Collagenous Colitis

Diarrhea is one of the most frequent of all gastrointestinal symptoms. Common causes include bacterial, viral, or parasitic diseases of the gastrointestinal tract, irritable bowel syndrome, lactose intolerance, inflammatory bowel disease, celiac disease, and effects of medication. Usually these disorders are relatively easy to diagnose. On occasion, however, the etiology of the diarrhea is unclear despite a variety of tests, as the following case illustrates.

Case Report

A 64-year-old female was referred for evaluation of chronic diarrhea. She reported having 6 to 8 watery, non-bloody stools per day for the preceding 10 months. Diarrhea was associated with mild discomfort in the lower abdomen which was relieved after passing stool. She denied nausea, vomiting, fever, chills, night sweats, anorexia, or weight loss, but the frequency of the diarrhea caused significant fatigue. There was no apparent relationship to any particular foods. She had not traveled outside the local area, and had not used antibiotics. She had tried using fiber supplements, bismuth subsalicylate, and loperamide, without success. Her bowel pattern prior to the onset was 1 or 2 formed stools daily, with an occasional episode of constipation. Past medical history included mild hypertension, distant history of peptic ulcer disease, reflux esophagitis, hypercholesterolemia and osteoarthritis. Medications included hydrochlorothiazide, omeprazole, lovastatin and ibuprofen. Physical examination revealed a well-developed, well-nourished female in no distress. Blood pressure was 146/88 mm Hg, pulse 83 beats/minute and regular, temperature 99.6?F. Pertinent findings included a soft and non-distended abdomen, and no hepatosplenomegaly, mass, tenderness, rebound or guarding. Bowel sounds were hyperactive. Rectal examination was normal and stool was negative for occult blood. Laboratory data previously performed included a normal complete blood count and a Westegren erythrocyte sedimentation rate of 25 mm/hr. Serum electrolytes were remarkable for sodium 134 meq/L, potassium 3.3 meq/L, chlorides 88 meq/L, bicarbonate 33 meq/L, blood urea nitrogen and creatinine normal. Liver tests were normal. Stool studies for routine pathogens, Giardia, Clostridium difficile toxin and parasites were negative. Previous flexible sigmoidoscopy revealed normal mucosa to 45 cm with negative biopsies.

After gastrointestinal consultation, the patient was asked to discontinue the ibuprofen, omeprazole, and lovastatin for several weeks, without significant improvement in symptoms. Further laboratory studies, including anti-endomysial antibody, tissuetransglutaminase, anti-nuclear antibody, thyroid tests, and fasting serum gastrin, were all normal. An upper gastrointestinal and small bowel series were normal. Colonoscopy revealed scattered diverticula, and completely normal-appearing mucosa to the cecum. Biopsies from the cecum, ascending, transverse and descending colon were taken. All demonstrated a

Figure 1. Collagenous colitis: thickened band of collagen

Figure 2. Lymphocytic colitis: subepithelial lymphocyte infiltrate

thickened subepithelial collagenous band in the mucosa and an increase in intraepithelial lymphocytes, with no evidence of mucosal ulceration, submucosal edema, crypt abcesses, or vasculitis, consistent with collagenous colitis, a form of microscopic colitis. Biopsies of the sigmoid colon and rectum were normal. The patient was initially treated with diphenoxylate hydrochloride up to e8 tablets per day without relief. Mesalamine, 1200 mg 3 times a day, was not helpful. Prednisone 20 mg daily resulted in a dramatic reduction is stool frequency to 3 soft stools per day within 2 weeks, but after prednisone was discontinued, the diarrhea returned. She was then re-treated with prednisone 10 mg per day for several months. With complete cessation of diarrhea, prednisone was able to be discontinued. There has been no recurrence of diarrhea for 14 months.

Treatment of these disorders includes stopping NSAIDs and other possible inciting drugs. Loperamide and diphenoxylate can be used safely and will frequently control the symptoms. If these drugs are ineffective, a 5-aminosalicylate (mesalamine) is frequently beneficial. Steroids (prednisone or budesonide) are usually effective in inducing remissions if other medications fail. In a prospective study on the response to treatment and long-term follow-up of microscopic colitis, all patients (37 with CC and 44 with LC) were treated with one or more of the above medications as needed to induce resolution of diarrhea. After cessation of diarrhea, patients were placed on maintenance therapy with the drug inducing remission for at least 3 months. Complete resolution of diarrhea was seen in all patients during initial treatment utilizing one of more of the treatment medications, although 19 patients with LC and 16 with CC required maintenance treatment for more than 6 months. Oral mesalamine was more effective in achieving early remission in patients with LC (86%) than in CC (42%). Patients with CC required oral steroids to achieve remission more often than LC (30% vs 4.5%). After cessation of diarrhea, 25% of patients with LC and 30% of patients with CC relapsed during the follow-up period lasting 37 months, with 70% achieving long-term remission.¹⁴

Conclusion

Microscopic colitis has 2 variant forms - collagenous colitis (characterized by a thickened subepithelial collagen band) and lymphocytic colitis (characterized by a subepithelial inflammatory lymphocytic infiltrate) - both of which produce identical clinical patterns of watery diarrhea. Diagnosis can only be made by biopsy of colonic mucosa and, frequently, sigmoid and rectal biopsies will be normal. Treatment includes avoiding drugs known to be associated with either CC or LC, testing for celiac disease (and if positive, treating with a gluten-free diet), and the use of anti-diarrheals, 5-aminosalicylates and steroids when indicated. Patients can be reassured that this disorder can be treated successfully in the majority of cases, and that there are no reports of progression to colorectal cancer. The takeaway lesson from this case is that microscopic colitis is a disease with increasing frequency, and should be considered in patients with persistent diarrhea and a negative work-up, and can be treated successfully.