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Collagenous colitis is a clinicopathologic syndrome characterized by chronic watery diarrhea and unique histopathologic features. Spontaneous colonic perforation in the setting of collagenous colitis is a highly unusual complication, with only three cases reported in the literature to date. We present a fourth case and propose a potential pathologic mechanism for acute colonic perforation in this patient population.

OBJECTIVE: This 1-year study aimed to assess low-dose budesonide therapy for maintenance of clinical remission in patients with collagenous colitis.DESIGN: A prospective, randomised, placebo-controlled study beginning with an 8-week open-label induction phase in which patients with histologically confirmed active collagenous colitis received budesonide (Budenofalk, 9 mg/day initially, tapered to 4.5 mg/day), after which 92 patients in clinical remission were randomised to budesonide (mean dose 4.5 mg/day; Budenofalk 3 mg capsules, two or one capsule on alternate days) or placebo in a 12-month double-blind phase with 6 months treatment-free follow-up. Primary endpoint was clinical remission throughout the double-blind phase.RESULTS: Clinical remission during open-label treatment was achieved by 84.5% (93/110 patients). The median time to remission was 10.5 days (95% CI (9.0 to 14.0 days)). The maintenance of clinical remission at 1 year was achieved by 61.4% (27/44 patients) in the budesonide group versus 16.7% (8/48 patients) receiving placebo (treatment difference 44.5% in favour of budesonide; 95% CI (26.9% to 62.7%), pCONCLUSIONS: Budesonide at a mean dose of 4.5 mg/day maintained clinical remission for at least 1 year in the majority of patients with collagenous colitis and preserved health-related quality of life without safety concerns. Treatment extension with low-dose budesonide beyond 1 year may be beneficial given the high relapse rate after budesonide discontinuation.TRIAL REGISTRATION NUMBERS: http://www.clinicaltrials.gov (NCT01278082) and http://www.clinicaltrialsregister.eu (EudraCT: 2007-001315-31).

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. (Inflamm Bowel Dis 2012)

Microscopic colitides, including lymphocytic (LC) and collagenous colitis (CC), are well-described pathologic conditions. An altered immune response is implicated in the pathogenesis of both entities. CD8+ T lymphocytes (CTLs) secrete interleukin 2 which stimulates proliferation of regulatory T cells (Tregs), and Tregs, in turn, inhibit CTLs, inducing cytotoxic tissue damage. In Tregs, Foxp3 regulates T-cell–related immune responses. The distribution of Tregs and CTLs in microscopic colitides has remained underexplored. To characterize differences in the distribution pattern of Foxp3 in biopsy specimens from patients with LC and CC, 71 colonic biopsy specimens from 69 consecutive patients were categorized into 1 of 3 diagnoses: no significant histopathologic abnormality (NSHPA), LC, or CC. Further immunohistochemical evaluation of all biopsy specimens was conducted using a panel of markers including CD8 and Foxp3. Our study demonstrated that CTL distribution pattern differences exist among these 2 colitides and that differences in the immunologic recruitment of Foxp3+ Tregs in the colonic mucosa correlate with differences in the spectrum of morphologic changes seen in patients with either LC or CC. Upon completion of this activity you will be able to: The ASCP is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The ASCP designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 Credit ™ per article. Physicians should claim only the credit commensurate with the extent of their participation in the activity. This activity qualifies as an American Board of Pathology Maintenance of Certification Part II Self-Assessment Module. The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose. Questions appear on p 1009. Exam is located at [www.ascp.org/ajcpcme][1]. [1]: http://www.ascp.org/ajcpcme

Collagenous colitis is a recognised cause of persistent, non-bloody, watery diarrhoea. There are few cases of collagenous colitis reported in children or occurring within families. To our knowledge, no familial cases under 14 years of age have been reported previously; we describe a case of familial collagenous colitis affecting a 6-year old girl and her mother. The relevant published literature is reviewed and management is discussed. Colonic mucosal biopsies should be considered in both adults and children presenting with persistent watery diarrhoea even in the absence of any macroscopic abnormality at colonoscopy.

Background: Collagenous colitis is a chronic inflammatory bowel disease of unknown etiology. It is fairly common in adult humans, but rare in infants, and has been associated with autoimmune disorders. Methods: We report four infant baboons (age 7–12 months) that had received a transplant at 3 months of age and subsequent immunosuppressive therapy for periods of 4–10 months. All presented identical symptoms within a period of 4 weeks, including weight loss associated with chronic watery diarrhea that was unresponsive to standard antimicrobial treatment. Results: Clinical chemistry evaluations were within normal ranges, viral causes were ruled out, and fecal and blood cultures were repeatedly negative. At necropsy, two infant baboons were found to have a form of collagenous colitis. In the remaining two baboons that had identical clinical features, immunosuppressive therapy was discontinued and treatment with budesonide was initiated. Both baboons recovered and remained well on no medication until the end of follow-up (24 months). Conclusions: Collagenous colitis has occasionally been reported in patients with organ transplants. It has been reported only once previously in baboons. The four cases reported here strongly suggest that 1) clinical features as well as histopathological findings of collagenous colitis in baboons are very similar to those in human patients; 2) it was associated with the immunocompromised state of the baboons, as two nonimmunosuppressed age-matched baboons in close proximity did not develop the condition; and 3) it may have had an infectious origin, as all four cases developed within a 4-week period of time. (Inflamm Bowel Dis 2012;)

Lymphocytic colitis (LC) and collagenous colitis (CC), 2 histologic forms of microscopic colitis, were recognized as rare disease entities 4 decades ago. An increasing body of evidence accumulated in the past 40 years reveals increasing incidence and prevalence rates, a wide spectrum of clinical presentations, and several histologic variants. Although several recent randomized clinical trials confirmed the efficacy of oral budesonide in treating LC and CC, disease relapse after a short-duration treatment is common. Despite their common clinical presentations and well-defined histologic diagnostic criteria, there are only few studies on the immunologic abnormalities in colonic tissue. The aim of this review is to (1) familiarize the pathologists in general practice with histomorphology of LC and CC, including the rare histologic variants and the clinical implication associated with these 2 diagnoses, (2) summarize the data from recent randomized clinical trials of oral budesonide, and (3) review immunological studies on colonic tissue. Overall, immunologic abnormalities of colonic tissue seem to explain for the histomorphologic features and the clinical symptomatology of LC and CC. Advances in the understanding of the underlying immunologic abnormalities in the colonic tissue may help develop novel and effective therapies for these 2 diseases.

