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Diagnostic difficulties in inflammatory bowel disease pathology.

This review summarizes some of the common diagnostic problems encountered by pathologists when evaluating patients with chronic colitis and in whom inflammatory bowel disease (IBD) is either suspected or within the differential diagnosis. Both ulcerative colitis (UC) and Crohn's disease (CD) show characteristic, but non-specific, pathological features that may overlap and result in a diagnosis of 'indeterminate colitis' (IC). However, other reasons why pathologists may entertain a diagnosis of IC include failure to recognize or accept certain 'hardcore' histological features as indicative of CD, an attempt to classify cases of chronic colitis based on mucosal biopsy material or in the absence of adequate clinical and radiographic information, and the presence of other disease processes that mask, or mimic, IBD. In addition, some cases of UC may show unusual CD-like features, such as discontinuous or patchy disease, ileal inflammation, extracolonic inflammation, granulomatous inflammation in response to ruptured crypts, aphthous ulcers, or transmural inflammation. Furthermore, other forms of colitis, such as microscopic colitis, diverticulitis and diversion colitis may, on occasion, also show IBD-like changes. The clinical and pathological features that aid in the distinction between these entities, and others, are covered in detail in this review.

Colitis, Ulcerative↗

[Endoscopy in inflammatory bowel disease].

Fiberoptic endoscopy is well established, safe and accurate for diagnosis and management of inflammatory bowel disease (IBD). Direct visualization of the mucosa and biopsy of suspected abnormalities are possible. The principal applications of endoscopy in IBD include discrimination of Crohn's disease from ulcerative colitis of o other inflammatory conditions (acute infectious colitis, chronic infections, microscopic colitis, ischemic/radiation colitis, colitis induced by NSAID), delineation of the sites of disease or extent, grading of endoscopic disease severity, and confirmation of complications such as stricture, fistula or mass. Finally, diagnosis of pouchitis, surveillance to detect precancer, or therapeutic interventions such as dilatation of strictures of electrocautery of bleeding sites are also important endoscopic applications.

Diagnosis, Differential↗

Collagenous colitis as a cause of chronic diarrhea.

Collagenous colitis should be considered in the differential diagnosis of chronic diarrheal syndromes. Colonoscopy or sigmoidoscopy in such patients should include biopsy of the mucosa proximal to the rectum, even though the mucosa appears grossly normal. Some patients have associated autoimmune disease, but the etiology of collagenous colitis is unclear. Microscopic colitis has been observed to precede collagenous colitis in some patients. Treatment with antimotility agents, sulfasalazine, oral 5-ASA compounds or corticosteroids may be effective in reducing symptoms.

Aged↗

Lymphocytic colitis. A definable clinical and histological diagnosis.

We reviewed colorectal biopsies and clinical records from 36 patients with chronic watery diarrhea who had been diagnosed as having microscopic colitis and compared their histologic features with the more detailed and precise criteria for lymphocytic colitis. Published pathologic criteria for lymphocytic colitis were applied to the biopsies and compared. Focal or diffuse nature of the lymphoid infiltrate were noted separately. The focal lymphoid infiltrate was related to lymphoid aggregates in the lamina propria of the mucosa. Eighteen cases had focal lymphoid cell infiltration, and 16 of them had associated diverticula, polyps, or both. Eighteen cases had diffuse lymphoid cell infiltration, and six of them had diverticula or polyps. Results indicate that focal cellular infiltration strongly predicts associated diverticula or polyps. The group with no diverticula or polyps most closely conformed to histologic criteria for lymphocytic colitis (Kruskal-Wallis P < 0.02). We conclude that lymphocytic colitis comprises a well-defined group of cases within the large and less-defined group of microscopic colitis.

Adult↗

Ulcerative colitis: electron microscopic studies with special reference to development of crypt abscesses.

Electron microscopy of the colonic mucosa was performed in 33 patients with acute ulcerative colitis. The process of the development of crypt abscesses was studied. Inflammatory cells migrated intercellularly from the lamina propria and did not destruct the neighboring epithelial cells. Abnormal maturation of the epithelial cells was observed. Loose connection and separation of immature epithelial cells may promote migration of inflammatory cells.

Abscess↗

Are collagenous colitis and lymphocytic colitis distinct syndromes?

