Analysis on lansoprazole-induced microscopic colitis in 62 patients

Issue Highlights

Chronic diarrhea

In recent years, microscopic colitis has been increasingly diagnosed. This review was carried out to evaluate demographic factors for microscopic colitis and to perform a systematic assessment of available treatment options. Relevant publications up to December 2013 were identified following searches of PubMed and Google Scholar using the key words 'microscopic colitis', 'collagenous colitis' and 'lymphocytic colitis'. Two-hundred and forty-eight articles were identified. The term microscopic colitis includes lymphocytic colitis and collagenous colitis. Both have common clinical symptoms but are well defined histopathologically. The clinical course is usually benign, but serious complications, including death, may occur. A peak incidence from 60 to 70years of age with a female preponderance is observed. Although most cases are idiopathic, associations with autoimmune disorders, such as coeliac disease and hypothyroidism, as well as with exposure to nonsteroidal anti-inflammatory drugs and proton-pump inhibitors, have been observed. The incidence and prevalence of microscopic colitis is rising and good-quality epidemiological research is needed. Treatment is currently largely based on anecdotal evidence and on results from limited clinical trials of budesonide. Long-term follow-up of these patients is not well established. The review synthesizes work on the definition of microscopic colitis and the relationship between collagenous and lymphocytic colitis. It reviews the international epidemiology and work on aetiology. In addition, it critically considers the efficacy of a range of treatments.

Population-based studies suggest an association between microscopic colitis and a variety of medications, including proton-pump inhibitors (PPIs), nonsteroidal anti-inflammatory drugs (NSAIDs), selective serotonin reuptake inhibitors (SSRIs), and statins. To further evaluate these potential relationships, investigators compared drug use in 1211 adults with microscopic colitis (including collagenous colitis and lymphocytic colitis) and 6041 age- and sex-matched controls identified …

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

The incidence of collagenous and lymphocytic colitis is not well known. We sought to assess the incidence of collagenous and lymphocytic colitis in a well-defined population during a 5-yr study period. From January 1, 1993, to December 31, 1997, all new patients diagnosed with collagenous or lymphocytic colitis living in the catchment area of the Hospital Mutua de Terrassa (Barcelona, Spain) were identified. Since 1993 all patients with chronic diarrhea were referred for a diagnostic colonoscopy. Multiple biopsy sampling of the entire colon was performed when appearance of the colonic mucosa was grossly normal. Twenty-three cases of collagenous colitis and 37 of lymphocytic colitis were diagnosed. The female:male ratios were 4.75:1 and 2.7:1 for collagenous and lymphocytic colitis, respectively. The mean age at onset of symptoms was 53.4+/-3.2 (range, 29-82) yr for collagenous colitis, and 64.3+/-2.7 (range, 28-87) yr for lymphocytic colitis (p = 0.012). The mean annual incidence per 100,000 inhabitants based on the year of onset of symptoms was 1.1 (95% confidence interval [CI], 0.4-1.7) for collagenous colitis, and 3.1 (95% CI, 2.0-4.2) for lymphocytic colitis. A peak incidence was observed in older women in both diseases. A rate of microscopic colitis of 9.5 per 100 normal-looking colonoscopies performed in patients with chronic watery diarrhea was observed. Normal rectal biopsies were found in 43 % and 8% of patients with collagenous and lymphocytic colitis, respectively. The incidence of lymphocytic colitis is three times higher than that of collagenous colitis. Microscopic colitis should be considered as a major possibility in the work-up of chronic diarrhea in older women.

Microscopic Colitis: A Concise Review for Clinicians

Quantifying intraepithelial lymphocytes and subepithelial collagen band in microscopic colitis, extracting insights into the interrelationship of lymphocytic and collagenous colitis

