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Colonic epithelial lymphocytosis without a thickened subepithelial collagen table: a clinicopathologic study of 40 cases supporting a heterogeneous entity.

Lymphocytic colitis (LC) is classically described as a triad of chronic nonbloody, watery diarrhea, normal or nearly normal endoscopy findings, and colonic epithelial lymphocytosis without a thickened subepithelial collagen table (SECT). It is unknown how often patients with colonic epithelial lymphocytosis without a thickened SECT actually present with this classic triad. Cases diagnosed histologically as lymphocytic or microscopic colitis were reviewed. Criteria for inclusion were the presence of at least 15 surface lymphocytes per 100 epithelial cells and the absence of a thickened SECT (<12 microm). Clinical features and course were recorded by chart review and telephone follow-up. Forty patients met the inclusion criteria, including 25 women and 15 men with a mean age of 63.2 years (range, 25-83 years). Twenty-eight patients had the classic triad and were designated as having classic LC. The other 12 patients fulfilled the histologic criteria but not the clinical or endoscopic criteria for classic LC and were classified as having atypical LC (constipation, five patients; macroscopic colitis at endoscopy, five patients; hematochezia, one patient; and incidental finding, one patient). Clinically, patients with classic LC were predominantly women and had a higher incidence of autoimmune disease (p = 0.03) than did those with atypical LC. Histologically, surface eosinophilia was significantly greater in patients with classic LC (p = 0.04). Twenty patients were using nonsteroidal antiinflammatory drugs at the time of their colonic biopsy. Surface epithelial lymphocyte counts were higher in these patients, particularly in the distal sigmoid colon (p = 0.02). Fourteen patients had associated autoimmune disease, including three patients with sprue diagnosed by small bowel biopsy, all of whom responded to gluten withdrawal. Diarrhea present in 25 patients, without documented evidence of celiac sprue, was self-limited in five, resolved with treatment in three, required intermittent treatment in eight, daily treatment in five, and was refractory to treatment in four. All eight patients who experienced spontaneous or treatment-related symptom resolution had classic LC. No histologic feature correlated with clinical course. In conclusion, our study shows that colonic epithelial lymphocytosis without a thickened SECT is a histologic finding seen in a heterogeneous group of patients. Within this heterogeneous group is a distinct subset of patients who have the classic clinicopathologic triad of LC. This subset of patients has striking similarities to patients with collagenous colitis, lending further support to a close relationship between these two entities. Atypical LC comprises a heterogeneous group and includes patients with idiopathic constipation, coexisting LC and inflammatory bowel disease, and possibly infectious colitides. Because of the clinical heterogeneity among our study population, the descriptive term colonic epithelial lymphocytosis may be a more prudent diagnosis than lymphocytic colitis in the absence of adequate clinical information.

Adult↗

[Collagenous colitis].

The features of collagenous colitis are briefly summarized on the basis of 24 own patients and a review of the literature. Collagenous colitis is a rare diarrheal disease first described in 1976. The hallmark of this syndrome consists in a thickened layer of subepithelial collagen in the entire colon. Clinically patients present with longstanding, watery diarrhea. Laboratory tests, radiology and colonoscopy are all normal. Therefore the diagnosis is only established, if an alert colonoscopist takes biopsies out of an endoscopically normal appearing mucosa. There is no specific treatment, but patients usually respond to symptomatic therapy with antidiarrheal drugs. Microscopic colitis may represent an early stage of collagenous colitis.

Adult↗

[Collagen colitis. Reflections apropos of 40 patients].

The aim of this study was to evaluate the frequency of a thickened subepithelial collagen band in the colon, its relationship to diarrhea, and the clinical relevance of its detection. During a 3.5 year period (May 1985-January 1989), a total of 3,323 biopsy specimens were obtained during 6,254 colonoscopies. A subepithelial collagen thickening greater than 10 microns was found in 40 patients (1.5 percent of the patients). Further assessment of these 40 patients showed that this histological lesion was characterized by a frequent association with chronic diarrhea (in 36 patients, i.e. 90 percent) whatever the cause, with diseases such as diabetes mellitus (8 cases) or inflammatory arthropathies (6 cases) and with a microscopic colitis in all cases. Course of collagen thickening was variable and independent of clinical course. Diarrhea was a constant finding when the collagen thickening was greater than 15 microns and frequently improved (12 patients/14) during treatment with Collagenan. This study suggests that a subepithelial thickened collagen band is an uncommon change in the colon and is frequently associated with chronic diarrhea. The significance of this morphological change is unknown, and its contribution to the pathogenesis of the diarrhea remains questionable.