The term microscopic colitis has largely evolved to be an umbrella term which includes the histopathological entities of lymphocytic colitis and collagenous colitis. The purpose of this review is to compare these two syndromes. Lymphocytic colitis and collagenous colitis are characterized by chronic watery diarrhea, normal radiographic and endoscopic findings, and abnormal colonic mucosa on biopsy with lymphocytic infiltration of the lamina propria but minimal crypt distortion. Collagenous colitis is further characterized by a thickened subepithelial collagen band. Lymphocytic colitis has an equal sex distribution, while collagenous colitis has a marked female predominance. Histocompatibility phenotypes are also dissimilar. These findings suggest that lymphocytic colitis and collagenous colitis may be related but distinct syndromes.

Colitis↗

Multiple displacement amplification of DNA from human colon and rectum biopsies: bacterial profiling and identification of Helicobacter pylori-DNA by means of 16S rDNA-based TTGE and pyrosequencing analysis.

Amplifying bacterial DNA by PCR from human biopsy specimens has sometimes proved to be difficult, mainly due to the low amount of bacterial DNA present. Therefore, nested or semi-nested 16S rDNA PCR amplification has been the method of choice. In this study, we evaluate the potential use of whole genome amplification of total DNA isolated from human colon and rectum biopsy specimens, followed by 16S rDNA PCR amplification of multiple displacement amplified (MDA)-DNA. Subsequently, a H. pylori-specific 16S rDNA variable V3 region PCR assay was applied directly on MDA-DNA and, combined with pyrosequencing analysis; the presence of H. pylori in some biopsies from colon in patients with microscopic colitis was confirmed. Furthermore, temporal temperature gradient gel electrophoresis (TTGE) of 16S rDNA amplicons using primers flanking variable regions V3, V4, and V9, was used to establish bacterial profiles from individual biopsies. A variation of the bacterial profiles in the colonic mucosa in microscopic colitis and in normal rectal mucosa was observed. In conclusion we find the MDA technique to be a useful method to overcome the problem of insufficient bacterial DNA in human biopsy specimens.

Base Sequence↗

[Lymphocytic colitis and Gougerot-Sjögren syndrome. Report of two cases].

INTRODUCTION: Microscopic colitis describes a subset of patients with chronic watery diarrhea of unknown origin, and normal endoscopic findings and microscopic evidence of an inflammatory infiltrate in the colonic mucosa. We report two cases associated with sicca syndrome. EXEGESIS: A 56-year-old woman and a 76-year-old man presented with a history of lymphocytic colitis associated with sicca syndrome. Drugs or infectious agents were not implicated in the cause of lymphocytic colitis, suggesting that sicca syndrome may be involved in the pathogenesis of microscopic colitis. CONCLUSION: These cases suggest that sicca syndrome should be detected in patients with lymphocytic colitis.

Aged↗

Colonoscopy and SeHCAT for investigation of chronic diarrhea.

BACKGROUND/AIMS: Chronic diarrhea is a common problem. Colonoscopy is the investigation of choice for diagnosis. Even a macroscopically normal mucosa on endoscopy can have abnormalities such as microscopic colitis and bile acid malabsorption (BAM). The aim of this study was to establish the value of colonoscopy with biopsies in patients with chronic diarrhea and to evaluate the additive value of a SeHCAT test for diagnosing BAM in these patients. METHODS: All patients who underwent a colonoscopy between November 1999 and December 2000 were included. Patient files, colonoscopy and pathology reports and SeHCAT test results were reviewed. RESULTS: 205 patients were included. The most common diagnoses were diarrhea-predominant IBS (n = 76) and IBD (n = 38). 158 patients had non-bloody diarrhea, 113 (72%) of them had a macroscopically normal appearing mucosa. In 40 (35%) of these patients, a histological diagnosis could be made and microscopic colitis was the most common diagnosis (n = 27). SeHCAT test was performed in 36 patients and 15 (42%) of them had BAM. In the 47 patients with bloody diarrhea, IBD was the main diagnosis (n = 23). CONCLUSION: Colonoscopy with biopsies must be performed when investigating chronic diarrhea and BAM should be excluded.

Bile Acids and Salts↗

Colonic biopsy practice for evaluation of diarrhea in patients with normal endoscopic findings: results from a national endoscopic database.

