Lymphocytic (microscopic) colitis

Lymphocytic colitis, formerly called microscopic colitis, is a clinicopathologic syndrome with chronic watery diarrhea and diffuse mucosal inflammatory changes with prominent intraepithelial lymphocytes. The 18 lymphocytic colitis patients studied presented with chronic watery diarrhea at a mean age of 53.8±17 years (±1 SD). Roentgenographic, endoscopic, and culture data were not diagnostic. In patients tested, there was a high prevalence of arthritis (82%) and autoantibodies (50%) but no increase in frequency of histocompatibility antigens associated with well-defined autoimmune disease (DR3, B8). Lymphocytic colitis patients were compared to 21 patients with collagenous colitis. Similarities included age, symptomatology, and nondiagnostic radiographic and endoscopic studies. However, the sex distribution was statistically different, with an equal male-to-female ratio in lymphocytic colitis and female predominance (80%) in collagenous colitis. Other differences included dissimilar histocompatibility phenotypes and collagen band on biopsies of collagenous but not lymphocytic colitis. These findings suggest that lymphocytic and collagenous colitis may be related yet distinct disorders.Presented in part at The National Foundation for Ileitis and Colitis Seminar in Ft. Lauderdale, Florida, October 1987.Supported in part by The Harvey M. and Lyn P. Meyerhoff Digestive Disease-Inflammatory Bowel Disease Center, The National Foundation for Ileitis and Colitis, and by an institutional grant from The Johns Hopkins University School of Medicine.Dr. Lazenby is a recipient of a fellowship from The National Foundation for Ileitis and Colitis.     

Contemporary methods for the diagnosis and treatment of microscopic colitis

Microscopic colitis is a common cause of chronic diarrhea. It is characterized by non-bloody watery diarrhea with macroscopically normal colonic mucosa. Its specific histological characteristics confirm the diagnosis. Two distinct histological forms can be identified, namely, collagenous colitis and lymphocytic colitis. In collagenous colitis, a thick colonic subepithelial collagenous deposit can be observed, whereas in lymphocytic colitis, a pronounced intraepithelial lymphocytic inflammation in the absence of a thickened collagen band can be identified. Microscopic colitis occurs more frequently in elderly females and its etiology is believed to be multifactorial, although smoking and consumption of several drugs have been identified as risks factors for the development of the disease. The treatment is based on avoiding the risks factors and administration of oral budesonide.     

Histopathological diagnosis of microscopic colitis

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

The epidemiology of microscopic colitis: a 10-year pathology-based nationwide Danish cohort study

Abstract

Objective. Microscopic colitis (MC) includes two main types: collagenous colitis (CC) and lymphocytic colitis (LC). Previous studies have indicated an increasing incidence, but these have mainly been based on regional databases. We found it important to study the epidemiology based on a comprehensive nationwide cohort. Material and methods. We studied the epidemiological data of MC in Denmark from 2002 to 2011. The cohort consisted of all patients with a recorded diagnosis of either CC or LC in the Danish Pathology Register during the study period. Data on all patients with a registered colon biopsy were also included. Results. A total of 7777 patients, 4749 (61%) with CC and 3028 (39%) with LC, were identified. Over the study period, the annual incidence of diagnosed cases of CC increased from 2.9/10⁵ to 14.9/10⁵ and of LC from 1.7/10⁵ to 9.8/10⁵. In 2011, the incidence of MC was 24.7/10⁵ inhabitants. The age-specific incidence showed that the risk of both CC and LC increased with age. The female/male ratio, distribution of the type of colitis and mean age at diagnosis were relatively stable during the study period. The annual number of registered colon biopsies in the pathology register increased from 21.583 in 2002 to 39.733 in 2011, indicating an increased diagnostic activity. Conclusion. In a nationwide cohort study, the incidence of CC and LC continued to increase from 2002 to 2011. An increased diagnostic activity could in part explain the increase in the number of diagnosed cases.     

