Inflammatory Bowel Disease

Epidemiology

prevalence of IBD is 1-2 million in the US; incidence of Crohn’s Disease is rising; incidence of Ulcerative Colitis is stable

men and women have similar risk

age of onset is early Þ peak around age 20

incidence increases in people of Jewish decent; people from US, Europe, Scandinavia

Etiology and Pathogenesis

largely unknown; in general, IBD results from genetically predisposed inappropriate immune activity in response to one or more environmental factors (diet, bacteria, virus, allergic, neurogenic, mucosal permiability)

immunologic component supported by: therapeutic responses to non-specific immunosuppressive drugs

genetic component supported by: familial associations;twin studies (60-70% concordance in monozygotic twins)

environmental factors supported by: changes in incidence when populations move; opposite affects of smoking on CD and UC; onset often after infection; lack of complete concordance in monozygotic twins

physiological intestinal inflammation: because of high surface area and exposure to antigens, the gut mucosa is in a constant state of controlled, low level immune activity (T cells, B cells, plasma cells, macrophages)

pathologic inflammation occurs when the tight regulation of physiological inflammation is disturbed

components of the standard immune response are present, but a cause-effect relationship has not been established

humoral: colonic Ab, lymphocytotoxic Ab, immune complexes are present Þ cause or effect?

mucosal: T cells proliferate Þ cause or effect?

cytokines (especially IL-1): immunoregulatory factors; good indicator of level of inflammation

possible role in pathogenesis: IL-1ra (receptor antagonist) normally blocks IL-1 receptors, preventing pathologic inflammation; in IBD, IL-1 and IL-1ra are both elevated, but IL-1 is elevated more so

deficiency in IL-1ra could lead to uncontrolled inflammation Þ possible treatment?

growth factors: important to healing after inflammation; Ý GF Þ possible treatment?

enteric nervous system: nervous and immune systems tightly linked (i.e. stress can bring on IBD)

intestinal flora are essential components Þ germ free animals don’t get IBD

Clinical Symptoms of IBD

(1) Crohn’s Disease

symptoms vary with portion of GI infected

diarrhea: secretory from inflammation; osmotic from malabsorption of food or bile salts; short circuit via fistula
abdominal pain: related to inflammation or stenosis; usually right lower quadrant; may be palpable mass
weight loss: food avoidance; malabsorption; catabolism of inflammation
rectal bleeding is rare because rectum is usually spared disease

stricturing and obstruction of the small bowel may cause nausea and vomiting; not seen in UC
with perianal disease: tenesmus (spasmatic sphincter); purulent drainage, constipation
children may present with a sudden drop in height growth-rate

(2) Ulcerative Colitis

proctitis (rectal inflammation) is sole involvement in 20% of cases; left sided colon is most involved
diarrhea and rectal bleeding 75% of the time; 50% report tenesmus; 50% report weight loss
may present with no clinical symptoms despite positive endoscopic or pathology results
increased risk of colon cancer (up to 50x) based on: length of colon involved; duration of disease; age at onset
mild: erythema, redness, granulation; severe: ulceration

Endoscopic Appearance

10% of cases are not distinguishable between CD and UC

UC may not show endoscopic evidence of disease, but biopsies will show histologic evidence

strictures are more common in CD but can be seen in UC

Ulcerative Colitis	Crohn’s Disease
rectum always involved; inflammation starts in rectum, progresses up colon	rectum may be spared; most common involvement is ileocolic
diffuse erythema	focal inflammation
continuous inflammation	discontinuous inflammation (‘skip lesions’) (areas of normal mucosa between lesions)
mucosal granularity (looks like sandpaper)	apthous ulceration
mucosal friability	linear, crossing ulcerations Þ cobblestone appearance
ulceration in inflamed mucosa; ulcers are broad-based	discrete fissuring ulcers in normal mucosa; ulcers are sharp knife-like clefts
pseudopolyps (non-neoplastic polyps)	fistulae

Radiologic Appearance

Ulcerative Colitis: may appear normal early on; limited distensibility and straightened appearance are apparent

with air contrast Þ discrete ulcers or granular appearance are seen

Crohn's Disease: apthous ulcers are seen; skip areas are apparent; narrowed ileum (from erythema, edema, fibrosis)

CT may show thickened bowel or inflammatory mass

Pathology of IBD

crypt abcess: dilated crypt filled with PMNs; crypt is eventually destroyed; regeneration of crypts is abnormal

Ulcerative Colitis	Crohn’s Disease
mostly left colon or whole colon	any part of GI tract
continuous inflammation from rectum	segmental inflammation / skip areas
mucosal inflammation only	transmural inflammation (muscle involved)
no	fissures, fistulas, adhesions
no	thickened fibrous walls (edema and fibrosis)
less common	stricture, obstruction
perianal lesions rare	perianal lesions common
rectum almost always involved	rectum spared
no	granulomas (may or may not be seen)
many crypt abcesses	few crypt abcesses

Therapy

Ulcerative Colitis

corticosteroids
5-ASA: 5-aminosalicylic acid (mesalamine); is attached to different vehicles for directed delivery (i.e. sulfasalazine is cleaved into 5-ASA by colonic bacteria)
proctocolectomy is a cure of UC and is definitely indicated when dysplasia is found

Crohn's Disease

corticosteroids
5-ASA: better if released in small bowel rather than colon
surgery is not a cure, but is indicated if: abcess, fistula, stricture, inflammatory mass, growth retardation in children

Extraintestinal Manifestations of IBD

erythema nodosum: painful red nodules on the pretibial lower extemities; more common in CD- pyoderma gangrenosum: ulcers that are often painless; more common in UC

colitic arthritis: involves large joints, is migratory; occurs in 20% of patients; symptoms parallel those of the IBD

ankylosing spondylitis: involves sacroiliac joints and spine; genetically linked to IBD; symptoms not related to IBD

PSC (primary sclerosing cholangitis): mild biliary inflammation seen primarily in UC patients

often requires a liver transplant