BACKGROUND: Microscopic colitis (MC) is an umbrella term for collagenous colitis (CC) and lymphocytic colitis (LC). The incidence of these diseases is increasing for unclear reasons.OBJECTIVE: To identify factors that may impact diagnosis rates of MC in a North American population.METHODS: Population-based pathology and endoscopy databases were searched to identify all cases of MC and the number of lower endoscopy (LE) procedures performed over a five-year period (January 2004 to December 2008) in a catchment area of 1.2 million people. Endoscopist characteristics were compared with diagnostic rates.RESULTS: MC incidence increased from 1.68 per 10,000 in 2004, to 2.68 per 10,000 in 2008, with an average annual increase of 12% per year (95% CI 7% to 16%; PCONCLUSION: The incidence of MC is rising due to increased diagnosis of LC, while CC incidence remains stable. Patients with MC symptoms have stable endoscopy rates but are being biopsied more often. Physician training, practice type and endoscopy volume impact the diagnostic rates of MC.

The mucosa of the esophagus, the stomach, the small intestine, the large intestine and rectum are unremittingly challenged by adverse micro-environmental factors, such as ingested pathogenic and non-pathogenic bacteria, and harsh secretions with digestive properties with disparate pH, as well as bacteria and secretions from upstream GI organs. Despite the apparently inauspicious mixture of secretions and bacteria, the normal GI mucosa retains a healthy state of cell renewal. To by-pass the tough microenvironment, the epithelia of the GI react by speeding-up cell exfoliation, by increasing peristalsis, eliminating bacteria through secretion of plasma cell-immunoglobulins and by increasing production of natural antibacterial enzymes (lysozyme) and host defense peptides (defensin-5). Lysozyme was recently found up-regulated in Barrett's esophagitis, in chronic gastritis, in gluten-induced atrophic duodenitis (celiac disease), in collagenous colitis, in lymphocytic colitis and in Crohn's colitis. This up-regulation is a response directed towards the special types of bacteria thriving in the microenvironment in each of the aforementioned clinical inflammatory maladies. The purpose of that up-regulation is to protect the mucosa affected by the ongoing chronic inflammation. Bacterial antibiotic resistance continues to exhaust our supply of effective antibiotics. The future challenge is how to solve the increasing menace of bacterial resistance to anti-bacterial drugs. Further research on natural anti-bacterial enzymes such as lysozyme, appears mandatory.

Background: Collagenous colitis is a chronic inflammatory bowel disease of unknown origin characterized by a thickened subepithelial collagen layer. Differential expression of matrix-metalloproteinases (MMPs) have been implicated in the pathogenesis of collagenous colitis. The aim was to assess genetic polymorphisms of MMP-1, -7, and -9 in a case-control setting for susceptibility to collagenous colitis. Methods: Seventy-five patients with symptomatic collagenous colitis and 334 healthy blood donors were genotyped for single nucleotide polymorphisms (SNPs) in MMP-1-1607, MMP-7-153, MMP-7-181, and MMP-9 exon 6 using TaqMan technology. Susceptibility to collagenous colitis was tested by comparison of the carrier status of the rare allele. Results: The carrier frequency of the allele GG of the coding SNP MMP-9 in exon 6 was 24 in patients with collagenous colitis and 14.3 in healthy blood donors (P = 0.039). The carriage of the allele GG significantly increased the risk for collagenous colitis with an odds ratio of 1.9 (95 confidence interval: 1.0-3.5). None of the other SNPs of MMP-1, MMP-7-153, and MMP-7-181 were associated with collagenous colitis. Conclusions: Allelic variation in the MMP-9 gene may be part of a complex genetic risk profile for collagenous colitis. Further studies are needed to confirm this observation and to explore the functional role of this gene polymorphism in collagenous colitis. (Inflamm Bowel Dis 2011;17:2295-2298)

he most common drug-induced colitis reported in the literature is onspecific colitis. Nonspecific colitis is characterized endoscopicaly by the presence of colonic mucosal edema, erythema, fragility, leeding, erosions, and ulcerations. Extreme cases include toxic egacolon and perforation. Histologically, there is no predominant ell type producing infiltration. Nonsteroidal anti-inflammatory drugs NSAIDs) are the most often associated with nonspecific colitis. Other rugs that have been linked to nonspecific colitis include chemotherpeutic agents, gold salts, antibiotics, corrosive agents, biological edications, and herbals (Table 1).

Matrix metalloproteinases play an important role in extracellular matrix remodelling. It has been proposed that matrix metalloproteinase-9 (MMP-9) is involved in epithelial damage in ulcerative colitis (UC). However, to our knowledge, no data are available in terms of MMP-9 expression in microscopic colitis. Determination of mucosal protein expression levels of MMP-9 in lymphocytic colitis (LC), collagenous colitis (CC) and UC. MMP-9 immunohistochemical expressions were analyzed in paraffin-embedded tissue samples by immunohistochemistry including patients with LC, CC, UC, active diverticulitis, inactive diverticular disease and healthy control subjects. UC was also subgrouped according to the severity of inflammation. Immunostaining was determined semiquantitatively. Independent colonic biopsies from healthy and severe UC cases were used for gene expression analyses. For further comparison MMP-9 serum antigen levels were also determined in patients with UC and control patients without macroscopic or microscopic changes during colonoscopy. MMP-9 mucosal expression was significantly higher in UC (26.7 ± 19.5%) compared to LC (6.6 ± 9.3%), CC (6.4 ± 7.6%), active diverticulitis (5.33 ± 2.4%), inactive diverticular disease (5.0 ± 2.2%) and controls (6.3 ± 2.6%) (P < 0.001). The immunohistochemical expression of MMP-9 in LC and CC was similar as compared to controls. MMP-9 expression was significantly higher in each inflammatory group of UC compared to controls (mild: 11.0 ± 2.8%, moderate: 23.9 ± 3.7%, severe UC: 52.6 ± 3.9% and 6.3 ± 2.6%, respectively, P < 0.005). The gene expression microarray data and RT-PCR results demonstrated a significantly higher expression of MMP-9 in severely active UC compared to healthy controls (P < 0.001). Significantly higher MMP-9 serum antigen concentrations were observed in UC patients compared with the control group (P < 0.05). MMP-9 seems to play no role in the inflammatory process of LC and CC. In contrast, the mucosal up-regulation of MMP-9 correlated with the severity of inflammation in UC. The increased MMP-9 expression could contribute to the severity of mucosal damage in active UC.

Background Microscopic colitis (MC), comprising lymphocytic and collagenous colitis (LC, CC), causes chronic diarrhoea. Lansoprazole can cause MC. Likelihood criteria defining the causative relationship between drugs and MC have not been applied to lansoprazole, nor has lansoprazole-related-MC been characterized. Aim To analyse a series of lansoprazole-related MC cases, and characterize lansoprazole-related CC and LC. Methods Cases were diagnosed over 23 months and causal relationship evaluated by established likelihood criteria. A systematic Medline search was conducted and publications analysed. Results Eight patients had lansoprazole-related MC. In all cases chronological and causality likelihood scores supported lansoprazole causative role. Discontinuation determined resolution without further treatment. Twenty-five cases of lansoprazole-related MC from 10 publications were grouped with the present series, and differences between CC and LC analysed. CC cases had more macroscopic alterations at colonoscopy (72.2 vs. 6.6%; p = 0.0002). Time between lansoprazole start and symptoms onset was longer for CC (median 60 vs. 28 days; p = 0.03). Conclusions Peculiar features of lansoprazole-related CC were described through the analysis of a newly diagnosed lansoprazole-related MC series in which the causative role of lansoprazole was for the first time defined by established likelihood criteria, and by pooled evaluation with other cases retrieved by a systematic literature review.

