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González-Castro AM, Fernández-Bañares F, Zabana Y, Farago-Pérez G, Ortega-Barrionuevo J, Expósito E, Guagnozzi D. Microscopic Colitis and Celiac Disease: Sharing More than a Diagnostic Overlap. Nutrients 2024; 16:2233. [PMID: 39064676 PMCID: PMC11279699 DOI: 10.3390/nu16142233] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2024] [Revised: 07/01/2024] [Accepted: 07/04/2024] [Indexed: 07/28/2024] Open
Abstract
Microscopic colitis (MC) is an emergent group of chronic inflammatory diseases of the colon, and celiac disease (CD) is a chronic gluten-induced immune-mediated enteropathy affecting the small bowel. We performed a narrative review to provide an overview regarding the relationship between both disorders, analyzing the most recent studies published at the epidemiological, clinical and pathophysiological levels. In fact, MC and CD are concomitantly prevalent in approximately 6% of the cases, mainly in the subset of refractory patients. Thus, physicians should screen refractory patients with CD against MC and vice versa. Both disorders share more than a simple epidemiological association, being multifactorial diseases involving innate and adaptive immune responses to known or unknown luminal factors based on a rather common genetic ground. Moreover, autoimmunity is a shared characteristic between the patients with MC and those with CD, with autoimmunity in the latter being quite well-established. Furthermore, CD and MC share some common clinical symptoms and risk factors and overlap with other gastrointestinal diseases, but some differences exist between both disorders. More studies are therefore needed to better understand the complex mechanisms involving the common pathogenetic ground contributing to the CD and MC epidemiological association.
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Affiliation(s)
- Ana María González-Castro
- Translational Mucosal Immunology Laboratory, Vall d’Hebron Institut de Recerca, 08035 Barcelona, Spain; (A.M.G.-C.); (E.E.)
- Neuro-Immuno-Gastroenterology Laboratory, Vall d’Hebron Institut de Recerca, 08035 Barcelona, Spain
| | - Fernando Fernández-Bañares
- Gastroenterology Department, University Hospital Mútua Terrassa, 08221 Terrassa, Spain (Y.Z.)
- Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBERehd, Instituto Carlos III), 28029 Madrid, Spain
| | - Yamile Zabana
- Gastroenterology Department, University Hospital Mútua Terrassa, 08221 Terrassa, Spain (Y.Z.)
- Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBERehd, Instituto Carlos III), 28029 Madrid, Spain
| | - Georgina Farago-Pérez
- Translational Mucosal Immunology Laboratory, Vall d’Hebron Institut de Recerca, 08035 Barcelona, Spain; (A.M.G.-C.); (E.E.)
| | - Jonathan Ortega-Barrionuevo
- Translational Mucosal Immunology Laboratory, Vall d’Hebron Institut de Recerca, 08035 Barcelona, Spain; (A.M.G.-C.); (E.E.)
| | - Elba Expósito
- Translational Mucosal Immunology Laboratory, Vall d’Hebron Institut de Recerca, 08035 Barcelona, Spain; (A.M.G.-C.); (E.E.)
- Neuro-Immuno-Gastroenterology Laboratory, Vall d’Hebron Institut de Recerca, 08035 Barcelona, Spain
| | - Danila Guagnozzi
- Translational Mucosal Immunology Laboratory, Vall d’Hebron Institut de Recerca, 08035 Barcelona, Spain; (A.M.G.-C.); (E.E.)
