What is microscopic colitis syndrome?
Microscopic colitis is a syndrome characterized by chronic secretory diarrhea, a normal gross appearance of the colonic mucosa, and a typical pattern of inflammation in colon biopsy specimens. This pattern includes changes of the surface epithelium (flattening and irregularity), intraepithelial lymphocytosis, and an increased density of inflammatory cells in the lamina propria. There are two varieties. The first type is collagenous colitis in which the subepithelial collagen layer is thickened, and the second type is lymphocytic colitis in which the subepithelial collagen layer is of normal thickness. Microscopic colitis is as common as Crohn’s disease in the general population. It occurs frequently in older patients and may be associated with fecal incontinence. In many cases, a rheumatologic or autoimmune disorder may be present. Treatment is variably effective: budesonide has the most evidence for efficacy; bile acid–binding drugs and bismuth subsalicylate have some efficacy.
MC is a clinical syndrome characterized by chronic, nonbloody, watery diarrhea with grossly normal-appearing colonic mucosa, but abnormal histologic features. The first case was reported in 1976 when a woman with chronic diarrhea and a normal endoscopic GI evaluation was found to have an abnormal colorectal biopsy with a thickened subepithelial collagen band and a slight increase in lymphocytes in the lamina propria. This entity was thus named collagenous colitis (CC). Subsequent reports identified similar findings in other patients with chronic diarrhea but without the thickened collagen band. This clinical entity was named lymphocytic colitis (LC). Since the first case reports, MC has become more widely recognized and may account for 10% to 20% of patients with chronic, watery diarrhea. To date, CC and LC are considered distinct but related clinical entities.
What are the features of the two types of MC (CC and LC)?
Contrasting Features for Collagenous and Lymphocytic Colitis
|Feature||Collagenous Colitis||Lymphocytic Colitis|
|Gender incidence (women:men)||7.5-15:1||2-3:1|
|Mean age onset||51 years||43 years|
|IELs||Yes||Yes (> 20 IELs per 100 epithelial cells)|
|Surface epithelial flattening or detachment||Yes||Yes|
|Subepithelial collagen band > 10 microns||Yes||No|
IEL, Increased intraepithelial lymphocyte.
What are the symptoms of Microscopic colitis syndrome?
The most common clinical symptoms of Microscopic colitis syndrome are chronic, nonbloody diarrhea (95%), weight loss (91%), abdominal pain (40%), urgency (29%), and nocturnal diarrhea (22%). These symptoms can be severe in some patients. Clinically, LC and CC are indistinguishable, although symptoms do tend to be worse in CC patients.
How are patients with Microscopic colitis syndrome distinguished from patients with irritable bowel syndrome (IBS)?
The gold standard is colorectal biopsy, which is normal in patients with IBS. There is considerable overlap of symptoms between MC and IBS. Celiac disease and lactose intolerance can also present with similar symptoms and should be ruled out. Studies have shown that as many as 33% of patients with biopsy-proven CC or LC will have a prior diagnosis of IBS and that as many as half of the patients diagnosed with MC will also meet the diagnostic criteria for IBS.
Are there any laboratory tests or imaging studies that can help establish the diagnosis of MC?
Laboratory tests and radiographic imaging are generally nondiagnostic; therefore there is no role for imaging studies in the diagnosis of MC. Fecal leukocytes may be present, but stool cultures are typically negative. C-reactive protein levels and erythrocyte sedimentation rates may be elevated; anemia may be present. Barium enemas and colonoscopy typically are normal, but can show subtle mucosal changes.
How common is MC?
The incidence of MC has been rising during the past two decades. Studies show CC incidence rates of 2.6 to 10.8 per 100,000 people and LC incidence rates of 2.2 to 14 per 100,000 people. Cases have been identified in the United States, Europe, Canada, Africa, Asia, Australia, and Latin America, suggesting worldwide distribution. The highest incidence has been in northern countries (the United States, Denmark, Canada) suggesting a north-south gradient, although this is not uniformly consistent. Additionally, MC tends to be more common in older adults, with an average age of diagnosis at 65. Overall, MC is more common in females. At least some of this increased incidence is attributed to enhanced clinical awareness.
Which parts of the colon are most commonly affected?
MC involves the colon discontinuously and the patchy involvement of the normal-appearing colon necessitates a minimum of four biopsies to establish the diagnosis of MC. In one prior study, the highest yield was from biopsies of transverse colon. Most cases can be diagnosed by biopsies taken within the range of flexible sigmoidoscopy; colonoscopy with biopsy of the right colon may be necessary to detect 10% of patients with isolated right-sided histopathologic findings.
What agents are associated with the pathogenesis of MC?
Nonsteroidal antiinflammatory drugs (NSAIDs) are thought to be an important pathogenic factor, although their role in this association is unclear. A case-controlled study showed that patients with CC were three times more likely to take NSAIDs. LC has been associated with the use of sertraline. Other potential medications associated with the development of MC include aspirin, acarbose, clozapine, entacapone, flavonoid, PPIs (especially lansoprazole), ranitidine, and ticlopidine . Of note, many of these drugs have an adverse effect of chronic diarrhea; therefore attributing a drug as the cause of MC is more challenging. Although the contribution of environmental factors is not clear, smoking has been associated with MC, including with development of disease 10 years earlier than nonsmokers. In one study, previous or current smoking had an odds ratio of 2.4 for CC and 1.6 for LC.
Are there associated conditions in MC patients?
A wide variety of associated conditions are described in case reports, including thyroid disease, celiac disease, diabetes, rheumatoid arthritis, and asthma and allergies in up to 40% to 50% of patients with MC . If a patient with celiac disease treated with a gluten-free diet continues to have diarrheal symptoms, colonoscopy should be considered to evaluate for concurrent MC.
What is the natural history of MC?
The natural history is not known. Often the disease is insidious, but may have acute onset in up to 40% of patients. In one study, 505 patients with MC experienced resolution of their symptoms after 3 years. However, as many as 30% of patients treated for MC will experience persistent diarrhea 10 years after diagnosis. The clinical course may be complicated by the patient’s response to medication. There is no increased risk of malignancy associated with MC; however, there are reports of colonic perforation thought to be related to mucosal tears seen during colonoscopy.
What are the treatment options?
Initially, patients with MC can make dietary changes (avoid caffeine, alcohol, and dairy products) and stop any medications that have been associated with MC. Some patients do well on antidiarrheal agents (loperamide) or on cholestyramine alone. A metaanalysis has shown that oral budesonide (9 mg daily) for 6 to 8 weeks has been effective in decreasing symptoms in 81% of patients with CC; however, symptoms recurred in 60% to 80% of patients with the cessation of budesonide. These patients responded to retreatment with budesonide and often required slow subsequent tapers. Budesonide has also been shown to be effective in treating LC. There are no evidence-based alternatives to budesonide. Bismuth subsalicylate and sulfasalazine-mesalamine have shown efficacy in some studies. Probiotics offered no benefit over placebo in studies. Some patients require stronger immunosuppressants such as methotrexate, 6-mercaptopurine, or azathioprine; there is ongoing research to determine the utility of anti–tumor necrosis factor therapy with infliximab and adalimumab. In rare cases, patients may require surgery, such as diverting ileostomy or colectomy, for severe and refractory disease.