Objectives: The characteristic clinical symptoms of collagenous colitis are non-bloody diarrhoea, urgency and abdominal pain. Treatment is aimed at reducing the symptom burden and the disease impact on patients' health-related quality of life. The objective of this study was to analyse health-related quality of life in patients with collagenous colitis. Methods: In a cross-sectional, postal HRQL survey, 116 patients with collagenous colitis at four Swedish hospitals completed four health-related quality of life questionnaires, two disease-specific (Inflammatory Bowel Disease Questionnaire and Rating Form of IBD Patient Concerns), and two generic (Short Form 36, SF-36, and Psychological General Well-Being, PGWB), and a one-week symptom diary. Demographic and disease-related data were collected. Results for the collagenous colitis population were compared with a background population controlled for age and gender (n = 8931). Results: Compared with a Swedish background population, patients with collagenous colitis scored significantly worse in all Short Form 36 dimensions (p < 0.01), except physical function. Patients with active disease scored worse health-related quality of life than patients in remission. Co-existing disease had an impact on health-related quality of life measured with the generic measures. Lower education level and shorter disease duration were associated with decreased well-being. Conclusion: Health-related quality of life was impaired in patients with collagenous colitis compared with a background population. Disease activity is the most important factor associated with impairment of health-related quality of life. Patients in remission have a health-related quality of life similar to a background population. (C) 2010 Published by Elsevier Ltd on behalf of Editrice Gastroenterologica Italiana S.r.l.

The aim of this study was to assess the activity of eosinophils, neutrophils, and CD4+ as well as CD8+ T-cells in 11 patients with active collagenous colitis (CC) before and after 8 weeks of budesonide treatment (9 mg once daily) compared to 10 healthy individuals.Clinical symptoms were recorded and intestinal biopsy samples were taken and analyzed by flow cytometry. Eosinophils with a high surface expression of CD44 and low CD9 expression were classified as activated. Neutrophil activity was assessed by their expression of CD66b, and CD69 was used as an activation marker for T-cells.All patients responded to the treatment. The eosinophils in active CC showed increased activity compared to controls. The activity was back to control levels after treatment. Neutrophils were not activated in CC patients before or after treatment. CD8+ T-cells from untreated CC patients had a lower activity than controls, and a tendency of lower activity was observed on CD4+ T-cells. After treatment, the activity was increased on both types of T-cells and was not different from controls.In the present study we demonstrated that the inflammation in CC is characterized by activated eosinophils but there is no neutrophil activity. CD4+ and CD8+ T-cells are increased in numbers in active CC but, surprisingly, they had a lower grade of activity than in control subjects. The major finding of this study is that budesonide treatment restores the normal activation of eosinophils and T-cells, accompanied by clinical remission.

Background and aims: The endoscopic aspect of the colorectal mucosa in those patients with collagenous colitis is usually normal, or with non-specific changes. Until now it had never been related to a mucosal pattern of mosaic type. Our aim was to determine the diagnostic accuracy of the presence of mosaic pattern in the colorectal mucosa for collagenous colitis. Methods: Patients who had undergone a colonoscopy with random biopsies performed in the diagnostic evaluation of chronic diarrhea between 2004 and 2008 were studied. We defined patients with chronic diarrhea and mosaic mucosal pattern as “cases”, and patients with chronic diarrhea without mosaic pattern as “controls”. The odds ratio (OR) of finding a collagenous colitis in view of a mosaic pattern in colon was determined; as well as sensitivity and specificity; positive and negative likelihood ratios (LR+, LR− ), considering this finding as a diagnostic instrument for collagenous colitis. Results: 252 patients who had undergone colonoscopý with biopsy due to chronic diarrhea were analyzed. In 6 patients, a mosaic pattern was identified in the colorectal mucosa. The histological diagnose of 36 of the 252 patients (14%) was microscopic colitis, 27 of which (11%) had collagenous colitis. The colonoscopy was found normal in 21 of these 27 patients; in 2 patients, congestion or petechiae was found in the rectum; and in 4 patients (15%), all women, a mosaic pattern was found in the rectosigmoid mucosa. The OR of this finding was 19.4 (CI95% 3.9–95.4) for collagenous colitis. It had a sensitivity of 14.8% (CI95% 6.8–20), a specificity of 99.1% (CI95% 98.2–99.7), LR+ of 16.6 (CI95% 3.7–76.4), and LR− of 0.86 (CI95% 0.80–0.95) for a collagenous colitis. Conclusion: The mosaic pattern in the colorectal mucosa of patients studied due to chronic diarrhea could be a distinguishing feature of collagenous colitis. * Abbreviations : VCC : colonoscopy OR : odds ratio LR+ : positive likelihood ratios LR− : negative likelihood ratios CI : confidence intervals 95%

Introduction Collagenous colitis can be the cause of chronic diarrhoea. Aim Assess the prevalence of collagenous colitis in a single centre. Patients All records of patients with diarrhoea in whom histological examination showed collagenous colitis, were retrieved. Demographic data, clinical presentation, associated diseases and treatment were studied. Results In a period of 15 years 83 patients were identified with collagenous colitis. These were 16 men and 67 women, mean age 60 years (range 20–87) at time of diagnosis. Thirty four patients (38%) complained of mushy stools and 49 (62%) of watery diarrhoea. Eight patients had rectal bleeding. Mucous discharge was noted by 18 patients. There was no weight loss in 55 patients. Six patients complained of loss of appetite, 9 had nausea, and 2 complained of vomitus. A macroscopically normal colon was present in 63 patients. Associated diseases, like celiac disease and hypothyroidism, only were seen in women. Twenty eight patients did not receive any treatment, ten patients received mesalazine. One patient was treated with steroids. Fourteen patients were treated for accompanying bacterial overgrowth. Fourteen patients used loperamide. Budesonide was applied with success in 17 patients. During follow-up 58 patients had no complaints anymore, 21 had mild diarrhoea, 3 moderate, while it was unknown in one patient. Conclusion Collagenous colitis has a higher prevalence as usually reported. There is an association with auto-immune disorders and dysbacteriosis.

