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.

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