3. The clinical presentation of inflammatory bowel disease most commonly includes diarrhea,
abdominal pain, and weight loss. Bloody diarrhea is characteristic of ulcerative colitis. These
symptoms are punctuated by spontaneous exacerbations and remissions.
4. The diagnosis of inflammatory bowel disease is generally made via colonoscopy with biopsy
if the colon is involved or gastrointestinal x-rays if the small intestine is involved.
5. The gastrointestinal complications of ulcerative colitis include hemorrhage, perforation, toxic
dilatation and colon cancer after 10 years of disease especially if pancolitis is present. The
bowel complications of Crohn’s disease include strictures, fistulas, intra-abdominal
abscesses and perianal disease. Cancer may occur in long-standing Crohn’s disease but is
less common than in ulcerative colitis.
6. Inflammatory bowel disease is associated with various extraintestinal manifestations
including peripheral and spinal arthritis, skin lesions including erythema nodosum and
pyoderma gangrenosum, inflammatory ophthalmic lesions and sclerosing cholangitis.
Because Crohn’s disease involves the small intestine, metabolic abnormalities may occur
including malabsorption, kidney stones and gallstones.
7. Medical therapy for inflammatory bowel disease includes anti-inflammatory agents such as 5-
aminosalicylates and corticosteroids as well as immunosuppressive medications such as 6-
mercaptopurine and cyclosporin. Cytokine inhibitors such as anti-TNF are new forms of
therapy. Surgical therapies are available and total colectomy is curative for ulcerative colitis.
Postoperative recurrence occurs in 60-70% of patients operated for Crohn’s disease.
8. Microscopic forms of colitis which may be related to ulcerative colitis or Crohn’s disease are
also recognized. They present with watery diarrhea, possible weight loss and a clinical
course characterized by spontaneous exacerbations and remissions. These conditions can
only be diagnosed by biopsy.
I. Types of IBD
A. Ulcerative colitis
B. Crohn’s disease
C. Microscopic colitis-mucosa appears grossly normal but microscopically inflamed
minor problem – (will not be discussed at this time)
IV. Etiology
A. Inflammatory bowel disease is thought to result from inappropriate and ongoing activation
of the mucosal immune system driven by the presence of normal luminal flora. This
aberrant response is most likely facilitated by defects in both the barrier function of the
intestinal epithelium and the mucosal immune system.
B. Familial occurrence in 10-25% of first degree relatives
C. Food antigens and bacterial products initiate a cascade reaction after they enter the gut
epithelium. Antigen presenting cells (dendritic cells) promotes differentiation of type 1
helper T cells (Th1) in Crohn’s and type 2 helper cells (Th2) in ulcerative colitis. Th1
secretes interferon-γ, which in turn activates macrophages. In addition to producing the
key cytokines that stimulate Th1 (interleukin-12, interleukin-18, and macrophage
migration inhibitor factor), macrophages produce a mix of inflammatory cytokines,
including interleukin-1, interleukin-6, and most notably tumor necrosis factor (TNF), which
target a broad variety of other types of cells. The latter include endothelial cells, which
then facilitate the recruitment of leukocytes to the mucosa from the vascular space, as
well as fibroblasts and epithelium, modulating their functional properties. These events
subsequently lead to the release of leukotrienes, proteases and free radicals, which are
toxic to gut epithelial cells. Significantly higher levels of TNF-α have been found in the
intestinal mucosa of patients with Crohn’s disease compared to controls. The
development of anti-TNF-α antibody, anti-interleukin-12, anti-interferon-γ, which inhibit
the bioavailability of the different cytokines, is an exciting new strategy in the treatment of
Crohn’s disease.