Sequential histologic evaluations in collagenous colitis

To evaluate the histologic manifestations of collagenous colitis and correlate histologic changes with disease behavior, 14 patients who had undergone sequential evaluations during 33±6 months of follow-up were studied. Two hundred twelve tissue specimens from all anatomic regions of the colon (mean, 15±3 samples per patient) were interpretated independently under code by two pathologists. Eight patients (57%) had histologic resolution after 14±4 months of empiric therapy and in only one of these (12%) did symptoms persist. Four patients (29%) had sequential histologic examinations from the same anatomic region that varied from classical collagenous colitis to ilflamed mucosa without a thickened collagen band to normal mucosa. Eight patients (57%) had varying histologic findings from different anatomic regions during the same examination that ranged from classical collagenous colitis to increased inflammation with resolution of the collagen band to normal mucosa. Normal mucosa was found mainly in specimens from the rectosigmoid, and proctosigmoidoscopic examinations alone would have missed the diagnosis of collagenous colitis in 40% of cases. Pathologic interpretations were concordant in 171 of 212 instances (81%). We conclude that histologic resolution of collagenous colitis can occur and it is associated with loss of symptoms. The histologic features of collagenous colitis are distinctive, but they may be patchy and inconsistently sampled. Rectosigmoid biopsies underestimate the diagnosis.Data analysis was performed in part using the CLINFO Data Analysis System.Presented in part at the annual meeting of the American College of Gastroenterology, October 16, 1991, Boston, Massachusetts.     

Collagenous and lymphocytic colitis in Iceland

The aim of this study was to determine the nationwide incidence of collagenous and lymphocytic colitis in Iceland and the location of histopathological changes in the large bowel. All pathology reports of patients diagnosed with or suspected of having collagenous colitis or lymphocytic colitis in the period 1995–1999 were identified. All pathology samples were reevaluated using strict diagnostic criteria. After reevaluation 125 patients fulfilled our diagnostic criteria, 71 as collagenous colitis and 54 as lymphocytic colitis. The mean annual incidence for collagenous colitis was 5.2/100,000 inhabitants, and the mean age at diagnosis was 66.1 years. The mean annual incidence for lymphocytic colitis was 4.0/100,000 inhabitants, the mean age at diagnosis was 68.7 years. Both diseases more commonly involved the colon than the rectum. The incidence of collagenous colitis and lymphocytic colitis is high in Iceland. The mean annual incidence of collagenous colitis is much higher in Iceland than hitherto reported elsewhere.     

Clinical features of microscopic colitis in a nation-wide follow-up study in Iceland

Objective. The long-term natural history of collagenous colitis (CC) and lymphocytic colitis (LC) is not well known. The few reports available that address these issues have a limited follow-up. The aims of this study were to evaluate the natural history of microscopic colitis (MC), to describe the treatment medications prescribed and to assess the use of non-steroidal anti-inflammatory drugs (NSAIDs) in MC. Material and methods. This study is based on an earlier epidemiological study conducted in Iceland where 125 patients with MC (71 with CC and 54 with LC) were diagnosed in the period 1995–99. All patients still alive and available were questioned about symptoms, treatment and NSAID use in the 3 months preceding the interview. Results. In a mean follow-up time of 6.4 years from diagnosis, 15% of the patients had diarrhoeal symptoms more than once a week, 30% less than once a week and 55% had no diarrhoea. Abdominal pain was reported in 18% of the patients. There was no statistically significant difference in symptoms of CC and LC patients. Forty-eight patients (50%) were receiving medication for MC, 16% used aminosalicylates and 14% corticosteroids. Patients using medication for MC had significantly more diarrhoeal symptoms compared with those who did not (p=0.002). Patients using NSAIDs regularly or as required, statistically did not have more symptoms related to MC than non-NSAID users. Conclusions. Only a minority of patients with MC had diarrhoea more than once a week in a long-term follow-up and the symptom pattern was similar between CC and LC patients. The use of NSAIDs was not associated with more diarrhoeal symptoms.     

