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Miyatani Y, Komaki Y, Komaki F, Micic D, Keyashian K, Sakuraba A. Factors associated with long-term clinical outcome in microscopic colitis. Ann Med 2024; 56:2365989. [PMID: 38900021 PMCID: PMC11191833 DOI: 10.1080/07853890.2024.2365989] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/31/2023] [Accepted: 05/07/2024] [Indexed: 06/21/2024] Open
Abstract
BACKGROUND AND AIMS Microscopic colitis has been increasingly recognized as a cause of chronic diarrhoea. We aimed to characterize the role of disease-related factors and treatments on the clinical outcomes of microscopic colitis. METHODS We retrospectively reviewed the medical records of patients with microscopic colitis who were treated at the University of Chicago and Oregon Health & Science University between August 2010 and May 2016. Patient characteristics and treatments were evaluated as predictors of clinical outcomes using univariate and multivariate analyses. Clinical remission was defined as no symptoms associated with microscopic colitis based on physician assessment and histologic remission was defined as no evidence of histological inflammation of microscopic colitis. RESULTS Seventy-two patients with microscopic colitis were included in the study (28 with lymphocytic colitis and 44 with collagenous colitis). Non-steroidal anti-inflammatory drugs, proton pump inhibitors and selective serotonin reuptake inhibitors were used in 23 (31.9%), 14 (19.4%) and 15 (20.8%), respectively, at the time of diagnosis. Among 46 patients with adequate follow-up data, 25 (54.3%) patients achieved clinical remission. Response to budesonide (p = .0002) and achieving histologic remission (p = .0008) were associated with clinical remission on univariate analysis. On multivariate analysis, budesonide response (p = .0052) was associated with clinical remission (odds ratio 25.00, 95% confidence interval 2.63-238.10). Among 22 patients who underwent a follow-up colonoscopy, five patients (22.7%) achieved histologic remission. All patients with histologic remission maintained clinical remission without medication, whereas only two patients (11.8%) were able to discontinue medical therapy when histologic inflammation was present (p = .0002). CONCLUSIONS In the present cohort of patients with microscopic colitis, a favourable response to budesonide was significantly associated with long-term clinical remission, and all patients achieving histological remission were able to maintain clinical remission without further medical therapy. Larger studies are required to confirm these findings.
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Affiliation(s)
- Yusuke Miyatani
- Inflammatory Bowel Disease Center, University of Chicago Medicine, Chicago, IL, USA
| | - Yuga Komaki
- Inflammatory Bowel Disease Center, University of Chicago Medicine, Chicago, IL, USA
- Digestive and Lifestyle Diseases, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
| | - Fukiko Komaki
- Inflammatory Bowel Disease Center, University of Chicago Medicine, Chicago, IL, USA
- Digestive and Lifestyle Diseases, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
| | - Dejan Micic
- Inflammatory Bowel Disease Center, University of Chicago Medicine, Chicago, IL, USA
| | - Kian Keyashian
- Department of Medicine, Division of Gastroenterology and Hepatology, Oregon Health & Science University, Portland, OR, USA
- Department of Medicine, Section of Gastroenterology and Hepatology, Stanford University, Stanford, CA, USA
| | - Atsushi Sakuraba
- Inflammatory Bowel Disease Center, University of Chicago Medicine, Chicago, IL, USA
- Division of Digestive Diseases and Nutrition, RUSH Center for Crohn’s and Colitis, RUSH University Medical Center, Chicago, IL, USA
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Redd WD, Anderson C, Peery AF, Keku TO, Woosley JT, Sandler RS. Follow-Up of Microscopic Colitis Patients and Diarrhea Controls at 1 Year. GASTRO HEP ADVANCES 2023; 3:336-343. [PMID: 38681976 PMCID: PMC11052583 DOI: 10.1016/j.gastha.2023.11.019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 05/01/2024]
Abstract
BACKGROUND AND AIMS Microscopic colitis (MC) is a common cause of chronic diarrhea; however, the clinical course of this disease is poorly understood. We aimed to investigate how patients diagnosed with MC were treated in routine clinical practice and how their symptoms compared to patients with other causes of chronic diarrhea at one year follow-up. METHODS We conducted a case-control study of patients undergoing outpatient colonoscopy to evaluate diarrhea. The study pathologist determined whether patients were classified as MC cases or non-MC controls. One year after colonoscopy, we interviewed cases (n = 74) and controls (n = 162) about their diagnosis, medications for diarrhea, and symptom burden. RESULTS At 1-year follow-up after colonoscopy, 10% of MC cases were unaware of the diagnosis, 60% had been prescribed a medication for diarrhea, 40% had fecal urgency, 32% had weight loss, and 21% had fecal incontinence. Among cases, 46% were treated with budesonide. Compared to cases, controls had worse symptoms based on the Microscopic Colitis Disease Activity Index score with a median score of 3.0 (interquartile range 1.9-4.2) vs 2.3 (interquartile range 1.4-3.2) at 1-year follow-up. Controls had more frequent stools, urgency, fecal incontinence, and abdominal pain. CONCLUSION In a cohort of patients with biopsy-confirmed MC and diarrhea controls, we found that some cases remained unaware of their diagnosis, many cases had persistent symptoms, and controls had worse symptoms than cases. These findings suggest there are opportunities to improve management of this chronic disease.
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Affiliation(s)
- Walker D. Redd
- Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
| | - Chelsea Anderson
- Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
- Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
| | - Anne F. Peery
- Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
- Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
| | - Temitope O. Keku
- Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
- Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
| | - John T. Woosley
- UNC Department of Pathology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
| | - Robert S. Sandler
- Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
- Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
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3
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Chauhan A, Das P, Singh A, Dutta R, Rajeshwari M, Rajput MS, Agarwal A, Banyal V, Upadhay A, Ahuja V, Makharia G. Pan-Gastrointestinal Tract Mucosal Pathologies in Patients with Celiac Disease with the Demonstration of IgA Anti-Transglutaminase Mucosal Deposits: A Case-Control Study. Dig Dis Sci 2022; 67:3649-3661. [PMID: 34499270 DOI: 10.1007/s10620-021-07246-1] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2021] [Accepted: 08/23/2021] [Indexed: 01/12/2023]
Abstract
BACKGROUND While celiac disease (CeD) is considered to affect primarily the small intestine, pathological changes in other parts of the gastrointestinal tract (GIT) are also known to occur. IgA anti-tissue transglutaminase-2 antibody (anti-TG2 Ab) deposits at the site of involvement is one of the methods to establish CeD-related tissue pathology. AIMS To explore the utility of IgA anti-TG2 Ab deposits in pan-gastrointestinal mucosal biopsies as evidence of CeD-related pathologies. METHODS Forty-two treatment-naive patients with CeD and 45 patients with irritable bowel syndrome were included as cases and controls, respectively. Mucosal biopsies were collected from the esophagus, stomach, duodenum, and rectosigmoid regions at baseline from cases and controls, and additionally after 6-months of gluten-free diet in cases. All biopsies were evaluated for histological changes and subjected to dual-color immunohistochemical staining for identifying IgA anti-TG2 Ab deposits. RESULTS Significantly higher number of patients with CeD had lymphocytic esophagitis (9.7% vs. 0%, P = 0.05), lymphocytic gastritis (35% vs. 8.8%, P < 0.01) and lymphocytic colitis (17.4% vs. 0%, P < 0.05) than that in controls. IgA anti-TG2 Ab deposits were observed in significantly more numbers in esophagus (30.9% vs. 6%, P < 0.001), stomach (62.2% vs. 9.3%, P < 0.01), duodenum (88.5% vs. 0%, P < 0.001) and rectum (17.4% vs. 0%, P < 0.05) than that in controls. There was a decline, but not statistically significant, in severity of lymphocytosis and intensity of IgA anti-TG2 Ab deposits in follow-up biopsies. CONCLUSION Significantly higher number of patients with CeD had evidence of lymphocytic infiltration and IgA anti-TG2 deposits along GIT suggesting that CeD affects other parts of GIT.
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Affiliation(s)
- Ashish Chauhan
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Prasenjit Das
- Department of Pathology, All India Institute of Medical Sciences, New Delhi, India
| | - Alka Singh
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Rimlee Dutta
- Department of Pathology, All India Institute of Medical Sciences, New Delhi, India
| | - Madhu Rajeshwari
- Department of Pathology, All India Institute of Medical Sciences, New Delhi, India
| | - Mahendra Singh Rajput
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Ashish Agarwal
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Vikas Banyal
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Ashish Upadhay
- Department of Biostatistics, All India Institute of Medical Sciences, New Delhi, India
| | - Vineet Ahuja
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Govind Makharia
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India.
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4
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Verhaegh BPM, Münch A, Guagnozzi D, Wildt S, Cebula W, Diac AR, Fernández-Bañares F, Al-Khalaf MAR, Pedersen N, Kupcinskas J, Bohr J, Macaigne G, Lucendo AJ, Lyutakov I, Tontini GE, Pigò F, Russo E, Hjortswang H, Miehlke S, Munck LK. Course of Disease in Patients with Microscopic Colitis: A European Prospective Incident Cohort Study. J Crohns Colitis 2021; 15:1174-1183. [PMID: 33433605 DOI: 10.1093/ecco-jcc/jjab007] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
BACKGROUND AND AIMS The disease course of microscopic colitis [MC] is considered chronic but benign. However, this assumption is based on mainly retrospective studies, reporting on incomplete follow-up of selective cohorts. Systematic, prospective and unbiased data to inform patients and healthcare professionals on the expected course of the disease and real-life response to therapy are warranted. METHODS A prospective, pan-European, multi-centre, web-based registry was established. Incident cases of MC were included. Data on patient characteristics, symptoms, treatment and quality of life were systematically registered at baseline and during real-time follow-up. Four disease course phenotypes were discriminated and described. RESULTS Among 381 cases with complete 1-year follow-up, 49% had a chronic active or relapsing disease course, 40% achieved sustained remission after treatment and 11% had a quiescent course. In general, symptoms and quality of life improved after 3 months of follow-up. A relapsing or chronic active disease course was associated with significantly more symptoms and impaired quality of life after 1 year. CONCLUSIONS A minority of MC patients follow a quiescent disease course with spontaneous clinical improvement, whereas the majority suffer a chronic active or relapsing disease course during the first year after diagnosis, with persisting symptoms accompanied by a significantly impaired quality of life.
