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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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