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.     

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.     

Efficacy of anti-TNF therapies in refractory severe microscopic colitis

Background

Refractory microscopic colitis is a rare condition with an unknown rate of occurrence. The efficacy of anti-tumor necrosis factor (TNF) therapy for microscopic colitis has never been reported.Aims1) To report the frequency of refractory microscopic colitis in the database of the participant hospitals. 2) To describe the therapeutic response to anti-TNF therapy among the refractory cases.

Methods

Patients with a histological diagnosis of collagenous colitis and lymphocytic colitis were identified through the Department of Pathology database and the IBD practice database. Patients refractory to medical treatment and with severe symptoms were offered anti-TNF therapy.

Results

Five of 372 MC patients (1.3%; 95% CI, 0.6 to 3.1) presented with severe symptoms refractory to standard medical therapies. One patient was denied therapy from her insurance carrier. The other 4 received infliximab therapy. The response was excellent after one dose experiencing a 60–90% decrease in bowel movements. Three patients were switched to adalimumab (2 allergic reactions and 1 early loss of response to infliximab). Long-term clinical remission (more than 1 year) was achieved in three cases (2 with adalimumab and 1 with infliximab). One patient on adalimumab had an early loss of response and was referred for colectomy.

Conclusions

Microscopic colitis with severe symptoms refractory to standard medical therapy including immunosuppressives is uncommon. In this setting, anti-TNF therapies may be a good option to avoid colectomy.     

Microscopic colitis. A review

Microscopic colitis (MC) is characterized by a triad of watery diarrhea, usually normal colonoscopic findings and typical microscopic findings. Two distinct histological forms of MC have been defined: lymphocytic colitis and collagenous colitis, but overlapping features may be present. The incidence of MC appears to be rising and in some countries it may account for as many as 10–20% of patients with non‐bloody watery diarrhea. The cause of MC remains unknown and is likely to be multifactorial. The pathogenesis is poorly defined, and numerous immunological abnormalities have been reported. MC is commonly associated with autoimmune diseases including celiac disease. Use of various medications, most notably non‐steroidal anti‐inflammatory agents and proton pump inhibitors, have been etiologically implicated but not firmly established as causative. In imperfect trials several agents have been reported to be effective in the treatment of MC; budesonide is the best studied and evidence supporting its effectiveness is the most persuasive. In cases of otherwise unexplained watery, non‐bloody diarrhea, MC should be considered and colonic biopsied specimens should be taken of normal‐appearing mucosa.     

Microscopic colitis: an underdiagnosed cause of chronic diarrhoea--the clue is in the biopsies

Microscopic forms of colitis (collagenous colitis and lymphocytic colitis) are uncommon but important causes of chronic diarrhoea that are often overlooked. The clinical features of these disorders are similar, and they are more common in middle-aged females, although the female predominance is greater in collagenous colitis. Although their cause is unclear, both are associated with a variety of autoimmune diseases. Colonoscopy and barium enema are typically normal, so that the diagnosis depends on the demonstration of characteristic changes on histopathological examination of colorectal biopsies. These should be taken in all patients undergoing colonoscopy for the investigation of chronic diarrhoea. There are no large controlled trials of therapy available. Treatment is empirical, generally using the same agents as for inflammatory bowel -disease. Assessment of therapy is also difficult as spontaneous remissions occur often.     