- Neuro-Immuno-Gastroenterology Laboratory, Vall d’Hebron Institut de Recerca, 08035 Barcelona, Spain
- Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBERehd, Instituto Carlos III), 28029 Madrid, Spain
- Gastroenterology Department, University Hospital Vall d’Hebron, 08035 Barcelona, Spain
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Zabana Y, Tontini G, Hultgren-Hörnquist E, Skonieczna-Żydecka K, Latella G, Østvik AE, Marlicz W, D'Amato M, Arias A, Mielhke S, Münch A, Fernández-Bañares F, Lucendo AJ. Pathogenesis of Microscopic Colitis: A Systematic Review. J Crohns Colitis 2022; 16:143-161. [PMID: 34272945 DOI: 10.1093/ecco-jcc/jjab123] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
BACKGROUND Whereas the exact aetiology of microscopic colitis [MC] remains unknown, a dysregulated immune response to luminal factors or medications is the most accepted pathogenesis hypothesis. METHODS We conducted a systematic review of the pathogenesis of MC. We applied the Joanna Briggs Institute methodologies and the PRISMA statement for the reporting of systematic reviews [PROSPERO Trial Identifier: CRD42020145008]. Populations, Exposure of interest, and Outcome [PEO] questions were used to explore the following topics in MC: 1] intestinal luminal factors; 2] autoimmunity; 3] innate immunity; 4] adaptive immunity; 5] extracellular matrix; 6] genetic risk factors; and 7] mechanism of diarrhoea. A search was done in PubMed, Embase, and Web of Science up to February 2020. A narrative description was performed explaining the findings for each aspect of MC aetiopathogenesis. RESULTS Thirty-eight documents provided evidence for PEO1, 100 for PEO2, 72 for PEO3 and 4, 38 for PEO5, 20 for PEO6, and 23 for PEO7. The majority of documents were cohorts, case reports, and case series, with a few case-control and some experimental studies. Consistency among data provided by different studies was considered to support pathogenetic hypotheses. MC is a multifactorial disease believed to involve innate and adaptive immune responses to luminal factors, genetic risk, autoimmunity, and extracellular matrix alterations, all contributing by varied mechanisms to watery diarrhoea. CONCLUSIONS This is the first systematic review on the aetiology of MC supporting the notion that MC is a multifactorial disease. However, high-profile studies are lacking, and most evidence derives from small heterogeneous studies.
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Affiliation(s)
- Yamile Zabana
- Gastroenterology Department, Hospital Universitari Mútua de Terrassa, Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Barcelona, Spain
| | - Gian Tontini
- Department of Pathophysiology and Transplantation, University of Milan and Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca'Granda Ospedale Maggiore Policlinico, Milan, Italy
| | | | | | - Giovanni Latella
- Gastroenterology Unit, Department of Life, Health and Environmental Sciences, University of L'Aquila, L'Aquila, Italy
| | - Ann Elisabeth Østvik
- Department of Clinical and Molecular Medicine [IKOM], Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway
- Department of Gastroenterology and Hepatology, Clinic of Medicine, St. Olav's University Hospital, Trondheim, Norway
| | - Wojciech Marlicz
- Department of Gastroenterology, Pomeranian Medical University, Szczecin, Poland
- Centre for Digestive Diseases Endoklinika, Szczecin, Poland
| | - Mauro D'Amato
- Gastrointestinal Genetics Lab, CIC bioGUNE - BRTA, Derio, Spain
- Ikerbasque, Basque Foundation for Science, Bilbao, Spain
| | - Angel Arias
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Barcelona, Spain
- Research Unit, Hospital General Mancha Centro, Alcázar de San Juan, Ciudad Real, Spain
| | - Stephan Mielhke
- Centre for Digestive Diseases, Internal Medicine Centre Eppendorf & Endoscopy Centre, University Hospital Hamburg Eppendorf, Hamburg, Germany
| | - Andreas Münch
- Department of Health, Medicine, and Caring Sciences, Linköping University, Linköping, Sweden
| | - Fernando Fernández-Bañares
- Gastroenterology Department, Hospital Universitari Mútua de Terrassa, Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Barcelona, Spain
| | - Alfredo J Lucendo
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Barcelona, Spain
- Gastroenterology Department, Hospital General de Tomelloso-Spain and Instituto de Investigación Sanitaria Princesa [IIS-IP], Madrid, Spain
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Westerlind H, Bonfiglio F, Mellander MR, Hübenthal M, Brynedal B, Björk J, Törkvist L, Padyukov L, Ohlsson B, Löfberg R, Hultcrantz R, Franke A, Bresso F, D'Amato M. HLA Associations Distinguish Collagenous From Lymphocytic Colitis. Am J Gastroenterol 2016; 111:1211-3. [PMID: 27481432 DOI: 10.1038/ajg.2016.215] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Affiliation(s)
- Helga Westerlind
- Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden.,Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
| | - Ferdinando Bonfiglio
- Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden
| | - Marie-Rose Mellander
- Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.,Gastrocentrum, Karolinska University Hospital, Stockholm, Sweden
| | - Matthias Hübenthal
- Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany
| | - Boel Brynedal
- Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