V. Differentiation of UC and Crohn’s
Ulcerative colitis Crohn’s
GI Sites Colon All (ileo-colonic)
Rectum Involved 95% Involved or spared
Distribution Continuous Skip areas
Inflammation Mucosal Transmural
Granulomas Absent May be present
Crypt abscesses Usually present Usually absent
Postoperative recurrences No 60-70%
Appendectomy Protective Not protective
Monozygotic twins 5 -15% concordance 50% concordance
Smoking May prevent disease May cause disease
F. Therapy
1. Medical: 5-aminosalicylates, corticosteroids, nicotine patch if ex-smoker,
immunosuppressives (azathioprine, 6-mercaptopurine), cyclosporine, antibiotics,
nutritional support. Investigational agents like (probiotics, rosiglitazone, heparin,
keratinocyte growth factor, anti-α4β7 integrin)
B. Clinical Presentation
1. Acute-right lower quadrant pain, mimicking appendicitis
2. Chronic
a) Pain, usually crampy, worsening, 1-2 hours after meals
b) Watery diarrhea
c) Fever
d) Weight loss
e) Perianal disease
f) Anemia or chronic disease, vitamin deficiency, or occult blood loss
g) Constitutional symptoms: fatigue, malaise, growth retardation in children
If Total:
<150 inactive or remission
>450 critically ill
C. Diagnosis
1. Laboratory studies similar to ulcerative colitis
2. Barium x-rays
a) small bowel x-rays-enteric involvement
1) Narrowing of bowel, especially terminal ileum (“string sign”), “skip” areas with
normal bowel interposed between diseased segments
2) Manifestations of transmural inflammation
b) Fistulas and sinus tracts
c) Inflammation and deep ulceration
d) Inflammatory masses-mesenteric thickening or abscesses with adherent bowel
loops
e) Barium enema-colonic involvement
1) Deep ulcerations
2) Strictures
3) Fistulas
4) “Skip” areas; rectal sparing
3. Colonoscopy, biopsy-colonic or terminal ileal involvement
a) Perianal disease, perineal ulceration
b) Apthoid lesions
c) Stellate ulcers, discreet ulcers, longitudinal ulcers, confluent ulcers
d) “Skip” areas or rectal sparing
e) Psuedopolyps
f) Transmural inflammation or granulomas on biopsy
D. Complications
1. Intestinal complications
a) Obstruction
b) Fistulas
1. Enteroenteric or enterocolic
2. Entero- (or colo-) vesical: entero- (or colo-) vaginal
3. Enterocutaneous
4. Retroperitoneal
c) Inflammatory masses or abscesses
d) Retroperitoneal complications
1. Hydonephrosis, hydroureter, especially on right
2. Psoas abscess
e) Cancer- in long-standing disease, less common than with ulcerative colitis
2. Systemic complications
a) Arthritis: peripheral or axial
b) Aphthous stomatitis
c) Episcleritis, uveitis
d) Skin lesions: erythema nodosum, pyoderma gangrenosum
e) Hepatobiliary: gallstones, sclerosing cholangitis (with colonic disease)
f) Kidney stones
g) Amyloidosis
h) Malabsorption: fistulas, bacterial overgrowth, short bowel syndrome, ileal disease
with bile acid loss
E. Therapy
1. Medical
a) 5-aminosalicylates-for distal small bowel or colonic disease
b) Corticosteroids
c) Immunosuppressive (azathioprine, 6-mercaptopurine)-for maintenance: steroid
sparing, fistulas
d) Antibiotics and metronidazole-for colonic or perianal disease
e) Newer agents includes immunosuppressive drugs (tacrolimus, mycophenolate
mofetil, thalidomide), anti-inflammatory cytokines (IL-10, IL-11, anti-interleukin-
12, interferon-γ), anti-α4β7 integrin, anti-α4 integrin, CDP571, a humanized
monoclonal antibody, fish oil, etc.
f) anti-TNF-α monoclonal antibody
1. Binds specifically to TNF-αand neutralizes its bioavailability in a dose-
dependent manner
2. Remission has been reported in up to 81% of steroid-resistant cases and
68% of cases with fistula
3. Indications
• Medically resistant disease
• Fistulizing disease
• Intolerance to corticosteroids or immunosuppressive therapy
• High surgical risk
• Maintenance of remission in anti TNF-α responders
• Retreatment of active disease in anti TNF-α responders
4. Potential complication
• Infection, hypersensitivity, infusion reaction, possible antibody
development, tuberculosis.
2. Surgery
Indications for surgery in Crohn’s disease include:
1. Fistulae unresponsive to medical therapy
2. Drainage of abscesses
3. Intestinal obstruction
4. Perforation
5. Uncontrollable symptoms
6. Toxic megacolon
Post-op recurrence is 50 - 70% in 10 years
References