Clinical characteristics and patterns and predictors of response to therapy in collagenous and lymphocytic colitis

Abstract

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

Collagenous colitis and lymphocytic colitis: Patient characteristics and clinical presentation

Objective. Collagenous colitis and lymphocytic colitis (collectively known as microscopic colitis) are characterized by chronic diarrhea, normal endoscopic and radiologic findings, and typical findings on histologic examination of colonic tissue. The purpose of this study was to define the background characteristics of patients with microscopic colitis, as well as to present symptoms, coexistent autoimmune diseases, and a possible association with the use of non-steroidal anti-inflammatory drugs (NSAIDs) and ticlopidine. Material and methods. A retrospective chart review was carried out on all cases of collagenous colitis and lymphocytic colitis diagnosed at a single center from July 1992 to July 2002. Results. Of the 104 patients identified, 66 had collagenous colitis, 35 had lymphocytic colitis, and 3 were diagnosed with both disorders at different times. The mean age of patients was 64 years (26–88 years), with a female:male ratio of 4.8:1. The most common presenting symptoms were diarrhea (95%), weight loss (41%), abdominal pain (40%), fecal urgency (29%), and nocturnal stools (22%). Autoimmune disease was diagnosed in 29% of patients, 35% were using an NSAID, and 2% were using ticlopidine. Conclusions. Collagenous colitis and lymphocytic colitis occur more often in females than in males, at a wide age range, with a mean in the seventh decade. Certain symptoms are characteristic, but are not specific to these disorders. There may be an association with the presence of a coexistent autoimmune disorder and the use of drugs such as NSAIDs.     

Original research: Incidence of collagenous colitis in NHS Lothian: a population-based study

ObjectiveIncreases in incidence of collagenous colitis (CC) have been documented across Europe; however, previous data from NHS Lothian (1998–2003) demonstrated this to be a low-prevalence area. We aimed to assess incidence of CC in NHS Lothian over time by comparing a more recent cohort (2013–2018) with our existing cohort.MethodsAll histologically confirmed diagnoses of CC between 2013 and 2018 were obtained from the NHS Lothian colorectal pathology department (Western General Hospital, Edinburgh). Case record review was performed to obtain relevant demographic and clinical data. Data were also collected regarding the availability of colonoscopy in NHS Lothian.Results224 cases of CC were diagnosed between 2013 and 2018, compared with 25 between 1998 and 2003. Mean annual incidence rose from 0.5/100 000 population to 4.3/100 000 population. Incidence in females ≥60 years old rose from 2.3/100 000 population to 22.4/100 000 population (p<0.001). The total number of colonoscopies performed increased by 179.1% from 15 262 (1998–2003) to 42 600 (2013–2018), with the number of CC cases per 1000 colonoscopies performed rising from 1.7 to 5.3 (p<0.001).ConclusionWe describe the increasing incidence of CC in Southeast Scotland, with temporal trends comparable to other European countries. The increase is particularly marked in older females and parallels increasing numbers of colonoscopies being performed.     

Collagenous colitis: oral low-dose methotrexate for patients with difficult symptoms: long-term outcomes

AIM: To perform a qualitative retrospective review of identified cases of collagenous colitis within the patient databases of local clinicians, with particular attention to the use and effectiveness of oral low-dose methotrexate. METHODS: Gastroenterologists in the referral area were invited to identify collagenous colitis cases from their own databases for inclusion in the study. Patients were considered eligible if they had a symptom history and colonic mucosal histology consistent with collagenous colitis. The retrospective analysis identified age at diagnosis, previous therapies, date of commencement and duration and effectiveness of methotrexate, side-effects, and repeat colonic mucosal histology (if available) after a period of treatment. RESULTS: Between 1986 and 2003, 43 eligible patients were identified, ranging in age from 32 years to 88 years at the time of diagnosis. Nineteen of the 43 received methotrexate over varying periods, and in 16 of these the clinical response was considered either 'Good' (14) or 'Partial' (2). In the methotrexate group 10 of the 19 underwent repeat colonoscopy and mucosal biopsy at some stage after commencing methotrexate. Of these, five had normal histology in comparison with pretreatment abnormal histology, two had improvement but not normalization of histology, and three had unchanged abnormal histology. CONCLUSION: The data from this retrospective review suggest that methotrexate may have a beneficial effect on symptoms of collagenous colitis and may improve the underlying histological abnormality. A controlled trial of adequate power and duration is needed to further clarify the usefulness of methotrexate in this condition.     