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Affiliation(s)
- Bas P M Verhaegh
- Division of Gastroenterology-Hepatology, Maastricht University Medical Center, Maastricht, the Netherlands
| | - Andreas Münch
- Department of Gastroenterology and Hepatology in Linköping and Department of Health, Medicine, and Caring Sciences, Linköping University, Linköping, Sweden
| | - Danila Guagnozzi
- Neuro-Immuno-Gastroenterology Group, Digestive Physiology and Pathophysiology Unit, Vall d'Hebron Research Institute; Digestive System Department, Vall d'Hebron University Hostpital, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain.,Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain
| | - Signe Wildt
- Department of Gastroenterology, Zealand University Hospital, Køge, Denmark.,Department of Clinical Medicine, University of Copenhagen, Denmark
| | - Wojciech Cebula
- Division of Gastroenterology, Department of Medicine, Nykoebing Falster Hospital, Nykoebing Falster, Denmark
| | - Andreea R Diac
- Division of Gastroenterology, Department of Medicine, Nykoebing Falster Hospital, Nykoebing Falster, Denmark
| | - Fernando Fernández-Bañares
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain.,Department of Gastroenterology, Hospital Universitari Mutua Terrassa, Terrassa, Spain
| | - Magid A R Al-Khalaf
- Division of Gastroenterology, Department of Medicine, Holbaek Hospital, Holbaek, Denmark
| | - Natalia Pedersen
- Department of Gastroenterology, Slagelse Hospital, Slagelse, Denmark
| | - Juozas Kupcinskas
- Department of Gastroenterology and Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas, Lithuania
| | - Johan Bohr
- Division of Gastroenterology, Department of Medicine, Örebro University Hospital, Faculty of Medicine and Health, Örebro University, Örebro, Sweden
| | - Gilles Macaigne
- Hepatogastroenterology Unit, Centre Hospitalier de Marne-la-Vallee, France
| | - Alfredo J Lucendo
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain.,Department of Gastroenterology, Hospital General de Tomelloso, Tomelloso, Spain.,Instituto de Investigación Sanitaria La Princesa, Madrid, Spain
| | - Ivan Lyutakov
- Department of Gastroenterology, Medical University of Sofia, University Hospital Tsaritsa Yoanna- ISUL, Sofia, Bulgaria
| | - Gian-Eugenio Tontini
- Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Gastroenterology and Endoscopy Unit, Department of Pathophysiology and Transplantation, University of Milan, Italy
| | - Flavia Pigò
- Gastroenterologia ed Endoscopia Digestiva, Ospedale Civile di Baggiovara, Modena, Italy
| | - Evangelos Russo
- Department of Gastroenterology, Imperial College Healthcare NHS Trust, London, UK
| | - Henrik Hjortswang
- Department of Gastroenterology and Hepatology in Linköping and Department of Health, Medicine, and Caring Sciences, Linköping University, Linköping, Sweden
| | - Stephan Miehlke
- Center for Digestive Diseases, Internal Medicine Center Eppendorf, Hamburg, Germany.,Center for Esophageal Disorders, University Hospital Eppendorf, Hamburg, Germany
| | - Lars K Munck
- Department of Gastroenterology, Zealand University Hospital, Køge, Denmark.,Department of Clinical Medicine, University of Copenhagen, Denmark
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5
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Olsen LM, Engel PJH, Goudkade D, Villanacci V, Thagaard J, Walbech JS, Bohr J, Kupcinskas J, Verhaegh B, Münch A, Guagnozzi D, Fernández-Bañares F, Munck LK, Fiehn AMK. Histological disease activity in patients with microscopic colitis is not related to clinical disease activity or long-term prognosis. Aliment Pharmacol Ther 2021; 54:43-52. [PMID: 34018208 DOI: 10.1111/apt.16381] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/09/2021] [Revised: 03/02/2021] [Accepted: 04/07/2021] [Indexed: 12/21/2022]
Abstract
BACKGROUND Microscopic colitis (MC) is a common cause of chronic watery diarrhea. Biopsies with characteristic histological features are crucial for establishing the diagnosis. The two main subtypes are collagenous colitis (CC) and lymphocytic colitis (LC) but incomplete forms exist. The disease course remains unpredictable varying from spontaneous remission to a relapsing course. AIM To identify possible histological predictors of course of disease. METHODS Sixty patients from the European prospective MC registry (PRO-MC Collaboration) were included. Digitised histological slides stained with CD3 and Van Gieson were available for all patients. Total cell density and proportion of CD3 positive lymphocytes in lamina propria and surface epithelium were estimated by automated image analysis, and measurement of the subepithelial collagenous band was performed. Histopathological features were correlated to the number of daily stools and daily watery stools at time of endoscopy and at baseline as well as the clinical disease course (quiescent, achieved remission after treatment, relapsing or chronic active) at 1-year follow-up. RESULTS Neither total cell density in lamina propria, proportion of CD3 positive lymphocytes in lamina propria or surface epithelium, or thickness of collagenous band showed significant correlation to the number of daily stools or daily watery stools at any point of time. None of the assessed histological parameters at initial diagnosis were able to predict clinical disease course at 1-year follow-up. CONCLUSIONS Our data indicate that the evaluated histological parameters were neither markers of disease activity at the time of diagnosis nor predictors of disease course.
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6
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Miehlke S, Guagnozzi D, Zabana Y, Tontini GE, Kanstrup Fiehn A, Wildt S, Bohr J, Bonderup O, Bouma G, D'Amato M, Heiberg Engel PJ, Fernandez‐Banares F, Macaigne G, Hjortswang H, Hultgren‐Hörnquist E, Koulaouzidis A, Kupcinskas J, Landolfi S, Latella G, Lucendo A, Lyutakov I, Madisch A, Magro F, Marlicz W, Mihaly E, Munck LK, Ostvik A, Patai ÁV, Penchev P, Skonieczna‐Żydecka K, Verhaegh B, Münch A. European guidelines on microscopic colitis: United European Gastroenterology and European Microscopic Colitis Group statements and recommendations. United European Gastroenterol J 2021; 9:13-37. [PMID: 33619914 PMCID: PMC8259259 DOI: 10.1177/2050640620951905] [Citation(s) in RCA: 123] [Impact Index Per Article: 30.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2020] [Accepted: 07/27/2020] [Indexed: 12/22/2022] Open
Abstract
INTRODUCTION Microscopic colitis is a chronic inflammatory bowel disease characterised by normal or almost normal endoscopic appearance of the colon, chronic watery, nonbloody diarrhoea and distinct histological abnormalities, which identify three histological subtypes, the collagenous colitis, the lymphocytic colitis and the incomplete microscopic colitis. With ongoing uncertainties and new developments in the clinical management of microscopic colitis, there is a need for evidence-based guidelines to improve the medical care of patients suffering from this disorder. METHODS Guidelines were developed by members from the European Microscopic Colitis Group and United European Gastroenterology in accordance with the Appraisal of Guidelines for Research and Evaluation II instrument. Following a systematic literature review, the Grading of Recommendations Assessment, Development and Evaluation methodology was used to assess the certainty of the evidence. Statements and recommendations were developed by working groups consisting of gastroenterologists, pathologists and basic scientists, and voted upon using the Delphi method. RESULTS These guidelines provide information on epidemiology and risk factors of microscopic colitis, as well as evidence-based statements and recommendations on diagnostic criteria and treatment options, including oral budesonide, bile acid binders, immunomodulators and biologics. Recommendations on the clinical management of microscopic colitis are provided based on evidence, expert opinion and best clinical practice. CONCLUSION These guidelines may support clinicians worldwide to improve the clinical management of patients with microscopic colitis.
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7
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Högger L, Vavricka S. [Microscopic Colitis]. PRAXIS 2018; 107:1195-1199. [PMID: 30376775 DOI: 10.1024/1661-8157/a003099] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/08/2023]
Abstract
Microscopic colitis (MC) is still an underestimated cause of chronic, non-bloody watery diarrhea. It is typically manifested in elderly patients with a female predominance. The incidence of microscopic colitis has been increasing. The aetiology and pathophysiology remain unclear. Conditions associated with it include autoimmune diseases. There may be a genetic predisposition, as familial cases have been described. As implicated by the name microscopic colitis, the diagnosis is found by histological examination. There are mainly two subtypes, the lymphocytic colitis (LC) and the collagenous colitis (CC). Even if the condition's long-term course is benign, a chronic recurrent course of the symptoms is frequent. Due to the symptoms, there is an impairment of patient's health-related quality of life. A correct diagnosis and therapy is therefore mandatory. The aim of this paper is to create awareness for microscopic colitis.
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MESH Headings
- Adult
- Aged
- Biopsy
- Chronic Disease
- Colitis, Collagenous/diagnosis
- Colitis, Collagenous/etiology
- Colitis, Collagenous/pathology
- Colitis, Lymphocytic/diagnosis
- Colitis, Lymphocytic/etiology
- Colitis, Lymphocytic/pathology
- Colitis, Microscopic/diagnosis
- Colitis, Microscopic/etiology
- Colitis, Microscopic/pathology
- Diagnosis, Differential
- Diarrhea/etiology
- Diarrhea/pathology
- Female
- Humans
- Intestinal Mucosa/pathology
- Male
- Middle Aged
- Quality of Life
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Affiliation(s)
- Lisa Högger
- 1 Klinik für Allgemein-, Viszeral- und Gefässchirurgie, Kantonsspital Baden
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Chande N, Al Yatama N, Bhanji T, Nguyen TM, McDonald JWD, MacDonald JK. Interventions for treating lymphocytic colitis. Cochrane Database Syst Rev 2017; 7:CD006096. [PMID: 28702956 PMCID: PMC6483541 DOI: 10.1002/14651858.cd006096.pub4] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
BACKGROUND Lymphocytic colitis is a cause of chronic diarrhea. It is a subtype of microscopic colitis characterized by chronic, watery, non-bloody diarrhea and normal endoscopic and radiologic findings. The etiology of this disorder is unknown.Therapy is based mainly on case series and uncontrolled trials, or by extrapolation of data for treating collagenous colitis, a related disorder. This review is an update of a previously published Cochrane review. OBJECTIVES To evaluate the efficacy and safety of treatments for clinically active lymphocytic colitis. SEARCH METHODS The MEDLINE, PUBMED and EMBASE databases were searched from inception to 11 August 2016 to identify relevant papers. Manual searches from the references of included studies and relevant review articles were performed.Abstracts from major gastroenterological meetings were also searched to identify research submitted in abstract form only. The trial registry web site www.ClinicalTrials.gov was searched to identify registered but unpublished trials. Finally, the Cochrane Central Register of Controlled Trials and the Cochrane Inflammatory Bowel Disease and Functional Bowel Disorders Group Specialized Trials Register were searched for other studies. SELECTION CRITERIA Randomized controlled trials assessing medical therapy for patients with biopsy-proven lymphocytic colitis were considered for inclusion DATA COLLECTION AND ANALYSIS: Data was independently extracted by at least two authors. Any disagreements were resolved by consensus. Data were analyzed on an intention-to-treat (ITT) basis. The primary outcome was clinical response as defined by the included studies. Secondary outcome measures included histological response as defined by the included studies, quality of life as measured by a validated instrument and the occurrence of adverse events. Risk ratios (RR) and 95% confidence intervals (CI) were calculated for dichotomous outcomes. The methodological quality of included studies was evaluated using the Cochrane risk of bias tool. The overall quality of the evidence supporting the primary outcome and selected secondary outcomes was assessed using the GRADE criteria. Data were combined for analysis if they assessed the same treatments. Dichotomous data were combined using a pooled RR along with corresponding 95% CI. A fixed-effect model was used for the pooled analysis. MAIN RESULTS Five RCTs (149 participants) met the inclusion criteria. These studies assessed bismuth subsalicylate versus placebo, budesonide versus placebo, mesalazine versus mesalazine plus cholestyramine and beclometasone dipropionate versus mesalazine. The study which assessed mesalazine versus mesalazine plus cholestyramine and the study which assessed beclometasone dipropionate versus mesalazine were judged to be at high risk of bias due to lack of blinding. The study which compared bismuth subsalicylate versus us placebo was judged as low quality due to a very small sample size and limited data. The other 3 studies were judged to be at low risk of bias. Budesonide (9 mg/day for 6 to 8 weeks) was significantly more effective than placebo for induction of clinical and histological response. Clinical response was noted in 88% of budesonide patients compared to 38% of placebo patients (2 studies; 57 participants; RR 2.03, 95% CI 1.25 to 3.33; GRADE = low). Histological response was noted in 78% of budesonide patients compared to 33% of placebo patients (2 studies; 39 patients; RR 2.44, 95% CI 1.13 to 5.28; GRADE = low). Forty-one patients were enrolled in the study assessing mesalazine (2.4 g/day) versus mesalazine plus cholestyramine (4 g/day). Clinical response was noted in 85% of patients in the mesalazine group compared to 86% of patients in the mesalazine plus cholestyramine group (RR 0.99, 95% CI 0.77 to 1.28; GRADE = low). Five patients were enrolled in the trial studying bismuth subsalicylate (nine 262 mg tablets daily for 8 weeks versus placebo). There were no differences in clinical (P=0.10) or histological responses (P=0.71) in patients treated with bismuth subsalicylate compared with placebo (GRADE = very low). Forty-six patients were enrolled in the trial studying beclometasone dipropionate (5 mg/day or 10 mg/day) versus mesalazine (2.4 g/day). There were no differences in clinical remission at 8 weeks (RR 0.97; 95% CI 0.75 to 1.24; GRADE = low) and 12 months of treatment (RR 1.29; 95% CI 0.40 to 4.18; GRADE = very low). Although patients receiving beclometasone dipropionate (84%) and mesalazine (86%) achieved clinical remission at 8 weeks, it was not maintained at 12 months (26% and 20%, respectively). Adverse events reported in the budesonide studies include nausea, vomiting, neck pain, abdominal pain, hyperhidrosis and headache. Nausea and skin rash were reported as adverse events in the mesalazine study. Adverse events in the beclometasone dipropionate trial include nausea, sleepiness and change of mood. No adverse events were reported in the bismuth subsalicylate study. AUTHORS' CONCLUSIONS Low quality evidence suggests that budesonide may be effective for the treatment of active lymphocytic colitis. This benefit needs to be confirmed by a large placebo -controlled trial. Low quality evidence also suggests that mesalazine with or without cholestyramine and beclometasone dipropionate may be effective for the treatment of lymphocytic colitis, however this needs to be confirmed by large placebo-controlled studies. No conclusions can be made regarding bismuth subsalicylate due to the very small number of patients in the study, Further trials studying interventions for lymphocytic colitis are warranted.
