Microscopic colitis

Microscopic colitis (MC) is viewed as an umbrella term applicable to both lymphocytic and collagenous colitis. The first case was published in 1976, a new entity with chronic watery diarrhea with lymphocytic colitis, with or without a subepithelial collagen deposition. Patients are usually middle-aged women, and the pathogenesis is unknown. The response to steroids and the female predominance underlines an autoimmune disease. Up to 40% NSAID's and Lanzoprazole-induced MC are well-known. Biopsies during sigmoidoscopy in unexplained diarrhea must be standard. Treatment is empirical. The most important step is to ban all NSAID's and other MC inducing agents. Immunosuppressive treatment must be considered. However the disease has a benign course and sometimes is selflimiting.     

Microscopic colitis

Microscopic colitis is a common cause of chronic watery diarrhea, especially among older persons. Diagnosis requires histologic analysis of colon biopsy samples in the appropriate clinical setting. Recent studies have shown an increase in the incidence of microscopic colitis, and several have addressed potential mechanisms. We review recent findings about the clinical features, diagnosis, epidemiology, pathophysiology, and treatment of microscopic colitis.     

Microscopic colitis

Microscopic colitis may be defined as a clinical syndrome, of unknown etiology, consisting of chronic watery diarrhea, with no alterations in the large bowel at the endoscopic and radiologic evaluation. Therefore, a definitive diagnosis is only possible by histological analysis. The epidemiological impact of this disease has become increasingly clear in the last years, with most data coming from Western countries. Microscopic colitis includes two histological subtypes [collagenous colitis (CC) and lymphocytic colitis (LC)] with no differences in clinical presentation and management. Collagenous colitis is characterized by a thickening of the subepithelial collagen layer that is absent in LC. The main feature of LC is an increase of the density of intra-epithelial lymphocytes in the surface epithelium. A number of pathogenetic theories have been proposed over the years, involving the role of luminal agents, autoimmunity, eosinophils, genetics (human leukocyte antigen), biliary acids, infections, alterations of pericryptal fibroblasts, and drug intake; drugs like ticlopidine, carbamazepine or ranitidine are especially associated with the development of LC, while CC is more frequently linked to cimetidine, non-steroidal antiinflammatory drugs and lansoprazole. Microscopic colitis typically presents as chronic or intermittent watery diarrhea, that may be accompanied by symptoms such as abdominal pain, weight loss and incontinence. Recent evidence has added new pharmacological options for the treatment of microscopic colitis: the role of steroidal therapy, especially oral budesonide, has gained relevance, as well as immunosuppressive agents such as azathioprine and 6-mercaptopurine. The use of anti-tumor necrosis factor-α agents, infliximab and adalimumab, constitutes a new, interesting tool for the treatment of microscopic colitis, but larger, adequately designed studies are needed to confirm existing data.     

Microscopic colitis

Opinion statement As the diagnosis of microscopic colitis (MC) is made on the basis of histologic criteria, it is crucial to render an accurate microscopic interpretation. Features include 20 or more lymphocytes per 100 epithelial cells, mixed lamina propria inflammatory infiltrate, and preservation of crypt architecture for both lymphocytic and collagenous colitis (CC). CC is further characterized by a collagen band at least 10 μm thick. Although the pathogenesis of MC is poorly understood, medication-induced toxicity to the colonic mucosa is important to recognize, as medication cessation leads to prompt improvement. If MC is mild, symptomatic treatment is all that is needed, because some cases are self-limiting. Budesonide, 9 mg daily for at least 8 weeks, is the best documented treatment of choice for more severe or protracted cases. A 75% response rate has been reported; however, when treatment is discontinued, relapse is common, and longer-term tapering dose therapy often is necessary. There are disadvantages and no advantage to other forms of steroid therapy. Cholestyramine, bismuth, and 5-aminosalicylate derivatives appear to be less efficacious but are reasonable therapeutic options for less severe cases. Use of immunosuppressant therapy such as azathioprine or 6-mercaptopurine should be highly restricted because MC is a benign condition that does not result in other complications. Probiotic therapy with Lactobacillus acidophilus and Bifidobacterium animalis has not been shown to be effective in reducing bowel frequency. Surgical diversion of the fecal stream can control diarrhea and improve histology but is very rarely indicated and should be reserved for highly selected cases of severely symptomatic steroid-refractory MC.     

Microscopic colitis

Microscopic colitis is an umbrella term used to include two idiopathic inflammatory bowel disorders that present with chronic watery diarrhea, normal endoscopic findings and characteristic inflammatory changes on histology. Collagenous colitis and lymphocytic colitis are distinguished by the presence of a thickened subepithelial collagen table. It is likely that they are a spectrum of one disease, but this is yet to be proven. The majority of cases tend to undergo spontaneous remission within a few years of onset, and their clinical course is benign, with no increase in risk of colorectal cancer. Sufficient evidence exists to suggest that microscopic colitis occurs as a response to one or more luminal antigens. A variety of medications have been reported in the treatment of this condition, but only colloidal bismuth and budesonide have thus far been shown to be effective in randomized controlled trials.     

