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Atypical forms of inflammatory bowel disease: microscopic colitis and pouchitis.

Three atypical colitides (and enterides) are collagenous colitis, lymphocytic colitis, and ileal pouchitis. Collagenous and lymphocytic colitis are similar inflammatory bowel disorders of unknown cause with symptoms including chronic watery diarrhea, occurring in middle age. Pouchitis is the most significant long-term complication in patients with ileoanal pouch anastomosis. The clinical and histologic features and management of these entities are discussed.

Journal Article↗

Microscopic colitis: a common diarrhoeal disease. An epidemiological study in Orebro, Sweden, 1993-1998.

BACKGROUND: Microscopic colitis, including collagenous colitis and lymphocytic colitis, mainly affects middle aged and older subjects, with a female predominance in collagenous colitis. The diseases have previously been regarded as rare. We present an epidemiological study of microscopic colitis in a well defined Swedish population. METHODS: Patients were retrospectively searched for in colonoscopy reports of those who had a colonoscopy in the period 1993-1998 for non-bloody diarrhoea. All colonic mucosal biopsies were reassessed using strict diagnostic criteria. RESULTS: Biopsies from 1018 patients were reassessed. Fifty one (45 female) collagenous colitis patients and 46 (31 female) lymphocytic colitis patients were diagnosed. Median age at diagnosis was 64 years in collagenous colitis and 59 years in lymphocytic colitis. The mean annual incidence of collagenous colitis was 4.9/10(5) inhabitants (95% confidence interval (CI) 3.6-6.2/10(5)) and of lymphocytic colitis 4.4/10(5) inhabitants (95% CI 3.1-5.7/10(5)). The annual incidence of collagenous colitis increased from 3.7/10(5) in 1993-1995 to 6.1/10(5) in 1996-1998 (difference 2.4/10(5) (95% CI -0.3-5.1/10(5))) whereas the incidence of lymphocytic colitis increased from 3.1/10(5) to 5.7/10(5) (difference 2.6/10(5) (95% CI 0.1-5.2/10(5))). CONCLUSIONS: The annual incidences of collagenous colitis and lymphocytic colitis are higher than considered previously and are now equal to the incidence of Crohn's disease in Sweden, and combined rates approach the incidence of ulcerative colitis. Microscopic colitis was diagnosed in 10% of all patients with non-bloody diarrhoea referred for colonoscopy and in almost 20% of those older than 70 years.

Adolescent↗

Systematic review: microscopic colitis.

BACKGROUND: Collagenous and lymphocytic colitis are fairly common causes of chronic non-bloody diarrhoea, especially in elderly female. AIM: To present a systematic review of microscopic colitis. METHODS: A PubMed search using the MeSH terms microscopic colitis, collagenous colitis, lymphocytic colitis and chronic diarrhoea was performed. RESULTS: Annual incidence of each disorder is 4-6/100,000 inhabitants. The aetiology is unknown. Clinical characteristics are well described and there is an association with autoimmune diseases. Budesonide is the best-documented short-term treatment of collagenous colitis. In meta-analysis pooled odds ratio for clinical response after 6-8 weeks of treatment was 12.3 (95% CI: 5.5-27.5) in comparison with placebo. The evidence for bismuth subsalicylate is weaker and the effectiveness of other alternatives such as loperamide, cholestyramine, aminosalicylates, probiotics, or Boswellia serrata extract is unknown. Although unproven, in unresponsive severe disease azathioprine or methotrexate may be tried. No controlled trials have been carried out in lymphocytic colitis. The long-term prognosis of microscopic colitis is good, serious complications are rare and there is no increased mortality. CONCLUSIONS: Clinical and epidemiological aspects of microscopic colitis are well described. Budesonide is the best-documented short-term therapy in collagenous colitis, but the optimal long-term strategy needs further study. Controlled treatment data of lymphocytic colitis are awaited for.

Aged↗

Microscopic colitis: the tip of the iceberg?

OBJECTIVES: The aims were to determine whether a wide variation exists between hospitals in the diagnosis of microscopic colitis and to assimilate clinical data. DESIGN: Retrospective study of 90 patients with microscopic colitis aged between 16 and 92 years from 11 hospitals in south-east England. METHODS: A questionnaire was designed to collect relevant data from all patients in whom a new diagnosis of microscopic colitis had been made at the source hospital between January 1990 and December 1996. The inclusion criteria were presentation with watery diarrhoea, a normal endoscopy and a histological report of microscopic colitis. Histology slides were then requested and reviewed. Clinical data were analysed with reference to the confirmed diagnosis. RESULTS: The number of patients diagnosed at each hospital ranged between zero and 30, with a median of six. Sixty-eight patients had histological slides reviewed. The numbers of patients with a final reviewed diagnosis of collagenous colitis, lymphocytic colitis and microscopic colitis, type undesignated, were 37, 18 and seven respectively. In thirty-one patients (34%) there was a recent history of the use of non-steroidal anti-inflammatory drugs. CONCLUSIONS: These data confirm that there is wide hospital variation in the diagnosis of microscopic colitis. Furthermore, the small group with the undesignated type may be associated with the use of non-steroidal anti-inflammatory drugs.

Adolescent↗

Evolving concepts on inflammatory bowel disease. Are we happy with the present nosology?

The term inflammatory bowel disease traditionally comprises ulcerative colitis, Crohn's disease and indeterminate colitis, an intermediate variant of the two major forms. The term is commonly used in the literature and in clinical practice even though it has never been revised in a Consensus Conference. The present nosology of inflammatory bowel disease seems not to be entirely satisfactory as it is limited to chronic diseases only and does not include several recently described idiopathic inflammatory bowel disorders. Although the aetiology of inflammatory bowel disease remains unknown, both ulcerative colitis and Crohn's disease are characterized by a similar pathogenesis which consists in a persistent intestinal inflammation resulting from disregulation of the gut mucosal immune system. The pathogenetic mechanisms could, therefore, provide a suitable criterion for the classification of idiopathic inflammatory bowel disease. A revised classification of inflammatory bowel disease is thus proposed. It seems reasonable to subclassify inflammatory bowel disease into acute and chronic forms. Acute forms should include the sudden attacks of ulcerative colitis and Crohn's disease with rapid and complete resolution and the so-called "acute self-limited colitis". The chronic forms should comprise, besides the classical forms of ulcerative colitis, Crohn's disease and indeterminate colitis, also other idiopathic inflammatory bowel conditions such as collagenous colitis, lymphocytic colitis and eosinophilic gastroenteritis.

Diagnosis, Differential↗

Familial microscopic colitis.

Collagenous and lymphocytic colitis are two inflammatory conditions of the colon that are often collectively referred to as microscopic colitis. The present report describes what is believed to be the third published case of familial microscopic colitis. A 55-year-old woman who suffered from chronic diarrhea was diagnosed with lymphocytic colitis on colonic biopsy. Subsequently, her 36-year-old daughter was diagnosed with collagenous colitis. The familial occurrence of these diseases may support an immunological hypothesis for their etiology. In addition, it supports the assumption that collagenous and lymphocytic colitis are two manifestations of the same disease process rather than two completely separate entities. The familial tendency of this disease may make a case for early colonoscopy and biopsy in relatives of patients diagnosed with microscopic colitis if they present with suggestive symptoms.

Abdominal Pain↗

Short- and long-term follow-up of treatment for lymphocytic and collagenous colitis.

Collagenous colitis and lymphocytic colitis cause chronic watery diarrhea. Multiple therapies have been found to improve symptoms but there have been few long-term follow-up studies. Our goal was to obtain long-term clinical follow-up on a cohort of patients with independently confirmed typical histopathologic changes. Pathology slides from 32 cases of collagenous or lymphocytic colitis patients from 1988-1992 were independently reviewed. Twenty-five cases were confirmed by both groups of pathologist as collagenous or lymphocytic colitis. For these 25 patients, charts were reviewed and telephone follow-up interviews were performed in 1992 and 1995. Seven of 32 (22%) of the original cases were not confirmed on independent pathologic interpretation. A 15.8% discordance rate was found between the different groups of pathologists. Patient demographics were similar to previously published reports except one-half of our patients had diarrhea of only 6 months or less. Eighty-one percent of patients receiving 5-ASA agents reported improvement as well as 100% of those receiving prednisone. At 23 month follow-up 86% of patients reported improvement in diarrhea and only 32% required routine medications. At 47 month follow-up all patients reported improved diarrhea and only 29% required routine medications. Collagenous and lymphocytic colitis can sometimes be identified in patients with relatively brief duration diarrhea. Clinical parameters and response to therapy are similar for collagenous or lymphocytic colitis. Most patients with lymphocytic and collagenous colitis improve with therapy such as 5-ASA preparations or steroids. Over a follow-up period of several years, most patients have improvement in diarrhea and generally do not require maintenance medications. Independent pathologic confirmation of the diagnosis should be obtained in patients not responding to therapy.

Aged↗

Collagenous and microscopic colitis: clinical importance.

Minimal-change colitis and microscopic colitis are clinicopathological terms for diarrhoea with normal endoscopic or barium enema findings. Some controversy about the exact definitions and terminology still exists. Some forms of minimal-change colitis may overlap with "self-limited" colitis (infectious colitis) or may be due to (surreptitious) use of laxatives or other drugs. In recent years it has become clear however that some genuine forms of chronic colitis can be diagnosed only by microscopic examination of multiple colonic biopsies while macroscopy is negative and hence can be called "microscopic colitis". Collagenous colitis and lymphocytic colitis are at present two forms of this type of colitis which are more or less well defined both clinically and pathologically. Chronic watery diarrhoea is the main symptom for both. The symptoms of collagenous colitis appear most commonly in the sixth decade. Women are affected about 4 times more frequently than men. The major microscopic characteristic is a thickened collagen layer underneath the intercryptal surface epithelium. The major characteristic of lymphocytic colitis is an increase in number of interepithelial lymphocytes. Both conditions are characterized by signs of mucosal inflammation. Clinically, collagenous colitis is characterized by long-lasting diarrhoea. In patients with lymphocytic colitis the period of chronic diarrhoea is usually shorter and female predominance is less apparent. Although the natural history of these forms of colitis is not precisely known, it appears from the data thus far published that the long-term consequences are unlikely to be dire. The true incidence, aetiology and pathogenesis are unknown for both conditions and treatment is unclear.(ABSTRACT TRUNCATED AT 250 WORDS)

Biopsy↗

Antireticulin antibodies in collagenous and lymphocytic (microscopic) colitis.

Serum antireticulin antibodies (ARAs) are often present in patients with dermatitis herpetiformis and celiac disease (CD), especially before instituting a gluten-free diet. In both collagenous colitis (CC) and lymphocytic (microscopic) colitis (LC) the colorectal mucosa shows surface epithelial damage with intraepithelial lymphocytes that is strikingly comparable to the small intestinal findings in CD. Also, CD may show subepithelial collagen deposition resembling that seen in CC. Because of these similarities, ARAs were measured in sera from patients with biopsy-proven CC and LC and compared with sera tested from CD patients. Antibody binding to reticulin was detected in frozen sections of rat liver and kidney by indirect immunofluorescent techniques. Whereas five of 14 CD patients (35.7%) had ARAs, only one of 29 CC patients (3.4%) (P = 0.010 versus CD) and none of 17 LC patients (0%) (P = 0.012 versus CD) had ARAs. The positive CC patient had IgA ARA titers of 1:20 noted in two sera taken 2 mo apart. The five positive CD patients had IgA ARA titers ranging from 1:20 to 1:320. The rare presence of ARAs noted in collagenous colitis and lymphocytic colitis was similar to its occurrence in normals, whereas the frequency of ARAs found in celiac disease (35.7%) was within the range reported for that disorder. Therefore, ARAs do not appear to be associated with CC or LC despite the morphologic similarities to CD.

Adult↗

[Are lymphocytic and collagenous colitis two forms of a single disease? Arguments taken from a biopsy quantitative study].

Collagenous colitis and lymphocytic colitis are defined by a clinicopathologic syndrome with chronic watery diarrhea, microscopic lesions of colonic biopsies, and normal barium enema and colonoscopy. A histopathological study was performed on multiple colorectal biopsies to compare 12 cases of collagenous colitis (defined by a subepithelial collagen thicker than 10 microns) and 7 cases of lymphocytic colitis (defined by a number of intraepithelial lymphocytes more than 20 per 100 epithelial cells at least in one biopsied site). The study included a semiquantitative analysis of inflammatory infiltrate in the lamina propria, crypts distortion and epithelial detachment. The number of intraepithelial lymphocytes per 100 epithelial cells was determined in surface epithelium and crypts. The subepithelial collagen thickening was studied by computerised morphometry. The intraepithelial lymphocytes, villous atrophy and thickness of the subepithelial collagen were also determined in gastric and duodenal biopsies. In collagenous colitis, the subepithelial collagenous thickness ranged from 10 to 40 microns in the colon (median 20.99 microns). In 4 cases of collagenous colitis, no thickening of the collagen plate was seen in the rectum. We found constant epithelial detachment and mucosal distortion. In lymphocytic colitis, the thickness of the subepithelial collagen ranged from 6 to 10 microns in 4 cases and was less than 6 microns in 3 cases (median 6.24 microns). The median number of intraepithelial lymphocytes in surface epithelium was 22.35 (range 18.2 to 40) in lymphocytic colitis versus 12.22 (range 4.6 to 24.4) in collagenous colitis. In conclusion, we observed an overlap of both the collagenous plate thickness and the number of intraepithelial lymphocytes in collagenous colitis and lymphocytic colitis. This result favours a unified histogenesis for these two entities.

Colitis↗

Lymphocyte subpopulations in Crohn's disease and chronic ulcerative colitis.

Lymphocyte subpopulations in peripheral blood were studied by the sheep red blood cell rosette technique for the identification of T-lymphocytes, and immunofluorescence staining with rabbit anti-human immunoglobulin sera for the identification of B-lymphocytes. In Crohn's disease, the total number of lymphocytes was found to be reduced and an almost equal reduction in all the lymphocyte subpopulations studied was found. In ulcerative colitis neither the number of T-lymphocytes nor of B-lymphocytes were found to differ significantly from normal values and the same was true of all B-lymphocyte subpopulations. However, the number of lymphocytes carrying neither surface immunoglobulin nor sheep red blood cell receptors was found to be significantly increased. The results were correlated to clinical data.

Adult↗

Microscopic colitis.

Microscopic colitis has 2 main subtypes, collagenous colitis and lymphocytic colitis, that are similar clinically and histologically and are distinguished mainly by the presence or absence of a thickened subepithelial collagen band. Microscopic colitis accounts for approximately 10% of chronic watery diarrhea and may be associated with abdominal pain and mild weight loss. It is typically diagnosed in the sixth to eighth decade of life, and there is a female pre-dominance that is more striking for collagenous colitis than for lymphocytic colitis. Endoscopic and radiographic findings of the colon appear normal. Diagnosis is made by colonic biopsy, which shows an intraepithelial lymphocytosis and a mixed inflammatory infiltrate in the lamina propria. Many potential treatments have been reported, but few have been subjected to controlled treatment trials. A stepwise approach to therapy often leads to satisfactory control of symptoms.

Anti-Inflammatory Agents↗

Microscopic colitis: a missed diagnosis?

CONTEXT: Collagenous colitis and lymphocytic colitis, collectively designated microscopic colitis, have until recently been considered as rare gastrointestinal disorders. New data suggest, however, that these disorders are relatively common, and to reach the correct diagnosis both the gastroenterologist and the pathologist must be aware of these diagnoses when evaluating patients with persistent watery non-bloody diarrhoea. STARTING POINT: In an epidemiological study of a well-defined Swedish population, Martin Olesen and colleagues show that microscopic colitis needs to be considered as a common gastrointestinal disorder (Gut 2004; 53: 346-50). In colonic biopsy specimens from 1018 patients who had a colonoscopy because of non-bloody diarrhoea in 1993-98, 97 patients (9.5%) were found to have microscopic colitis. In about a third of these cases, the diagnosis was missed in the primary histological evaluation. Median age at diagnosis was 64 years for collagenous colitis and 59 years for lymphocytic colitis. The annual incidence of the diseases was higher than previously considered and matched the incidence of Crohn's disease, and in combination they approached the incidence of ulcerative colitis. WHERE NEXT: The high regional incidence of microscopic colitis means that both clinicians and pathologists need to be more aware of the diagnosis, especially in the elderly female population with a clinical picture of watery non-bloody diarrhoea. Because of the potentially disabling symptoms, clinicians need to develop and evaluate new therapies.

Colitis, Microscopic↗

Microscopic colitis with giant cells.

AIMS: Collagenous colitis and lymphocytic colitis are the two types of microscopic colitis with specific morphological features. In this report we describe a new histopathological subtype of microscopic colitis. METHODS AND RESULTS: Colonoscopy in four patients with chronic watery diarrhoea showed no macroscopic abnormalities. The random biopsies from the colon showed subepithelial multinucleated giant cells in combination with the features of collagenous colitis in three patients and lymphocytic colitis in one patient. These multinucleated giant cells were positive for CD68. The density of macrophages was highest in the most superficial part of the lamina propria. In one patient, a previous biopsy showed features consistent with collagenous colitis without multinucleated giant cells. Treatment with budesonide led to the disappearance of diarrhoea in all four patients. CONCLUSIONS: The clinical and histopathological features of the four presented patients indicate that there exists a histopathological subtype of microscopic colitis characterized by the presence of subepithelial multinucleated giant cells, which probably arise from fusion of subepithelial macrophages. Analysis of more patients with this histopathological subtype of microscopic colitis is necessary to determine whether they also form a clinically distinct group.

Aged↗

The role of mucosal biopsy in the diagnosis of chronic diarrhea: value of multiple biopsies when colonoscopic finding is normal or nonspecific.

OBJECTIVES: There are controversies about taking routine mucosal biopsy when the gross colonoscopic finding is normal. This study was conducted to determine the frequency of clinically important histological abnormalities, prospectively, in chronic diarrhea patients with grossly normal or nonspecific colonoscopic findings. METHODS: One hundred and eighteen patients suffering from nonbloody diarrhea with average frequency of more than two times a day for more than 4 weeks were included. Multiple biopsies (cecum, ascending colon, mid-transverse colon, descending colon, sigmoid colon and rectum) were taken during colonoscopic examinations and each biopsy specimen was reviewed by one pathologist after H&E and Masson-trichrome staining. RESULTS: Clinically significant abnormalities (2 collagenous colitis, 1 lymphocytic colitis, 1 eosinophilic enterocolitis, 1 ulcerative colitis and 4 melanosis coli) were observed in 9 patients (7.6%). Sixteen cases (13.6%) of borderline histological abnormalities were observed (8 cases of possible collagenous colitis and 8 cases showing some features of lymphocytic colitis). Ninety two cases (78.8%) showed nonspecific inflammation only. CONCLUSION: Clinically important histological lesions can exist in significant percentage in spite of normal or nonspecific colonoscopic findings, which can justify routine mucosal biopsy in the evaluation of chronic diarrhea patients. The clinical significance of borderline histological abnormalities needs to be determined by careful follow-up studies.

Adolescent↗

Association of lymphocytic (microscopic) colitis with tropical sprue.

Lymphocytic (microscopic) colitis is a disease of unknown aetiology which manifests as long-standing intermittent diarrhoea. Diagnosis is confirmed on histological examination of the colon. An association of this uncommon disease with tropical sprue is described. Tetracycline therapy resulted in a favourable clinical response.

Biopsy↗

Histologic study of colonic mucosa in patients with chronic diarrhea and normal colonoscopic findings.

BACKGROUND: There are controversies about the importance of biopsies of normal colon mucosa in the investigation of patients with chronic diarrhea. STUDY: Colonic and terminal ileum biopsies of 167 patients were reviewed. In 5 patients, used as controls, colonoscopy was done due to family history of colon cancer. RESULTS: The 5 patients without symptoms had no histologic abnormalities. The histologic findings in 162 patients with chronic diarrhea were as follows: 110 patients (67.9%) with normal histology, microscopic colitis not otherwise specified, and isolated small granulomas; 17 (10.5%) patients had findings of borderline diagnostic significance, including possible collagenous colitis, some features of lymphocytic colitis and melanosis coli; and 35 (21.6%) patients, with diagnostic significant histologic findings as collagenous colitis, lymphocytic colitis, minimal change microscopic colitis, eosinophilic colitis, pericrypt eosinophilic enterocolitis, intestinal spirochetosis, schistosomiasis, and Crohn's disease. Of the 52 patients with either borderline or significant diagnostic abnormalities, in 8 (15.4%) the diagnosis was done only with a proximal study (ascending, transverse, or descending colons). CONCLUSIONS: Histologic lesions of possible diagnostic value could exist in 32.1% of chronic diarrhea patients with normal colonoscopy, which can justify, in certain cases, mucosa biopsies, which might contribute for a more precise etiologic diagnosis; also, the distribution of these histologic changes has pointed out the importance of having all colon segments biopsied.

Adolescent↗