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Affiliation(s)
- Nilesh Chande
- London Health Sciences Centre ‐ Victoria HospitalRoom E6‐321A800 Commissioners Road EastLondonONCanadaN6A 5W9
| | - Noor Al Yatama
- University of Western OntarioDepartment of MedicineLondonONCanada
| | - Tania Bhanji
- University of Western OntarioDepartment of MedicineLondonONCanada
| | - Tran M Nguyen
- Robarts Clinical TrialsCochrane IBD Group100 Dundas Street, Suite 200LondonONCanada
| | - John WD McDonald
- Robarts Clinical TrialsCochrane IBD Group100 Dundas Street, Suite 200LondonONCanada
| | - John K MacDonald
- University of Western OntarioDepartment of MedicineLondonONCanada
- Robarts Clinical TrialsCochrane IBD Group100 Dundas Street, Suite 200LondonONCanada
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9
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Pardi DS. Diagnosis and Management of Microscopic Colitis. Am J Gastroenterol 2017; 112:78-85. [PMID: 27897155 DOI: 10.1038/ajg.2016.477] [Citation(s) in RCA: 95] [Impact Index Per Article: 11.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/01/2015] [Accepted: 09/01/2016] [Indexed: 12/11/2022]
Abstract
Microscopic colitis (MC) is a relatively common cause of chronic watery diarrhea, especially in older persons. Associated symptoms, including abdominal pain and arthralgias, are common. The diagnosis is based upon characteristic histological findings in the presence of diarrhea. The two types of MC, collagenous and lymphocytic colitis, share similar clinical features, with the main difference being the presence or absence of a thickened subepithelial collagen band. There are several treatment options for patients with MC, although only budesonide has been well studied in multiple controlled clinical trials. This review will describe the clinical features, epidemiology, pathophysiology, diagnostic criteria, and treatment of patients with MC.
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Affiliation(s)
- Darrell S Pardi
- Inflammatory Bowel Disease Clinic, Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, Minnesota, USA
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Fernández-Bañares F, Zabana Y, Aceituno M, Ruiz L, Salas A, Esteve M. Prevalence and Natural History of Microscopic Colitis: A Population-Based Study With Long-term Clinical Follow-up in Terrassa, Spain. J Crohns Colitis 2016; 10:805-11. [PMID: 26818762 DOI: 10.1093/ecco-jcc/jjw037] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND AND AIMS Few studies have assessed the prevalence of microscopic colitis (MC) and the natural history of this disease is not well known. The aim of this study was to evaluate the prevalence rate of MC, the burden of disease in terms of loss of health and the long-term natural history of MC in a population-based cohort study. METHODS Cases were obtained from the pathology department registry Hospital Universitari Mutua Terrassa. Belonging to the catchment area, maintaining residence in that area, and being alive on August 31, 2014 were confirmed for each case. Adjusted prevalence rates were calculated. Current active drugs for MC and diarrhoea persistence in every patient were recorded. RESULTS The prevalence rate of MC was 107 per 10(5) inhabitants. The rate of patients with active disease, i.e. those representing the true burden of the disease in terms of loss of health, was 31 per 10(5) inhabitants. After a follow-up of 7.8±0.38 years from diagnosis, 75% of the patients experienced prolonged disease remission, defined as clinical remission without requiring drugs for 1 year or more. The only variable associated with prolonged MC remission was how clinical remission was achieved (spontaneous 93.3%, drug-induced, 60.5%; odds ratio 8.4, 95% confidence interval 2.7-26). CONCLUSIONS The rate of patients with MC and active disease, which represents the true disease burden in terms of loss of health, is low. Most patients with MC experience prolonged disease remission, with key differences between spontaneous and drug-induced clinical remission.
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Affiliation(s)
- Fernando Fernández-Bañares
- Department of Gastroenterology, Hospital Universitari Mutua Terrassa, Terrassa, Spain Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Terrassa, Spain
| | - Yamile Zabana
- Department of Gastroenterology, Hospital Universitari Mutua Terrassa, Terrassa, Spain Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Terrassa, Spain
| | - Montserrat Aceituno
- Department of Gastroenterology, Hospital Universitari Mutua Terrassa, Terrassa, Spain Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Terrassa, Spain
| | - Laura Ruiz
- Department of Gastroenterology, Hospital Universitari Mutua Terrassa, Terrassa, Spain Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Terrassa, Spain
| | - Antonio Salas
- Department of Pathology, Hospital Universitari Mutua Terrassa, Terrassa, Spain Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Terrassa, Spain
| | - Maria Esteve
- Department of Gastroenterology, Hospital Universitari Mutua Terrassa, Terrassa, Spain Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Terrassa, Spain
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11
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Villanacci V, Antonelli E, Salemme M, Bassotti G. Shedding light on the dark side of microscopic colitis. Tech Coloproctol 2016; 20:429-31. [PMID: 27241139 DOI: 10.1007/s10151-016-1493-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/03/2015] [Accepted: 01/22/2016] [Indexed: 12/23/2022]
Affiliation(s)
- V Villanacci
- Istituto di Anatomia Patologica, Spedali Civili di Brescia, Piazza Spedali Civili 1, 25100, Brescia, Italy.
| | - E Antonelli
- Division of Gastroenterology, Perugia General Hospital, Perugia, Italy
| | - M Salemme
- Istituto di Anatomia Patologica, Spedali Civili di Brescia, Piazza Spedali Civili 1, 25100, Brescia, Italy
| | - G Bassotti
- Division of Gastroenterology and Hepatology, Department of Clinical and Experimental Medicine, University of Perugia, Perugia, Italy
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12
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Rasmussen J, Engel PJH, Wildt S, Fiehn AMK, Munck LK. The Temporal Evolution of Histological Abnormalities in Microscopic Colitis. J Crohns Colitis 2016; 10:262-8. [PMID: 26520162 PMCID: PMC4957467 DOI: 10.1093/ecco-jcc/jjv200] [Citation(s) in RCA: 59] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/10/2015] [Accepted: 10/21/2015] [Indexed: 12/22/2022]
Abstract
BACKGROUND AND AIMS Microscopic colitis (MC) is a common cause of chronic watery diarrhoea but long-term follow-up data are sparse. METHODS We performed a retrospective review of health records and all pathology reports in a regional cohort of patients with MC to describe the change in pre- and post-diagnostic colon biopsies. RESULTS MC was diagnosed in 468 patients with collagenous colitis (CC), 361 with lymphocytic colitis (LC) and 226 with incomplete MC (MCi). The 2014 incidence of CC, LC and MCi was 14.5, 14.9 and 5 per 10(5). Biopsies from both right and left colon were obtained in 237 (51%) patients with CC, 200 (55%) with LC and 107 (47%) with MCi. The diagnostic sensitivities of both left- and right-sided biopsies for MC were high and did not differ. Pre-diagnostic biopsies were obtained in 150 patients and lamina propria inflammation was described in 59, 47 and 43% of patients with a diagnosis of CC, LC and MCi respectively within 1 year, while histology was normal in 16, 13 and 21%. Post-diagnostic biopsies were obtained in 283 patients. MC persisted for up to one year in 77% with CC, 64% with LC and 45% with MCi, of whom 6, 9 and 18% respectively changed to a different MC subgroup. CONCLUSIONS Colonic biopsies obtained prior to the MC diagnosis often revealed increased lamina propria inflammation. The pathological changes of CC and LC are more persistent than those of MCi. Biopsies from the descending or sigmoid colon are sufficient to elucidate whether a patient with chronic watery diarrhoea has MC.
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Affiliation(s)
- Julie Rasmussen
- Department of Medicine, Køge University Hospital, Køge, Denmark
| | - Peter Johan Heiberg Engel
- Department of Pathology, Roskilde University Hospital, Roskilde, Denmark Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Signe Wildt
- Department of Medicine, Køge University Hospital, Køge, Denmark
| | | | - Lars Kristian Munck
- Department of Medicine, Køge University Hospital, Køge, Denmark Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
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El-Salhy M, Hausken T. The role of the neuropeptide Y (NPY) family in the pathophysiology of inflammatory bowel disease (IBD). Neuropeptides 2016; 55:137-44. [PMID: 26431932 DOI: 10.1016/j.npep.2015.09.005] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2015] [Revised: 09/11/2015] [Accepted: 09/15/2015] [Indexed: 12/15/2022]
Abstract
Inflammatory bowel disease (IBD) includes three main disorders: ulcerative colitis, Crohn's disease, and microscopic colitis. The etiology of IBD is unknown and the current treatments are not completely satisfactory. Interactions between the gut neurohormones and the immune system are thought to play a pivot role in inflammation, especially in IBD. These neurohormones are believed to include members of the neuropeptide YY (NPY) family, which comprises NPY, peptide YY (PYY), and pancreatic polypeptide (PP). Understanding the role of these peptides may shed light on the pathophysiology of IBD and potentially yield an effective treatment tool. Intestinal NPY, PYY, and PP are abnormal in both patients with IBD and animal models of human IBD. The abnormality in NPY appears to be primarily caused by an interaction between immune cells and the NPY neurons in the enteric nervous system; the abnormalities in PYY and PP appear to be secondary to the changes caused by the abnormalities in other gut neurohormonal peptides/amines that occur during inflammation. NPY is the member of the NPY family that can be targeted in order to decrease the inflammation present in IBD.
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Affiliation(s)
- Magdy El-Salhy
- Section for Gastroenterology, Department of Medicine, Stord Hospital, Stord, Norway; Section for Neuroendocrine Gastroenterology, Division of Gastroenterology, Department of Clinical Medicine, University of Bergen, Bergen, Norway; National Centre for Functional Gastrointestinal Disorders, Department of Medicine, Haukeland University Hospital, Bergen, Norway.
| | - Trygve Hausken
- Section for Neuroendocrine Gastroenterology, Division of Gastroenterology, Department of Clinical Medicine, University of Bergen, Bergen, Norway; National Centre for Functional Gastrointestinal Disorders, Department of Medicine, Haukeland University Hospital, Bergen, Norway.
