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Microscopic colitis: epidemiology and treatment.

Microscopic colitis, a chronic diarrheal condition, is characterized by colonic intraepithelial lymphocytosis, expansion of the lamina propria with acute and chronic inflammatory cells, and preserved crypt architecture. These changes, in association with a thickened subepithelial collagen band, are termed collagenous colitis, whereas changes occurring without a thickened collagen band are classified as lymphocytic colitis. Population-based epidemiologic studies confirm that microscopic colitis is most frequently diagnosed in middle-aged or elderly women and that its incidence is rising. Although these disorders diminish patients' quality of life, they are not associated with an increased risk of colorectal cancer, and survival is not diminished. Clinical and histologic improvement after therapy have been noted in one randomized trial of bismuth subsalicylate and three randomized clinical trials of oral delayed-release budesonide. A treatment algorithm for microscopic colitis is proposed.

Chronic Disease↗

Colonic subepithelial collagenous thickening in diabetic patients.

PURPOSE: This study was designed to investigate the effect of intestinal subepithelial collagenous thickening on diabetic diarrhea because one of the seven patients diagnosed with collagenous colitis was diabetic. METHODS: Rectosigmoidoscopic rectal biopsies were taken from 50 diabetic patients (8 with and 42 without diarrhea), 20 nondiabetic patients with diarrhea, and 10 healthy patients. Histopathologic examinations and measurements of subepithelial collagen layers were performed on these biopsies. RESULTS: In diabetic patients who had diarrhea, the subepithelial collagen layer (SCL) was thicker than it was in diabetics without diarrhea (P < 0.05). In diabetic groups, the SCL was thicker than it was in both nondiabetics with diarrhea and those without diarrhea (P < 0.05). There was no statistical difference between nondiabetics with diarrhea and those without (P > 0.05). There was no correlation between collagen thickness, age, and diabetes duration (P > 0.05). CONCLUSIONS: It was concluded that there was a thickening of the colonic SCL in diabetic patients.

Colitis↗

Lymphocytic venulitis: an unusual association with microscopic colitis.

A 79 year old man presented with occult gastrointestinal bleeds and anaemia for two years. He had received 40 units of blood over a period of one year, following which he had a subtotal colectomy as no definite cause of the bleeding was apparent. Macroscopically the colon appeared unremarkable. Light microscopy showed prominent lymphocytic venulitis in the proximal portion, gradually merging into lymphocytic and collagenous colitis distally.

Aged↗

Collagenous and lymphocytic colitis: subject review and therapeutic alternatives.

OBJECTIVE: To review the published studies on collagenous and lymphocytic (microscopic) colitis with specific emphasis on clinical features, investigational studies, characteristic histology, possible pathogenesis, disease course, and empirical treatment. DESIGN: Comprehensive synopsis of the stated objective, prepared for the physician treating patients with collagenous or lymphocytic colitis. MATERIALS AND METHODS: The medical literature on collagenous and lymphocytic colitis. RESULTS: Collagenous and lymphocytic colitis are chronic diarrheal illnesses of indeterminate etiology that typically present in the late sixth or early seventh decade of life. These disorders may be distinct entities, although some data support the idea that they are only different manifestations of the same disease. The pathogenesis is unknown but may be on an inflammatory, possibly autoimmune, basis. Physical examination and investigational studies are normal or nonspecific, with fecal leukocytosis the only abnormality found in the majority of patients tested. Association with various gastrointestinal, autoimmune, and rheumatologic conditions has been observed in some patients. Clinical and occasional histologic response has been observed after treatment with anti-inflammatory agents such as 5-aminosalicylate and corticosteroids, and should be used when there is no response to symptomatic therapy. CONCLUSIONS: Collagenous and lymphocytic colitis are uncommon but important causes of chronic diarrhea which are important to diagnose and treat.

Algorithms↗

Side effects of nonsteroidal anti-inflammatory drugs on the small and large intestine in humans.