Introduction: Microscopic colitis (MC) is an inflammatory bowel condition with two subtypes, lymphocytic colitis (LC) and collagenous colitis (CC). Unlike patients with ulcerative colitis (UC) and non-inflamed individuals, MC patients have reduced risk of developing colorectal cancer, possibly due to increased immune surveillance in MC patients.Aim: To examine differences in levels of immunomodulatory molecules, including those involved in immune checkpoint mechanisms, in sera from patients with MC and in colonic biopsies from patients with MC and UC compared with controls.Methods: Using Luminex, 23 analytes (4-1BB, 4-1BBL, APRIL, BAFF, BTLA, CD27, CD28, CD80, CTLA-4, E-cadherin, Galectin-3, GITR, HVEM, IDO, IL-2Rα, LAG-3, MICA, MICB, PD-1, PD-L1, PD-L2, sCD40L and TIM-3) were studied in serum from patients with active MC (n = 35) and controls (n = 23), and in colonic biopsies from patients with active LC (n = 9), active CC (n = 16) and MC in histological remission (LC n = 6, CC n = 6), active UC (n = 15) and UC in remission (n = 12) and controls (n = 58).Results: In serum, IDO, PD-1, TIM-3, 4-1BB, CD27, and CD80 were decreased whereas 4-1BBL and IL-2Rα were increased in MC patients compared with controls. In contrast, in biopsies, levels of PD-L2 and 4-1BB were increased in MC and UC patients with active disease. Furthermore, in biopsies from CC and UC but not LC patients with active disease, CTLA-4, PD-1, APRIL, BAFF, and IL-2Rα were increased compared with controls. PD-L1 was increased in CC but not UC or LC patients. CD27 and TIM-3 were decreased in biopsies from MC patients in comparison to controls whereas levels of MICB were decreased in patients with active UC compared with controls.Conclusions: Compared with non-inflamed controls, levels of soluble and membrane-bound immunomodulatory molecules were systemically and locally altered in MC and UC patients, with most analytes being decreased in serum but enhanced in colonic biopsies. These findings contribute to knowledge about checkpoint molecules and their role as biomarkers in MC and may also contribute to knowledge about possible mechanisms behind the seemingly protective effects of MC against colorectal cancer.

Introduction: Microscopic colitis (MC) refers to 2 medical conditions that cause chronic diarrhea: collagenous colitis (CC) and lymphocytic colitis (LC). Previous studies have reported an increased prevalence of microscopic colitis in the celiac disease population. These studies were limited by small numbers, and further characterization of the patients who harbor both conditions is needed. The aims of this study were: 1) to determine the strength of the association between MC and celiac disease; and 2) to compare the demographic and clinical characteristics of patients with MC and celiac sprue to those of patients with MC alone. Methods: Miraca Life Sciences is a nationwide pathology laboratory that receives specimens submitted by approximately 1,500 gastroenterologists distributed throughout the United States. From the electronic database of Miraca Life Sciences we extracted all patients who had an upper gastrointestinal endoscopy (EGD) and colonoscopy with biopsy sampling from the duodenum and colon between January 2008 and December 2013. We extracted demographic, clinical, and histopathologic information and stratified patients based on the presence of MC. We then performed a search of patients with celiac sprue, defined as duodenal villous atrophy (Marsh type 3a, b, or c histology), in a population of patients with MC, compared to a control population of patients without MC. Results: There were 156,399 patients who had both duodenal and colon biopsies during the study period. Of these, 4,417 had MC (2,266 with CC and 2,151 with LC). The mean age of the MC population was 61.9 years, with a female:male ratio of 3.83:1. Celiac sprue was diagnosed in 1,113 patients, of whom 116 also had microscopic colitis. Compared to controls without MC, there was a greater association of celiac sprue in patients with CC (OR 4.08; 95% CI 3.36, 4.96), LC (OR 4.71; 95% CI 3.66, 6.05), and all MC (OR 4.08; 95% CI 3.36, 4.96). In patients with MC and celiac sprue versus MC alone, average age was 54.0 years vs. 61.9 years (p<0.0001) with a similar female:male predominance (ratio 4.04:1). Of the 116 subjects with MC and celiac sprue, microscopic colitis was diagnosed before celiac sprue in 32 (28%) cases, simultaneously in 58 (50%), and after celiac sprue in 26 (22%). Conclusion: In a large nationwide pathology database, we found a significantly increased association of microscopic colitis and celiac disease. Such association could reflect on a shared set of risk factors or a common pathophysiology of the 2 disease entities. Disclosure - Dr. Genta is an employee of Miraca Life Sciences. Drs. Yen and Sonnenberg declare no relevant conflicts of interest.