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14
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Fernández-Bañares F, Casanova MJ, Arguedas Y, Beltrán B, Busquets D, Fernández JM, Fernández-Salazar L, García-Planella E, Guagnozzi D, Lucendo AJ, Manceñido N, Marín-Jiménez I, Montoro M, Piqueras M, Robles V, Ruiz-Cerulla A, Gisbert JP. Current concepts on microscopic colitis: evidence-based statements and recommendations of the Spanish Microscopic Colitis Group. Aliment Pharmacol Ther 2016; 43:400-26. [PMID: 26597122 DOI: 10.1111/apt.13477] [Citation(s) in RCA: 48] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/14/2015] [Revised: 10/01/2015] [Accepted: 10/23/2015] [Indexed: 12/15/2022]
Abstract
BACKGROUND Microscopic colitis (MC) is an underdiagnosed inflammatory bowel disease. AIM To develop an evidence-based clinical practice guide on MC current concepts. METHODS Literature search was done on the Cochrane Library, EMBASE and MEDLINE electronic databases, which were consulted covering the period up until March 2015. Work groups were selected for each of the reviewed topics, with the purpose of drafting the initial statements and recommendations. They subsequently underwent a voting process based on the Delphi method. Each statement/recommendation was accompanied by the result of the vote the level of evidence, and discussion of the corresponding evidence. The grade of recommendation (GR) using the GRADE approach was established for diagnosis and treatment recommendations. RESULTS Some key statements and recommendations are: advancing age increases the risk of developing MC, mainly in females. The symptoms of MC and IBS-D may be similar. If MC is suspected, colonoscopy taking biopsies is mandatory. Treatment with oral budesonide is recommended to induce clinical remission in patients with MC. Oral mesalazine is not recommended in patients with collagenous colitis for the induction of clinical remission. The use of anti-TNF-alpha drugs (infliximab, adalimumab) is recommended for the induction of remission in severe cases of MC that fail to respond to corticosteroids or immunomodulators, as an alternative to colectomy. CONCLUSIONS This is the first consensus paper on MC based on GRADE methodology. This initiative may help physicians involved in care of these patients in taking decisions based on evidence.
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Affiliation(s)
- F Fernández-Bañares
- Hospital Universitari Mutua Terrassa, Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Barcelona, Spain
| | - M J Casanova
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Barcelona, Spain
- Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP), Madrid, Spain
| | | | - B Beltrán
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Barcelona, Spain
- Hospital La Fe, Valencia, Spain
| | - D Busquets
- Hospital Doctor Josep Trueta, Girona, Spain
| | - J M Fernández
- Hospital Universitario Fundación Alcorcón, Madrid, Spain
| | | | | | | | - A J Lucendo
- Hospital General de Tomelloso, Ciudad Real, Spain
| | - N Manceñido
- Hospital Infanta Sofía, San Sebastián de los Reyes, Spain
| | - I Marín-Jiménez
- Hospital General Universitario Gregorio Marañón, Madrid, Spain
| | | | | | - V Robles
- Hospital Vall d'Hebron, Barcelona, Spain
| | | | - J P Gisbert
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Barcelona, Spain
- Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP), Madrid, Spain
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15
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Nyhlin N, Wickbom A, Montgomery SM, Tysk C, Bohr J. Long-term prognosis of clinical symptoms and health-related quality of life in microscopic colitis: a case-control study. Aliment Pharmacol Ther 2014; 39:963-72. [PMID: 24612051 DOI: 10.1111/apt.12685] [Citation(s) in RCA: 52] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/18/2013] [Revised: 10/18/2013] [Accepted: 02/12/2014] [Indexed: 12/17/2022]
Abstract
BACKGROUND Microscopic colitis, comprising collagenous colitis (CC) and lymphocytic colitis (LC), is a common cause of chronic diarrhoea. The long-term prognosis is not well described. AIM To study outcome of symptoms and health-related quality of life (HRQoL). METHODS A case-control study using a postal questionnaire with three population-based controls per patient matched for age, sex and municipality. HRQoL was assessed by the Short Health Scale (SHS). Patients in clinical remission, defined as a mean of <3 stools/day, were evaluated separately (CC; n = 72, LC; n = 60). RESULTS The study included 212 patients and 627 matched controls. Median disease duration was 5.9 (range 0.5-27) years and 6.4 (0.3-14.8) years for CC and LC respectively. Abdominal pain, fatigue, arthralgia, myalgia, faecal incontinence and nocturnal defecation were significantly more prevalent in CC patients compared with controls. These differences persisted in CC patients in clinical remission with respect to abdominal pain (36% vs. 21%), fatigue (54% vs. 34%), arthralgia (61% vs. 41%) and myalgia (53% vs. 37%). In LC patients, abdominal pain, fatigue, faecal incontinence and nocturnal defecation were more prevalent compared with controls. In LC patients in clinical remission, fatigue was more prevalent compared with controls (54% vs. 37%). These differences were statistically significant (P < 0.05). All four HRQoL dimensions (symptom burden, social function, disease-related worry, general well-being) were impaired in patients with active CC and LC. CONCLUSIONS Although considered to be in clinical remission, patients with microscopic colitis suffer from persisting symptoms such as abdominal pain, fatigue, arthralgia or myalgia several years after diagnosis.
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Affiliation(s)
- N Nyhlin
- Department of Medicine, Division of Gastroenterology, Örebro University Hospital, Örebro, Sweden; School of Health and Medical Sciences, Örebro University, Örebro, Sweden
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16
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Ingle SB, Adgaonkar BD, (Ingle) CRH. Microscopic colitis: Common cause of unexplained nonbloody diarrhea. World J Gastrointest Pathophysiol 2014; 5:48-53. [PMID: 24891975 PMCID: PMC4024520 DOI: 10.4291/wjgp.v5.i1.48] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/05/2013] [Accepted: 11/05/2013] [Indexed: 02/06/2023] Open
Abstract
Microscopic colitis (MC) is characterized by chronic, watery, secretory diarrhea, with a normal or near normal gross appearance of the colonic mucosa. Biopsy is diagnostic and usually reveals either lymphocytic colitis or collagenous colitis. The symptoms of collagenous colitis appear most commonly in the sixth decade. Patients report watery, nonbloody diarrhea of a chronic, intermittent or chronic recurrent course. With collagenous colitis, the major microscopic characteristic is a thickened collagen layer beneath the colonic mucosa, and with lymphocytic colitis, an increased number of intraepithelial lymphocytes. Histological workup can confirm a diagnosis of MC and distinguish the two distinct histological forms, namely, collagenous and lymphocytic colitis. Presently, both forms are diagnosed and treated in the same way; thus, the description of the two forms is not of clinical value although this may change in the future. Since microscopic colitis was first described in 1976 and only recently recognized as a common cause of diarrhea, many practicing physicians may not be aware of this entity. In this review, we outline the epidemiology, risk factors associated with MC, its etiopathogenesis, the approach to diagnosis and the management of these individuals.
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17
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Sonnenberg A, Genta RM. Lymphocytic and collagenous colitis: epidemiologic differences and similarities. Dig Dis Sci 2013; 58:2970-5. [PMID: 23709158 DOI: 10.1007/s10620-013-2718-6] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/12/2013] [Accepted: 05/08/2013] [Indexed: 12/22/2022]
Abstract
BACKGROUND It is unknown whether the subtypes of microscopic colitis (MC) represent distinct nosologic entities or related presentations of the same disease. Our aim was to search for epidemiologic differences among its various histopathologic subtypes. METHODS In a computerized database of 789,568 colon pathology reports, we compared the characteristics of 8,745 MC patients with those of the remaining population. RESULTS MC was diagnosed as three distinct histopathologic subtypes: lymphocytic colitis (LC) in 51 %, collagenous colitis (CC) in 43 %, and incomplete colitis (IC) in 6 % of patients. Only 0.65 % was simultaneously diagnosed with more than one subtype of MC. The prevalence of all three subtypes showed an age-dependent rise, with the average age (SD) being 63.3 (14.3) years in LC, 66.4 (12.1) years in CC, and 67.3 (12.7) years in IC (p < 0.0001). There was a striking female predominance in all three subtypes, the female fraction being 72 % in LC, 82 % in CC, and 79 % in IC (p < 0.0001). All three subtypes showed similar geographic distributions among different US states. They were similarly associated with diarrhea and weight loss, the odds ratios for all MC being 45.92 (43.35-48.63) and 5.12 (4.68-5.60), respectively, compared to control patients without MC. All three subtypes also harbored significantly less colonic adenomas, the overall odds ratio being 0.11 (0.10-0.12). CONCLUSION MC comes in three distinct histopathologic entities, which show striking similarities of their general epidemiologic features. The slight differences in their demographic characteristics could point at varying sets of environmental influences that affect the occurrence of subtypes.
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Affiliation(s)
- Amnon Sonnenberg
- Department of Gastroenterology, Portland VA Medical Center P3-GI, 3710 SW US Veterans Hospital Road, Portland, OR, 97239, USA,
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18
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Makkar R, Lopez R, Shen B. Clinical utility of retrograde terminal ileum intubation in the evaluation of chronic non-bloody diarrhea. J Dig Dis 2013; 14:536-42. [PMID: 23777610 DOI: 10.1111/1751-2980.12082] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVE The aims of this study were to investigate the frequency and factors involved in the terminal ileum intubation of patients with chronic, non-bloody diarrhea and to compare diagnostic yields of colonoscopy and ileocolonoscopy. METHODS The medical records of 945 patients undergoing colonoscopy for chronic, non-bloody diarrhea were reviewed. Findings of microscopic colitis, Clostridium difficile colitis, celiac disease, inflammatory bowel disease or tropical sprue were considered as definitive causes of diarrhea. RESULTS A total of 689 patients met the diagnosis of chronic, non-bloody diarrhea, in which 370 (53.7%) underwent ileocolonoscopy. Specific histological diagnosis could explain the patient's symptoms in 107 (15.5%) patients. The diagnostic yield were 15.0% in the colonoscopy-only group, 16.9% in the ileocolonoscopy without biopsy group, and 15.5% in the ileocolonoscopy with biopsy group. Of the 19 patients with an abnormal terminal ileal biopsy, six (31.6%) had an otherwise normal colonic appearance which would have been diagnosed as normal if the ileum had not been reached and biopsied. In those with Crohn's disease (n = 7), five had ileocolitis and two had colitis only. A multivariate analysis showed that age of the patients and otherwise normal gross endoscopic results to be the only factors associated with a lower likelihood of ileal intubation by endoscopists. CONCLUSIONS The ileal intubation rate was 53.7% in our patients with chronic, non-bloody diarrhea. Diagnostic yield of ileocolonoscopy with biopsy in US patients with chronic, non-bloody diarrhea appeared to be low, if the colon side was normal on endoscopy. But this may provide supportive evidence in patients diagnosed with ileocolonic Crohn's disease.
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Affiliation(s)
- Rohit Makkar
- Department of Gastroenterology and Hepatology, The Cleveland Clinic Foundation, Cleveland, Ohio, USA
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19
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Jegadeesan R, Liu X, Pagadala MR, Gutierrez N, Butt M, Navaneethan U. Microscopic colitis: Is it a spectrum of inflammatory bowel disease? World J Gastroenterol 2013; 19:4252-4256. [PMID: 23864791 PMCID: PMC3710430 DOI: 10.3748/wjg.v19.i26.4252] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/04/2013] [Revised: 05/04/2013] [Accepted: 05/17/2013] [Indexed: 02/06/2023] Open
Abstract
Lymphocytic and collagenous colitis are forms of microscopic colitis which typically presents in elderly patients as chronic watery diarrhea. The association between microscopic colitis and inflammatory bowel disease is weak and unclear. Lymphocytic colitis progressing to ulcerative colitis has been previously reported; however there is limited data on ulcerative colitis evolving into microscopic (lymphocytic or collagenous) colitis. We report a series of six patients with documented ulcerative colitis who subsequently were diagnosed with collagenous colitis or lymphocytic colitis suggesting microscopic colitis could be a part of the spectrum of inflammatory bowel disease. The median duration of ulcerative colitis prior to being diagnosed with microscopic colitis was 15 years. We noted complete histological and/or symptomatic remission in three out of six cases while the other three patients reverted back into ulcerative colitis suggesting lymphocytic or collagenous colitis could present as a continuum of ulcerative colitis. The exact molecular mechanism of this histological transformation or the prognostic implications is still unclear. Till then it might be prudent to follow up these patients to assess for the relapse of inflammatory bowel disease as well as for dysplasia surveillance.