Collagenous gastritis (CG) characterized by the deposition of a subepithelial collagen band and accompanying inflammatory infiltrate is a rare disorder. The natural history and pathogenesis of CG remain unclear. We describe the histologic features (23 gastric, 18 duodenal, and 4 colonic biopsies) and clinical findings of an additional 12 cases. Histologic features including active or chronic inflammation, surface epithelial injury, intraepithelial lymphocytosis, intestinal metaplasia, and Helicobacter pylori, and measurement of thickness of subepithelial collagenous band were evaluated in gastric biopsies. The clinical features, endoscopic findings, and follow-up were obtained and correlated with histologic features. There was an even number of males (n=6) and females (n=6). Four patients were children/young adults, 3 of whom (75%) presented with anemia and gastric nodularity. Eight patients were adults, 6 of whom (75%) had an associated autoimmune disease (1 with Hashimoto thyroiditis and polymyositis) or other intestinal disease (3 with celiac sprue, 1 with collagenous colitis, 1 with collagenous sprue), in contrast to none in the 4 children/young adults, P=0.06. The range of subepithelial collagen thickness was 15 to 120 microm in CG. The collagenous layer showed surface epithelial injury and entrapped inflammatory cells. On presentation, the thickened collagen distribution in the antrum and body was variably patchy and diffuse. Four (33%) patients showed lymphocytic gastritis (3 within the same biopsy); one of these patients also had celiac sprue and another had collagenous sprue. Three (25%) patients had celiac sprue (2 had duodenal biopsy proven and 1 had a clinical diagnosis of celiac sprue). An additional patient had duodenal biopsies showing collagenous sprue. Four patients had follow-up biopsies during a 3 to 119-month period after the diagnosis of CG. CG persisted on the follow-up gastric biopsies in 3 (75%) of the 4 patients, and the other patient had lymphocytic gastritis, a finding not seen in previous biopsies. CG is a rare disorder with a distinct presentation and association in pediatric and adult patients. An absence of associated intestinal and autoimmune diseases characterizes the pediatric population. Association with lymphocytic gastritis, celiac or collagenous sprue, collagenous colitis, and autoimmune disorders are frequently seen in adult patients.

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 colitis is increasingly recognized as a common diarrheal disorder of inflammatory origin. Intestinal inflammation is generally associated with increased mucosal permeability, but little is known about barrier function in microscopic colitis. Our aim was to investigate the mucosal barrier to nonpathogenic bacteria in collagenous colitis.The study included 33 individuals, 25 with collagenous colitis (14 in clinical remission, 11 with active disease, and 8 of these again after 6 weeks budesonide treatment) and 8 control patients. Bowel movements were registered for 1 week. Endoscopic biopsies from the sigmoid colon were mounted in modified Ussing chambers and assessed for short-circuit current (I(sc)), transepithelial resistance (TER), and transmucosal passage of chemically killed Escherichia coli K12.Bacterial uptake was increased in patients in remission, 1.6 U (1.1-3.0) and in those with active disease, 4.6 U (2.5-5.8; median (IQR)), compared to controls, 0.7 U (0.1-1.1; P=0.004 and P-0.001, respectively). Active disease also had significant decrease in transepithelial resistance (TER) after 120 min, -9.7 Omega cm(2) ((-13)-(-4.3)), compared to controls, -5.2 Omega cm(2) ((-7.2)-(-3.1)), P-0.03; or patients in remission, -4.8 Omega cm(2) ((-8.0)-(-1.2)), P=0.04. Budesonide decreased median stool frequency to 1.9 (1.3-2.2) compared to 3.8 (3.7-4.2) before treatment (P=0.01), but bacterial uptake was still increased after budesonide 2.9 U (1.5-3.8), (P=0.006 compared to controls), and there were no significant changes in histology.Collagenous colitis presents with significantly increased uptake and altered mucosal reactivity to nonpathogenic bacteria. Budesonide induces clinical remission and restores mucosal reactivity but does not abolish the increased bacterial uptake. An underlying barrier dysfunction may explain the frequent and rapid relapses in CC.

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.

Background & Aims Oral budesonide effectively induces clinical remission in patients with collagenous colitis, a debilitating illness characterized by chronic watery/loose diarrhea, but there is a high rate of relapse after treatment cessation. Methods This randomized, double-blind, placebo-controlled, multicenter study evaluated the efficacy and safety of long-term therapy with oral budesonide (Entocort CIR capsules) for maintenance of clinical remission of collagenous colitis. Patients were aged >18 years with histologically proven collagenous colitis and >3 watery/loose stools per day on ≥4 of the prior 7 days. Open-label oral budesonide 9 mg/d was administered to all patients for 6 weeks. Patients in clinical remission (≤3 stools per day) at week 6 were subsequently randomized to double-blind oral treatment with budesonide 6 mg/d or matching placebo for 6 months. Relapse was defined as >3 stools per day on ≥4 consecutive days (and included patients withdrawn because of adverse events). Results Of 48 enrolled patients, 46 (96%) achieved clinical remission at week 6 and were randomized to maintenance budesonide or placebo. There were 21 relapses during maintenance therapy, and almost all occurred during the first 2 months. Budesonide therapy was associated with a significantly lower cumulative rate of relapse compared with placebo (6/23 [26%] and 15/23 [65%], respectively; P = .022), and high correlation between clinical remission and histologic improvement was observed. Budesonide was well tolerated with no serious adverse events. Conclusions Oral budesonide 6 mg/d is efficacious and well tolerated for long-term maintenance of clinical remission in patients with collagenous colitis.

Confocal laser endomicroscopy enables in vivo microscopy of the mucosal layer of the GI-tract with subcellular resolution during ongoing endoscopy. Endomicroscopy opens a new door for immediate tissue and vessel analysis. Different types of diseases can be diagnosed with optical surface and subsurface analysis. Analysis of the in vivo microarchitecture can be used for targeting biopsies to relevant areas. Furthermore, subsurface imaging can unmask microscopic diseases - (microscopic colitis) or bacterial infection (Helicobacter pylori), for example. Molecular imaging is becoming feasible, and this will shortly open the door to new indications in gastrointestinal endoscopy. This chapter reviews the currently rapidly expanding clinical data about endomicroscopy and gives a look into future research.

Objectives The rare complication of colonic perforation in collagenous colitis following colonoscopy or barium enema is reported in this series of 12 patients. Methods Patients with collagenous colitis complicated by perforation were collected from the authors' consultation files between 1992 and 2007. Colectomy and biopsy specimens were reviewed and the corresponding clinical data were analyzed. Results The patients ranged in age from 44 to 80 yr, with a female-to-male ratio of 11:1. Perforation occurred during colonoscopy in 2 patients, within 0-5 days following colonoscopy in 8 patients, and during barium enema in 2 patients. The most notable colonoscopic findings were bleeding linear ulcers of the right colon in 9 patients, several of which developed under direct visualization during endoscopy. The perforation culminated in right hemicolectomy in 11 patients. Linear fissuring ulcers were identified in the resections of 8 patients along with features of perforation, including pneumatosis in 4 patients and barium extravasation within the muscularis propria in 2 patients. Conclusions This is the largest published series to date, and the first to uncover several novel clinicopathologic features of perforation in collagenous colitis, including the right colonic predilection (corresponding to disease severity), the association with not only colonoscopy, but also barium enema, the occurrence of recognizable perforation actually developing during the procedure, and a more detailed information on the marked histologic severity of these patients' collagenous colitis. An awareness of this rare but potentially fatal complication of collagenous colitis may facilitate its diagnosis and management.