BACKGROUND: The colonic biopsy is the only reliable method for identification of microscopic colitis in patients with chronic diarrhea and normal endoscopic findings. METHODS: The Clinical Outcomes Research Initiative national endoscopic database was analyzed to determine the rate at which colonic biopsy specimens were obtained in patients undergoing colonoscopy for the evaluation of diarrhea with no visible mucosal abnormality. RESULTS: Between January 2000 and December 2003, 5565 unique adult patients underwent colonoscopy for evaluation of diarrhea without detection of any mucosal abnormality. Colonic mucosal biopsy specimens were obtained in 4410 (79.2%) of these patients. The rates at which biopsy specimens were obtained differed among the sites where colonoscopy was performed; biopsy specimens were obtained from more patients undergoing colonoscopy in university-affiliated settings (86.8%) compared with Veterans Affairs Medical Centers (VAMC) (78.5%) or community sites (78.6%) ( p < 0.001). On multivariate analysis, biopsy specimens were more likely to be obtained in younger patients (OR 0.7: 95%CI[0.6, 0.8] for age >50 years vs. <50 years), women patients (OR 1.4: 95% CI[1.2, 1.6] in community setting; OR 4.1: 95% CI[1.6, 10.5] in VAMC setting), and patients seen in university-affiliated medical centers (university center OR 2.1: 95% CI[1.5, 3.0] vs. community setting). CONCLUSIONS: Biopsy specimens are obtained in four fifths of patients with diarrhea and normal colonoscopy findings to exclude microscopic colitis. Variation in biopsy practice exists among endoscopy site types and by gender. Clear guidelines are needed for the endoscopic approach to these patients.

Adult↗

Collagenous colitis: pathophysiologic considerations.

Collagenous colitis, a cause of watery diarrhea characterized by a distinctive band of collagen under the surface epithelium of the colon, has been recognized with increasing frequency in recent years. The pathophysiology of collagenous colitis remains obscure. The thickening of the subepithelial collagen layer may be a response to chronic inflammation or a local abnormality of collagen synthesis. The precise mechanism of the diarrhea in collagenous colitis is also unclear, and it has not been possible to link the diarrhea directly to the excess collagen deposition. The relationship between collagenous colitis and lymphocytic colitis, another type of microscopic colitis, remains to be defined; elucidating the relationship between the two disorders may provide clues to the pathophysiology of both.

Colitis↗

Oral budesonide therapy improves quality of life in patients with collagenous colitis.

INTRODUCTION: Collagenous colitis is an idiopathic microscopic colitis characterised by watery diarrhoea. The impact of collagenous colitis on quality of life has not been assessed. Our aim was to assess quality of life in patients with this condition and compare the effect of treatment with budesonide capsules or placebo on this parameter. METHODS: Patients with chronic diarrhoea and histologically-proven collagenous colitis were randomised to receive either budesonide controlled-release capsules (Entocort capsules, AstraZeneca, Lund, Sweden), 9 mg/day, or placebo for 6 weeks. Quality of life was measured using the validated Gastrointestinal Quality of Life Index (GIQLI) at baseline and after 6 weeks. With the GIQLI, scores range from 0 to 144, with higher scores representing better quality of life. RESULTS: Complete quality of life assessment was available in 29 patients (budesonide: n=17; placebo: n=12). At baseline, quality of life was low in patients with collagenous colitis (mean 76). After 6 weeks of treatment, the mean GIQLI score increased significantly in the budesonide group (from 67 to 92, p<0.001), but remained unchanged in the placebo group (86-88). The mean score of the dimensions symptoms (p=0.001), emotional functioning (p=0.003) and physical functioning (p=0.017) increased significantly in the budesonide group compared with the placebo group. A significantly larger proportion of patients in the budesonide group experienced improved stool consistency (p<0.01) and a significant reduction in the mean stool frequency compared with those in the placebo group (p<0.01). CONCLUSION: Quality of life is seriously reduced in patients with collagenous colitis. Six-week treatment with oral budesonide controlled-release capsules significantly improves quality of life and clinical symptoms compared with placebo in these patients.

Administration, Oral↗

Budesonide treatment for collagenous colitis: a randomized, double-blind, placebo-controlled, multicenter trial.

BACKGROUND & AIMS: Collagenous colitis is an idiopathic microscopic colitis characterized by chronic watery diarrhea, a typical subepithelial collagen layer, and lymphoplasmacellular infiltration. We investigated the effect of budesonide on symptoms and histology in patients with collagenous colitis in a randomized, double-blind, placebo-controlled multicenter trial. METHODS: Patients with chronic diarrhea and histologically proven collagenous colitis were randomized to receive either oral budesonide (Entocort capsules; AstraZeneca, Sodertalje, Sweden) 9 mg/day for 6 weeks or placebo. Complete colonoscopy was performed before and after treatment. Histopathology was assessed by a single pathologist blinded to the patients' treatment. Clinical symptoms were assessed by standardized questionnaires. RESULTS: Fifty-one patients were randomized; 45 patients were available for per protocol analysis. The rate of clinical remission was significantly higher (P < 0.001) in the budesonide group than in the placebo group (per protocol 86.9% vs. 13.6%, respectively; intention-to-treat 76.9% vs. 12.0%, respectively). Histologic improvement was observed in 14 patients of the budesonide group (60.9%) and in 1 patient of the placebo group (4.5%; P < 0.001). Two patients in the budesonide group (7.7%) and 1 patient in the placebo group (4.0%) discontinued treatment prematurely because of side effects. CONCLUSIONS: Oral budesonide (Entocort capsules) is an effective and safe treatment modality for patients with collagenous colitis. Long-term follow-up of these patients is necessary to investigate whether clinical and histologic remission is sustained.