| | - Jan Björk
- Gastrocentrum, Karolinska University Hospital, Stockholm, Sweden
| | - Leif Törkvist
- Gastrocentrum, Karolinska University Hospital, Stockholm, Sweden
| | - Leonid Padyukov
- Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden
| | - Bodil Ohlsson
- Department of Clinical Sciences, Skåne University Hospital, Lund University, Lund, Sweden
| | - Robert Löfberg
- Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.,Sophiahemmet Hospital, Stockholm, Sweden
| | - Rolf Hultcrantz
- Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden
| | - Andre Franke
- Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany
| | - Francesca Bresso
- Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden.,Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.,Gastrocentrum, Karolinska University Hospital, Stockholm, Sweden
| | - Mauro D'Amato
- Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden.,BioCruces Health Research Institute and IKERBASQUE, Basque Foundation for Science, Cruces University Hospital, Barakaldo, Spain
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Abstract
Collagenous and lymphocytic/microscopic colitis represent a distinct histopathologic spectrum of findings, with occasional transition, observed in patients with normal or near-normal colonoscopic findings and chronic watery diarrhea (watery diarrhea- colitis syndrome). Biopsies are characterized by surface epithelial damage, an increased number of chronic inflamatory cells in the lamina propria, intraepithelial lymphocyto sis, intact crypt architecture, and in the cases of collagenous colitis, a thickened subepi thelial collagen layer (SCL). While their precise interrelationship is unclear, as their clinicopathologic similarities far outweigh their differences, it appears reasonable for pathologists and clinicians to consider them conceptually together as part of a syn drome of chronic watery diarrhea and colitis distinct from other forms of chronic inflammatory bowel disease. The etiology and pathogenesis of this syndrome are un clear. Colorectal surface epithelial damage appears to be for the most part responsible for the secretory diarrhea, while the thickened SCL appears to be a variable response to the surface epithelial damage. Why the thickened SCL occurs only in some cases, why it does not occur in other forms of colitis, and whether it functions as a diffusion barrier are unknown. The propensity of the watery diarrhea-colitis syndrome to pref erentially affect middle-aged and elderly women, an association with autoimmune disorders, and clinicopathologic similarities to celiac disease suggest that host immune factors are important. Other dietary factors, medications, or other agents may also play a role, and this is currently under investigation. Small bowel villous atrophy appears to account for the presence of steatorrhea noted in some reports. Definitive diagnosis is facilitated by the procurement of multiple, well-oriented biopsies, prefera bly extending at least into the proximal left colon. A thickened SCL occasionally can only be demonstrated in biopsies from the right colon. An appreciation of the normal variation found in colorectal biopsies and recognition of artifactual thickening of the subepithelial basement membrane in maloriented sections and in relation to bowel preparation will eliminate overdiagnosis of normal biopsies, while the absence of fea tures typical for other forms of inflammatory bowel disease facilitates differential diag nosis. Patients may respond dramatically to therapeutic intervention with drugs often used for ulcerative colitis and Crohn's disease, however, spontaneous remissions are well documented. A colitis-dysplasia-carcinoma sequence has not as yet been docu mented to occur in this patient population. In just over one decade the morphologic features of the watery diarrhea-colitis syndrome have come to be recognized. Hope fully, the next decade of observation and investigation will help to clarify the precise relationship between cases with and without a thickened SCL, as well as the etiology and pathogenesis of the secretory diarrhea. Int J Surg Pathol 1 (1): 65-82, 1993
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Affiliation(s)
- Scott H. Saul
- Department of Pathology, Chester County Hospital, 701 East Marshall Street, West Chester, PA 19380
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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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Vigren L, Tysk C, Ström M, Kilander AF, Hjortswang H, Bohr J, Benoni C, Larson L, Sjöberg K. Celiac disease and other autoimmune diseases in patients with collagenous colitis. Scand J Gastroenterol 2013; 48:944-50. [PMID: 23800241 DOI: 10.3109/00365521.2013.805809] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
