the frameshift 1007fs-found within the region

ofCARD15 thatencodes a leucine-rich repeat,

which is responsible for bacterial recognition.

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DLG5 gene(Disc Large Homolog 5)

Two haplotypes ofDLG5, which encodes a

scaffoldingprotein that helps to maintain

epithelial integrity, have been associated with

Crohns disease.

Located on chromosome 10.

Single-nucleotide polymorphism-113G>A in

DLG5 is associated with CARD15 mutations in

patients with Crohns disease.

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SLC22A4 and SLC22A5Two functional variants

of the organic cation transporters OCT

N1 andOCTN2.

Located on chromosome 5.

1672C>T in exon 9 of the OCTN1 gene and

207G>C in the OCTN2 promoter region have

been suggested as causative mutations to

increase susceptibility to CD., affect the

transcription and function of these carnitine and

organic cation transporters.

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PPAR gene- (peroxisome proliferative-activated receptor gamma).

Located on chromosome 3.

PPAR is a nuclear receptor that inhibits NF

Bactivity.

ATG16L1 gene

A variant ATG16L1 T300A is also reported to be

associated with increased disease risk. Murinenorovirus(MNS)-could be a contributor.

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IMMUNE RESPONSE

Activated innate (macrophage, dendritic

cells and neutrophils) and acquired (T and

B cell)immune responses and loss oftolerance to enteric commensal bacteria.

Antibody-neutralization studies have

implicated tumor necrosis factor- (TNF)

and IL-12 in the pathogenesis of Crohnsdisease.

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INNATE IMMUNE RESPONSE

Macrophages and dendritic cells

in the lamina propria are

increased in CD.

Expression of most

proinflammatory cytokinesand chemokines is upregulated

In Crohns disease.

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PAMPs INVOLVED IN CROHNS DISEASE

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T-CELLRESPONSES

The TH1 cytokine profile, which includes IFN-and IL-12, is dominant in patients

with Crohns disease.

TH1 and TH17-related cytokines

(e.g. IL-12, IL-23,IL-17 and IL-27)

are selectively activated in CD.

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OTHER FACTORS INVOLVED

Smoking Patients with CD are more likely to havebeen smokers and smoking may worsen CD andincrease the risk of relapse/surgical intervention.

Diet Active CD may improve when a normal diet is

changed to a liquid formula diet.Bacterial and Viral infection There is some

evidence implicating E. coli, M. paratuberculosis,measles virus, muronorovirus and L. monocytogenesin the pathogenesis of CD. This data is controversial

and requires further research to clarify.Drugs the oral contraceptive pill has been linked

epidemiologically with CD.

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SYMPTOMS

GASTROINTESTINAL SYMPTOMS

Persistent or recurrent diarrhea (possibly with

blood, mucus, or pus).

Abdominal pain.

Fever.

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SIGNSAND SYPTOMS UNRELATED

TO GI TRACT

y Reddening and inflammation of the eye (iritis).

y Joint pain, which sometimes migrates from one joint

to another (migrating arthralgia).

y Skin lesions, including tender

red nodules on the skins

(erythema nodosum).

Another skin lesion, pyoderma

gangrenosum, is typically

a painful ulcerating nodule.

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DIAGNOSIS

Laboratory testsIncreased WBC and ESR count.

Fine-needle aspiration cytology (FNAC)

Colonoscopic biopsy

GI Endoscopy.

CAPSULE Endoscopy.

Radiology testsBarium X-rays.

CT scan.

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TREATMENT

Treatment of cronhs disease involves firsttreating the acute sympoms and maintaining

remission.

Involves the use of antibiotics, anti-inflammatory

drugs, immunosupressing drugs andcorticosteroids.

Surgery may be required for complications such

as obstructions or abscesses.

ANTIBIOTICS

Ciprofloxacin(CIPRO)and

Metronidazole(FLAGYL).

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ANTI-INFLAMMATORY DRUGS

5-Aminosalicylate anti-inflammatory drugs

y Sulfasalazine, Mesalazine(PENTASA, ASACOL).

y Maintaining remission.

Corticosteroid anti-inflammatory drugs

y Prednisone, Budesonide.

y Inhibition of inflammatory pathways.

IMMUNOSUPRESSING DRUGS

Azathioprine .

6-Mercaptopurine.

Reduces the number of immune cells.

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INFLIXIMABRemicade, is a mouse-human chimeric monoclonalantibody that targets tumour necrosis factor(TNF), a cytokine in the inflammatory response.

Maintains fistulizing CD.

COMPLEMENTARYANDALTERNATIVE

MEDICINE

Accupuncture.Herbal treatment- Boswellia seratta.Helminthic therapy.

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CONCLUSION

The crohns disease is chronic inflammatory

disease that is still continuing and as of now,

the exact etiology of the disease is still

behind the screens.

In future, let us hope for the development of

advanced diagnostic procedures and

treatments that can clinically identify andtreat or even cure this chronic inflammatory

condition.

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REFERENCES

Sartor RB. Mechanisms of Disease: pathogenesis of Crohns

disease and ulcerative colitis. Nature Clinical Practice

Gastroenterology & Hepatology 3: 390-407 (2006)

Loftus EV Jr. Clinical epidemiology of inflammatory bowel

disease: incidence, prevalence,and environmental influences.

Gastroenterology126:15041517(2004)

Simmons A. Crohns Disease-Genes,Viruses and Microbes.

Nature 466:699-700(2010)

Cadwell,K et al.Crohns Disease. Cell 141:1135-1145(2010).

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