BACKGROUND: It is not widely appreciated that nonsteroidal anti-inflammatory drugs (NSAIDs) may cause damage distal to the duodenum. We reviewed the adverse effects of NSAIDs on the large and small intestine, the clinical implications and pathogenesis. METHODS: A systematic search was made through Medline and Embase to identify possible adverse effects of NSAIDs on the large and small intestine. RESULTS: Ingested NSAIDs may cause a nonspecific colitis (in particular, fenemates), and many patients with collagenous colitis are taking NSAIDs. Large intestinal ulcers, bleeding, and perforation are occasionally due to NSAIDs. NSAIDs may cause relapse of classic inflammatory bowel disease and contribute to serious complications of diverticular disease (fistula and perforation). NSAIDs may occasionally cause small intestinal perforation, ulcers, and strictures requiring surgery. NSAIDs, however, frequently cause small intestinal inflammation, and the associated complications of blood loss and protein loss may lead to difficult management problems. The pathogenesis of NSAID enteropathy is a multistage process involving specific biochemical and subcellular organelle damage followed by a relatively nonspecific tissue reaction. The various possible treatments of NSAID-induced enteropathy (sulphasalazine, misoprostol, metronidazole) have yet to undergo rigorous trials. CONCLUSIONS: The adverse effects of NSAIDs distal to the duodenum represent a range of pathologies that may be asymptomatic, but some are life threatening.

Animals↗

Microscopic colitis: pathologic considerations, changing dogma.

Microscopic colitis as an entity was first recognized in 1976, and has become one of the most frequent diseases to exclude on colonic mucosal biopsies. In some pathology practices, up to 30% of colonic biopsies received are from patients in whom microscopic colitis is the clinical question. In this review, the evolution of the terminology and early studies describing the pathology of microscopic colitis are discussed. The pathology of lymphocytic and collagenous colitis is reviewed in detail, including common diagnostic pitfalls, and what is currently known about the pathogenesis of these diseases. The differential diagnosis of microscopic colitis includes other idiopathic inflammatory bowel diseases (Crohn's and ulcerative colitis), infections, and drug reactions. The distinction between these entities and microscopic colitis is discussed in detail. Finally, recent studies have revealed new histopathologic changes in microscopic colitis that challenge the currently held concepts of how microscopic colitis fits into the spectrum of inflammatory bowel diseases.

Colitis↗

Microscopic colitis.

Microscopic colitis (MC) is viewed as an umbrella term applicable to both lymphocytic and collagenous colitis. The first case was published in 1976, a new entity with chronic watery diarrhea with lymphocytic colitis, with or without a subepithelial collagen deposition. Patients are usually middle-aged women, and the pathogenesis is unknown. The response to steroids and the female predominance underlines an autoimmune disease. Up to 40% NSAID's and Lanzoprazole-induced MC are well-known. Biopsies during sigmoidoscopy in unexplained diarrhea must be standard. Treatment is empirical. The most important step is to ban all NSAID's and other MC inducing agents. Immunosuppressive treatment must be considered. However the disease has a benign course and sometimes is selflimiting.

Colitis↗

Sonographic detection of longitudinal ulcers in Crohn disease.

BACKGROUND: The purpose of this study was to investigate the characteristic sonographic features, such as focal disappearance of the wall stratification sign (FD sign), of longitudinal ulcers in patients with Crohn disease (CD). METHODS: A total of 545 sonographic examinations of patients with Crohn disease (n = 166), ulcerative colitis (n = 196), bacterial colitis (n = 78), ischemic colitis (n = 63), pseudomembranous colitis (n = 32), Behçet's disease (n = 7), and collagenous colitis (n = 3) were extracted. The sonographic findings were compared with those of a barium contrast study, colonoscopy, and resected specimens. In transverse views of the bowel segment, wall stratification was investigated. The FD sign was defined as the disappearance of the layered structure observed in a single portion of the bowel circumference. Prevalence of the FD sign was investigated for each disease. RESULTS: Eighty lesions (76 CD, 1 ulcerative colitis, 2 ischemic colitis, 1 Behçet's disease) with active single longitudinal ulcers were detected by barium contrast study and endoscopy. Among them, the FD sign was detected by ultrasonography (US) in 73 lesions (91.3%). No lesions with the FD sign were found by US without radiological or endoscopic findings of longitudinal ulcers. An in vitro study (water-immersion method) of resected specimens revealed that the FD sign reflected the focal destruction of wall stratification caused by the deep longitudinal ulceration. CONCLUSIONS: Ultrasonographic findings of FD sign are correlated with the existence of deep longitudinal ulcers, which are most frequently found in CD. US is a useful diagnostic modality for detecting longitudinal ulcers in patients with CD.