BACKGROUND AND AIMS Collagenous colitis (CC) is associated with autoimmune disorders. The aim of the present study was to investigate the relationship between CC and autoimmune disorders in a Swedish multicenter study. METHODS Patients with CC answered questionnaires about demographic data and disease activity. The patient's files were scrutinized for information about autoimmune diseases. RESULTS A total number of 116 CC patients were included; 92 women, 24 men, median age 62 years (IQR 55-73). In total, 30.2% had one or more autoimmune disorder. Most common were celiac disease (CeD; 12.9%) and autoimmune thyroid disease (ATD, 10.3%), but they also had Sjögren's syndrome (3.4%), diabetes mellitus (1.7%) and conditions in skin and joints (6.0%). Patients with associated autoimmune disease had more often nocturnal stools. The majority of the patients with associated CeD or ATD got these diagnoses before the colitis diagnosis. CONCLUSION Autoimmune disorders occurred in one-third of these patients, especially CeD. In classic inflammatory bowel disease (IBD), liver disease is described in contrast to CC where no cases occurred. Instead, CeD was prevalent, a condition not reported in classic IBD. Patients with an associated autoimmune disease had more symptoms. Patients with CC and CeD had an earlier onset of their colitis. The majority of the patients with both CC and CeD were smokers. Associated autoimmune disease should be contemplated in the follow-up of these patients.
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Affiliation(s)
- Lina Vigren
- Department of Clinical Sciences, Division of Gastroenterology, Skåne University Hospital, Lund University, Malmö, Sweden.
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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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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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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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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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Lymphocytic colitis and collagenous colitis: a review of clinicopathologic features and immunologic abnormalities. Adv Anat Pathol 2012; 19:28-38. [PMID: 22156832 DOI: 10.1097/pap.0b013e31823d7705] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Lymphocytic colitis (LC) and collagenous colitis (CC), 2 histologic forms of microscopic colitis, were recognized as rare disease entities 4 decades ago. An increasing body of evidence accumulated in the past 40 years reveals increasing incidence and prevalence rates, a wide spectrum of clinical presentations, and several histologic variants. Although several recent randomized clinical trials confirmed the efficacy of oral budesonide in treating LC and CC, disease relapse after a short-duration treatment is common. Despite their common clinical presentations and well-defined histologic diagnostic criteria, there are only few studies on the immunologic abnormalities in colonic tissue. The aim of this review is to (1) familiarize the pathologists in general practice with histomorphology of LC and CC, including the rare histologic variants and the clinical implication associated with these 2 diagnoses, (2) summarize the data from recent randomized clinical trials of oral budesonide, and (3) review immunological studies on colonic tissue. Overall, immunologic abnormalities of colonic tissue seem to explain for the histomorphologic features and the clinical symptomatology of LC and CC. Advances in the understanding of the underlying immunologic abnormalities in the colonic tissue may help develop novel and effective therapies for these 2 diseases.
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Cubick EE, Quezada VY, Schumer AD, Davis CM. Sustained release myofascial release as treatment for a patient with complications of rheumatoid arthritis and collagenous colitis: a case report. Int J Ther Massage Bodywork 2011; 4:1-9. [PMID: 22016756 PMCID: PMC3184472 DOI: 10.3822/ijtmb.v4i3.112] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/02/2023] Open
Abstract
BACKGROUND Myofascial release (MFR) is a manual therapeutic technique used to release fascial restrictions, which may cause neuromusculoskeletal and systemic pathology. PURPOSE This case report describes the use of sustained release MFR techniques in a patient with a primary diagnosis of rheumatoid arthritis (RA) and a secondary diagnosis of collagenous colitis. Changes in pain, cervical range of motion, fatigue, and gastrointestinal tract function, as well as the impact of RA on daily activities, were assessed. METHODS A 54-year-old white woman presented with signs and symptoms attributed to RA and collagenous colitis. Pre and post measurements were taken with each treatment and during the interim between the initial and final treatment series. The patient recorded changes in pain, fatigue, gastrointestinal tract function, and quality of life. Cervical range of motion was assessed. Six sustained release MFR treatment sessions were provided over a 2-week period. Following an 8-week interim, two more treatments were performed. RESULTS The patient showed improvements in pain, fatigue, gastrointestinal tract function, cervical range of motion, and quality of life following the initial treatment series of six sessions. The patient maintained positive gains for 5 weeks following the final treatment, after which her symptoms returned to near baseline measurements. Following two more treatments, positive gains were achieved once again. CONCLUSIONS In a patient with RA and collagenous colitis, the application of sustained release MFR techniques in addition to standard medical treatment may provide short-term and long-term improvements in comorbid symptoms and overall quality of life.