Background: Microscopic colitis (MC) is an increasingly recognized, frequent cause of chronic diarrhea. Its epidemiology was described in several Western countries, however epidemiologic data from Eastern Europe is lacking. We aimed to investigate MC cases in our single tertiary referral center cohort. Methods: All cases of microscopic colitis diagnosed at colonoscopy over a 17-year period (January 1997 – August 2014) were retrieved at the 1st Department of Pathology and retrospectively reviewed. The diagnostic criteria for lymphocytic colitis (LC) were ≥20 intraepithelial lymphocytes per 100 epithelial cells, and for collagenous colitis (CC) a collagenous layer of ≥10 µm. Several demographic and clinical parameters were analyzed. Results: 110 patients (91 patients with LC, and 19 patients with CC) were included in the study. 79 (71%) patients were female with a mean age of 52.0 years (SD ± 16.8) for LC and a mean age of 57.5 years (SD ± 17.0) for CC. Comparing the period 1997 – 2005 and 2006 – 2014, the incidence increased in both genders (30 females, 9 males vs. 49 females, 23 males). Chronic, watery diarrhea was the most common symptom (74%). The diagnosis of LC would have been missed in 11% of cases, if only left-sided biopsies had been taken, whereas all cases (100%) of CC were diagnosed with distal colonic biopsies alone. Osteodensitometry was performed in only 20% of cases, however it was pathological in 64% of the cases: osteoporosis was diagnosed in 46% and osteopenia in 18% of these cases. Among associated autoimmune diseases, celiac disease was the most common with 9%, followed by hypothyroidism (7.3%). 31.5% of patients were taking any of the previously associated drugs (proton pump inhibitors, ACE inhibitors, beta blockers, calcium antagonists, statins, acetylsalicylic acid or antidepressants). Conclusions: The incidence of MC is increasing in Hungary, but still below of that reported in Western countries. LC seems to be more common than CC, but this might be due to underdiagnosis. Our results should be further examined in multicenter studies. This study was supported by the Hungarian Scientific Research Fund (OTKA-K111743 grant).

Microscopic colitis includes lymphocytic colitis and collagenous colitis. The entity is considered as an important cause for unknown chronic diarrhea, but rarely reported in China before. This study aimed to determine the prevalence of microscopic colitis in patients with chronic diarrhea and normal colonoscopy findings in Southern China, and to reveal the clinical feature of microscopic colitis in these patients. Patients with chronic diarrhea and normal colonoscopic findings were enrolled from three hospitals in Southern China from January, 2009 to June, 2010. Multiple colorectal biopsies were obtained in these patients and histological examination was underwent with hematoxyin and eosin stain, Masson's trichrome stain and immunohistochemistry for tenascin to screen lymphocytic colitis and collagenous colitis. The clinical symptom and risk factor of microscopic colitis were assessed by comparing with controls. The diagnostic overlap between microscopic colitis and irritable bowel syndrome or functional diarrhea was also analyzed. Randomly mucosal biopsies were performed in 613 patients with chronic diarrhea and normal or near normal colonoscopic finding. Fifty-nine cases of lymphocytic colitis and 28 cases of collagenous colitis were found by histological examination. The rates of rheumatoid arthritis in lymphocytic colitis group (15.4 %) and collagenous colitis group (14.3 %) were significant higher than in control group (2.2 %). Rheumatoid arthritis was confirmed as the risk factor of microscopic colitis by logistic regression analysis. There was no difference on the symptoms among the controls, patients with lymphocytic colitis, and patients with collagenous colitis. There were 13.8 % (12/87) of patients with microscopic colitis fulfilled Rome III criteria of irritable bowel syndrome and 42.5 % (37/87) fulfilled the criteria of functional diarrhea. Microscopic colitis is not an uncommon disorder in Chinese population. Rheumatoid arthritis is the risk factor of microscopic colitis. Microscopic colitis has a symptomatic overlap with irritable bowel syndrome and functional diarrhea. It is reasonable to obtain multiple biopsies in patients with chronic diarrhea when the mucosa grossly normal at colonoscopy.

Microscopic colitis (MC) encompasses the two morphologically distinct entities of collagenous colitis (CC) and lymphocytic colitis (LC). MC was first described less than 30 years ago but is presently recognized as a relatively common cause of chronic diarrhea in the adult population. Remarkably, up to 10% of adults who have a colonoscopy for the investigation of chronic diarrhea, and have endoscopically normal appearing mucosa, may have MC. Patients with MC generally present with chronic diarrhea, which can be associated with cramping and bloating. Endoscopic and radiological examinations are usually normal. Histological assessment reveals inflammation consisting predominantly of lymphocytic infiltration, and a thickened subepithelial collagen band is diagnostic of CC. Both LC and CC can be associated with autoimmune diseases such as celiac disease, diabetes, arthritis and thyroiditis, yet the mechanisms involved in the pathogenesis remain unclear. Emerging studies suggest that a stepwise approach be taken in the medical management of MC. This approach includes antidiarrheal agents and stopping of any offending agents; budesonide or bismuth subsalicylate; and cholestyramine or 5-acetylsalicylic acid agents. In resistant cases, oral corticosteroids and other immune modulatory therapy have been used.

Colitis microscópica y exposición a fármacos: una revisión crítica