Microscopic colitis syndrome.

The colorectal biopsy specimens from 30 patients with chronic watery diarrhoea but normal endoscopic and radiographic findings were studied by light microscopy, morphometry, immunohistochemistry, and two patients with electron microscopy. The histological changes in the colorectum were originally diagnosed in six patients as lymphocytic colitis and in 24 patients as collagenous colitis. The analysis of the specimens for this study could delineate three distinct groups of microscopic colitis: lymphocytic colitis (six patients), collagenous colitis without lymphocytic attack on the surface epithelium (seven patients), and a mixed form presenting with both thickening of the collagen plate and increased number of intraepithelial lymphocytes (17 patients). No transformation was seen from one type to another during follow up of six patients for four to seven years. Increased numbers of active pericryptal myofibroblasts were found with the electron microscope in one patient with mixed microscopic colitis showing also myofibroblasts entrapped within the collagen layer. Hitherto undescribed flat mucosa of the ileum was found in one patient with lymphocytic colitis and both flat mucosa and thickening of the collagen plate in the ileum were seen in one patient with the mixed form of the disease. In another patient with mixed microscopic colitis, normalisation of the colorectal morphology occurred after temporary loop ileostomy, followed by the reappearance of both diarrhoea, inflammation, and thickening of the collagen plate after the ileostomy was reversed. No association was found between non-steroid anti-inflammatory drug (NSAID) consumption and collagenous or mixed microscopic colitis. The primary cause of microscopic colitis is probably an immunological reaction to luminal antigen/s, perhaps of ileal origin. The engagement of the pericryptal myofibroblasts in the disease process might result in the development of the various forms of microscopic colitis. An inverse relation between intraepithelial lymphocyte count and collagen thickness may indicate that microscopic colitis is a spectral disease.     

Microscopic colitis. A review

Microscopic colitis (MC) is characterized by a triad of watery diarrhea, usually normal colonoscopic findings and typical microscopic findings. Two distinct histological forms of MC have been defined: lymphocytic colitis and collagenous colitis, but overlapping features may be present. The incidence of MC appears to be rising and in some countries it may account for as many as 10–20% of patients with non‐bloody watery diarrhea. The cause of MC remains unknown and is likely to be multifactorial. The pathogenesis is poorly defined, and numerous immunological abnormalities have been reported. MC is commonly associated with autoimmune diseases including celiac disease. Use of various medications, most notably non‐steroidal anti‐inflammatory agents and proton pump inhibitors, have been etiologically implicated but not firmly established as causative. In imperfect trials several agents have been reported to be effective in the treatment of MC; budesonide is the best studied and evidence supporting its effectiveness is the most persuasive. In cases of otherwise unexplained watery, non‐bloody diarrhea, MC should be considered and colonic biopsied specimens should be taken of normal‐appearing mucosa.     

Microscopic colitis: an update

Microscopic colitis is an increasingly common cause of chronic diarrhea, and often causes abdominal pain and weight loss. The colonic mucosa appears normal or nearly normal endoscopically, and the diagnosis is made in the appropriate clinical setting when there is intraepithelial lymphocytosis and a mixed lamina propria inflammatory infiltrate. The 2 subtypes, collagenous and lymphocytic colitis, are similar clinically and histologically, and are distinguished by the presence or absence of a thickened subepithelial collagen band. Many potential pathophysiologic mechanisms have been proposed, but no convincing unifying mechanism has been identified. There are many anecdotal reports on treatment, but few controlled trials have been performed in these patients, although a systematic approach to therapy often leads to the satisfactory control of symptoms.     

Microscopic colitis: a review

Microscopic colitis is a relatively common cause of chronic watery diarrhea, often accompanied by abdominal pain and weight loss. The colonic mucosa appears normal grossly, and the diagnosis is made when there is an intraepithelial lymphocytosis and a mixed inflammatory infiltrate in the lamina propria. The two main subtypes, collagenous and lymphocytic colitis, are similar clinically and histologically, distinguished by the presence or absence of a thickened subepithelial collagen band. Many potential pathophysiological mechanisms have been described, although none have been conclusively proved. There is a paucity of randomized treatment trials in these patients, although a rational approach to therapy often leads to satisfactory control of symptoms.     

Microscopic colitis: A therapeutic challenge

The treatment of microscopic colitis is mainly based on the use of budesonide, the only drug found effective in controlled clinical trials. After an initial course at a dose of 9 mg daily, however, most patients relapse when the drug is discontinued, hence a maintenance therapy at doses of 6 mg daily or lower is necessary. In order to avoid steroid dependence and drug toxicity different pharmacological agents should be considered as an alternative to indefinite long-term budesonide treatment. Evidence-based guidelines are currently lacking due to the lack of conclusive data concerning the use of either immunosuppressive or anti-tumor necrosis factor agents. For the time being in clinical practice the skilled physician should therefore tailor long term management of microscopic colitis on the single patient.