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Affiliation(s)
- Erin E Cubick
- Department of Physical Therapy, University of Miami, Coral Gables, FL, USA
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14
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Kao KT, Pedraza BA, McClune AC, Rios DA, Mao YQ, Zuch RH, Kanter MH, Wirio S, Conteas CN. Microscopic colitis: A large retrospective analysis from a health maintenance organization experience. World J Gastroenterol 2009; 15:3122-7. [PMID: 19575491 PMCID: PMC2705734 DOI: 10.3748/wjg.15.3122] [Citation(s) in RCA: 76] [Impact Index Per Article: 4.8] [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 examine the demographic data on a large multi-ethnic population of patients with microscopic colitis (MC) in Southern California and to determine the association of MC with inflammatory bowel disease (IBD) and colorectal cancer.
METHODS: All patients diagnosed with MC by colonic biopsy from 1996-2005 were identified utilizing a pathology database. All biopsies were reviewed by experienced pathologists utilizing standard histologic criteria. Patients’ medical records were reviewed and data regarding patient age, co-morbidities, sex, ethnicity, and medications were analyzed. An age- and sex-matched standard control group was also generated. Chi-square test was used to evaluate the associations of co-morbidities between lymphocytic colitis (LC), collagenous colitis (CC) and the control group.
RESULTS: A total of 547 cases of MC were identified, 376 patients with LC and 171 patients with CC. The female/male ratio was 3:1 in CC and 2.7:1 in LC patients. Celiac disease (P < 0.001), irritable bowel syndrome (IBS) (P < 0.001), and thyroid diseases (P < 0.001) were found to have a higher occurrence in MC compared to the control group. No statistical differences in the occurrence of colorectal cancer, diabetes and IBD were found between the MC group and the control group.
CONCLUSION: This is the largest group of patients with MC known to the authors that has been studied to date. Conditions such as celiac disease, IBS, and thyroid diseases were found to be related to MC. Furthermore, neither an increased risk of colorectal cancer nor IBD was associated with MC in this study.
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Association d’une colite lymphocytaire à une maladie cœliaque probablement déclenchée par la prise de venlafaxine (Effexor®). Rev Med Interne 2009; 30:74-7. [DOI: 10.1016/j.revmed.2008.04.005] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2008] [Revised: 04/07/2008] [Accepted: 04/09/2008] [Indexed: 11/20/2022]
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Abstract
OBJECTIVES Coeliac disease (CD) is common in patients with microscopic colitis (MC). The human leucocyte antigen (HLA)-DR3-DQ2 haplotype is strongly associated with CD, and there is evidence for an association with MC. We analysed the genetic background of MC by assessing the haplotypes of HLA-DR3-DQ2 and HLA-DR4-DQ8. In addition, TNFalpha gene polymorphism (-308) associated with susceptibility to several autoimmune diseases was studied. METHODS Eighty patients with MC including 29 with collagenous colitis (CC) and 51 with lymphocytic colitis (LC) were typed for HLA-DR3-DQ2, and HLA-DR4-DQ8 molecule encoding genes using either an allele-specific PCR, or hybridization with sequence-specific oligonucleotides. Duodenal biopsies (N=78) confirmed the diagnosis of CD in 15 (18.8%) patients. TNFalpha(308) alleles were analyzed in 78 patients with MC (27 with CC and 51 with LC). A control group of 3627 patients was used in the HLA study and 178 patients in the TNFalpha study. RESULTS HLA-DR3-DQ2 haplotype was more frequent in patients with MC (43.8%) including both subgroups (LC, 44.8%; CC, 43.1%; P<0.001), and MC with CD (86.7%; P<0.001) and without CD (33.3%; P=0.003), compared with the controls (18.1%). Similarly, the TNF2 carrier rate was higher in MC (46.2%; P<0.001) including both CC (44.4%; P=0.031) and LC (47.1%; P=0.001), and both MC patients with CD (66.7%; P=0.001) and without CD (39.3%; P=0.019), compared with the controls (23%). CONCLUSION Both CC and LC are associated with the HLA-DR3-DQ2 haplotype and with TNF2 allele carriage. These associations are present also in MC patients without CD. The shared predisposing HLA-DR3-DQ2 haplotype and the high prevalence of CD in patients with MC suggest an epidemiological overlap, and probably some similarities in the pathogenesis of CD and MC.