Use of Budesonide in the Treatment of Microscopic Colitis

Collagenous colitis and lymphocytic colitis, the two types of microscopic colitis, cause watery diarrhea. Budesonide, a glucocorticoid medication with limited systemic availability, is commonly used to treat these illnesses. Budesonide has proven efficacy in the induction of clinical remission in both collagenous colitis and lymphocytic colitis. Budesonide is effective as a maintenance drug for patients with collagenous colitis, but has not been studied for this indication in patients with lymphocytic colitis. This drug improves quality of life in patients while causing few mild adverse events. Budesonide is an effective treatment of microscopic colitis that is safe and well tolerated.     

Clinical characteristics of collagenous and lymphocytic colitis

Background: Microscopic colitides (MC), collagenous colitis (CC) and lymphocytic colitis (LC) share clinical features, but their mutual relationship is unclear, and clinical comparative studies are rare. We aimed to examine the clinical features in CC and LC by focusing on concomitant diseases. Methods: Patients with MC (30 with CC, 54 with LC) were identified in the pathology databases and by reviewing biopsies. Controls included 84 age‐ and sex‐matched persons. The clinical data collected from patient records were prospectively completed by interviews. Results: The female:male ratio was 2:1 in CC and 5.75:1 in LC. Mean age at diagnosis was 53 in CC and 55.4 years in LC. There were no differences in the pattern of symptoms. Concomitant autoimmune diseases were more common in CC (53.3%) than in LC (25.9%; P?=?0.017). Celiac disease was common in both CC (20%) and LC (14.8%). Bronchial asthma was associated with LC (25.9%), but not with CC (6.7%; P?=?0.042). Colon diverticulosis was rare in MC (16%) compared with the controls (39%; P?=?0.001). Hypolactasia was common in MC (45%; 76% in CC, 54% in LC) compared to its prevalence in the Finnish general population (17%). Conclusions: CC and LC are largely similar clinically, but the differences in the occurrence of autoimmune conditions and bronchial asthma suggest that they differ in immunopathogenesis. MC is associated with reduced lactose tolerance and shows a negative association with diverticular disease, possibly related to the small intestinal pathology and abnormal stool consistency.     

Association of lymphocytic (microscopic) colitis with tropical sprue

Abstract 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.     

Role of bile acids and bile acid binding agents in patients with collagenous colitis

BACKGROUND: In a retrospective study bile acid malabsorption was observed in patients with collagenous colitis. AIMS: To study the occurrence of bile acid malabsorption and the effect of bile acid binders prospectively in patients with chronic diarrhoea and collagenous colitis. METHODS: Over 36 months all patients referred because of chronic diarrhoea completed a diagnostic programme, including gastroscopy with duodenal biopsy, colonoscopy with biopsies, and the (75)Se-homocholic acid taurine ((75)SeHCAT) test for bile acid malabsorption. Treatment with a bile acid binder (cholestyramine in 24, colestipol in three) was given, irrespective of the results of the (75)SeHCAT test. RESULTS: Collagenous colitis was found in 28 patients (six men, 22 women), 27 of whom had persistent symptoms and completed the programme. Four patients had had a previous cholecystectomy or a distal gastric resection. The (75)SeHCAT test was abnormal in 12/27 (44%) of the collagenous colitis patients with (75)SeHCAT values 0.5-9.7%, and normal in 15 patients (56%). Bile acid binding treatment was followed by a rapid, marked, or complete improvement in 21/27 (78%) of the collagenous colitis patients. Rapid improvement occurred in 11/12 (92%) of the patients with bile acid malabsorption compared with 10/15 (67%) of the patients with normal (75)SeHCAT tests. CONCLUSION: Bile acid malabsorption is common in patients with collagenous colitis and is probably an important pathophysiological factor. Because of a high response rate without serious side effects, bile acid binding treatment should be considered for collagenous colitis, particularly patients with bile acid malabsorption.