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New Treatments for Inflammatory Bowel Disease

There are two idiopathic inflammatory bowel diseases afflicting the gastrointestinal tract. Ulcerative colitis and Crohn's disease can be considered siblings as they share much in common, but they are fraternal and not identical siblings as they also have important differences. This presentation will cover differences separately and combine similarities with ulcerative colitis and Crohn's disease.

Ulcerative Colitis

Definition

A disease of the colon in which the mucosa is affected by acute inflammation with the predominant cell type being the polymorphonuclear leukocyte. The inflammation may affect only the rectum, or spread proximally in a contiguous fashion until the entire colon is involved. The small bowel is not involved in the process except in rare instances where a short segment of terminal ileum is involved with inflammation and is given the term "backwash ileitis". The disease occurs in both men and women with nearly equal incidence. It tends to be a young persons disease, but can occur in the older population as well, where it is frequently misdiagnosed as ischemic colitis.

Etiology

The etiology of ulcerative colitis is not known. The various theories regarding its pathogenesis have varied from the psychiatric, to the food induced, allergic, immunologic, and infectious. To date, the psychiatric, food induced and allergic causes have largely fallen by the wayside. The immunologic and infectious causes have many supporters but as yet no one has the definite proof if either is the one. To some extent, the fact that antibiotics have a role in treatment of the disease represents the most powerful support for the infectious etiology theory.

Crohn's Disease

Definition

Crohn's disease is an inflammatory disease of the gastrointestinal tract, which may involve separated segments, or portions of the entire gastrointestinal tract from mouth to anus. These two features set Crohn's disease squarely apart from ulcerative colitis in which only the colon is affected and the disease process is contiguous.

The typical site of disease is the terminal ileum, with the next common areas being the terminal ileum and cecum, followed by involvement of the colon alone. It is not unusual to have significant skipping of bowel between segments of disease.

Clinical manifestations

In Crohn's disease, the major pathology is submucosal in location, and the process becomes transmural early on. The surface is involved later in the course of the disease. Thus the typical symptoms include pain as the lumen of the gut becomes narrowed by the fibrosing and stricturing outcome of the inflammation. Fever and diarrhea are noted, but bleeding is less common. Prior to the mid 1960s, it was thought that bleeding in Crohn's was very unusual, but it is now accepted that bleeding may be common. The general clinical features parallel those in ulcerative colitis.

Systemic manifestations

The systemic manifestations in Crohn's disease are the same as those noted in ulcerative colitis. Thus, uveitis, sclerosing cholangitis, pyoderma gangrenosum, erythema nodosum, arthritis, sacroiliac disease, ankylosing spondylitis, liver disease are noted in Crohn's disease.

Diagnosis

The diagnosis is made on the basis of clinical and pathologic criteria. Because the mucosa may not be immediately involved, it may at times be difficult to make this diagnosis. The hallmark of the pathology is the granuloma which is non-caseating, and may be noted anywhere in the gut and may be seen in up to 50% of patients. It is possible to see the granuloma even in areas of normal looking mucosa. The inflammation is transmural and is responsible for the classic manifestations of the disease: narrowing of the lumen, and development of fistulas.

Treatment Strategies in Crohn's disease

The general principles of treatment for Crohn's disease are the same as those outlined for ulcerative colitis. The specific differences deal with the use of Pentasa as the 5-ASA of choice in small bowel Crohn's since this is the only drug designed to release the active ASA in the small bowel and not in the colon. 6-mercaptopurine has been used extensively in Crohn's but it must be remembered that it has a 2-4 month lag between the initiation of therapy and the onset of a beneficial effect. This means that it is not useful to treat an acute episode of the disease, but is meant to be used in the management of steroid dependent disease.

Metronidazole may have a special role in the treatment of Crohn's disease. It has been especially useful in the treatment of fistulous disease. Vitamin E in doses of 800 units per day has been used as part of the treatment strategy in both ulcerative colitis and Crohn's.

Miscellaneous Conditions of the Gut

Lymphocytic colitis is a poorly understood condition in which patients present with diarrhea as the major clinical manifestation. Biopsy of the colon shows the epithelial cell layer to be infiltrated by lymphocytes. In most instances the disease is self limited and treatment with sulfasalazine may be effective in decreasing the symptoms. There may be an association with celiac disease although the colitis is not gluten sensitive. The condition bears no relation to IBD.

Collagenous colitis is another variant in which diarrhea is the presenting complaint. In this condition, there is no important inflammation. Biopsy of the colon shows a greatly thickened collagen layer just below the epithelial cells. It is not understood how this layer of collagen results in the diarrhea characteristic of this condition. There is no specific treatment and again there is frequently a limited course.

Bypass colitis is an inflammatory condition that occurs in bypassed colon. Thus, if the colon is bypassed at any level by an ileostomy or a colostomy, and a blind Hartman pouch is left in place, the blind pouch will frequently develop inflammation which is indistinguishable from classic ulcerative colitis. Crypt abscess, friability, bleeding and exudation are clearly seen. In most instances, it can be shown that the original colon was free from inflammation. Careful investigation has shown the cause of the inflammation to be the absence of essential short chain fatty acids.