Patrick Yao, M.D.
A 58-year-old healthy female presented with a change in her bowel habits for the past 3 months. She reported having up to 5 bowel movements per day. She occasionally had to get out of bed at night to have a bowel movement. She had moderate abdominal cramping. She denied any bloody stools, weight loss, anorexia, or any recent increase in her psychological stress level. She also had no recent unusual ingestion, antibiotics use, or travel. She had avoided dairy products without improvement and did not consume any sugar-free products. She saw another physician who thought she had functional bowel syndrome and instructed her to increase her intake of fiber. However, the extra fiber in her diet did not improve her symptoms.
On physical examination, she was afebrile and had a benign abdomen. Her stool tests were negative for any blood cells, bacteria, Clostridium difficile, ova and parasites, and fat. She was referred to gastroen-terologist. A colonoscopy was performed which revealed a grossly normal-appearing colon. Random biopsies taken at multiple sites revealed changes consistent with microscopic collagenous colitis (Figure 1). The patient was treated with loperamide
hydrocholoride with fair control of her symptoms. Her diarrhea began to abate, and she eventually had spontaneous resolution after several months following the diagnosis. She has been in remission over the past 2 years.
Microscopic colitis encompasses two main subtypes: lymphocytic and collagenous colitis. The conditions share the histological pattern of chronic mucosal inflammation but differ in that collagenous colitis also has a thickened subepithelial band. It remains unclear whether the conditions are distinct entities or part of a disease spectrum.
In the United States, the estimated incidence of micro-scopic colitis has increased from 0.8% in 1985 through 1989, to 19.1% in 1998 through 2001 in patients with non-bloody diarrhea.1 The apparent rising trend in the incidence can be attributed to modi-fications in diagnostic criteria as well as an increasing awareness of the disease.2 The condition is most common in the sixth to eighth decades of life. Female-to-male ratio has been reported as high as 20:1, especially for collagenous colitis.3 In contrast to ulcerative colitis, microscopic colitis does not seem to be linked to an increase risk of colon cancer.3 It is controversial whether there is an association between microscopic colitis and celiac sprue. A small fraction of patients with microscopic colitis have small intes-tinal mucosa changes consistent with celiac sprue. Positive serologic testing for celiac sprue, on the other hand, can be found in 17% of the patients with micro-scopic colitis.3
Patients with microscopic colitis typically present with chronic or intermittent diarrhea which is described as watery and non-bloody. The diarrhea is frequently accompanied by abdominal cramping and mild weight loss. Nausea and fecal incontinence are more rare features. Fever, hematochezia, and stear-rhea are absent and suggest another diagnosis. Arthralgia and autoimmune conditions occur commonly in patients with microscopic colitis. Non-steroidal anti-inflammatory drugs (NSAIDs) and other agents such as dairy products, caffeine, and alcohol may exacerbate the condition.3
Blood counts and chemistry are typically normal. With the exception of fecal leukocytes found in half of the patients, other stool assays and cultures are normal. An elevated sedimentation rate and positive anti-nuclear antibodies have been observed in some patients.3 Endoscopic and radiographic tests involving the colon are often normal or near-normal.
Differential diagnoses include conditions such irri-table bowel syndrome (IBS), inflammatory bowel disease, and celiac sprue. The symptoms of micro-scopic colitis have been often mistakenly attributed to IBS given the two conditions have a female predomi-nance and are accompanied by similar symptoms such as abdominal cramping or bloating. They are usually marked by a benign course in the absence of any alarming signs such as malabsorption, gastrointestinal bleeding, or significant weight loss. Lastly, they both typically have a grossly normal-appearing colonic mucosa on endoscopy. Microscopic colitis neverthe-less should be suspected based on several differences. First, microscopic colitis typically presents in an older population. Also, whereas the abdominal symptoms are frequently stimulated by eating and stress in func-tional gastrointestinal disorders, microscopic colitis appears to be less affected by such factors. Lastly, in contrast to microscopic colitis, constipation tends to be a main component of function bowel disorders, except in cases of diarrhea-predominant irritable bowel disease. Therefore, presumed cases of func-tional disorders of the bowel should be further inves-tigated if the patients do not respond to standard treat-ments and have unusual features.
The diagnosis of microscopic colitis relies on a distinctive histological colonic mucosa pattern on biopsy. Microscopically, the colonic tissue should exhibit an increased number of intraepithelial lymphocytes with more than 10 lymphocytes per 100 epithelial cells. Additionally the biopsy shows surface epithelial damage with a variable mixed inflammatory infiltrate consisting of lymphocytes, esosinophils, mast cells, and neutrophils in the lamina propria. In the instance of collagenous colitis, the subepithelial collagen band is abnormally thickened, with an irregular inferior edge and entrapped erythro-cytes and inflammatory cells. The biopsy can be obtained from the descending colon via flexible sigmoidoscopy, but biopsies taken from the descending and transverse colon via colonoscopy provide higher diagnostic yields.4 Because these histological changes are not specific for microscopic colitis and can be seen in other patients, clinical correlation is important.
Treatment of the condition begins with dietary avoid-ance of caffeine and NSAIDs. Only a few controlled trials with small sample sizes have been performed to study treatment of microscopic colitis. Antidiarrheal agents such as loperamide hydrocholoride and diphe-noxylate hydrocholoride/atropine appear effective in about 70% of the patients and are often used as first-line agents. Bismuth subsalicylate at a dosage of 8 tablets per day has been shown in placebo-controlled studies to be beneficial in many patients.7,8 If the patients are refractory to the above medications, a course of mesalamine or sulfasalazine should be considered, but these agents seem to offer only modest benefits. Cholestyramine has also been studied but has been somewhat difficult to tolerate due to its texture.
Corticosteroids should be considered in refractory cases. In a randomized, double-blind, placebo-controlled study of 45 patients by Mieklke et al, budesonide at 9 mg per day for 6 weeks has been shown to be an effective treatment in collagenous colitis both in terms of clinical response and histological improvement.5 However, the relapse rate appears to be high after cessation of corticosteroids and the median time to replase can be as short as few weeks.6 Before the usage of steroids, other diagnoses and coexisting conditions such as celiac sprue should be ruled out. Lastly, immunosuppressive agents such as azathioprune, 6-mercaptopurine, cyclosporine, and methotrexate have been evaluated, but to date there is no strong evidence supporting their use.9 Surgical resection of the colon is rarely indicated.
Optimal duration of therapy is uncertain, but it is reasonable to discontinue treatment after 6 to 8 weeks. The natural history of microscopic colitis is charac-terized by a benign, waxing-and-waning course. Remission occurs in approximately 1 out of 5 patients, so there is a good chance of spontaneous and medication-related resolution.
Submitted on September 23, 2005