Crohns Disease

Natasha bhagwandin, MSIV Specialized Pathology - Winter 2012

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 20.2 cases per 100,000 cases Weak seasonal variation with spring more likely for flares

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 and Hispanics

Up to 25% of individuals may have a first degree relative with Crohns or UC, with more than 100 loci identified

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

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

More risk factors?

Increased amounts of refined sugar (but not with UC)
Decreased fruits and vegetables Lower levels of n-3 polyunsaturated fatty acids, unlike Japan Smoking

OCPs

clues
Abdominal pain (95%) Weight loss (80%) Diarrhea (77%) Hematochezia (60%)

Growth failure (30%)

Extraintestinal manifestations (20%)

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 to 42%, as mucogingivitis, mucosal tags, ulcers, cobblestoning

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

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

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

gross pathology
Most commonly involves terminal ileum and proximal colon Skip lesions that are transmural instead of confined to mucosal 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

microscopically
Presence of granulomas, irregular crypts and villi, stenotic segments, lymphoid hyperplasia, fibrin plugs, mucosal edema

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

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 Clinical Medicine. 6th Ed. McGraw Hill Medical: New York, 2010: 360-363. UpToDate