In this study, we evaluated immunohistochemically whether increased thickness of the colon subepithelial collagen layer in diabetic patients relates to collagenous colitis. A total of 100 patients (25 in each group) were included in this study. There were diabetic patients with chronic diarrhea in the first group, diabetic patients without chronic diarrhea in the second group, non-diabetic patients with chronic diarrhea in the third group, and control patients in the fourth group. The endoscopic biopsy specimens were obtained from the rectum, sigmoid colon, and descending colon. The thickness of the subepithelial collagen layer was measured using the ocular micrometer method. The immunohistochemical staining was performed with type 1 collagen and fibronectin antibody. The thickness of the colon subepithelial collagen layer in diabetic patients with or without diarrhea was significantly greater than that in control patients. This thickened subepithelial collagen layer in diabetic patients was stained with fibronectin antibody, but not with type 1 collagen antibody in the immunohistochemical study. These immunohistochemical staining characteristics were not similar to those in collagenous colitis, but were similar to those in normal subjects. Increased colon subepithelial collagen layer thickness in diabetic patients does not relate to collagenous colitis.

Background Common variable immunodeficiency (CVID) is characterized by a host of gastrointestinal (GI) lesions that can mimic other conditions. Methods We reviewed clinical documentation and samples from 132 separate GI biopsy or resection sites on 20 CVID patients obtained over a 26-year period, including biopsies from the colon (34), esophagus (19), small intestine (38), and stomach (35), a partial gastrectomy, small bowel resection, colectomy, 2 cholecystectomies, and 1 appendectomy. Results There were 13 males and 7 females. Nine patients were children (10 y and younger) and 11 were adults. Age at diagnosis ranged from 6 months to 62 years (median, 35.5 y), and age at biopsy ranged from 10 months to 67 years (median, 38 y). Esophageal samples often showed intraepithelial neutrophils, accompanied by candida. Half of patients' esophageal biopsies had prominent intraepithelial lymphocytosis, one of which also had prominent apoptosis. The stomachs of 67% of patients lacked plasma cells. Most showed lymphoid aggregates. An increase in apoptosis was detected in biopsies from a third. About 20% had a lymphocytic gastritis pattern. Intraepithelial neutrophils were found in a subset, accompanied by various infections [cytomegalovirus (CMV), Helicobacter pylori, and Cryptosporidium]. Granulomas were found in 1 patient. Gastric adenocarcinoma was identified in one patient. There was a paucity of small bowel plasma cells in the majority of patients (68%). The small bowel showed prominent lymphoid aggregates in about half (47%). An increase in apoptosis was detected in specimens from about 20%. Increased intraepithelial lymphocytes (IELs) were found in samples from over half of patients (63%), most of whom (83%) also had villous blunting, mimicking celiac disease. Intraepithelial neutrophils were found in a subset (32%) and correlated with CMV and Cryptosporidium infections. Granulomas were seen in biopsies from 2 patients (11%). One patient had a collagenous enteritis pattern (accompanied by a collagenous colitis pattern). One patient had autoimmune enteritis; biopsies from this patient were initially relatively normal but later displayed prominent crypt apoptosis and loss of goblet cells. In colon samples, a paucity of plasma cells was seen in 10 patients (63%). The colon showed lymphoid aggregates in most patients (81%). Apoptosis was prominent in samples from half of the patients (50%). Biopsies from 6 patients had a lymphocytic colitis pattern (38%) and 2 patients had a collagenous colitis pattern. Intraepithelial neutrophils were found in samples from most patients (88%). Crypt distortion was seen in 6 of these patients (43%), thereby mimicking ulcerative or Crohn colitis. Granulomas were found in 3 patients (19%). CMV was detected in 1 patient. The appendix from 1 patient showed Cryptosporidium and acute serositis with a paucity of plasma cells and an increase in apoptosis. The gallbladder from 1 patient showed acute cholecystitis, and another patient's gallbladder lacked plasma cells. Conclusions GI tract CVID displays a wide spectrum of histologic patterns. Its features can mimic lymphocytic colitis, collagenous enterocolitis, celiac disease, lymphocytic gastritis, granulomatous disease, acute graft-versus-host disease, and inflammatory bowel disease. In fact, in our series, we found patients with a prior diagnosis of celiac disease (25%) and inflammatory bowel disease (35%), including Crohn disease (15%). The diagnosis of CVID may be suspected on the basis of the lack of plasma cells in a GI biopsy, but because this feature is only present in about two-thirds of patients, the diagnosis cannot always be suggested in isolation of other clinical and laboratory findings.

The objective of this study was to investigate the effect of Boswellia serrata extract (BSE) on symptoms, quality of life, and histology in patients with collagenous colitis. Patients with chronic diarrhea and histologically proven collagenous colitis were randomized to receive either oral BSE 400 mg three times daily for 6 weeks or placebo. Complete colonoscopy and histology were performed before and after treatment. Clinical symptoms and quality of life were assessed by standardized questionnaires and SF-36. The primary endpoint was the percentage of patients with clinical remission after 6 weeks (stool frequency ≤3 soft /solid stools per day on average during the last week). Patients of the placebo group with persistent diarrhea received open-label BSE therapy for a further 6 weeks. Thirty-one patients were randomized; 26 patients were available for per-protocol-analysis. After 6 weeks, the proportion of patients in clinical remission was higher in the BSE group than in the placebo group (per protocol 63.6%; 95%CI, 30.8–89.1 vs 26.7%, 95%CI, 7.7–55.1; p = 0.04; intention-to-treat 43.8% vs 26.7%, p = 0.25). Compared to placebo, BSE treatment had no effect on histology and quality of life. Five patients discontinued BSE treatment prematurely. Discontinuation was due to adverse events (n = 1), unwillingness to continue (n = 3), or loss to follow-up for unknown reasons (n = 1). Seven patients received open-label BSE therapy, five of whom achieved complete remission. Our study suggests that BSE might be clinically effective in patients with collagenous colitis. Larger trials are clearly necessary to establish the clinical efficacy of BSE.

Collagenous colitis is an inflammatory mucosal disorder of the colon with distinctive histopathological features, including a thickened subepithelial collagen layer. The clinical course is usually benign, but serious complications, including death, may occur. In the present report, a 69-year-old woman with watery diarrhea and collagenous colitis developed bloody diarrhea that was refractory to treatment medications, including corticosteroids and azathioprine. Endoscopic and histopathological studies showed a focal neutrophilic inflammatory process that progressed to a diffuse and extensive form of colitis, eventually requiring total proctocolectomy. Careful histological review of the resected colon showed no evidence of persistent collagenous colitis. These findings suggest an important need for continued long-term follow-up of patients with collagenous colitis because superimposed and serious colonic complications may occur, including a severe and extensive pancolitis refractory to medications and necessitating total proctocolectomy.