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MESH Headings
- Adolescent
- Adult
- Aged
- Aged, 80 and over
- Biopsy
- Colitis, Collagenous/classification
- Colitis, Collagenous/diagnosis
- Colitis, Collagenous/pathology
- Colitis, Collagenous/therapy
- Colitis, Lymphocytic/classification
- Colitis, Lymphocytic/diagnosis
- Colitis, Lymphocytic/pathology
- Colitis, Lymphocytic/therapy
- Colitis, Ulcerative/classification
- Colitis, Ulcerative/diagnosis
- Colitis, Ulcerative/pathology
- Colitis, Ulcerative/therapy
- Colon/pathology
- Colonoscopy
- Female
- Humans
- Male
- Middle Aged
- Predictive Value of Tests
- Recurrence
- Remission Induction
- Time Factors
- Treatment Outcome
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El-Salhy M, Gundersen D, Hatlebakk JG, Hausken T. Clinical presentation, diagnosis, pathogenesis and treatment options for lymphocytic colitis (Review). Int J Mol Med 2013; 32:263-70. [PMID: 23695201 DOI: 10.3892/ijmm.2013.1385] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2013] [Accepted: 04/29/2013] [Indexed: 12/16/2022] Open
Abstract
Lymphocytic colitis (LC) is characterized by chronic or relapsing non-bloody watery diarrhea and a macroscopically normal colon. However, histopathological examination of colonic biopsy samples reveals an increased intraepithelial infiltration of lymphocytes (≥20/100 enterocytes), and increased inflammatory cells within the lamina propria, but with a normal mucosal architecture. The reported prevalence of LC varies from 14.2 to 45 per 100,000 individuals, while its reported incidence is between 0.6 and 16 per 100,000 individuals. LC has a high rate of spontaneous symptomatic remission and is not associated with an increased risk of colon cancer or inflammatory bowel disease. The diagnosis is based on the histopathological findings. The density of colonic chromogranin A-positive cells provides an effective diagnostic tool with high sensitivity and specificity in both the right and left colon. Gastrointestinal infections, drugs, and/or autoimmunity may trigger chronic colonic low-grade inflammation. Colonic nitric oxide, serotonin and peptide YY (PYY) cell densities are markedly increased in patients with LC. It has been hypothesized that the low-grade inflammation in LC through the endocrine-immune axis causes this increase. It has been postulated further that these abnormalities in the neuroendocrine system of the colon are responsible for the diarrhea observed in patients with LC. The benign course and rate of spontaneous remission of LC denotes that drugs with severe side-effects should be avoided if possible. The drug cost and drug coverage may also be limiting factors for some patients. These aspects should be taken into account when making decisions regarding treatment options.
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Affiliation(s)
- Magdy El-Salhy
- Section for Gastroenterology, Department of Medicine, Stord Helse-Fonna Hospital, Stord, Norway
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21
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Abstract
BACKGROUND Microscopic colitis and irritable bowel syndrome (IBS) are the common causes of watery diarrhea, abdominal discomfort, and other gastrointestinal symptoms. Previous retrospective data and post hoc analysis of information from a randomized controlled trial have suggested that there is considerable overlap between the symptoms seen in patients with microscopic colitis and the symptom-based criteria for IBS. We sought to study this overlap in a prospective cohort. METHODS A random cohort of patients with biopsy-proven microscopic colitis seen at our institution were administered a symptom questionnaire. Based on their responses, the proportion of patients who met various definitions for IBS was determined. Clinical characteristics of those meeting IBS criteria were compared with those who did not. RESULTS In the 120 patients who were included, 38% to 58% met the diagnostic criteria for IBS. These patients tended to be younger and more likely female than those who did not meet IBS criteria. CONCLUSIONS Patients with microscopic colitis frequently meet the diagnostic criteria for IBS. Therefore, these criteria are not specific enough to exclude the presence of microscopic colitis. In patients with watery diarrhea, colonoscopy with mucosal biopsies should be performed if symptoms are not controlled by antidiarrheal medications.
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Vigren L, Olesen M, Benoni C, Sjöberg K. Are collagenous and lymphocytic colitis different aspects of the same disease? Scand J Gastroenterol 2012; 47:1448-53. [PMID: 23016916 DOI: 10.3109/00365521.2012.729085] [Citation(s) in RCA: 49] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVE Collagenous colitis (CC) and lymphocytic colitis (LC) are two subtypes of microscopic colitis (MC). Even though they most often are described as different entities they share many clinical and histological features. The aim of this study was to investigate the occurrence of conversion between CC and LC in a larger cohort of patients. MATERIALS AND METHODS All 664 patients in our Pathology register with a diagnosis of CC and LC were scrutinized and those where additional endoscopies had been carried out were included, and their biopsies were re-examined. RESULTS Sixty-five patients (55 women, 10 men, median age 58 years; range 29-86) fulfilled our criteria for inclusion. The primary diagnosis was CC in 47 patients (39 women, 8 men, median age 58 years; range 29-86) and LC in 18 patients (16 women, 2 men, median age 58 years; range 33-74). Conversion occurred in nine of the 65 patients (14%, all women, median age 59 years; range 41-72), three from CC to LC and six from LC to CC. CONCLUSION This study has found that patients can show histological features consistent with both CC and LC over time. These patients could represent a subgroup with a true conversion between two separate entities. Alternatively, MC could be a spectral disease where the varying histological features are manifestations of the natural fluctuation. A third possibility could be that the histological changes reflect different manifestations during the disease course and consequently, the diagnostic criteria could be too vague.
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Affiliation(s)
- Lina Vigren
- Department of Medicine, Division of Gastroenterology, Trelleborg Hospital, Trelleborg, Sweden.
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Melcescu E, Hogan RB, Brown K, Boyd SA, Abell TL, Koch CA. The various faces of autoimmune endocrinopathies: non-tumoral hypergastrinemia in a patient with lymphocytic colitis and chronic autoimmune gastritis. Exp Mol Pathol 2012; 93:434-40. [PMID: 23043903 PMCID: PMC5098702 DOI: 10.1016/j.yexmp.2012.09.025] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2012] [Accepted: 09/29/2012] [Indexed: 01/10/2023]
Abstract
Serum gastrin levels exceeding 1000pg/ml (normal, <100) usually raise the suspicion for a neuroendocrine tumor (NET) that secretes gastrin. Rarely, such elevated gastrin levels are seen in patients with pernicious anemia which most commonly is associated with autoimmune gastritis (AG). AG can occur concomitantly with other autoimmune disorders including lymphocytic colitis (LC). Gastrin stimulates enterochromaffin-like cells which increase histamine secretion. Histamine excess can cause diarrhea as can bacterial overgrowth or LC. We present a 57-year-old woman with diarrhea, sporadic epigastric pain, and bloating. She also had a history of interstitial cystitis and took pentosan polysulfate and cetirizine. She had no history of ulcers, renal impairment or carcinoid syndrome. Fasting serum gastrin was 1846pg/ml. Esophagoduodenal gastroscopy and biopsies revealed chronic gastritis and a pH of 7 with low stomach acid. Serum gastrin and plasma chromogranin A were suggestive of a gastrinoma or NET. Pernicious anemia was unlikely. Imaging studies did not reveal any tumor. Random colonic biopsy was compatible with LC, possibly explaining her diarrhea, although we also considered excessive histamine from elevated gastrin, bacterial overgrowth, and pentosan polysulfate which can cause diarrhea and be misleading in this setting, pointing to the diagnosis of gastrinoma. At 4year follow-up in 2012, fasting serum gastrin was 1097pg/ml and the patient asymptomatic taking only cetirizine for nasal allergies. This case illustrates that diarrhea may be associated with very high serum gastrin levels in the setting of chronic gastritis, LC, and interstitial cystitis (pentosan use), without clear evidence for a gastrinoma or NET. If no history of ulcers or liver metastases is present in such cases, watchful observation rather than an extensive/invasive and costly search for a NET may be justified. Considering the various forms of polyglandular syndrome, this may represent a variant and we here provide an algorithm for working up such patients, while also reviewing literature on the intertwined relationship between the immune and endocrine systems.
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Affiliation(s)
- Eugen Melcescu
- Department of Medicine, University of Mississippi Medical Center, Jackson, MS 39216, USA
| | - Reed B. Hogan
- Gastrointestinal Associates and Endoscopy Center, Jackson, MS 39202, USA
| | - Keith Brown
- Gastrointestinal Associates and Endoscopy Center, Jackson, MS 39202, USA
| | - Stewart A. Boyd
- Department of Medicine, University of Mississippi Medical Center, Jackson, MS 39216, USA
| | - Thomas L. Abell
- Department of Medicine, University of Mississippi Medical Center, Jackson, MS 39216, USA
| | - Christian A. Koch
- Department of Medicine, University of Mississippi Medical Center, Jackson, MS 39216, USA
- Medical Service, G.V. (Sonny) Montgomery VA Medical Center, Jackson, MS, USA
- Cancer Institute, UMMC, USA
- Department of Medicine, University of Dresden, Dresden, Germany
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Ianiro G, Cammarota G, Valerio L, Annicchiarico BE, Milani A, Siciliano M, Gasbarrini A. Microscopic colitis. World J Gastroenterol 2012; 18:6206-6215. [PMID: 23180940 PMCID: PMC3501768 DOI: 10.3748/wjg.v18.i43.6206] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Microscopic colitis may be defined as a clinical syndrome, of unknown etiology, consisting of chronic watery diarrhea, with no alterations in the large bowel at the endoscopic and radiologic evaluation. Therefore, a definitive diagnosis is only possible by histological analysis. The epidemiological impact of this disease has become increasingly clear in the last years, with most data coming from Western countries. Microscopic colitis includes two histological subtypes [collagenous colitis (CC) and lymphocytic colitis (LC)] with no differences in clinical presentation and management. Collagenous colitis is characterized by a thickening of the subepithelial collagen layer that is absent in LC. The main feature of LC is an increase of the density of intra-epithelial lymphocytes in the surface epithelium. A number of pathogenetic theories have been proposed over the years, involving the role of luminal agents, autoimmunity, eosinophils, genetics (human leukocyte antigen), biliary acids, infections, alterations of pericryptal fibroblasts, and drug intake; drugs like ticlopidine, carbamazepine or ranitidine are especially associated with the development of LC, while CC is more frequently linked to cimetidine, non-steroidal antiinflammatory drugs and lansoprazole. Microscopic colitis typically presents as chronic or intermittent watery diarrhea, that may be accompanied by symptoms such as abdominal pain, weight loss and incontinence. Recent evidence has added new pharmacological options for the treatment of microscopic colitis: the role of steroidal therapy, especially oral budesonide, has gained relevance, as well as immunosuppressive agents such as azathioprine and 6-mercaptopurine. The use of anti-tumor necrosis factor-α agents, infliximab and adalimumab, constitutes a new, interesting tool for the treatment of microscopic colitis, but larger, adequately designed studies are needed to confirm existing data.
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El-Salhy M, Gundersen D, Hatlebakk JG, Hausken T. High densities of serotonin and peptide YY cells in the colon of patients with lymphocytic colitis. World J Gastroenterol 2012; 18:6070-5. [PMID: 23155335 PMCID: PMC3496883 DOI: 10.3748/wjg.v18.i42.6070] [Citation(s) in RCA: 56] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/03/2012] [Revised: 07/26/2012] [Accepted: 07/29/2012] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate colonic endocrine cells in lymphocytic colitis (LC) patients.
METHODS: Fifty-seven patients with LC were included. These patients were 41 females and 16 males, with an average age of 49 years (range 19-84 years). Twenty-seven subjects that underwent colonoscopy with biopsies were used as controls. These subjects underwent colonoscopy because of gastrointestinal bleeding or health worries, where the source of bleeding was identified as haemorrhoids or angiodysplasia. They were 19 females and 8 males with an average age of 49 years (range 18-67 years). Biopsies from the right and left colon were obtained from both patients and controls during colonoscopy. Biopsies were fixed in 4% buffered paraformaldehyde, embedded in paraffin and cut into 5 μm-thick sections. The sections immunostained by the avidin-biotin-complex method for serotonin, peptide YY (PYY), pancreatic polypeptide (PP) enteroglucagon and somatostatin cells. The cell densities were quantified by computerised image analysis using Olympus software.
RESULTS: The colon of both the patient and the control subjects were macroscopically normal. Histopathological examination of colon biopsies from controls revealed normal histology. All patients fulfilled the diagnosis criteria required for of LC: an increase in intraepithelial lymphocytes (> 20 lymphocytes/100 epithelial cells) and surface epithelial damage with increased lamina propria plasma cells and absent or minimal crypt architectural distribution. In the colon of both patients and control subjects, serotonin-, PYY-, PP-, enteroglucagon- and somatostatin-immunoreactive cells were primarily located in the upper part of the crypts of Lieberkühn. These cells were basket- or flask-shaped. There was no statistically significant difference between the right and left colon in controls with regards to the densities of serotonin- and PYY-immunoreactive cells (P = 0.9 and 0.1, respectively). Serotonin cell density in the right colon in controls was 28.9 ± 1.8 and in LC patients 41.6 ± 2.6 (P = 0.008). In the left colon, the corresponding figures were 28.5 ± 1.9 and 42.4 ± 2.9, respectively (P = 0.009). PYY cell density in the right colon of the controls was 10.1 ± 1 and of LC patients 41 ± 4 (P = 0.00006). In the left colon, PYY cell density in controls was 6.6 ± 1.2 and in LC patients 53.3 ± 4.6 (P = 0.00007).
CONCLUSION: The change in serotonin cells could be caused by an interaction between immune cells and serotonin cells, and that of PYY density might be secondary.
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Münch A, Aust D, Bohr J, Bonderup O, Fernández Bañares F, Hjortswang H, Madisch A, Munck LK, Ström M, Tysk C, Miehlke S. Microscopic colitis: Current status, present and future challenges: statements of the European Microscopic Colitis Group. J Crohns Colitis 2012; 6:932-45. [PMID: 22704658 DOI: 10.1016/j.crohns.2012.05.014] [Citation(s) in RCA: 160] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2012] [Accepted: 05/18/2012] [Indexed: 02/06/2023]
Abstract
Microscopic colitis (MC) is an inflammatory bowel disease presenting with chronic, non-bloody watery diarrhoea and few or no endoscopic abnormalities. The histological examination reveals mainly two subtypes of MC, lymphocytic or collagenous colitis. Despite the fact that the incidence in MC has been rising over the last decades, research has been sparse and our knowledge about MC remains limited. Specialists in the field have initiated the European Microscopic Colitis Group (EMCG) with the primary goal to create awareness on MC. The EMCG is furthermore a forum with the intention to promote clinical and basic research. In this article statements and comments are given that all members of the EMCG have considered being of importance for a better understanding of MC. The paper focuses on the newest updates in epidemiology, symptoms and diagnostic criteria, pathophysiology and highlights some unsolved problems. Moreover, a new treatment algorithm is proposed on the basis of new evidence from well-designed, randomized control trials.
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Affiliation(s)
- A Münch
- Div. of Gastroenterology and Hepatology, Dept. of Clinical and Experimental Medicine, Faculty of Health Science, Linköping University, Sweden.
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Tuteja AK, Fang JC, Al-Suqi M, Stoddard GJ, Hale DC. Double-blind placebo-controlled study of mesalamine in post-infective irritable bowel syndrome--a pilot study. Scand J Gastroenterol 2012; 47:1159-64. [PMID: 22783919 DOI: 10.3109/00365521.2012.694903] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVE Post-infective irritable bowel syndrome (PI-IBS) is characterized by continuing symptoms of irritable bowel syndrome, typically diarrhea-predominant, following an episode of acute gastroenteritis. There is often an increase in sub-epithelial inflammatory and neuroendocrine cells on colonic mucosal biopsy. Mesalamine is an anti-inflammatory agent, effective in the treatment of inflammatory bowel disease. The goal of this study was to compare mesalamine to placebo on symptoms and quality-of-life (QOL) in PI-IBS. MATERIAL AND METHODS Twenty patients who developed diarrhea-predominant IBS after gastroenteritis were randomized to receive mesalamine (Asacol®) 1.6 gm b.i.d. or placebo for 12 weeks in a double-blind placebo-controlled study. QOL was assessed using the IBS-QOL questionnaire. Stool frequency, stool consistency, urgency, severity of abdominal pain, severity of bloating, and global-improvement scale were recorded in daily diaries for 7 days at baseline and every 4 weeks. Data were analyzed by comparing the change from baseline to last follow-up. RESULTS One patient withdrew after randomization; data were incomplete in two patients. Thus, data were analyzed from 17 patients (11 men and 6 women, median age: 27 years, range 22-45 years). Mesalamine was not associated with significant improvement in global symptoms, abdominal pain, bloating, stool urgency, frequency, or consistency (all p ≥ 0.11) or QOL (p ≥ 0.16). CONCLUSIONS There was no significant improvement in global symptoms or overall QOL with mesalamine in patients with PI-IBS.
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Affiliation(s)
- Ashok K Tuteja
- Division of Gastroenterology, University of Utah, School of Medicine, 30 N 1900 E, Salt Lake City, UT 84132, USA.
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Abstract
Diarrhea is a common clinical feature of inflammatory bowel diseases and may be accompanied by abdominal pain, urgency, and fecal incontinence. The pathophysiology of diarrhea in these diseases is complex, but defective absorption of salt and water by the inflamed bowel is the most important mechanism involved. In addition to inflammation secondary to the disease, diarrhea may arise from a variety of other conditions. It is important to differentiate the pathophysiologic mechanisms involved in the diarrhea in the individual patient to provide the appropriate therapy. This article reviews microscopic colitis, ulcerative colitis, and Crohn's disease, focusing on diarrhea.
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Affiliation(s)
- Heimo H Wenzl
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, Graz, Austria.
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29
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Cerilli LA, Greenson JK. The Differential Diagnosis of Colitis in Endoscopic Biopsy Specimens: A Review Article. Arch Pathol Lab Med 2012; 136:854-64. [DOI: 10.5858/arpa.2012-0205-ra] [Citation(s) in RCA: 66] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
Context.—A variety of inflammatory disorders may affect the colon, with widely differing clinical outcomes and management. These conditions encompass a spectrum of acute and chronic conditions.
Objective.—Review the pathology of the major colitides and highlight the most diagnostically useful features.
Data Sources.—Review of recent literature supplemented with personal experience in the field of gastrointestinal pathology.
Conclusions.—The etiologies associated with the various types of colitis are diverse and the range of histologic changes is somewhat limited. Nevertheless, the combination of clinical and endoscopic data coupled with histopathology allows for accurate classification in the majority of cases.
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Affiliation(s)
- Lisa A. Cerilli
- From the Department of Pathology, University of Michigan Medical School, Ann Arbor
| | - Joel K. Greenson
- From the Department of Pathology, University of Michigan Medical School, Ann Arbor
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Rasmussen MA, Munck LK. Systematic review: are lymphocytic colitis and collagenous colitis two subtypes of the same disease - microscopic colitis? Aliment Pharmacol Ther 2012; 36:79-90. [PMID: 22670660 DOI: 10.1111/j.1365-2036.2012.05166.x] [Citation(s) in RCA: 88] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Revised: 04/25/2012] [Accepted: 05/14/2012] [Indexed: 12/13/2022]
Abstract
BACKGROUND Despite similar clinical symptoms, collagenous colitis (CC) and lymphocytic colitis (LC) are considered two distinct disease entities. AIM To compare pathoanatomical findings, clinical presentations, risk factors, course of diseases and response to treatment in CC and LC to establish whether they could be subtypes of the same disease, microscopic colitis (MC). METHODS The MEDLINE was searched for CC, LC and MC, and clinical studies of >20 patients were included. Pooled results with 95% confidence intervals were calculated based on the number of patients. RESULTS An abnormal number of intraepithelial lymphocytes are found in 45% (40-50%) with CC, and an abnormal subepithelial collagen band in 16% (13-20%) with LC suggesting a histological overlap. The incidence of CC and LC has increased in parallel. Mean age (CC 63 years; LC 60 years) and clinical presentation are indistinguishable, and females are predominant in CC (77%; 75-79%) as well as LC (68%; 66-70%). Risk factors such as nonsteroid anti-inflammatory drugs consumption CC 39% (36-42%); LC 32% (29-35%) are similar and prevalence of concomitant autoimmune diseases such as coeliac disease (CC 5%; CI: 4-6% and LC 7%; CI: 6-9%) do not differ. Bile acid diarrhoea is highly prevalent in CC (41%; 37-45%) and LC (29%; 24-34%). The effect of budesonide is identical. CONCLUSIONS CC and LC could be considered histological subtypes of the same disease, MC. To facilitate recruitment to clinical trials, all MC patients could be included in future trials and stratified for subtypes.
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MESH Headings
- Anti-Inflammatory Agents/therapeutic use
- Budesonide/therapeutic use
- Colitis, Collagenous/classification
- Colitis, Collagenous/drug therapy
- Colitis, Collagenous/pathology
- Colitis, Lymphocytic/classification
- Colitis, Lymphocytic/drug therapy
- Colitis, Lymphocytic/pathology
- Colitis, Microscopic/classification
- Colitis, Microscopic/drug therapy
- Colitis, Microscopic/pathology
- Diagnosis, Differential
- Humans
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Affiliation(s)
- M A Rasmussen
- Faculty of Health and Medical Sciences, University of Copenhagen, Denmark
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31
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Chetty R, Govender D. Lymphocytic and collagenous colitis: an overview of so-called microscopic colitis. Nat Rev Gastroenterol Hepatol 2012; 9:209-18. [PMID: 22349169 DOI: 10.1038/nrgastro.2012.16] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
The entity of 'microscopic colitis' is being diagnosed with increasing frequency and is a well-established clinicopathological diagnosis that is underpinned by a triad of watery diarrhea, normal results on endoscopy and characteristic microscopic findings. Careful histopathological evaluation and awareness of its numerous associations (especially with drugs and celiac disease) and mimics will lead to the correct diagnosis of microscopic colitis. The etiology of microscopic colitis remains enigmatic and is multifactorial with different elements being more influential in different individuals. Treatment includes antidiarrheal agents and anti-inflammatory drugs (including steroids). The purpose of this article is to provide some clarity on nomenclature, discuss the multitude of conditions that can occur synchronously or metachronously with microscopic colitis and their role in the etiopathogenesis of this condition, provide a detailed review of the pathological aspects of the disease and to briefly discuss treatment trends.
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Affiliation(s)
- Runjan Chetty
- Department of Cellular Pathology, Oxford University Hospitals Trust and University of Oxford, Level 1 Academic Centre, John Radcliffe Hospital, Headley Way, Oxford OX3 9DU, UK.