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Abstract
Both diarrhea and colitis associated with clozapine have been reported. In this article, the authors present a case of clozapine-induced microscopic colitis (MC)-the first reported in the literature. The definitive diagnosis was suggested on colon biopsy, which showed an intraepithelial lymphocytosis (with >20 lymphocytes for every 100 epithelial cells) more striking in the surface epithelium than in the crypts. In addition, there were a mixed inflammatory infiltrate in the lamina propria (with lymphocytes predominating over eosinophils and neutrophils), an architecturally preserved colonic mucosa (particularly in the crypts), and a subepithelial collagen band normally thickened (<10 microm). Clozapine was thought to be the culprit and discontinued. After some days, the patient gradually improved. Diarrhea and spiking fever disappeared within 72 hours. Multiple colon biopsies taken after 7 days from the discontinuation of the clozapine revealed no abnormal histological findings. It is important to clarify the issue of clozapine-induced MC because MC may require the use of expensive or potentially toxic treatments and can occasionally be life-threatening (eg, hypokalemia). Thus, any case of MC that can be cured by withdrawal of the clozapine must be investigated and identified.
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Freeman HJ, Berean KW, Nimmo M. Evolution of collagenous colitis into severe and extensive ulcerative colitis. CANADIAN JOURNAL OF GASTROENTEROLOGY = JOURNAL CANADIEN DE GASTROENTEROLOGIE 2007; 21:315-8. [PMID: 17505568 PMCID: PMC2657714 DOI: 10.1155/2007/950154] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Collagenous colitis is an inflammatory mucosal disorder of the colon with distinctive histopathological features, including a thickened subepithelial collagen layer. The clinical course is usually benign, but serious complications, including death, may occur. In the present report, a 69-year-old woman with watery diarrhea and collagenous colitis developed bloody diarrhea that was refractory to treatment medications, including corticosteroids and azathioprine. Endoscopic and histopathological studies showed a focal neutrophilic inflammatory process that progressed to a diffuse and extensive form of colitis, eventually requiring total proctocolectomy. Careful histological review of the resected colon showed no evidence of persistent collagenous colitis. These findings suggest an important need for continued long-term follow-up of patients with collagenous colitis because superimposed and serious colonic complications may occur, including a severe and extensive pancolitis refractory to medications and necessitating total proctocolectomy.
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Affiliation(s)
- Hugh J Freeman
- Department of Medicine, University of British Columbia, Vancouver, Canada.
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19
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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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20
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Abstract
Collagenous and lymphocytic colitis have been recognized as chronic intestinal inflammatory disorders causing watery diarrhea, which have been recognized in the past three to two decades, respectively. Collagenous colitis is primarily a disorder of middle-aged women and is characterized on biopsy by increased subepithelial collagen as well as increased inflammatory cells in the lamina propria and increased intraepithelial lymphocytes. Key to the correct diagnosis in this condition is recognizing that there are two words in this diagnostic entity, and colitis is, by definition, present. Focusing solely on the collagen band can result in both over- and underdiagnosis. Newer therapeutic options are available in this condition, and patients are now frequently being treated either with budesonide or with high dose bismuth preparations. Whereas collagenous colitis is a tightly coherent clinical pathologic entity, lymphocytic colitis has a more varied clinical picture. Lymphocytic colitis is also seen in middle-aged patients but has a more equal female-to-male ratio. Lymphocytic colitis is defined by increased intraepithelial lymphocytes, with the median being 30 lymphocytes per 100 epithelial cells. There are also an increase in inflammatory cells in the lamina propria, but the increase may be milder than in collagenous colitis and there are usually minimal eosinophils. Although numerous studies have described lymphocytic colitis causing a chronic diarrhea, more recent studies suggest that patients may have a single attack in approximately 60% of cases. Although most cases of lymphocytic colitis are idiopathic, there is a clear association with multiple drugs, celiac disease, and there may be an infectious trigger. Approximately 10% of lymphocytic colitis patients have a positive family history of some type of inflammatory intestinal disease, including ulcerative colitis, Crohn's disease, collagenous colitis, and celiac disease. Therapy in lymphocytic colitis is less well studied, but the same medications are used with success, including budesonide and high dose bismuth.