Summary Background Microscopic colitis shares certain common clinical manifestations with functional bowel disorders, especially diarrhoea-dominant irritable bowel syndrome (IBS) and functional diarrhoea. However, the exact relationship between microscopic colitis and functional bowel disorders has not been systematically assessed. Aim To conduct a systematic review and meta-analysis on the diagnostic overlap between functional bowel disorders and microscopic colitis. Methods We searched MEDLINE, EMBASE and SCOPUS databases, as well as the abstract books of the major gastroenterology meetings, to investigate the prevalence of microscopic colitis among patients with functional bowel disorders (considering all subtypes of both disorders) and vice versa. Data were pooled with a random-effects model. Results Of 227 references identified, data were collected from 26 studies and a total of 5,099 adult patients. The pooled prevalence any type of functional bowel disorders in patients who present diagnostic criteria of microscopic colitis was 39.1% (95% CI: 22.8–56.6%; I2: 97%) and was higher for lymphocytic colitis than for collagenous colitis (40.7% vs. 28.4%, respectively; P = 0.58). The prevalence of microscopic colitis in functional bowel disorders patients was 7% (95% CI: 3.6–11.4%), reaching 9.8% (95% CI: 4.4–17.1%; I2: 95%) in patients exhibiting diarrhoea-dominant IBS, nonsignificantly higher than microscopic colitis rates among patients with constipation-dominant IBS (1.3%) or mixed-dominant IBS (1.9%). Conclusions There is a significant overlap of symptoms between microscopic colitis and functional bowel disorders, especially in diarrhoeal subtypes. The high proportion of microscopic colitis among diarrhoea-dominant functional syndromes should serve as a call for more active diagnosis in selected patients.

Background: The relationship between clinical and histological parameters in collagenous colitis (CC) is poorly understood. Smoking is a risk factor for CC, whereas its impact on clinical activity and outcome is not well known. Methods: In a post hoc analysis of pooled data from two randomized controlled trials we assessed the association between demographic data (gender, age, smoking habits, family history of inflammatory bowel disease), clinical variables (duration of symptoms, mean number of stools/watery stools per day, abdominal pain, clinical remission) and histological data (thickness of the collagen band, inflammation of the lamina propria, total numbers of intraepithelial lymphocytes, degeneration). Moreover, we analysed the predictive value of baseline parameters for clinical outcome in a logistic regression model. Results: Pooled data were available from 202 patients with active CC, of whom 36% were current smokers, 29% former smokers and 35% non-smokers. Smoking status was associated with decreased ability to achieve clinical remission (current smokers vs non-smokers: odds ratio [OR] 0.31, 95% confidence interval [CI] 0.10–0.98, p = 0.045; former smokers vs non-smokers: OR 0.19, 95% CI 0.05–0.73, p = 0.016). Current smokers had an increased mean number of watery stools at baseline compared with non-smokers ( p = 0.051) and increased mean number of watery stools per se was associated with decreased likelihood of obtaining clinical remission (OR 0.63, 95% CI 0.47–0.86, p = 0.003). Patient characteristics and histology at baseline had no association with clinical parameters and no predictive value for clinical outcome. Conclusion: Smoking worsens clinical symptoms in CC and is associated with an increased number of watery stools and decreased likelihood of achieving clinical remission. There is no significant association between histology and clinical data.

ObjectiveCollagenous colitis (CC) is a major cause of chronic non-bloody diarrhoea, particularly in the elderly female population. The aetiology of CC is unknown, and still poor is the understanding of its pathogenesis. This possibly involves dysregulated inflammation and immune-mediated reactions in genetically predisposed individuals, but the contribution of genetic factors to CC is underinvestigated. We systematically tested immune-related genes known to impact the risk of several autoimmune diseases for their potential CC-predisposing role.DesignThree independent cohorts of histologically confirmed CC cases (N=314) and controls (N=4299) from Sweden and Germany were included in a 2-step association analysis. Immunochip and targeted single nucleotide polymorphism (SNP) genotype data were produced, respectively, for discovery and replication purposes. Classical human leucocyte antigen (HLA) variants at 2-digit and 4-digit resolution were obtained via imputation from single marker genotypes. SNPs and HLA variants passing quality control filters were tested for association with CC with logistic regression adjusting for age, sex and country of origin.ResultsForty-two markers gave rise to genome-wide significant association signals, all contained within the HLA region on chromosome 6 (best p=4.2×10−10for SNP rs4143332). Among the HLA variants, most pronounced risk effects were observed for 8.1 haplotype alleles including DQ2.5, which was targeted and confirmed in the replication data set (p=2.3×10−11; OR=2.06; 95% CI (1.67 to 2.55) in the combined analysis).ConclusionsHLA genotype associates with CC, thus implicating HLA-related immune mechanisms in its pathogenesis.

OBJECTIVE: Microscopic colitis (MC) includes two main types: collagenous colitis (CC) and lymphocytic colitis (LC). Previous studies have indicated an increasing incidence, but these have mainly been based on regional databases. We found it important to study the epidemiology based on a comprehensive nationwide cohort.MATERIAL AND METHODS: We studied the epidemiological data of MC in Denmark from 2002 to 2011. The cohort consisted of all patients with a recorded diagnosis of either CC or LC in the Danish Pathology Register during the study period. Data on all patients with a registered colon biopsy were also included.RESULTS: A total of 7777 patients, 4749 (61%) with CC and 3028 (39%) with LC, were identified. Over the study period, the annual incidence of diagnosed cases of CC increased from 2.9/10(5) to 14.9/10(5) and of LC from 1.7/10(5) to 9.8/10(5). In 2011, the incidence of MC was 24.7/10(5) inhabitants. The age-specific incidence showed that the risk of both CC and LC increased with age. The female/male ratio, distribution of the type of colitis and mean age at diagnosis were relatively stable during the study period. The annual number of registered colon biopsies in the pathology register increased from 21.583 in 2002 to 39.733 in 2011, indicating an increased diagnostic activity.CONCLUSION: In a nationwide cohort study, the incidence of CC and LC continued to increase from 2002 to 2011. An increased diagnostic activity could in part explain the increase in the number of diagnosed cases.