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Bjørnbak C, Engel PJH, Nielsen PL, Munck LK. Microscopic colitis: clinical findings, topography and persistence of histopathological subgroups. Aliment Pharmacol Ther 2011; 34:1225-34. [PMID: 21967618 DOI: 10.1111/j.1365-2036.2011.04865.x] [Citation(s) in RCA: 82] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
BACKGROUND Uncertainty remains on topography and persistence of histological subgroups of microscopic colitis (MC). AIM To assess longitudinal clinical, endoscopic, histological, and therapeutic description of MC subgroups including patients with incomplete findings of MC (MCi). METHODS Retrospective review of a consecutive cohort with MC and histological reassessment of MCi. RESULTS Clinical characteristics of 168 patients with lymphocytic colitis (LC), 270 with collagenous colitis (CC) and 101 with MCi were similar. At colonoscopy 95% (95% CI: 91-98%) of CC and 98% (93-100%) of LC cases had diagnostic histopathology of MC in both left and right colon. Eight and three patients had characteristics of MC only in the left and right colon, respectively. Histology findings resembling coexistence of the other MC subtype was present in 48% (40-55%) with CC and 24% (18-31%) with LC. A first diagnosis of MC was made in 49 (30%) of 164 patients only at repeat endoscopy. Another 34 of 115 (30%) with MC in the first endoscopy did not fulfil the MC criteria at repeat endoscopy. Only seven cases had a primary endoscopy without histopathological abnormalities. Fifteen percentage of MCi were reclassified as MC. Ileal inflammation was present in 33 of 81 patients. Budesonide was efficacious in all MC subgroups irrespective of bile acid malabsorption. CONCLUSIONS Clinical characteristics of microscopic colitis subgroups are indistinguishable. Biopsies from the left colon suffice to exclude microscopic colitis, and the histological diagnosis of microscopic colitis is inconsistent over time. Ileal inflammation is common. The term microscopic colitis should perhaps be considered one clinical entity and include lymphocytic colitis, collagenous colitis, and incomplete findings of microscopic colitis.
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Affiliation(s)
- C Bjørnbak
- Section of Gastroenterology, Department of Medicine, Køge Hospital, Køge, Denmark
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Abstract
BACKGROUND Microscopic colitis is a relatively common cause of chronic diarrhoea in predominantly older adults, traditionally termed lymphocytic colitis and collagenous colitis. Increased mast cells found in the colonic biopsies of some patients with chronic diarrhoea may represent a distinct type of microscopic colitis. AIM To provide an updated review of the epidemiology, diagnosis and treatment of microscopic colitis, and to discuss the role of mast cells in the gastrointestinal tract and their potential role in cases of functional diarrhoea. METHOD A MEDLINE literature search was performed to identify pertinent articles. Relevant clinical abstracts were also reviewed. RESULTS Incidence rates of microscopic colitis (lymphocytic and collagenous colitis) have increased over time, to levels comparable with other forms of inflammatory bowel disease. The possibility of drug-induced microscopic colitis and concomitant coeliac sprue are important considerations when evaluating these patients. There are few controlled treatment trials in microscopic colitis, with much of the data on treatment coming from retrospective studies. Mast cells have been implicated in functional bowel disorders, with increased mast cells possibly contributing to cases of otherwise unexplained chronic diarrhoea, although this concept requires further investigation. CONCLUSIONS In patients with microscopic colitis, a systematic approach to therapy often leads to satisfactory control of symptoms. The role of mast cells in chronic diarrhoea represents an evolving field, with the potential to offer alternative treatment pathways in patients with otherwise unexplained functional diarrhoea.
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Affiliation(s)
- E F Yen
- Division of Gastroenterology, University of Chicago, Pritzker School of Medicine, NorthShore University HealthSystem, Evanston, IL, USA.
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35
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Calabrese C, Gionchetti P, Liguori G, Areni A, Fornarini GS, Campieri M, Rizzello F. Clinical course of microscopic colitis in a single-center cohort study. J Crohns Colitis 2011; 5:218-21. [PMID: 21575884 DOI: 10.1016/j.crohns.2011.01.004] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/04/2010] [Revised: 01/18/2011] [Accepted: 01/18/2011] [Indexed: 02/08/2023]
Abstract
BACKGROUND AND AIMS The long-term natural history of collagenous (CC) and lymphocytic colitis (LC) is not well known. The aims of this study were to evaluate the clinical course of microscopic colitis (MC) and to describe the morbidity evolution of the disease. MATERIAL AND METHODS This study is based on a cohort of 54 patients (35 LC/19 CC), previously included in a randomized trial treated with mesalazine with or without cholestyramine. Patients were followed-up closely during the subsequent 5 years, undergoing clinical, endoscopic and histologic evaluation at least yearly. After this period, they were encouraged to undergo periodical clinical evaluations. RESULTS In a mean follow-up time of 104.9 ± 14.1 months (range 81-138 months) at the end of the therapy, 12 patients (7 LC and 5 CC) relapsed. Of these patients, 4 reported a mild clinical relapse self-treated with antidiarrheal medication. In total 49 patients are clinically free from diarrhea, to date. At multivariate analysis the only predictive factor of relapse seems to be a slow response to treatment. CONCLUSIONS Only a minority of patients with MC had diarrhea more than once a week in a long-term follow-up and the symptom pattern was similar between CC and LC patients.
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Affiliation(s)
- Carlo Calabrese
- Department of Clinical Medicine, University of Bologna, Italy.
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Abstract
Microscopic colitis is a common cause of chronic watery diarrhea, especially among older persons. Diagnosis requires histologic analysis of colon biopsy samples in the appropriate clinical setting. Recent studies have shown an increase in the incidence of microscopic colitis, and several have addressed potential mechanisms. We review recent findings about the clinical features, diagnosis, epidemiology, pathophysiology, and treatment of microscopic colitis.
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Affiliation(s)
- Darrell S Pardi
- Inflammatory Bowel Disease Clinic, Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, Minnesota, USA.
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Tysk C, Wickbom A, Nyhlin N, Eriksson S, Bohr J. Recent advances in diagnosis and treatment of microscopic colitis. Ann Gastroenterol 2011; 24:253-262. [PMID: 24713787 PMCID: PMC3959332] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/05/2011] [Accepted: 09/11/2011] [Indexed: 11/23/2022] Open
Abstract
Microscopic colitis, comprising collagenous colitis and lymphocytic colitis, is a common cause of chronic diarrhea. It is characterized clinically by chronic watery diarrhea and a macroscopically normal colonic mucosa where diagnostic histopathological features are seen on microscopic examination. The annual incidence of each disorder is 4-6/100,000 inhabitants, with a peak incidence in individuals 60-70 years old and a noticeable female predominance in collagenous colitis. The etiology is unknown. Chronic diarrhea, abdominal pain, weight loss, fatigue, and fecal incontinence are common symptoms that impair the health-related quality of life of the patient. There is an association with other autoimmune disorders, such as celiac disease, thyroid disorders, diabetes mellitus, and arthritis. Budesonide is the best-documented treatment, both short-term and long-term. Recurrence of symptoms is common after withdrawal of successful budesonide therapy, and the optimal long-term treatment strategy needs further study. The long-term prognosis is good, and the risk of complications including colon cancer is low. We review the epidemiology, clinical features, diagnosis and treatment of microscopic colitis.
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Affiliation(s)
- Curt Tysk
- Department of Medicine, Division of Gastroenterology, Örebro University Hospital and School of Health and Medical Sciences,Örebro University, Örebro, Sweden (Curt Tysk, Anna Wickbom, Nils Nyhlin, Johan Bohr)
| | - Anna Wickbom
- Department of Medicine, Division of Gastroenterology, Örebro University Hospital and School of Health and Medical Sciences,Örebro University, Örebro, Sweden (Curt Tysk, Anna Wickbom, Nils Nyhlin, Johan Bohr)
| | - Nils Nyhlin
- Department of Medicine, Division of Gastroenterology, Örebro University Hospital and School of Health and Medical Sciences,Örebro University, Örebro, Sweden (Curt Tysk, Anna Wickbom, Nils Nyhlin, Johan Bohr)
| | - Sune Eriksson
- Department of LaboratoryMedicine, Division of Pathology, Örebro University Hospital,Örebro, Sweden (Sune Eriksson)
| | - Johan Bohr
- Department of Medicine, Division of Gastroenterology, Örebro University Hospital and School of Health and Medical Sciences,Örebro University, Örebro, Sweden (Curt Tysk, Anna Wickbom, Nils Nyhlin, Johan Bohr)
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Miehlke S, Madisch A, Karimi D, Wonschik S, Kuhlisch E, Beckmann R, Morgner A, Mueller R, Greinwald R, Seitz G, Baretton G, Stolte M. Budesonide is effective in treating lymphocytic colitis: a randomized double-blind placebo-controlled study. Gastroenterology 2009; 136:2092-100. [PMID: 19303012 DOI: 10.1053/j.gastro.2009.02.078] [Citation(s) in RCA: 86] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/28/2008] [Revised: 02/24/2009] [Accepted: 02/27/2009] [Indexed: 12/13/2022]
Abstract
BACKGROUND & AIMS Budesonide is effective in treating collagenous colitis, but no treatment is established for lymphocytic colitis. We performed a randomized, double-blind, placebo-controlled study to evaluate the effects of budesonide in patients with lymphocytic colitis. METHODS Forty-two patients (median age, 61 years) with lymphocytic colitis and chronic diarrhea were randomly assigned to groups that were given oral doses of budesonide (9 mg/d) or placebo for 6 weeks. Nonresponders at week 6 were given open-label budesonide (9 mg/d) for 6 additional weeks. A complete colonoscopy and histologic and quality-of-life analyses were performed at baseline and at week 6. The primary end point was clinical remission at 6 weeks, with last observation carried forward (LOCF). All patients who left the study in clinical remission were followed for relapse. RESULTS At week 6, 86% of patients given budesonide were in clinical remission (with LOCF) compared with 48% of patients given placebo (P = .010). Furthermore, open-label budesonide therapy induced clinical remission in 7 of 8 patients given placebo. Histologic remission was observed in 73% of patients given budesonide compared with 31% given placebo (P = .030). Only 1 patient discontinued budesonide therapy prematurely. During a mean follow-up period of 14 months, 15 patients (44.1%) experienced a clinical relapse (after a mean of 2 months); 8 of the relapsing patients were retreated with and responded again to budesonide. CONCLUSIONS Budesonide effectively induces clinical remission in patients with lymphocytic colitis and significantly improves histology results after 6 weeks. Clinical relapses occur but can be treated again with budesonide.
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Affiliation(s)
- Stephan Miehlke
- Medical Department I, Technical University Hospital, Dresden, Germany.
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Tysk C, Bohr J, Nyhlin N, Wickbom A, Eriksson S. Diagnosis and management of microscopic colitis. World J Gastroenterol 2008; 14:7280-8. [PMID: 19109861 PMCID: PMC2778111 DOI: 10.3748/wjg.14.7280] [Citation(s) in RCA: 51] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2008] [Revised: 12/03/2008] [Accepted: 12/10/2008] [Indexed: 02/06/2023] Open
Abstract
Microscopic colitis, comprising collagenous and lymphocytic colitis, is characterized clinically by chronic watery diarrhea, and a macroscopically normal colonic mucosa where diagnostic histopathological features are seen on microscopic examination. The annual incidence of each disorder is 4-6/100,000 inhabitants, with a peak incidence in 60-70-year-old individuals and a noticeable female predominance for collagenous colitis. The etiology is unknown. Chronic diarrhea, abdominal pain, weight loss, fatigue and fecal incontinence are common symptoms, which impair the health-related quality of life of the patient. There is an association with other autoimmune disorders such as celiac disease, diabetes mellitus, thyroid disorders and arthritis. Budesonide is the best-documented short-term treatment, but the optimal long-term strategy needs further study. The long-term prognosis is good and the risk of complications including colonic cancer is low.
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Sveinsson OA, Orvar KB, Birgisson S, Agnarsdottir M, Jonasson JG. Clinical features of microscopic colitis in a nation-wide follow-up study in Iceland. Scand J Gastroenterol 2008; 43:955-60. [PMID: 19086278 DOI: 10.1080/00365520801958600] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
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.