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Affiliation(s)
- Audrey J Lazenby
- Department of Pathology, University of Alabama School of Medicine, Birmingham 35429, USA.
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Abstract
Autoimmune hepatitis is a rare, chronic inflammatory disorder which has been associated with a number of other auto-immune conditions. However, there are no reports in the medical literature of an association with microscopic (lymphocytic) colitis. We report the case of a 53-year-old woman with several autoimmune conditions, including lymphocytic colitis, who presented with an acute hepatitis. On the basis of the clinical features, serology, and histopathology, we diagnosed autoimmune hepatitis. To our knowledge, this is the first report of autoimmune hepatitis in association with lymphocytic colitis, and lends support to the theory of an autoimmune etiology for lymphocytic colitis.
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Affiliation(s)
- Edmond M Cronin
- Department of Gastroenterology, Cork University Hospital, Wilton, Cork, Ireland.
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22
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Laing AW, Pardi DS, Loftus EV, Smyrk TC, Kammer PP, Tremaine WJ, Schleck CD, Harmsen WS, Zinsmeister AR, Melton LJ, Sandborn WJ. Microscopic colitis is not associated with cholecystectomy or appendectomy. Inflamm Bowel Dis 2006; 12:708-11. [PMID: 16917225 DOI: 10.1097/00054725-200608000-00006] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
BACKGROUND Microscopic colitis is a common cause of chronic watery diarrhea of unknown origin. Some patients develop diarrhea after cholecystectomy, and some patients with microscopic colitis have evidence of bile acid malabsorption. However, the association between cholecystectomy and microscopic colitis has not been studied. A protective effect of appendectomy on the development of ulcerative colitis also has been reported, but its relationship with microscopic colitis has not been studied. The aim of this study was to assess cholecystectomy and appendectomy as potential risk factors for the development of microscopic colitis in a nested case-control study. MATERIALS AND METHODS Using the Rochester Epidemiology Project, we identified all Olmsted County (Minnesota) residents with an initial diagnosis of microscopic colitis between January 1, 1985, and December 31, 2001. Rates of antecedent cholecystectomy or appendectomy in patients with microscopic colitis were compared with age-, gender-, and calendar year-matched community controls through conditional logistic regression. RESULTS Microscopic colitis was identified in 130 cases. Cholecystectomy preceded the diagnosis of microscopic colitis in 12 cases (9%) compared with 17 (13%) in the control group (odds ratio [OR] 0.7; 95% CI 0.3-1.5). Appendectomy preceded the diagnosis of microscopic colitis in 39 subjects (30%) compared with 28 (22%) in the control group (OR 1.6; 95% CI 0.9-2.7). Similar results were obtained when the analysis was restricted to microscopic colitis subtype (lymphocytic colitis or collagenous colitis). CONCLUSIONS In this population-based nested case-control study, no significant association was seen between cholecystectomy or appendectomy and the development of microscopic colitis or its subtypes.