Chronic Disease↗

[Inflammatory bowel disease in children].

Beside Crohn's disease (CD) and ulcerative colitis (UC), paediatric chronic inflammatory bowel diseases encompass variety of different inflammatory conditions: allergic colitis in infancy, colitis of hypereosinophilic syndrome, Behcet colitis, microscopic colitides etc. Paediatric CD characterises predominance of inflammatory and obstructive disease variant. Because of their growth suppression an early introduction of azathioprine in steroid dependent and steroid refractory cases is frequently indicated. In teenage period resection procedures may be an elective and initial therapeutic option due to necessity of proper pubertal mental and physical development. Paediatric UC frequently manifests initially as pancolitis what indicates higher rate of colectomy rate. Therapy is still dispute about an optimal surgical procedure: restorative proctocolectomy or ileo-anal pull through techniques. Allergic colitis in infancy may mimic ulcerative colitis and rises a possibility of diagnostic and therapeutic confusions. Its treatment is strictly nutritive.

Child↗

Collagenous and lymphocytic colitis. evaluation of clinical and histological features, response to treatment, and long-term follow-up.

OBJECTIVE: Data on collagenous colitis (CC) and lymphocytic colitis (LC) have been based on retrospective studies of registries of patients from multiple hospitals. Such studies may induce a selection of patients with severe forms of the disease, and conclusions about the clinical spectrum of the disease and treatment efficacy are difficult to be drawn. The aim of this study was to compare the clinical features, response to treatment, and long-term follow-up of CC and LC in a large group of patients prospectively diagnosed in a single center. METHODS: A specific program was undertaken to prospectively diagnose all patients with microscopic colitis from those referred for a full colonoscopy because of recurrent or chronic diarrhea. Detailed clinical and histological features, response to treatment, and long-term follow-up were compared in patients with confirmed CC and LC. RESULTS: Thirty-seven patients with CC and 44 with LC were included. Patients with CC were significantly younger and had a significantly longer duration of diarrhea before diagnosis than those with LC. Otherwise, clinical presentation was similar. Drug-induced disease was suspected for ticlopidine, flutamide, gold salts, and bentazepam in LC. Complete resolution of diarrhea was achieved in all patients, spontaneously occurring in nearly 20% of them. Response to salicylates (mainly, mesalazine) was significantly better in LC than in CC (86% vs 42%, p = 0.005). Cholestyramine was highly effective in patients of both groups with concomitant bile acid malabsorption. Patients with CC required prednisone more often than those with LC (30% vs 4.5%, p = 0.005). Both prednisone and budesonide controlled ileal release were highly effective in patients with CC (82% and 89% efficacy). After cessation of diarrhea, 25% of patients with LC and 30% of those with CC relapsed after a mean follow-up of around 3 yr. CONCLUSIONS: CC and LC share a similar clinical picture and have a benign course with long-term cessation of diarrhea in more than 70% of patients. Mesalazine and budesonide seem to be good options as first-line treatment in LC and CC, respectively. Cholestyramine may be a good alternative in patients with concomitant bile acid malabsorption.

Aged↗

[Inflammatory bowel disease: 3 mainly by histology detectable variant forms].

Over the past years, a number of idiopathic, chronic, inflammatory gastrointestinal diseases have been recognized, which can be distinguished from Crohn's disease and ulcerative colitis. These entities are grouped under the term "variant forms" of IBD. In this review, three distinctive, variant-IBD entities--all of which with individual and uniform histories and characteristic, histological abnormalities, but unremarkable or even absent endoscopical features--are presented: 1. The adult form of primary eosinophilic esophagitis mainly affects male patients and leads to a history of acute and recurrent dysphagia with a typical on-off-phenomenon. 2. Patients with celiac disease often present a long history of anemia and complain of symptoms resembling irritable bowel syndrome. 3. The main symptom of microscopic colitis is watery diarrhea, sometimes associated with weight loss. Faced with one of these histories, it is necessary to insist, that during the endoscopic procedures--even in the absence of mucosal alterations--representative biopsy specimens are taken and histologically worked up with adequate stainings.

Acute Disease↗

[Inflammatory bowel diseases--imaging diagnostics].