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Affiliation(s)
- Olafur A Sveinsson
- Department of Medicine, Division of Gastroenterology, Landspitali University Hospital, Reykjavik, Iceland
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Erdem L, Yildirim S, Akbayir N, Yilmaz B, Yenice N, Gültekin OS, Peker &O. Prevalence of microscopic colitis in patients with diarrhea of unknown etiology in Turkey. World J Gastroenterol 2008; 14:4319-23. [PMID: 18666319 PMCID: PMC2731182 DOI: 10.3748/wjg.14.4319] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the prevalence and demography of microscopic colitis in patients with diarrhea of unknown etiology and normal colonoscopy in Turkey.
METHODS: Between March, 1998 to July, 2005, 129 patients with chronic non-bloody diarrhea of unexplained etiology who had undergone full colonoscopy with no obvious abnormalities were included in the study. Two biopsies were obtained from all colonic segments and terminal ileum for diagnosis of microscopic colitis. On histopathologic examination, criteria for lymphocytic colitis (intraepithelial lymphocyte ≥ 20 per 100 intercryptal epithelial cells, change in surface epithelium, mononuclear infiltration of the lamina propria) and collagenous colitis (subepithelial collagen band thickness ≥ 10 &mgr;m) were explored.
RESULTS: Lymphocytic colitis was diagnosed in 12 (9%) patients (Female/Male: 7/5, mean age: 45 year, range: 27-63) and collagenous colitis was diagnosed in only 3 (2.5%) patients (all female, mean age: 60 years, range: 54-65).
CONCLUSION: Biopsy of Turkish patients with the diagnosis of chronic non-bloody diarrhea of unexplained etiology and normal colonoscopic findings will reveal microscopic colitis in approximately 10% of the patients. Lymphocytic colitis is 4 times more frequent than collagenous colitis in these patients.
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Beaugerie L. [Microscopic colitis: nosological face-lift and research tracks]. ACTA ACUST UNITED AC 2008; 32:686-8. [PMID: 18572338 DOI: 10.1016/j.gcb.2008.04.022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
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Nyhlin N, Bohr J, Eriksson S, Tysk C. Microscopic colitis: a common and an easily overlooked cause of chronic diarrhoea. Eur J Intern Med 2008; 19:181-6. [PMID: 18395161 DOI: 10.1016/j.ejim.2008.01.001] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/21/2008] [Accepted: 01/22/2008] [Indexed: 02/08/2023]
Abstract
Microscopic colitis, comprising collagenous colitis and lymphocytic colitis, is characterised clinically by chronic watery diarrhoea, a macroscopically normal colonic mucosa where diagnostic histopathological features are seen on microscopic examination. The annual incidence of each disorder is 4-6/100,000 inhabitants, with a peak incidence in 60-70 year old individuals and a noticeable female predominance in collagenous colitis. The aetiology is unknown. Abdominal pain, weight loss, fatigue, and faecal incontinence are common symptoms in addition to chronic diarrhoea that impair the health-related quality of life of the patient. There is an association to other autoimmune disorders such as celiac disease, diabetes mellitus, thyroid disorders and arthritis. Budesonide is the best-documented short-term treatment, but the optimal long-term strategy needs further study. The long-term prognosis is good and the risk of complications including colonic cancer is low.
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Affiliation(s)
- Nils Nyhlin
- Department of Medicine, Division of Gastroenterology, Orebro University Hospital, Orebro, Sweden
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Abstract
BACKGROUND Lymphocytic colitis is a cause of chronic diarrhea. Therapy is based mainly on case series and uncontrolled trials, or by extrapolation of data for treating collagenous colitis, a related disorder. This review was performed to identify therapies for lymphocytic colitis that have been proven in randomized controlled trials. OBJECTIVES To determine effective treatments for patients with clinically active lymphocytic colitis. SEARCH STRATEGY The MEDLINE, PUBMED and EMBASE databases were searched using the search criteria "microscopic colitis" or "lymphocytic colitis" and "treatment" or "therapy" or "management" to identify relevant papers published between 1970 and December 2007. Manual searches from the references of identified papers and relevant review papers were performed. Abstracts from major gastroenterological meetings were searched to identify research submitted in abstract form only. The trial registry website www.ClinicalTrials.gov was searched to identify registered but unpublished trials. Finally, the Cochrane Central Register of Controlled Trials and the Cochrane Inflammatory Bowel Disease and Functional Bowel Disorders Group Specialized Trials Register were searched for other studies. SELECTION CRITERIA Five randomized controlled trials were identified. Three of these studies, which assessed bismuth subsalicylate vs. placebo, budesonide vs. placebo, and mesalazine vs. mesalazine vs. cholestyramine in treating active disease, are included in this review. DATA COLLECTION AND ANALYSIS Data were extracted independently by each author onto 2x2 tables (treatment versus placebo or active comparator and response versus no response). For therapies assessed in one trial only, P values were derived using the chi-square test. MAIN RESULTS Forty-one patients were enrolled in the trial studying budesonide (9 mg/day for 6 weeks versus placebo). Budesonide was more effective than placebo at inducing both clinical (P = 0.004; NNT = 3) and histological responses (P = 0.04; NNT = 3). Forty-one patients were enrolled in the study assessing mesalazine versus mesalazine plus cholestyramine. A high proportion of patients in each group responded to treatment. However, no statistically significant difference in clinical response was found between the two treatment groups (P = 0.95). Five patients were enrolled in the trial studying bismuth subsalicylate (nine 262 mg tablets daily for 8 weeks vs. placebo). There were no differences in clinical (P=0.10) or histological responses (P=0.71) in patients treated with bismuth subsalicylate compared with placebo. AUTHORS' CONCLUSIONS A single trial studying budesonide suggests that it may be effective for the treatment of active lymphocytic colitis. An ongoing placebo-controlled trial may confirm the benefit of budesonide. There is weaker evidence that mesalazine with or without cholestyramine may be effective for the treatment of lymphocytic colitis, but this benefit needs to be confirmed in a placebo-controlled study. No conclusions can be made regarding bismuth subsalicylate. These agents require further study before they can be recommended as treatment options for lymphocytic colitis. Further trials studying interventions for lymphocytic colitis are warranted.
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Affiliation(s)
- N Chande
- LHSC - South Street Hospital, Mailbox 55, 375 South Street, London, Ontario, Canada, N6A 4G5.
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Williams JJ, Kaplan GG, Makhija S, Urbanski SJ, Dupre M, Panaccione R, Beck PL. Microscopic colitis-defining incidence rates and risk factors: a population-based study. Clin Gastroenterol Hepatol 2008; 6:35-40. [PMID: 18166476 DOI: 10.1016/j.cgh.2007.10.031] [Citation(s) in RCA: 98] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS The burden and determinants of microscopic colitis (MC) in North America are inadequately defined. We determined the incidence rate of and risk factors for MC in a well-defined North American population. METHODS A population-based cohort study was conducted between April 1, 2002, and March 31, 2004. All adults with a pathologic diagnosis of MC were identified and comprehensive chart review was undertaken to confirm the diagnosis and identify risk factors. Category-specific risks for developing MC were reported as rate ratios (RRs) with exact 95% confidence intervals (CIs). RESULTS MC was identified in 164 individuals for an annual incidence rate of 10.0 per 100,000 person-years (lymphocytic colitis, 5.4; collagenous colitis, 4.6 per 100,000). Patients older than the age of 65 were more than 5 times more likely to develop MC (RR, 5.6; 95% CI, 4.0-7.7). Women were at higher risk of acquiring MC for both collagenous colitis (RR, 3.44; 95% CI, 2.07-5.97) and lymphocytic colitis (RR 6.29; 95% CI, 3.21-13.74). Elderly women with a history of malignancy were associated with a higher risk of MC (RR, 3.59; 95% CI, 1.68-7.01), as were patients with celiac disease (RR, 7.9; 95% CI, 4.0-14.2) and hypothyroidism (RR, 6.1; 95% CI, 3.5-10.0). CONCLUSIONS This was a large population-based cohort study of MC and our incidence rates were consistent with previously reported population-based studies in North America and Europe. An increased incidence of MC was observed in several disease states with the novel finding of an increased risk of MC with malignancy.
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Non-IBD and noninfectious colitis. ACTA ACUST UNITED AC 2008; 5:28-39. [DOI: 10.1038/ncpgasthep1005] [Citation(s) in RCA: 53] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2007] [Accepted: 10/04/2007] [Indexed: 12/25/2022]
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Riddell J, Hillman L, Chiragakis L, Clarke A. Collagenous colitis: oral low-dose methotrexate for patients with difficult symptoms: long-term outcomes. J Gastroenterol Hepatol 2007; 22:1589-93. [PMID: 17845686 DOI: 10.1111/j.1440-1746.2007.05128.x] [Citation(s) in RCA: 79] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
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.
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Affiliation(s)
- James Riddell
- Calvary Clinic, Canberra, Australian Capital Territory, Australia
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Limsui D, Pardi DS, Camilleri M, Loftus EV, Kammer PP, Tremaine WJ, Sandborn WJ. Symptomatic overlap between irritable bowel syndrome and microscopic colitis. Inflamm Bowel Dis 2007; 13:175-81. [PMID: 17206699 DOI: 10.1002/ibd.20059] [Citation(s) in RCA: 99] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
BACKGROUND Microscopic colitis is diagnosed on the basis of histologic criteria, and irritable bowel syndrome (IBS) is diagnosed by symptom-based criteria. There has been little investigation into the symptomatic overlap between these conditions. Our aim was to assess the prevalence of symptoms of irritable bowel syndrome in a population-based cohort of patients with microscopic colitis. METHODS The Rochester Epidemiology Project (REP), a medical records linkage system providing all health care data for the defined population of Olmsted County, Minnesota, was used to identify all county residents with a diagnosis of microscopic colitis between 1985 and 2001. The medical records of these individuals were reviewed to ascertain symptoms consistent with Rome, Rome II, and Manning criteria for irritable bowel syndrome. RESULTS One hundred thirty-one cases of microscopic colitis were identified. Median age at diagnosis was 68 years (range, 24-95); 71% were women. Sixty-nine (53%) and 73 (56%) met Rome and Rome II criteria for irritable bowel syndrome, respectively. Fifty-four (41%) had three or more Manning criteria. Forty-three (33%) had previously been diagnosed with irritable bowel syndrome. CONCLUSIONS In this population-based cohort of histologically confirmed microscopic colitis, approximately one-half met symptom-based criteria for the diagnosis of irritable bowel syndrome. The clinical symptom-based criteria for irritable bowel syndrome are not specific enough to rule out the diagnosis of microscopic colitis. Therefore, patients with suspected diarrhea-predominant irritable bowel syndrome should undergo biopsies of the colon to investigate for possible microscopic colitis if symptoms are not well controlled by antidiarrheal therapy.
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Affiliation(s)
- David Limsui
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, Minnesota, USA
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Thorsen AJ. Noninfectious colitides: collagenous colitis, lymphocytic colitis, diversion colitis, and chemically induced colitis. Clin Colon Rectal Surg 2007; 20:47-57. [PMID: 20011361 PMCID: PMC2780148 DOI: 10.1055/s-2007-970200] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
Approximately 10% of patients with chronic diarrhea carry a diagnosis of microscopic colitis. The endoscopic appearance of both collagenous colitis and lymphocytic colitis may be normal; however, biopsies confirm the diagnosis. Available treatments include antidiarrheals, bismuth salicylate, and budesonide. Although most patients with fecal diversion may have endoscopic evidence of colitis, a much smaller percentage of patients are symptomatic. Some cases of diversion colitis respond to treatment with short-chain fatty acid enemas; however, return of the fecal stream is the most successful therapy. A variety of oral, intravenous, and per rectum chemicals may cause colitis; symptoms usually abate when chemical exposure is discontinued.
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Affiliation(s)
- Amy J Thorsen
- Division of Colon and Rectal Surgery, Department of Surgery, University of Minnesota, St. Paul, Minnesota 55104, USA.
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