BACKGROUND: Collagenous colitis (CC) and lymphocytic colitis (LC) are chronic inflammatory disorders of the colon. There is a paucity of data on differences in etiology, natural history, and treatment response between CC and LC. METHODS: Between 2002 and 2013, we identified new diagnoses of CC and LC using the Research Patient Data Registry in a tertiary referral center. We used chi square or Fischer's exact test and Wilcoxon rank-sum tests to compare the differences in clinical characteristics, treatment types, and response rates between LC and CC. RESULTS: Through 2013, we confirmed 131 patients with a new diagnosis of microscopic colitis (MC) (55 LC, 76 CC). Compared to cases of LC, patients with a diagnosis of CC were more likely to be women (86% vs. 69%, p = 0.03), have elevated erythrocyte sedimentation rate (mean 28 vs. 13 mm/h, p = 0.04), and less likely to be diabetic (5% vs. 18%, p = 0.02). Budesonide was the most effective treatment for both CC and LC (94% and 80%, respectively). However, there were no statistically significant differences in response to various treatments according to the type of MC (all p > 0.10). Older age at the time of diagnosis was associated with better response to bismuth subsalicylate (odds ratio: 1.76; 95% confidence interval: 1.21-2.56 for every 5-year increase) for both CC and LC. CONCLUSION: Despite differences in the clinical characteristics, response rates to available treatments appeared to be similar in both LC and CC. Older patients may have a better response to bismuth subsalicylate therapy.

Aim The aim of this study was to evaluate the long-term outcome of patients with collagenous colitis 10 years after the diagnosis. Patients and methods In 1989/1990, 65 patients were diagnosed to have collagenous colitis. Initially and after an interval of ten years these patients were asked to complete a questionnaire including onset and duration of diarrhea, stool frequency and consistency, other gastrointestinal symptoms including weight loss, drug history, treatment response and concomitant diseases. Results Questionnaires from 47 patients (72.3 %) (female 40; mean age 68 years, range 41 - 95 years) were available for analysis. After a follow-up of ten years, 11 patients (23.4 %) had persistent diarrhea with no change of frequency and consistency compared to baseline. Four patients (8.5 %) showed a reduction of diarrhea frequency of at least 50 %. Diarrhea was resolved in 23 patients (48.9 %) during the follow-up period. Of those, 20 patients received anti-inflammatory treatment. After a complete resolution of diarrhea during the long-term follow-up, 9 patients (19.2 %) showed recurrence of diarrheal symptoms. None of the patients developed any malignancies of the GI-tract. Conclusion The long-term outcome of CC is benign with a resolution of diarrhea in up to 50 % of patients receiving anti-inflammatory treatment. About 30 % of patients may experience persistent diarrhea even 10 years after diagnosis. Our data confirm that CC is a chronic disorder with a variable course of symptoms during a long-term follow-up.

Collagenous colitis is characterised by watery diarrhoea, normal colonic mucosa on endoscopy, diffuse colitis with surface epithelial injury, and a distinctive thickening of the subepithelial collagen table on histology. Some patients can develop medically refractory collagenous colitis, in which case they may require surgical intervention. This is the first report of collagenous pouchitis in a collagenous colitis patient with proctocolectomy and ileal pouch-anal anastomosis. A patient with medically refractory collagenous colitis who underwent a total proctocolectomy and ileal pouch-anal anastomosis was sequentially evaluated with an endoscopy and histology of the colon, distal small intestine, and ileal pouch. A 58-year-old female had a 10-year history of collagenous colitis before having a total proctocolectomy and ileal pouch-anal anastomosis for medically refractory disease. The histologic features of collagenous colitis were present in all colon and rectum biopsy or resection specimens, but were absent in the distal ileum specimen. The post-operative course was complicated by persistent increase of stool frequency, abdominal cramps, and incontinence. A pouch endoscopy was performed 3 years after ileal pouch-anal anastomosis which showed the histologic features of collagenous colitis in the ileal pouch, collagenous pouchitis, while the pre-pouch neo-terminal ileum had no pathologic changes. After antibiotic therapy, the histologic changes of collagenous pouchitis resolved. This is the first reported case of collagenous pouchitis. Since the abnormal collagen table and its associated features were only present in the pouch and absent in the neo-terminal ileum, and the patient had histologic improvement after antibiotic therapy, it would suggest that faecal stasis and bacterial load may play a role in the pathogenesis.

Background: Microscopic colitis (MC) is an inflammatory disorder of unknown aetiology. Aim: To characterise the mucosal cytokine profile of MC, with a view to understanding its potential pathogenic mechanisms. Methods: Cytokine profiles of mucosal biopse specimens taken at flexible sigmoidoscopy from 18 patients (8 with lymphocytic colitis and 10 with collagenous colitis) were analysed using real-time reverse transcriptase-PCR, in comparison with those from 13 aged-matched controls with diarrhoea-predominant irritable bowel syndrome. Biopsy specimens from six patients with histologically documented remission were available for comparative analysis. Biopsy specimens were also taken to determine the cellular expression of cytokine and cytokine-related proteins using immunohistochemistry. Results: Mucosal mRNA levels were 100 times greater for interferon (IFN)γ and interleukin (IL) 15, 60 times greater for tumour necrosis factor α, and 35 times greater for inducible nitric oxide synthase in MC compared with controls. Apart from a trend for increased levels of IL10, levels of other T helper cell type 2 (TH2) cytokines including IL2 and IL4 were too low to be accurately quantified. Mucosal IFNγ mRNA levels correlated with the degree of diarrhoea, and returned to normal in remission. The immunohistochemical expression of cell junction proteins E-cadherin and ZO-1 was reduced in active disease. No differences were noted between lymphocytic and collagenous colitis for any of the above parameters. Conclusions: MC demonstrates a TH1 mucosal cytokine profile with IFNγ as the predominantly upregulated cytokine, with concurrent induction of nitric oxide synthase and down regulation of IFNγ-related cell junction proteins. This pattern is similar to that in coeliac disease and suggests that it might represent a response to a luminal antigen.

Objective: The etiology of microscopic colitis is unclear; an autoimmune response and pharmacological induction have been proposed as possible mechanisms. We conducted a multicentre cross-sectional study to compare the antibody profiles of patients with collagenous and lymphocytic colitis with those of a control group. Methods: The medical histories and antibody profiles of 26 patients with collagenous and 16 patients with lymphocytic colitis were compared with the corresponding data of 43 controls without gastroenterological disease. Antibodies to the following structures were determined: intestinal goblet cells, antinuclear antibodies (ANA), antineutrophil cytoplasmic antibodies, anti-Saccharomyces cerevisiae antibody (ASCA), tissue transglutaminase, gliadin, pancreatic acini, glutamate decarboxylase, tyrosine phosphatase IA-2 and thyroid (microsomal anitbodies, MAB). Results: Patients with collagenous and lymphocytic colitis had been treated significantly more often with H2-receptor antagonists and non-steroidal anti-inflammatory drugs (P = 0.026 and 0.014, respectively). Additional diseases of presumed autoimmune etiology were present in 43% (18/42) of patients. Comparison with the controls showed significantly more positive findings for ANA immunoglobulin G (IgG), gliadin immunoglobulin A (IgA) and ASCA (IgA and IgG) in patients with collagenous colitis but not in those with lymphocytic colitis. Collagenous colitis was associated with positive ASCA in 15% of patients and lymphocytic colitis in 13%. Conclusions: The autoantibodies investigated are of no diagnostic relevance to microscopic colitis. Positive ANA and strong associations with other autoimmune diseases point to an autoimmune etiology. H2-receptor antagonists and non-steroidal anti-inflammatory drugs might also be of pathogenetic significance.

