Post on 04-Jun-2018
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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