The basic diagnostic procedure in ulcerative colitis is an endoscopy of gastrointestinal tract. It allows the macroscopic evaluation as well as the specimen taking for histological assessment what is the basis for ultimate diagnosis. In case of Crohn's disease the radiological diagnostics is of equal importance as endoscope evaluation. The imaging of inflammatory changes in Crohn's disease still poses some difficulties, especially, that located in the small intestine. Lately, the range of accessible examinations has been wider. We have in disposal the ultrasonography, the computed tomography, the magnetic resonance imaging and the capsular endoscopy. All of them are of great use in the diagnosis of Crohn's disease. In case of microscopic colitis all the imaging diagnostics has no use. The only one mean to establish the diagnosis is a histological assessment. What is more, in the period of remission the colon tissue could be normal. In this paper we discussed the traditional and contemporary intestine imaging methods in inflammatory bowel diseases. The conclusion is that the further progress in science offers a better imaging and, what is even more important, the more efficient diagnostics and treatment of these diseases.

Humans↗

Colitis in sheep due to a Campylobacter-like bacterium.

Epidemic diarrhoea was observed in approximately 2,000 of 6,700 sheep on 9 farms. The disease, called weaner colitis, caused mortality of 1%, while morbidity varied from 20 to 75%. Colon contents from affected sheep were inoculated into 17 sheep, 13 of which developed diarrhoea 5 to 7 days after inoculation. Naturally and experimentally infected sheep had mild, erosive typhlitis and colitis. Microscopic examination of washed scrapings of colonic mucosa from all affected sheep revealed masses of curved bacteria that were not seen in controls. Electron microscopic examination showed similar bacteria adherent to colonic epithelium of an experimentally infected sheep. Curved, motile bacteria were isolated from 2 naturally occurring cases. One isolate was inoculated into 9 sheep, 2 of which developed diarrhoea. The other isolate was given to 4 sheep without observable effect. The curved bacteria grew only on media containing blood, in an atmosphere of approximately 10% air, 10% CO2 and 80% H2. They were Gram-negative, with a polar flagellum at one or both ends, they did not ferment glucose or give a positive catalase reaction. It is suggested that these bacteria are a new Campylobacter species and that they play a major role in the aetiology of weaner colitis.

Animals↗

Lawsonia intracellularis infection in the large intestines of pigs.

In this study we examined the proliferative enteropathy, caused by the obligate intracellular bacterium Lawsonia intracellularis, in colon of naturally infected pigs, using immunohistochemistry, in situ hybridisation and scanning confocal laser microscopy. When 396 pigs submitted for routine laboratory examination were investigated, large intestinal gross lesions were seen in 93, including 74 cases of L. intracellularis colitis (proliferative enteropathy). Fifty-one pigs without recorded colonic gross lesions revealed L. intracellularis colitis microscopically. In four cases, L. intracellularis was only revealed in colon. Fifty-seven pigs were positive for L. intracellularis in the small intestines only. Thus, the overall prevalence of colonic infection in L. intracellularis-positive animals was as high as 69% (125 out of 182). In comparison, the large intestinal pathogens Brachyspira hyodysenteriae and Salmonella enterica were only isolated from 5 and 4 of the 93 cases, respectively. Morphologically, an unforeseen severe involvement of the subepithelial mucosa with multiple L. intracellularis found free and within large macrophages was observed in areas with acute infection. The distribution of whole L. intracellularis organisms was confirmed by in situ hybridisation and scanning confocal laser microscopy. The significance and possible role of subepithelial infection in the proliferative enteropathy is discussed. In conclusion, the study shows that L. intracellularis is a prevalent cause of naturally acquired colitis in pigs.

Animals↗

Effects of prolonged exposure to histamine on guinea pig intestinal neurons.

Intracellular microelectrodes were used to study the effects of prolonged exposure to histamine on the electrophysiological behavior of AH/type-2 neurons in the myenteric plexus of the guinea pig small intestine. Application of histamine activated H2 receptors to convert the neurons to a heightened state of excitability. Heightened excitability was evident as repetitive spike discharge made possible, in part, by suppression of postspike after-hyperpolarization. The hyperexcitable state persisted unchanged for prolonged periods of 4.5 hr in the continued presence of histamine, suggesting that desensitization may never occur in vivo. The results are interpreted as a neural correlate for the pathophysiology associated with microscopic colitis and other inflammatory conditions involving mast cell hyperplasia.

Animals↗

Postinfectious irritable bowel syndrome.