Administration, Oral↗

Collagenous colitis: an electron microscopic study including comparison with the chronic fibrotic stage of ulcerative colitis.

Light and electron microscopic studies of 14 cases of collagenous colitis are reported. Comparative electron microscopic examinations were carried out on 13 cases of ulcerative colitis in the chronic fibrotic stage of the disease. Separation of pericryptal fibroblasts which showed enhanced fibre-forming activity, proliferation of myofibroblasts, accumulation of mast cells and a pericapillary collagen accumulation were noted in both groups. Based on these results, collagenous colitis was considered to result from scar formation secondary to previous superficial inflammation.

Adult↗

Subnormal alanine aminotransferase values in blood of patients with Crohn disease.

BACKGROUND: It was observed that several patients from the outpatient clinic with Crohn disease (CD) occasionally had subnormal values of alanine aminotransferase (ALAT) in blood. Subnormal ALAT values have previously been reported only in renal failure. METHODS: A retrospective study of clinical chemistry values going back 10 years was conducted in all patients from the outpatient clinic with CD or ulcerative colitis (UC). Exclusion criteria were age >50 years, a daily alcohol consumption, known liver disease or other chronic diseases with a possible effect on liver function (n=42). The remaining patients (n=123) were classified as UC, CD or indeterminate colitis (ID). Eight patients with microscopic colitis (MC) were also included. RESULTS: It was found that 49/50 CD patients had subnormal ALAT on one or several occasions (mean 7 U/L, range 5-9). Only 1/67 patients with UC had subnormal ALAT values. The mean ALAT value in UC was 20 U/L, range 10-40. In IC, 5/6 patients had subnormal ALAT. None of the 8 patients with MC had subnormal ALAT. CONCLUSIONS: The demonstration that subnormal ALAT values are almost entirely seen in CD as compared with UC may have clinical importance and adds to the information on the pathophysiological differences between these two diseases.

Adult↗

Progression of collagenous colitis to ulcerative colitis.

Collagenous colitis is a form of microscopic colitis that results in chronic watery diarrhea. The disorder predominantly affects middle-aged women, and its course tends to be benign. It is not thought to be a precursor of overt inflammatory bowel disease; however, apparent progression to ulcerative colitis has been reported on one previous occasion. We describe two further patients with symptoms and histologic features of collagenous colitis who subsequently developed ulcerative colitis. The first patient developed ulcerative colitis 13 months after diagnosis of collagenous colitis, although she gave a 23-year history of profuse watery diarrhea, which had not been adequately investigated. In the second patient, collagenous colitis was diagnosed soon after the onset of watery diarrhea, and 12 months later, progression to ulcerative colitis was documented. Both patients tested positive for perinuclear antineutrophil cytoplasmic antibody after they developed ulcerative colitis; the first patient was initially negative. In conclusion, these two cases, in addition to the one other in the literature, suggest that collagenous colitis and ulcerative colitis may represent extremes in the spectrum of inflammatory bowel disease and that collagenous colitis may evolve to ulcerative colitis. Therefore, progression to ulcerative colitis should be considered in any patient with known collagenous colitis whenever bloody diarrhea occurs, or if red cells, as well as white cells, are noted on stool microscopy.

Aged↗

Amebiasis in four ball pythons, Python reginus.

Between September 13th and November 18th in 1999, four ball pythons, Python reginus kept in the same display, showed anorexia and died one after another. At necropsy, all four snakes had severe hemorrhagic colitis. Microscopically, all snakes had severe necrotizing hemorrhagic colitis, in association with ameba-like protozoa. Some of the protozoa had macrophage-like morphology and others formed protozoal cysts with thickened walls. These protozoa were distributed throughout the wall in the large intestine. Based on the pathological findings, these snakes were infested with a member of Entamoeba sp., presumably with infection by Entamoeba invadens, the most prevalent type of reptilian amoebae.

Animals↗