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Affiliation(s)
- Aran W Laing
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Mayo Clinic College of Medicine, Rochester, Minnesota, USA
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Narváez J, Montala N, Busquets-Pérez N, Nolla JM, Valverde J. Collagenous colitis and spondylarthropathy. ACTA ACUST UNITED AC 2006; 55:507-12. [PMID: 16739191 DOI: 10.1002/art.21995] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/20/2023]
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Abstract
This review summarizes some of the common diagnostic problems encountered by pathologists when evaluating patients with chronic colitis and in whom inflammatory bowel disease (IBD) is either suspected or within the differential diagnosis. Both ulcerative colitis (UC) and Crohn's disease (CD) show characteristic, but non-specific, pathological features that may overlap and result in a diagnosis of 'indeterminate colitis' (IC). However, other reasons why pathologists may entertain a diagnosis of IC include failure to recognize or accept certain 'hardcore' histological features as indicative of CD, an attempt to classify cases of chronic colitis based on mucosal biopsy material or in the absence of adequate clinical and radiographic information, and the presence of other disease processes that mask, or mimic, IBD. In addition, some cases of UC may show unusual CD-like features, such as discontinuous or patchy disease, ileal inflammation, extracolonic inflammation, granulomatous inflammation in response to ruptured crypts, aphthous ulcers, or transmural inflammation. Furthermore, other forms of colitis, such as microscopic colitis, diverticulitis and diversion colitis may, on occasion, also show IBD-like changes. The clinical and pathological features that aid in the distinction between these entities, and others, are covered in detail in this review.
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Affiliation(s)
- R K Yantiss
- Department of Pathology, Weill Medical College of Cornell University, New York, NY, USA
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25
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Kane S. Colon lesions: pathology specific to women. Gastrointest Endosc Clin N Am 2006; 16:165-73. [PMID: 16546031 DOI: 10.1016/j.giec.2006.01.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Lymphocytic colitis and collagenous colitis represent two conditions that fall under the category of microscopic abnormalities within the lamina propria of the colon. Patients are predominantly women in the sixth decade of life who present with non-bloody watery diarrhea. Few other symptoms exist. Diagnosis is based upon finding characteristic abnormalities in the colonic mucosa, more likely to be found on the right side of the colon than the left. Treatment is symptomatic, although some newer therapies suggest regression of the lesion. Other autoimmune associations have been described, including celiac disease, and appropriate work-up for this condition should be considered for the patient who has seemingly refractory colitis. The natural history is benign, and most patients experience resolution of their symptoms.
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Affiliation(s)
- Sunanda Kane
- Department of Medicine, University of Chicago, IL 60637, USA
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26
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Abstract
Collagenous mucosal inflammatory diseases involve the columnar-lined gastric and intestinal mucosa and have become recognized increasingly as a significant cause of symptomatic morbidity, particularly in middle-aged and elderly women, especially with watery diarrhea. Still, mechanisms involved in the pathogenesis of this diarrhea remain poorly understood and require further elucidation. The prognosis and long-term outcome of these disorders has been documented only to a limited extent. Recent clinical and pathologic studies have indicated that collagenous mucosal inflammatory disease is a more extensive pathologic process that concomitantly may involve several sites in the gastric and intestinal mucosa. The dominant pathologic lesion is a distinct subepithelial hyaline-like deposit that has histochemical and ultrastructural features of collagen overlying a microscopically defined inflammatory process. An intimate relationship with other autoimmune connective tissue disorders is evident, particularly celiac disease. This is intriguing because these collagenous disorders have not been shown to be gluten dependent. Collagenous mucosal inflammatory disorders may represent a relatively unique but generalized inflammatory response to a multitude of causes, including celiac disease, along with a diverse group of pharmacologic agents. Some recent reports have documented treatment success but histopathologic reversal has been more difficult to substantiate owing to the focal, sometimes extensive nature, of this pathologic process.
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Affiliation(s)
- Hugh J Freeman
- Department of Medicine (Gastroenterology), University of British Columbia, Vancouver, Canada.
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27
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Abstract
Microscopic colitis is an increasingly common cause of chronic diarrhea, and often causes abdominal pain and weight loss. The colonic mucosa appears normal or nearly normal endoscopically, and the diagnosis is made in the appropriate clinical setting when there is intraepithelial lymphocytosis and a mixed lamina propria inflammatory infiltrate. The 2 subtypes, collagenous and lymphocytic colitis, are similar clinically and histologically, and are distinguished by the presence or absence of a thickened subepithelial collagen band. Many potential pathophysiologic mechanisms have been proposed, but no convincing unifying mechanism has been identified. There are many anecdotal reports on treatment, but few controlled trials have been performed in these patients, although a systematic approach to therapy often leads to the satisfactory control of symptoms.
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Affiliation(s)
- Darrell S Pardi
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, MN, USA.
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28
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Pokorny CS, