[Microscopic Colitis]. / Mikroskopische Kolitis.

Microscopic colitis (MC) is still an underestimated cause of chronic, non-bloody watery diarrhea. It is typically manifested in elderly patients with a female predominance. The incidence of microscopic colitis has been increasing. The aetiology and pathophysiology remain unclear. Conditions associated with it include autoimmune diseases. There may be a genetic predisposition, as familial cases have been described. As implicated by the name microscopic colitis, the diagnosis is found by histological examination. There are mainly two subtypes, the lymphocytic colitis (LC) and the collagenous colitis (CC). Even if the condition's long-term course is benign, a chronic recurrent course of the symptoms is frequent. Due to the symptoms, there is an impairment of patient's health-related quality of life. A correct diagnosis and therapy is therefore mandatory. The aim of this paper is to create awareness for microscopic colitis.

Family history, comorbidity, smoking and other risk factors in microscopic colitis: a case-control study.

OBJECTIVES: Data on heredity, risk factors and comorbidity in microscopic colitis, encompassing collagenous colitis (CC) and lymphocytic colitis (LC), are limited. AIM: The aim was to carry out a case-control study of family history, childhood circumstances, educational level, marital status, smoking and comorbidity in microscopic colitis. METHODS: A postal questionnaire was sent in 2008-2009 to microscopic colitis patients resident in Sweden and three population-based controls per patient, matched for age, sex and municipality. RESULTS: Some 212 patients and 627 controls participated in the study. There was an association with a family history of microscopic colitis in both CC [odds ratio (OR): 10.3; 95% confidence interval (CI): 2.1-50.4, P=0.004] and LC (OR not estimated, P=0.008). Current smoking was associated with CC [OR: 4.7; 95% CI: 2.4-9.2, P<0.001) and LC (OR: 3.2; 95% CI: 1.6-6.7, P=0.002). The median age at diagnosis was around 10 years earlier in ever-smokers compared with never-smokers.CC was associated with a history of ulcerative colitis (UC) (OR: 8.7, 95% CI: 2.2-33.7, P=0.002), thyroid disease (OR: 2.3; 95% CI: 1.1-4.5, P=0.02), coeliac disease (OR: 13.1; 95% CI: 2.7-62.7, P=0.001), rheumatic disease (OR 1.9; 95% CI: 1.0-3.5, P=0.042) and previous appendicectomy (OR: 2.2; 95% CI: 1.3-3.8, P=0.003), and LC with UC (OR: 6.8; 95% CI: 1.7-28.0, P=0.008), thyroid disease (OR: 2.4; 95% CI: 1.1-5.4, P=0.037) and coeliac disease (OR: 8.7; 95% CI: 2.8-26.7, P<0.001). CONCLUSION: Association with a family history of microscopic colitis indicates that familial factors may be important. The association with a history of UC should be studied further as it may present new insights into the pathogenesis of microscopic colitis and UC.

Association of lymphocytic colitis and lactase deficiency in pediatric population.

Characterized by colonic mucosa intraepithelial lymphocytosis, lymphocytic colitis is primarily an entity presented in the middle-aged to elderly patient population. Very few large series of lymphocytic colitis of childhood occurrence are available in the medical literature. Ten cases each of lymphocytic colitis and of colonic lymphocytosis of other diagnosis, all with duodenal disaccharidases analysis data, were collected from the files of our institution. The electronic medical records were reviewed and multiple variables were analyzed. The ten patients with lymphocytic colitis presented with diarrhea. Of these, three had abdominal pain. The age range was 2-18 years. Nearly all patients were Caucasian (90%) and 70% were female. Endoscopically, most had normal appearing colonic mucosa. Significant past medical history, family medical history and associated comorbidities included celiac disease, Down syndrome, juvenile arthritis and other autoimmune diseases. Interestingly, the most revealing observation was that the majority of cases (80%) were associated with lactase deficiency and, for the most part, gastrointestinal symptoms improved simply by treatment with Lactaid or avoidance of dairy products. This association is statistically significant. Our clinicopathological study indicates that the typical pediatric patient is a female Caucasian. A large of portion of the patients had associated lactase deficiency and improved on Lactaid supplement alone.

Clinical presentation, diagnosis, pathogenesis and treatment options for lymphocytic colitis (Review).

Lymphocytic colitis (LC) is characterized by chronic or relapsing non-bloody watery diarrhea and a macroscopically normal colon. However, histopathological examination of colonic biopsy samples reveals an increased intraepithelial infiltration of lymphocytes (≥20/100 enterocytes), and increased inflammatory cells within the lamina propria, but with a normal mucosal architecture. The reported prevalence of LC varies from 14.2 to 45 per 100,000 individuals, while its reported incidence is between 0.6 and 16 per 100,000 individuals. LC has a high rate of spontaneous symptomatic remission and is not associated with an increased risk of colon cancer or inflammatory bowel disease. The diagnosis is based on the histopathological findings. The density of colonic chromogranin A-positive cells provides an effective diagnostic tool with high sensitivity and specificity in both the right and left colon. Gastrointestinal infections, drugs, and/or autoimmunity may trigger chronic colonic low-grade inflammation. Colonic nitric oxide, serotonin and peptide YY (PYY) cell densities are markedly increased in patients with LC. It has been hypothesized that the low-grade inflammation in LC through the endocrine-immune axis causes this increase. It has been postulated further that these abnormalities in the neuroendocrine system of the colon are responsible for the diarrhea observed in patients with LC. The benign course and rate of spontaneous remission of LC denotes that drugs with severe side-effects should be avoided if possible. The drug cost and drug coverage may also be limiting factors for some patients. These aspects should be taken into account when making decisions regarding treatment options.

Impact of current smoking on the clinical course of microscopic colitis.

BACKGROUND: Whether current smoking worsens the clinical course of microscopic colitis (MC) is unknown. The aim was to evaluate the impact of smoking on the clinical course of MC. METHODS: One hundred and eighty-four patients (72% women; age, 62.4 ± 1.1 years) with MC (118 collagenous colitis (CC) and 66 lymphocytic colitis (LC) were evaluated (39 of them were current smokers). In all the patients, smoking habits and clinical data at presentation, response to therapy, and clinical relapses during follow-up were prospectively recorded. Risk factors for clinical relapse were studied in 160 patients after a mean follow-up of 28 ± 1 months. Cox regression analysis was used to adjust for confounding variables. RESULTS: Age at diarrhea onset was 63.0 ± 1.4 years in nonsmokers and 50.4 ± 2.1 years in current smokers (P < 0.001). There was no significant influence of smoking habit on either clinical symptoms at diagnosis or clinical remission rate. Clinical relapse rate was 25.5% for CC and 29.6% for LC, with the mean relapse-free time 28.8 months (95% confidence interval, 26.3-31.4) for CC and 26.9 months (95% confidence interval, 26-30.3) for LC (P = 0.5). Multivariate analysis showed that age at diagnosis (<50 years versus others; adjusted hazard ratio, 2.8; 95% confidence interval, 1.3-6; P = 0.01) was associated with risk of relapse of CC but not LC. Current smoking was not an independent risk factor for either CC or LC relapse. CONCLUSIONS: Active smokers developed MC more than a decade before nonsmokers. Age at diagnosis, but not smoking, was an independent risk factor of relapse in patients with CC.

Epidemiological risk factors in microscopic colitis: a prospective case-control study.

BACKGROUND: The cause of collagenous colitis (CC) and lymphocytic colitis (LC) is unknown and epidemiological risk factors for CC and LC are not well studied. The aim was to evaluate in a case-control study epidemiological risk factors for CC and LC. METHODS: In all, 120 patients with CC, 70 with CL, and 128 controls were included. For all cases and controls information was prospectively recorded. A binary logistic regression analysis was performed separately for CC and LC. RESULTS: Independent associations observed with the diagnosis of CC were: current smoking (odds ratio [OR], 2.4), history of polyarthritis (OR, 20.8), and consumption of lansoprazole (OR, 6.4), low-dose aspirin (OR, 3.8), beta-blockers (OR, 3.6), and angiotensin II receptor antagonists (OR 0.20). In the case of LC they were: current smoking (OR, 3.8), associated autoimmune diseases (OR, 8), and consumption of sertraline (OR, 17.5), omeprazole (OR 2.7), low-dose aspirin (OR, 4.7), and oral antidiabetic drugs (OR, 0.14). CONCLUSIONS: The consumption of drugs, current smoking, and associated autoimmune diseases were independently associated with the risk of microscopic colitis.

Current and past cigarette smoking significantly increase risk for microscopic colitis.

BACKGROUND: Cigarette smoking is an important environmental factor affecting inflammatory bowel disease. The role of smoking has not been rigorously studied in microscopic colitis (MC). The aim of this study was to compare the association of cigarette smoking in individuals with MC compared to a control population without MC. METHODS: We reviewed the records of patients with a clinical and histologic diagnosis of collagenous colitis (CC) or lymphocytic colitis (LC). Clinical history, including alcohol and smoking status at the time of diagnosis of MC, were reviewed. In this case-control study, age- and gender-matched patients without diarrhea presenting for outpatient colonoscopy served as the control population. RESULTS: We analyzed a total of 340 patients with MC: 124 with CC and 216 with LC. Overall, any smoking status (former or current) was associated with MC (odds ratio [OR] 2.12, 95% confidence interval [CI]: 1.56-2.88). This risk was more prominent in current smokers (adjusted OR 5.36, 3.81, and 4.37 for CC, LC, and all MC, respectively, 95% CI all greater than 1). The association of smoking was not significantly affected by gender or average alcohol consumption. CONCLUSIONS: In our study population, cigarette smoking is a risk factor for the development of both forms of microscopic colitis. There were no significant differences between LC and CC, and current smoking and the development of microscopic colitis affected men and women similarly. We feel that these data are sufficient to discuss the potential risks of tobacco use in patients with microscopic colitis.

Evolution of the incidence of collagenous colitis and lymphocytic colitis in Terrassa, Spain: a population-based study.

BACKGROUND: Previous studies suggest an increase in the incidence rate of microscopic colitis in recent decades. The aim was to evaluate changes in the population-based incidence rate of microscopic colitis and its subtypes over time in Terrassa, Spain. METHODS: This was a prospective study during the period 2004-2008, with a comparison of data from the period 1993-1997. The catchment area was a mixed rural-urban type, with nearly 290,000 inhabitants. All patients with nonbloody chronic diarrhea referred for a diagnostic colonoscopy were included. Multiple biopsy specimen samples were obtained when the macroscopic appearance of the colonic mucosa was normal to rule out microscopic colitis. Crude and adjusted incidence rates based on either the year of diagnosis or the date of onset of symptoms were calculated. RESULTS: Forty patients with collagenous colitis (CC) and 32 with lymphocytic colitis (LC) were identified. The mean annual incidence of CC and LC based on the year of onset of symptoms was 2.6/10(5) inhabitants (95% confidence interval [CI], 1.9-3.3), and 2.2/10(5) inhabitants (95% CI, 1.5-3.0), respectively. Incidence rates for CC based on the year of onset of symptoms were significantly higher in the period 2004-2008 than in 1993-1997 (2.6 versus 1.1/10(5) ; P = 0.012). The increase in CC incidence was more marked in women (P = 0.047) than in men (P = 0.19). CONCLUSIONS: The annual incidence of CC in Terrassa increased over time, mainly in women. Nevertheless, the rates were much lower than those observed in northern Europe, suggesting that there is a north-south difference in the incidence of microscopic colitis.

Microscopic colitis: an update.

Microscopic colitis (MC) causes chronic diarrhea, abdominal cramping, nausea, and weight loss. Colonic mucosa appears normal on endoscopy; however, biopsies show abnormalities such as intraepithelial lymphocytosis in lymphocytic colitis, and a thickened subepithelial collagen band in collagenous colitis. Epidemiologic data demonstrates that MC is a more common cause of diarrhea than previously shown. Although the etiology of this condition is unclear, certain well-defined risk factors exist. Recently there has been more research on the pathophysiology of MC, and studies on treatment have demonstrated budesonide to be most effective, although other treatments also hold promise.

Collagenous and lymphocytic colitis: systematic review and update of the literature.

Collagenous and lymphocytic colitis are well-described conditions causing chronic watery diarrhoea. A peak incidence from 60 to 70 years of age with a female predominance mainly in collagenous colitis is observed. Both conditions are characterised by a (near) normal colonoscopy, but with specific histologic findings on colonic biopsies. Histopathologically, both conditions are characterised by distinct epithelial abnormalities and a dense lymphoplasmocytic infiltrate. Distinct features consist of a characteristic collagen band deposition in the subepithelial layer in collagenous colitis and a markedly increased number of intra-epithelial lymphocytes in lymphocytic colitis. Although most cases are idiopathic, certain drugs can induce microscopic colitis. In addition, either condition can be associated with coeliac disease. For a long time patients with microscopic colitis were treated with non-specific anti-diarrhoeal agents, anti-inflammatory agents such as mesalazine, or systemic steroids, but with disappointing results. Bismuth subsalicylate was reported to be effective in a small controlled series of patients with collagenous colitis. Now, randomised controlled trials have shown the effectiveness of budesonide over placebo in collagenous colitis and more recently in lymphocytic colitis. The histologic response is variable, but a decrease in the subepithelial collagen layer and a decrease in the lymphoplasmocytic infiltrate in the lamina propria is observed in about half of the patients. In general, patients respond within 2 weeks with no major side effects. However, relapse is common (63-80% of patients) when budesonide is stopped. Longer-term treatment is effective but does not seem to reduce relapse rates upon discontinuation.

Lymphocytic colitis in a child with non-responsive celiac disease.

In celiac disease, symptoms usually improve with strict adherence to diet. Some patients however do not show improvement despite of diet therapy. We here report a girl with non-responsive celiac disease whose diarrhea did not improve despite of a gluten free diet. A 12-year-old girl with recurrent diarrhea and failure to thrive was diagnosed with celiac disease. After six months of gluten-free diet her symptoms persisted. Adherence to diet was considered as correct and complete by a dietitian evaluation and by anti-endomysial antibodies that had become negative. Treatment with pancreatic enzymes, metronidazole or lactose free diet did not improve her symptoms. Colonoscopy was performed and lymphocytic colitis was diagnosed on histology from colonic biopsies. After mesalamine therapy diarrhea ceased, and weight and height z scores increased. Lymphocytic colitis, which is uncommonly seen in children compared to adults, should be considered in nonresponsive celiac disease in children.

[Microscopic colitis: collagenous colitis and lymphocytic colitis]. / Les colites microscopiques : colite collagène et colite lymphocytaire.

Microscopic colitis is currently classified as a chronic inflammatory bowel disorder and encompasses two entities: lymphocytic colitis and collagenous colitis. Patients with microscopic colitis present with a well-tolerated chronic watery diarrhea, sometimes with abdominal pain. Colonoscopy is normal. Diagnosis of microscopic colitis is established by histologic examination of colonic biopsies, showing a thickened subsurface collagen band higher than 10 microm in collagenous colitis, and an increased number of surface intra-epithelial lymphocytes higher than 20 lymphocytes per 100 epithelial cells in lymphocytic colitis. Causes of microscopic colitis are still unknown, although a drug-induced etiology is found in some cases. Patients are usually treated with budesonide but recurrences are frequent.

Seasonal pattern of onset in lymphocytic colitis.

BACKGROUND: The etiology of lymphocytic colitis, a microscopic colitis syndrome, has remained elusive. Because 1) many infectious enteritides exhibit seasonal variability in incidence and 2) a few investigators have proposed some infectious mechanism in lymphocytic colitis, our aim was to determine if any variability in symptom onset existed among lymphocytic colitis patients diagnosed at our institution. STUDY: We identified 71 nonduplicated, consecutive patients with lymphocytic colitis over a 4-year period using rigorous clinicopathologic inclusion criteria: 1) chronic watery diarrhea, 2) endoscopically normal colon, 3) no evidence for celiac sprue or drug-induced colitis, 4) diffuse colitis with increased intraepithelial lymphocytes of at least 10 lymphocytes per 100 epithelial cells, 5) evidence of surface epithelial damage, and 6) no significant neutrophilic infiltrates, architectural distortion of the mucosa, or subepithelial collagen deposits. The date of diagnosis was corrected for month of onset of symptoms. RESULTS: The distribution of month of onset of symptoms showed a statistically significant (chi test of homogeneity, P = 0.0008) temporal variability and seasonal incidence pattern with excess cases during summer and fall and a paucity of cases during colder months. CONCLUSIONS: To our knowledge, this is the first study to examine systematically and report a significant seasonal incidence pattern of lymphocytic colitis. Our observations may support a potential link to an infectious source in lymphocytic colitis.

Collagenous colitis and lymphocytic colitis: patient characteristics and clinical presentation.

OBJECTIVE: Collagenous colitis and lymphocytic colitis (collectively known as microscopic colitis) are characterized by chronic diarrhea, normal endoscopic and radiologic findings, and typical findings on histologic examination of colonic tissue. The purpose of this study was to define the background characteristics of patients with microscopic colitis, as well as to present symptoms, coexistent autoimmune diseases, and a possible association with the use of non-steroidal anti-inflammatory drugs (NSAIDs) and ticlopidine. MATERIAL AND METHODS: A retrospective chart review was carried out on all cases of collagenous colitis and lymphocytic colitis diagnosed at a single center from July 1992 to July 2002. RESULTS: Of the 104 patients identified, 66 had collagenous colitis, 35 had lymphocytic colitis, and 3 were diagnosed with both disorders at different times. The mean age of patients was 64 years (26-88 years), with a female:male ratio of 4.8:1. The most common presenting symptoms were diarrhea (95%), weight loss (41%), abdominal pain (40%), fecal urgency (29%), and nocturnal stools (22%). Autoimmune disease was diagnosed in 29% of patients, 35% were using an NSAID, and 2% were using ticlopidine. CONCLUSIONS: Collagenous colitis and lymphocytic colitis occur more often in females than in males, at a wide age range, with a mean in the seventh decade. Certain symptoms are characteristic, but are not specific to these disorders. There may be an association with the presence of a coexistent autoimmune disorder and the use of drugs such as NSAIDs.

Lymphocytic colitis: a clue to bacterial etiology.

AIM: To find out the role of bacteria as a possible etiological factor in lymphocytic colitis. METHODS: Twenty patients with histopathological diagnosis of lymphocytic colitis and 10 normal controls were included in this study. Colonoscopic biopsies were obtained from three sites (hepatic and splenic flexures and rectosigmoid region). Each biopsy was divided into two parts. A fresh part was incubated on special cultures for bacterial growth. The other part was used for the preparation of histologic tissue sections that were examined for the presence of bacteria with the help of Giemsa stain. RESULTS: Culture of tissue biopsies revealed bacterial growth in 18 out of 20 patients with lymphocytic colitis mostly Escherichia coli (14/18), which was found in all rectosigmoid specimens (14/14), but only in 8/14 and 6/14 of splenic and hepatic flexure specimens respectively. In two of these cases, E coli was associated with proteus. Proteus was found only in one case, Klebsiella in two cases, and Staphylococcus aureus in one case. In the control group, only 2 out of 10 controls showed the growth of E coli in their biopsy cultures. Histopathology showed rod-shaped bacilli in the tissue sections of 12 out of 14 cases with positive E coli in their specimen's culture. None of the controls showed these bacteria in histopathological sections. CONCLUSION: This preliminary study reports an association between E coli and lymphocytic colitis, based on histological and culture observations. Serotyping and molecular studies are in process to assess the role of E coli in the pathogenesis of lymphocytic colitis.