crohn's disease- final

8/13/2019 Crohn's Disease- Final

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Crohns DiseaseNatasha bhagwandin, MSIV

Specialized Pathology - Winter 2012


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Basics/EPIDemiology

Also referred to as regional enteritis

Type of IBD, distinct from Ulcerative Colitis

Transmural inflammation, skip lesions from mouth to

perianal region

Roughly similar incidence to UC, ranging from 3.1 to 20.2cases per 100,000 cases

Weak seasonal variation with spring more likely for flares


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Who gets it?

Usually between ages 15-40 years old, but there may be

another peak in the 60-80s

Women tend to be slightly more affected by Crohns,especially during later years of adolescence and early

adulthood

Less likely for Asians, Middle Easterners, blacks andHispanics

Up to 25% of individuals may have a first degree relative

with Crohns or UC, with more than 100 loci identified


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In Children

Incidence is increasing- studies in Sweden and Finland

show doubling of rates over 10 to 15 year period

More likely to have extensive intestinal involvement, rapid

progression

Mean age at dx - 10.3 years (48% ages 6-12, 37% ages

13-17


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possible risk factors

Less likely to have been breast-fed

More likely to have cows milk protein sensitivity

Prior diarrheal illness during infancy

Antibiotics against anaerobes

Persistent measles causing chronic granulomatous

vasculitis

Hygiene Hypothesis


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clues

Abdominal pain (95%)

Weight loss (80%)

Diarrhea (77%)

Hematochezia (60%)

Growth failure (30%)

Extraintestinal manifestations (20%)


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at the extremes

Perianal disease may occur

in up to 30%, ranging from

skin tags and anal fissures

to perianal abscesses,

fistulae or rectal

Oral lesions are also

common, occurring in up to42%, as mucogingivitis,

mucosal tags, ulcers,

cobblestoning


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Pathophysiology

Thousands of SNPs in several categories of susceptibility

genes that encode for modulators of immune function and

interact with microorganisms

Mice that lack TH-1 inhibiting cytokine, IL-10, develop a

Crohns-like granulomatous inflammation

TH-1 leads to INF-Gamma, TNF-Alpha, IL-2 secretion

Anti-TNF agents help


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pathophysiology

T-cells from mucosa shows inc. proliferation to antigens

in vitro --> excessively responding to normal gut

antigens?

Increased circulating B cells and autoantibodies

More likely to have anti-Saccharomyces cerevisiae

antibodies

Presence of PMNs in lamino propria, which shouldnt be

there --> bind to endothelial cells --> prothrombotic?

Altered intestinal mucous, more bacteria, inc.

permeability


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pathophysiology

54% of pts with Crohns vs. 10% of controls had immune

response against a specific bacterial DNA segment

Anything that alters the epithelium or leads to destruction

of the epithelium allowing bacteria/food to pass through

may stimulate the immune system

Overly sensitized mucosal immune system then mounts

an inflammatory response


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gross pathology

Most commonly involves terminal ileum and proximal

colon

Skip lesions that are transmural instead of confined tomucosal surface-- cobblestoning

Small 1-2 mm multiple rounded nodules or superficial

erosions known as aphthoid lesions

Confluent areas of erosion give rise to serpiginous ulcers

Fat wrapping, or overgrowth of mesenteric fat


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microscopically

Presence of granulomas, irregular crypts and villi, stenotic

segments, lymphoid hyperplasia, fibrin plugs, mucosal

edema


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management

Location specific meds like budesonide for ileum and

ascending colon, or ASA enemas for rectum and left

colon

Abx for perianal fistulae, sx for intraabdominal abscesses

or strictures, nutrition therapy for growth failure

Usually induce with glucocorticoids, intensify with

mesalamine/sulfasalazine and abx or mercaptopurine

May need AZA, MTX or anti-TNF agents like Infliximab

Surgical resection may provide relief, but not curative


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Resources

Geboes, K. Histopathology of Crohns Disease and

Ulcerative Colitis. 2003: 255-276.

Hyams J, Markowitz J, Lerer T, et al. The natural history

of corticosteroid therapy for ulcerative colitis in children.

Clin Gastroenterol Hepatol 2006; 4:1118.

McPhee, Stephen J. and Gary D. Hammer.

Pathophysiology of Disease: An Introduction to ClinicalMedicine. 6th Ed. McGraw Hill Medical: New York, 2010:

360-363.

UpToDate
http://www.uptodate.com.libproxy2.upstate.edu/contents/overview-of-the-management-of-crohns-disease-in-children-and-adolescents/abstract/1http://www.uptodate.com.libproxy2.upstate.edu/contents/overview-of-the-management-of-crohns-disease-in-children-and-adolescents/abstract/1http://www.uptodate.com.libproxy2.upstate.edu/contents/overview-of-the-management-of-crohns-disease-in-children-and-adolescents/abstract/1http://www.uptodate.com.libproxy2.upstate.edu/contents/overview-of-the-management-of-crohns-disease-in-children-and-adolescents/abstract/1http://www.uptodate.com.libproxy2.upstate.edu/contents/overview-of-the-management-of-crohns-disease-in-children-and-adolescents/abstract/1http://www.uptodate.com.libproxy2.upstate.edu/contents/overview-of-the-management-of-crohns-disease-in-children-and-adolescents/abstract/1

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