Gluten Sensitivity and
Dr. Fine's Curriculum Vitae
What is Microscopic Colitis?
The term microscopic colitis was coined in 1980 as a descriptive term for patients with non-bloody, chronic secretory diarrhea who, on biopsy of their endoscopically normal colon, had histologic evidence of inflammation. A similar scenario had been described four years earlier for a patient with chronic watery diarrhea except colonic biopsies from this patient, in addition to containing microscopic inflammation, revealed excess collagen. This entity was called collagenous colitis. The clinical features of these chronic diarrheal syndromes are nearly identical. Recently, the attention of GI pathologists has been drawn to the presence of lymphocytes in the colonic epithelium in this disorder which has spawned the name "lymphocytic colitis" for microscopic colitis without collagen table thickening, even though the numbers of these lymphocytes usually are increased to a similar extent in patients with collagenous colitis. This is why there are three different terms used for what appears to be one syndrome that sometimes shows thickening of collagen under the colonic surface cells. I prefer the term microscopic colitis whether there is excess collagen or not. Treatment response seems to be the same whether or not the collagen is present.
Patients with microscopic colitis usually present in middle age but occasionally in childhood or late in life. There is no bleeding or other evidence by history, physical, or stool analysis that these patients have colitis. Diarrhea is the main symptom, and although its severity may fluctuate, it usually persists for months to years. Stool weight can range from 400 to 1400 g/day. Typically, there is no malabsorption of dietary nutrients although some patients can also have a disease called celiac sprue which if severe, causes malabsorption.
Colon biopsies under the microscope show numerous inflammatory cells in the tissue (mainly plasma cells but sometimes neutrophils). The number of lymphocytes and eosinophils usually is normal. As mentioned above, the number of intraepithelial lymphocytes is increased in nearly all patients with microscopic colitis. Secretory chemical mediators elaborated by inflammatory cells are the likely cause of diarrhea.
The cause of microscopic colitis is not fully understood, but several possibilities exist. It seems there is a genetic predisposition to autoimmune disorders and it is possible that microscoppic colitis also is an autoimmune disorder. This implies that the immune system has gotten confused and begins recognizing its own tissue (in this case the colon) as a foreign substance or a pathologic invader. However, it seems more likely based on studies in animals and our experience in humans that the immune system is reacting to the contents of the colonic lumen, the latter of which comprises mainly bacteria. There may be too much of one kind of bacteria, not enough of another, or both. Parallels have been drawn between the pathologic features of microscopic colitis and the small intestinal lesion of celiac sprue, leading some to propose the possibility that a dietary antigen, possibly gluten (a protein in wheat, barley, rye, and oats that causes celiac sprue of the small intestine), may get down to the colon inciting the inflammatory response. Although this may be the cause in a minority of patients, this does not seem to be the main cause in microscopic colitis. Non-steroidal anti-inflammatory drugs (often called NSAID's which include aspirin, ibuprofen, and many others) seem to bring on the condition, and make treatment difficult if they are continued.
Microscopic colitis has not been consistently linked with other diseases, although some association with inflammatory arthritis (including rheumatoid arthritis), other autoimmune diseases, and thyroid disease has been seen. Development of ulcerative colitis or Crohn's colitis sometime after microscopic colitis had been diagnosed probably represents an initial presentation of these other forms of colitis at a microscopic stage (i.e., prior to ulceration or more classic manifestations). There is no evidence to date that microscopic colitis leads to cancer.
Prednisone and other steroids seem to temporarily reduce the amount of diarrhea in microscopic colitis but they do not resolve the inflammatory process and diarrhea usually returns when the drugs are tapered or stopped. The only other drug studied in this condition but one showing the best promise for control of diarrhea, resolution of colitis, and prolonged remission is bismuth subsalicylate (Pepto Bismol). I have shown in a published pilot study that bismuth subsalicylate can resolve diarrhea and histologic colitis in patients with microscopic colitis (published in the journal Gastroenterology in January 1998, volume 114, pages 29-36). In this study, twelve patients were treated with eight chewable 262 mg bismuth subsalicylate tablets per day for eight weeks. Patients recorded the frequency of bowel movements daily. 48-hour stool collections and flexible sigmoidoscopy with biopsies were carried out pre- and post-treatment in each patient. Eleven had a resolution of diarrhea and a reduction in fecal weight. The average time to respond was two weeks. Nine patients resolved their microscopic colitis on biopsies during the eight week period, and another did so subsequently. The response was the same whether or not patients had subepithelial collagen thickening. Subepithelial collagen thickening, when present pre-treatment, disappeared. An example of this response is shown in the figure below. Those completing the trial experienced no side effects. Post-treatment follow-up for 19-40 months reveals that: eight patients remain well having had no further treatment; three are well but required retreatment; one has continued diarrhea but is improving with our newest treatment regimen. (More information on this will be forthcoming.)
Building on this pilot study, I designed and carried out an NIH-funded, double-blind, placebo-controlled trial of bismuth subsalicylate for the treatment of microscopic colitis. The protocol called for the same 8-week treatment period that was used in the pilot study. Treatment with either nine 262mg bismuth subsalicylate or eight placebo tablets per day was begun after baseline stool, blood, and colonic tissue specimens are obtained. The treatment period was followed by repeat stool, blood, and colonic tissue specimen analysis. 20 patients with microscopic colitis were randomized into one of the treatment groups. Nineteen patients completed the study (9 having received placebo and 10 active drug). Only one patient experienced slight clinical improvement during the 8-week placebo phase whereas 9 patients taking active drug had a resolution or significant improvement of their diarrhea.
Further studies have shown that many patients with microscopic colitis, because of shared causative genes for the syndromes, are immunologically sensitive to dietary gluten. In fact further analysis has shown that patients who experience relapses after Pepto Bismol treatment or the rare patients who do not respond are all gluten sensitive. Thus, testing for the presence of gluten sensitivity in patients with microscopic colitis, sometimes combined with assessment for the presence of the gluten-sensitive gene, is necessary in many if not all such patients. Unfortunately, the currently used test for this is a blood test that rarely if ever picks this up in patients with colitis (because it was designed for patients with full blown celiac sprue). However, my new stool test (which is available from the enterolab portion of this site or at www.enterolab.com) can detect this.
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