Adolescent↗

Topographic mapping of collagenous gastritis.

A 74-year-old woman was investigated for abdominal pain and diarrhea. Endoscopic examinations including biopsies of the stomach and colon demonstrated the typical subepithelial deposits characteristic of collagenous gastritis and collagenous colitis. Histochemical and ultrastructural methods confirmed the presence of collagen in the subepithelial deposits. The topographic distribution of these collagen deposits and their relationship to the inflammatory process in the stomach were then defined by endoscopic mapping and multiple site biopsies of the mucosa in the gastric body and antrum. These studies indicate that collagenous gastritis not only is distinctive, but also is a far more extensive and diffuse inflammatory process than has previously been appreciated.

Aged↗

Disrupted barrier function through epithelial cell apoptosis.

Epithelial barrier function is determined by trans- and paracellular permeabilities, the latter of which is mainly influenced by tight junctions (TJs) and apoptotic leaks within the epithelium. The present article aims to present experimental evidence for a functional role of epithelial apoptoses by means of cell culture models as well as in tissues from patients with inflammatory bowel disease. It is shown that epithelial apoptoses are sites of elevated conductance within the intestinal epithelium and that proinflammatory cytokines like TNF-alpha upregulate both the apoptotic rate and single apoptotic conductivity, making cytokine-induced apoptosis functionally far more relevant than is spontaneous apoptosis. In ulcerative colitis and Crohn's disease (CD), but not in collagenous colitis, apoptotic rates are increased to about 5%, in mild-to-moderately inflamed colon specimens, where as the control apoptotic rate is about 2%. Thus, epithelial apoptoses lead to a loss of ions and water into the intestinal lumen, causing leak flux diarrhea and enabling small antigens of <4,000 Da in the intestinal lumen to enter the intestinal mucosa, thereby perpetuating inflammatory responses. In addition to TNF-alpha, interleukin (IL)-13 is an important inductor of epithelial apoptosis in Th2 immune responses. Therapeutically,TNF-alpha-antibodies (infliximab) can restore barrier function in Crohn's disease by downregulating epithelial apoptoses, while epithelial TJs are unaffected.

Apoptosis↗

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↗

Sequential clinical and histopathological changes in collagenous and lymphocytic colitis over time.

We conducted this retrospective study to evaluate the relationship between symptoms, histological findings, and treatment of collagenous (CC) and lymphocytic colitis (LC). We identified 19 CC and 12 LC patients having multiple colonoscopic procedures with colonic biopsies during their course of illness. A detailed histological review of all biopsies was performed. Clinical history, including symptoms and medications, was obtained in 25 of the 31 patients and was correlated with their histological findings. In all, 25% of the CC patients and 50% of the LC patients who had biopsies prior to their definitive diagnosis had the pathognomonic histological features on their prior biopsies to some extent (but were not recognized by the pathologists); however, these features were more pronounced on the biopsies from the procedure that established the diagnosis. Nonetheless, 10 of 12 such patients with clinical data available had symptoms and were being treated at the time of prior biopsies. Assessment of the relationship among histological, clinical and therapeutic data showed no association between symptoms or histological findings and treatment with any medication. In summary, in this sample of CC and LC patients, symptoms often precede fully developed histological features. No change in symptoms or histological findings was found to be associated with medication.