A small but significant subgroup of patients with irritable bowel syndrome (IBS) report a sudden onset of their IBS symptoms after a bout of gastroenteritis. Population-based surveys show that although a history of neurotic and psychologic disorders, pain-related diseases, and gastroenteritis are all risk factors for developing IBS, gastroenteritis is the most potent. More toxigenic organisms increase the risk 11-fold, as does an initial illness lasting more than 3 weeks. Hypochondriasis and adverse life events double the risk for postinfective (PI)-IBS and may account for the increased proportion of women who develop this syndrome. PI-IBS is associated with modest increases in mucosal T lymphocytes and serotonin-containing enteroendocrine cells. Animal models and some preliminary human data suggest this leads to excessive serotonin release from the mucosa. Both the histologic changes and symptoms in humans may last for many years with only 40% recovering over a 6-year follow-up. Celiac disease, microscopic colitis, lactose intolerance, early stage Crohn's disease, and bile salt malabsorption should be excluded, as should colon cancer in those over the age of 45 years or in those with a positive family history. Treatment with Loperamide, low-fiber diets, and bile salt- binding therapy may help some patients. Serotonin antagonists are logical treatments but have yet to be evaluated.

Bacterial Infections↗

Primary sclerosing cholangitis in childhood.

Thirteen children (8 female) with primary sclerosing cholangitis are described, in whom the diagnosis was confirmed by the presence of characteristic changes on endoscopic retrograde cholangiopancreatography. Nine had clinical features of chronic inflammatory bowel disease 1 mo to 5 yr before the onset of primary sclerosing cholangitis (6 patients) or appearing simultaneously with primary sclerosing cholangitis (3 patients). In 4 patients clinical evidence of chronic inflammatory bowel disease was absent but 1 of the 4 was found to have microscopic colitis in colonoscopic biopsy specimens. Biopsies were not performed in the remaining 3 patients. High immunoglobulin G concentrations and positive antinuclear or smooth muscle antibodies were present in all patients except 1 who had been given immunosuppressants. In 7 patients treated with immunosuppressants and followed up for 9 mo to 10 yr there was modest symptomatic improvement. This improvement was accompanied by a fall in transaminase levels in 6 of the patients and histologic improvement in 3 of 4 patients who had undergone biopsy. Greater use of endoscopic retrograde cholangiopancreatography in the last 6 yr led to the identification of 10 of these 13 cases, suggesting a higher incidence of primary sclerosing cholangitis in childhood than would appear from the literature.

Adolescent↗

The prevalence, anatomic distribution, and diagnosis of colonic causes of chronic diarrhea.

BACKGROUND: The prevalence of chronic diarrhea from a colonic disease and the optimal method of its diagnosis have not been ascertained. METHODS: Eight hundred nine patients with chronic non-bloody diarrhea unassociated with human immunodeficiency virus (HIV) infection underwent colonoscopy with biopsy specimen taken from throughout the colon and, if reached, the terminal ileum. The prevalence and anatomic distribution of ileocolonic histopathology and whether flexible sigmoidoscopy or colonoscopy represents the safest and most cost-effective test for diagnosis were determined. RESULTS: 122 of 809 patients (15%) had colonic histopathology (microscopic colitis in 80 patients, Crohn's disease in 23, melanosis coli in 8, ulcerative colitis in 5, other forms of colitis in 5, and nodular lymphoid hyperplasia in 1). A correct assessment of colonic histology (normal or abnormal) could have been made from biopsies of the distal colon in 99.7% of patients. CONCLUSION: In a referral setting, colonic histopathology occurs in 15% of patients with chronic diarrhea without HIV infection. According to this prevalence and the nearly universal diffuse anatomic distribution of colonic disease in these patients, a diagnostic investigation for chronic colonic diarrhea using a 60 cm flexible sigmoidoscope is highly efficient and cost-effective.

Biopsy↗

Routine colonic mucosal biopsy and ileoscopy increases diagnostic yield in patients undergoing colonoscopy for diarrhea.

BACKGROUND AND AIMS: In patients undergoing colonoscopy for diarrhea, when the examination is normal, the role of routine mucosal biopsy remains controversial, particularly in the open-access setting. It is uncertain whether routine ileoscopy adds anything to colonoscopy alone. We aimed to assess the yield of mucosal biopsy and ileoscopy in patients with diarrhea. METHODS: We retrospectively reviewed all colonoscopies performed for diarrhea over a 9-year period in a tertiary referral center with an open-access service. We then selected cases where the examination was normal and biopsies were performed. The histopathology reports of these selected cases were then reviewed. RESULTS: There were 1131 cases identified. The mucosal examination was normal in 465 cases (41%); 362 of these had colonic biopsies performed. Histology was normal in 316 cases (87%) and was non-specific in 28 cases (8%). Significant histopathology was present in 18 cases (5%) with a significantly higher prevalence of microscopic colitis in patients above 60 years old. Ileoscopy was performed in 508 cases and was abnormal in 26 cases (5%). The abnormality on ileoscopy was the sole abnormality in 13 cases (3%). CONCLUSIONS: Routine colonic mucosal biopsy and ileoscopy each identify significant additional pathology in 5% of cases when investigating patients with diarrhea, and are recommended as routine practice in this setting. We found ileal biopsy unhelpful when ileoscopy was normal.

Biopsy↗

Diarrhea associated with lansoprazole.

Lansoprazole is a proton pump inhibitor widely prescribed for gastroesophageal reflux and benign peptic ulcer disease. According to the manufacturer's package insert (TAP Pharmaceuticals, Lake Forest, IL, USA), the most common side-effects are diarrhea, headache and abdominal pain, which occur in approximately 3% of patients and are reversible with drug discontinuation. An unusual case of microscopic colitis is reported in a previously asymptomatic patient who developed new-onset diarrhea after initiation of lansoprazole. The case is reviewed and possible mechanisms of diarrhea secondary to proton pump inhibitors are discussed.

2-Pyridinylmethylsulfinylbenzimidazoles↗

The prevalence and causes of chronic diarrhea in patients with celiac sprue treated with a gluten-free diet.

BACKGROUND & AIMS: The majority of patients with celiac sprue experience diarrhea before diagnosis. There have been no studies of the prevalence or causes of chronic diarrhea in these patients after treatment with a gluten-free diet. METHODS: Seventy-eight patients with celiac sprue (59 women and 19 men) treated with a gluten-free diet for at least 12 months were surveyed about their bowel habits. Those with chronic diarrhea, defined as passage of loose stools three or more times per week for 6 months, underwent an extensive diagnostic evaluation to determine its cause. RESULTS: Sixty-two of the 78 patients (79%) experienced diarrhea before treatment, and 13 (17%) had chronic diarrhea (of lesser severity) after treatment. The causes of diarrhea in 11 patients consenting to this study were microscopic colitis, steatorrhea secondary to exocrine pancreatic insufficiency, dietary lactose or fructose malabsorption, anal sphincter dysfunction causing fecal incontinence, and the irritable bowel syndrome. Only 1 patient had antigliadin antibodies detected in serum or small intestinal villous atrophy. CONCLUSIONS: After treatment of celiac sprue with a gluten-free diet, chronic diarrhea persists in a substantial percentage of patients. Although ongoing gluten ingestion is one possible cause, other causes may be more frequent. Therefore, diagnostic investigation of diarrhea in celiac sprue after treatment seems warranted.

Adult↗

Confocal laser endomicroscopy: technical status and current indications.

Confocal laser endomicroscopy is a newly introduced endoscopic tool that makes it possible to carry out confocal microscopic examination of the mucosal layer during ongoing endoscopy. Different types of tissue and diseases can be diagnosed immediately, facilitating early diagnosis of gastrointestinal cancer. Analysis of the in vivo microarchitecture is helpful in targeting biopsies to relevant areas. In addition, 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 (e.g., in vivo receptor analysis).

Barrett Esophagus↗

The prevalence of occult gastrointestinal bleeding in celiac sprue.

BACKGROUND: Iron deficiency complicating celiac sprue is usually attributed to the malabsorption of dietary iron or the loss of iron from the intestinal mucosa. There has been little investigation of the role of intestinal loss of blood in patients with this condition. The purpose of this study was to determine the prevalence of occult gastrointestinal bleeding in patients with celiac sprue. METHODS: We tested one 48- or 72-hour stool collection from each of 8 patients with partial villous atrophy and 28 patients with total villous atrophy using a guaiac-impregnated card (Hemoccult). Serving as controls were 18 normal subjects, each studied before and during laxative-induced diarrhea; 17 patients with idiopathic chronic diarrhea; 63 patients with microscopic colitis; 23 patients with pancreatic steatorrhea; and 7 patients with treated celiac sprue who had normal intestinal histologic features. All the patients underwent a diagnostic workup that included esophagogastroduodenoscopy, colonoscopy, and barium radiography of the small bowel. RESULTS: Positive Hemoccult tests were infrequent in each of the control groups, occurring in 0 to 8 percent of the subjects, whereas 2 of the 8 patients with partial villous atrophy (25 percent) and 15 of the 28 patients with total villous atrophy (54 percent) had positive tests. When the patients with total villous atrophy were classified according to their subsequent responses to a gluten-free diet, 7 of the 17 who were responsive to gluten withdrawal (41 percent) were Hemoccult-positive, as compared with with 8 of the 11 who did not respond to the diet (73 percent). CONCLUSIONS: Occult gastrointestinal bleeding can be detected in about half of patients with celiac sprue and should be added to the list of factors that can contribute to iron deficiency in patients with this disorder.

Adolescent↗