A typical symptom of microscopic colitis (MC) is chronic watery diarrhea with normal endoscopic findings and characteristic inflammatory changes in histopathology. Treatment of the disease is mainly empiric. MC has two main subtypes: lymphocytic colitis and collagenous colitis. There are also untypical histopathological forms of MC: MC with giant cells, MC not otherwise specified (NOS) and cryptal lymphocytic coloproctitis. Some other histopathological changes in MC have been observed, especially Paneth cell hyperplasia or epithelial degeneration. Eosinophilic colitis, acute colitis, amyloidosis, ulcerative colitis and Crohn's disease should be taken into consideration in differential diagnosis. The most reliable biopsy material for histopathological examination are samples obtained from transverse colon. Some studies proved that treatment of MC makes it possible to reduce not only clinical, but also histopathological, manifestations.

Matrix metalloproteinases (MMPs) and their endogenous inhibitors, tissue inhibitors of MMPs (TIMPs), are produced in the gastrointestinal tract by several structural cells. The balance between MMPs and TIMPs is essential for many physiological processes in the gut. However, imbalance between MMPs and TIMPs plays an important role in the pathophysiology of diverse intestinal inflammatory conditions. We reviewed the role of the MMP/TIMP system in the pathogenesis of intestinal inflammatory diseases and pharmacologic perspectives for the use of compounds that restore the MMP/TIMP balance.

Lymphocytic colitis (LC) and collagenous colitis (CC), both known as microscopic colitis (MC), are uncommon entities with increasing incidence as more clinicians take biopsies from macroscopically normal colons and as pathologists use more rigorous diagnostic criteria to be confident of the diagnosis. Information on the incidence of this type of colitis is limited and based on reported cases. The purpose of this work is to estimate the incidence of LC and CC in reviewed routine colonoscopies. We reviewed 2815 colonoscopies performed at a tertiary referral center with an open-access service using restricted histological criteria in order to establish the frequency rate of LC and CC in routine colonoscopic biopsy material. Cases suspicious for MC were stained with Masson's trichrome or Congo red stain and immunohistochemically for lymphocytes, where appropriate. Review of routine colonoscopic biopsies showed that MC is underreported in our colonoscopic material. Incidence rates of LC and CC (0.9 and 0.4, respectively) were based on morphological assessment of colonoscopic biopsies using stringent criteria together with clinical data and after differentiation with other lesions which can mimic MC. The 10.2% rate of this type of colitis in patients with chronic watery diarrhea indicates the necessity to consider these lesions in older individuals with diarrhea and normal endoscopical colonic mucosa.

Collagenous colitis (CC) is a chronic inflammatory bowel disease that affects the colon. However, some patients with CC present with accompanying pathologic small-bowel manifestations such as coeliac disease, defects in bile acid absorption and histopathologic changes in small-intestinal biopsies, indicating that CC is a pan-intestinal disease. In small-intestinal disease, the intestinal barrier function may be impaired, and the permeability of the small intestine altered. The purpose of this research was to study small-bowel function in patients with CC as expressed by intestinal permeability.Ten patients with CC and chronic diarrhoea participated in the study. Coeliac disease was excluded by small-bowel biopsy and/or serology. Intestinal permeability was assessed as urinary excretion (ratios) 2, 4 and 6 h after ingestion of 14C-labelled mannitol (14C-mannitol) and 99mTc-labelled diethylenetriamine-pentaacetic acid (99mTc-DTPA). Data were compared with the results from healthy controls.No difference was found between groups in urinary excretion of 14C-mannitol and 99mTc-DTPA after 2, 4 or 6 h, respectively. Likewise, no significant differences in the 99mTc-DTPA/14C-mannitol ratios between patients and controls were detected after 2 h: 0.030 (0.008-0.130) versus 0.020 (0.007-0.030), p = 0.19, after 4 h: 0.040 (0.009-0.180) versus 0.020 (0.008-0.040), p = 0.14 or after 6 h: 0.040 (0.012-0.180) versus 0.020 (0.010-0.040), p = 0.17.No alterations in intestinal permeability in patients with CC could be demonstrated. Impairment of the integrity of the mucosa of the small bowel and the presence of a general dysfunction of the small intestine in patients with CC seem unlikely.

Lymphocytic colitis and collagenous colitis represent two conditions that fall under the category of microscopic abnormalities within the lamina propria of the colon. Patients are predominantly women in the sixth decade of life who present with non-bloody watery diarrhea. Few other symptoms exist. Diagnosis is based upon finding characteristic abnormalities in the colonic mucosa, more likely to be found on the right side of the colon than the left. Treatment is symptomatic, although some newer therapies suggest regression of the lesion. Other autoimmune associations have been described, including celiac disease, and appropriate work-up for this condition should be considered for the patient who has seemingly refractory colitis. The natural history is benign, and most patients experience resolution of their symptoms.

Collagenous and lymphocytic colitis have been recognized as chronic intestinal inflammatory disorders causing watery diarrhea, which have been recognized in the past three to two decades, respectively. Collagenous colitis is primarily a disorder of middle-aged women and is characterized on biopsy by increased subepithelial collagen as well as increased inflammatory cells in the lamina propria and increased intraepithelial lymphocytes. Key to the correct diagnosis in this condition is recognizing that there are two words in this diagnostic entity, and colitis is, by definition, present. Focusing solely on the collagen band can result in both over- and underdiagnosis. Newer therapeutic options are available in this condition, and patients are now frequently being treated either with budesonide or with high dose bismuth preparations. Whereas collagenous colitis is a tightly coherent clinical pathologic entity, lymphocytic colitis has a more varied clinical picture. Lymphocytic colitis is also seen in middle-aged patients but has a more equal female-to-male ratio. Lymphocytic colitis is defined by increased intraepithelial lymphocytes, with the median being 30 lymphocytes per 100 epithelial cells. There are also an increase in inflammatory cells in the lamina propria, but the increase may be milder than in collagenous colitis and there are usually minimal eosinophils. Although numerous studies have described lymphocytic colitis causing a chronic diarrhea, more recent studies suggest that patients may have a single attack in approximately 60% of cases. Although most cases of lymphocytic colitis are idiopathic, there is a clear association with multiple drugs, celiac disease, and there may be an infectious trigger. Approximately 10% of lymphocytic colitis patients have a positive family history of some type of inflammatory intestinal disease, including ulcerative colitis, Crohn's disease, collagenous colitis, and celiac disease. Therapy in lymphocytic colitis is less well studied, but the same medications are used with success, including budesonide and high dose bismuth.