Abdominal Pain↗

[Microscopic colitis].

A 38-year old woman is admitted in the gastroenterology unit for a disabling episode of watery diarrhoea, not bloody and refractory to anti-diarrheic drugs. Different diagnostic exams remain negatives, with the exception of colic biopsies who disclose a lymphocytic colitis, one of the forms of the microscopic colitis entity. Microscopic colitis is an anatomo-clinic syndrome characterized by the presence of histological abnormalities on colic biopsies amongst patients suffering from chronic watery diarrhoea without endoscopic anomalies. Two clinical entities are today well known: collagenous colitis is characterized by a thickening of the sub-epithelial collagen band of the colon; lymphocytic colitis is defined as an increased level of lymphocytic cells, more than 20%, in the epithelial surface of colorectal mucosa. Inflammatory lesions of the chorion and alterations of the epithelial surface are seen in the two types of colitis. Their etiology remains unknown. It could be due to inflammatory lesions from autoimmune origin, activated by various exogenous agents such as bacteria and drugs. Clinical (feminine prevalence, frequent association with auto-immune diseases) and morphological similarities lead to argue and to hypothesis that both entities could represent different stages of the same disease, the lymphocytic colitis being the early stage. Various treatments have been proposed, for instance 5-aminosalicylates, but today mainly synthetic corticoids are used, especially budesonide. Others entities are recently been described: the chronic pericrypt eosinophilic enterocolitis and the colonic epithelial lymphocytosis ("epidemic").

Adult↗

Predisposing HLA-DQ2 and HLA-DQ8 haplotypes of coeliac disease and associated enteropathy in microscopic colitis.

OBJECTIVE: To assess the presence of both genetic and serological markers of coeliac disease in patients with microscopic colitis, and whether there was associated enteropathy. METHODS: HLA-DQ2, HLA-DQ8, serum immunoglobulin A-antiendomysial and immunoglobulin A-anti-tissue transglutaminase antibodies were investigated in 59 patients with microscopic colitis. Seventy healthy subjects acted as the control group. Endoscopic biopsies from the distal duodenum were obtained in DQ2-positive or DQ8-positive patients. Patients with histological changes compatible with gluten-sensitive enteropathy were started on a gluten-free diet. RESULTS: Seventeen of 70 (24.3%) healthy controls were DQ2-positive. Twelve of 25 (48%) patients with lymphocytic colitis (P = 0.027 versus controls), and 11 of 34 (32.3%) with collagenous colitis (P = 0.38 versus controls) were DQ2-positive. There were no differences in the frequency of DQ8-positivity. The coeliac serology was positive in one patient. Duodenal biopsies were performed in 23 DQ2-positive and/or DQ8-positive patients. None had villous atrophy (Marsh III lesion) (0%; 95% confidence interval, 0-6.1). A Marsh type I lesion was found in four patients. Three of these patients were put on a gluten-free diet with disappearance of diarrhoea. CONCLUSIONS: The results suggest that there is an association of lymphocytic colitis with HLA-DQ2 genes, which might be relevant in the pathogenesis of this disease. The association of microscopic colitis with Marsh type III coeliac disease seems to be rare, making it unnecessary to routinely screen for coeliac disease in microscopic colitis patients.

Aged↗

Microscopic colitis.

Microscopic colitis is an umbrella term used to include two idiopathic inflammatory bowel disorders that present with chronic watery diarrhea, normal endoscopic findings and characteristic inflammatory changes on histology. Collagenous colitis and lymphocytic colitis are distinguished by the presence of a thickened subepithelial collagen table. It is likely that they are a spectrum of one disease, but this is yet to be proven. The majority of cases tend to undergo spontaneous remission within a few years of onset, and their clinical course is benign, with no increase in risk of colorectal cancer. Sufficient evidence exists to suggest that microscopic colitis occurs as a response to one or more luminal antigens. A variety of medications have been reported in the treatment of this condition, but only colloidal bismuth and budesonide have thus far been shown to be effective in randomized controlled trials.

Anti-Inflammatory Agents↗

Lymphocytic colitis: clinical features, treatment, and outcomes.

OBJECTIVE: There are no reports of the clinical features or treatment outcomes in large series of patients with lymphocytic colitis, and it is not known whether treatments that appear to be beneficial in patients with collagenous colitis are also beneficial in lymphocytic colitis. We sought to analyze these issues in our patients with lymphocytic colitis. METHODS: All patients with biopsy-proven lymphocytic colitis evaluated at our institution between January 1, 1997, and December 31, 1999, were identified. Clinical features on presentation and treatment outcomes were abstracted from the medical records. RESULTS: A total of 170 patients with lymphocytic colitis were identified (median age 67 yr, 61% female). Diarrhea, bloating, rectal urgency, fecal incontinence, weight loss, concomitant autoimmune disorders, and aspirin or nonsteroidal anti-inflammatory drug use were common. Loperamide, diphenoxylate/atropine, and bismuth subsalicylate were effective therapies and were well tolerated. However, no therapy produced a complete response in more than 40% of patients. CONCLUSIONS: Lymphocytic colitis typically presents in elderly patients as chronic diarrhea. Nocturnal stools, urgency, and abdominal pain occur frequently, as do weight loss, fecal incontinence, and concomitant autoimmune disorders. Many empiric treatment options are used, but overall response rates are disappointing. Randomized controlled trials are needed to determine the optimum therapeutic approach to these patients.

Adolescent↗

Microscopic colitis: prevalence and distribution throughout the colon in patients with chronic diarrhoea.

BACKGROUND: Microscopic colitis presents with chronic diarrhoea with or without abdominal pain. Microscopic colitis is an important cause of chronic diarrhoea. It can be distributed throughout the colon, as well as limited to the right colon. Microscopic colitis is associated with coeliac disease. We studied the prevalence and distribution of microscopic colitis in patients with diarrhoea and normal colonoscopy and we studied the association with coeliac disease. METHODS: Colonoscopy was performed. Biopsies were taken from every segment of the colon. Lymphocytic colitis was defined as the presence of more than 20 lymphocytes per 100 epithelial cells and collagenous colitis was defined as thickening of the basal membrane of more than 10 microm. Upper endoscopy was performed if upper intestinal symptoms were present. If this was the case, small bowel biopsies were taken. RESULTS: Microscopic colitis was found in 13 out of 103 patients. The distribution was diffuse throughout the colon in ten and restricted to the right colon in three patients. In seven patients, upper endoscopy was performed. Marsh I/II lesions were found in six out of seven patients. CONCLUSION: Microscopic colitis was limited to the right colon in 23% of patients. Biopsies of macroscopically normal colonic mucosa in patients with diarrhoea is mandatory.

Adolescent↗

Crohn's disease associated with seropositive rheumatoid arthritis.

We report two cases of rheumatoid arthritis (RA) associated with Crohn's disease (CD). The first case was a 60-year-old man with longstanding CD who next developed a seropositive, nodular RA. This patient also had bilateral sacroiliitis, but without positive HLA B27. The second was a 65-year-old female with a 15-year history of seropositive RA who presented secondarily a CD. No sacroiliitis or nodules were found in this patient. Both patients were DR1 (DRB1* 0101). Gold salts were only given in the second case and were stopped many years before the gastrointestinal symptoms. A similar case report has been previously described consisting in an ulcerative colitis complicating a seronegative HLA-B27 RA with sacroiliitis. The gastrointestinal involvement in RA may be broad and includes many causes: drug-induced colitis (including gold enterocolitis) vasculitis and amyloidosis located in the gut, associated bowel disease such as collagenous colitis, and also infectious agents. In addition, erosive polyarthritis associated with gastrointestinal manifestations can present a problem in the differential diagnosis between RA and an enteropathic arthritis. Finally, the coexistence by chance of inflammatory bowel disease and RA is suggested by the low occurrence of these two conditions in the same patient.

Aged↗