<B>Crohn's Disease(Granulomatous Ileitis and Colitis) </B>

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Crohn's Disease(Granulomatous Ileitis and Colitis)

Etiology:

• The etiology of Crohn's Disease is unknown. The search for an etiology has focused on the following areas:
• Infectious agents-M.paratuberculosis has received the most attention although the findings are inconclusive.
• Diet-A disordered immune response to some ingested antigen has been considered but no definite food antigen has been identified.
• Genetic-The strong concordance in monozygotic twins and not in dizygotic in contrast to the lack of any association in Ulcerative Colitis has not resulted in any specific gene abnormality being identified. In addition there is a tenfold risk among first degree relatives.
• Immune-There is increasing evidence that an abnormal immune response to unspecified and possible non-specific antigens, may result in abnormal upregulation and down-regulation of inflammatory mediators leading to the inflammatory tissue changes which are a hallmark of the disease.
• It is possible that the etiology of this disease is multifactorial with the comon pathway being abnormal regulation of inflammatory mediators.

Pathogenesis:

• The pathogenesis is unknown, but the epidemiologic and etiologic factors already described suggest a disordered inflammatory reaction secondary to an abnormal immune response to a yet unspecified antigen.

Epidemiology:

• Crohn's Disease is found world wide but with a higher incidence in the Western developed countries.
• Women may be slightly more affected than men, and caucasian's slightly more than non-caucasians.
• There is a 3-5X greater incidence in jews vs. non-jews.This true regardless of geography.
• Peak age incidence is 2cd to 3rd decade with a much smaller peak inthe elderly.
• The incidence of Crohn's Disease is increasing worldwide.

General Gross Description:

• Crohn's Disease involves the colon alone in 30% of cases, the Small intestine alone in 40% of cases, and the small and large intestine in 30% of cases.
• The intestine is affected in segmental fashion the intervening segments being normal.
• The wall is thickened and at first is pliable and edematous, but as fibrosis occurs the wall becomes stiff with luminal narrowing and occasional stenosis.
• The serosa is granular red with increased mesenteric fat (creeping fat), and the attached mesentery may also show
• The mucosal appearance varies widely with varying degrees of reddening and edema.
• Small aphthous ulcers may be present, and can coalesce into longitudinal linear ulcers which can extend through the entire thickness of the bowel wall leading to entero-entero or entero-cutaneous fistulas.

General Microscopic Description:

• The hallmarks of Crohn's Disease are transmural inflammation, predominantly lymphocytic and mononuclear and granulomatous inflammation.
• Granulomas are found in less than 50% of cases unless very lare number of sections are examined. Sarcoid type epitheliod granulomas may be seen and these are frequently submucosal or sersal, particularly associated with lymphoid nodules found throughout the intestinal wall and particulartly in the serosa.
• The mucosa shows patchy acute inflammation which may form crypt abcesses, but there is a disproportionate submucosal involvement with chronic inflammation.
• The degree of crypt distortion is minimal for the amount of disease present and there is less evidence of metaplasia reflecting the lesser degree of epithelial destruction.
• The changes present very with the intensity and stage of disease.

Clinical Correlations:

• The two most common symptoms of Crohn' Disease are intermitent colicky lower abdominal pain and diarrhea.
• Low grade fever and mild weight loss may also be present.
• Massive rectal bleeding is uncommon occurring in 1-2% of cases. Microscopic bleeding is not uncommon.
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