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Crohn's disease
Definition
Crohn's disease is an inflammatory bowel disease that affects any part
of the gut and involves all the different layers of the bowel wall. Of all
cases of Crohn's disease, about 35% involve the ileum; about 45% involve
the ileum and colon; and about 20% involve the colon alone. Occasionally,
the entire small bowel is involved, and rarely, the stomach, duodenum, or
esophagus. The perianal region is also affected in one-quarter to one-third
of cases.
- Occurs in approximately 0.05% of U.S. population
- Most commonly develops between ages of 15 and 25 years
- Is equally prevalent among males and females
Pathophysiology
A variety of cellular processes and pro-inflammatory mediators influence
the pathogenesis of Crohn's disease.
- T-lymphocytes (T-cells)
T-cells are important in the normal regulation of intestinal immune responses
and the pathogenesis of Crohn's disease. The CD4+ T-cells regulate
key aspects of the immune response. These cells are classified as either
T-helper 1 (Th1) or T-helper 2 (Th2) cells based on their function and
secretion of certain cytokines. Under normal conditions, antigens derived
from food and bacteria in the gut are continually in contact with the
intestinal mucosa. However, the action of cytokines secreted by Th2 cells
prevents cell-mediated immune responses to these antigens. In the case
of Crohn's disease, however, there is a shift toward pro-inflammatory
Th1-secreted cytokines, such as tumor necrosis factor alpha (TNF-alpha).
- Tumor necrosis factor alpha (TNF-alpha):
The continuous hyperstimulation and chronic inflammation of the bowel
in Crohn's disease can be attributed in part to the increased production
of pro-inflammatory cytokines, especially TNF-alpha. TNF-alpha is present
in excess in the mucosa of patients with Crohn's disease, and increases
in TNF-alpha are associated with the release of other pro-inflammatory
cytokines, including interleukin 1, 6, and 8. Other biological activities
attributed to TNF-alpha include enhancement of leukocyte migration by
increasing endothelial layer permeability and expression of adhesion molecules
by endothelial cells and leukocytes, activation of neutrophil and eosinophil
functional activity, as well as tissue-degrading enzymes produced by synoviocytes
and/or chondrocytes
Clinical suspicion and diagnosis
Crohn's disease manifests with symptoms of malabsorption,
anemia, fever,
rectal bleeding and intestinal problems requiring further investigation.
The most common intestinal complications are intestinal structures and fistulas.
Approximately 6% of Crohn's disease patients develop fistulas, and 15% develop
anal complications (fistula, fissure, abscess) within five years of diagnosis.
Extra gastrointestinal manifestations include eye inflammation (uveitis,
episcleritis, conjunctivitis), arthritis, kidney stones, venous thrombo-embolism,
skin changes (erythema nodosum, pyoderma gangrenosum, vasculitis).
It is diagnosed visualization of the sigmoid colon by sigmoidoscopy.
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Treatment
During active disease therapy is similar to UC with aminosalicylates
as the drug of choice. Sulfasalazine is used when the colon is involved
however when the small intestine is involved one of the more specific 5
ASAs are used.
Glucocorticoids are used in active disease as UC and in extraintestinal
manifestations but not in maintenance.
Antibiotics such as metronidazol 250 mg bid- qid or ciprofloxacin
are effective in active disease and in maintenance for those who cannot
tolerate other drugs.
Immunomodulators such as Azathioprine and 6MP are used as is methotrexate
in active disease as adjunct to gluccorticoids to reduce their dose and
also in maintenance.
Biological response modifiers: Therapies specifically focusing
on the inflammatory process underlying Crohn's disease have the potential
for providing disease modification. Infliximab (REMICADE) neutralizes the
biological activity of TNF-alpha by binding with high affinity to the soluble
and transmembrane forms of TNF-alpha and inhibits binding of TNF-alpha with
its receptors. In clinical studies of infliximab, patients with Crohn's
disease have achieved rapid reduction in clinical signs and symptoms, substantiated
by both endoscopic and microscopic evaluation. Infliximab is indicated for
reducing signs and symptoms and inducing and maintaining clinical remission
in patients with moderately to severely active Crohn?s disease who have
had an inadequate response to conventional therapy. Infliximab is also indicated
for reducing the number of draining enterocutaneous and rectovaginal fistulas
and maintaining fistula closure in patients with fistulizing Crohn?s disease.
For anal disease metronidazole, co-trimoxazole should be given for several
weeks.
Diet replacement especially B12 supplements if terminal ileum is involved.
Treatment of complications
Which may include surgical treatment of perianal disease, fistulas and Intestinal
obstruction.
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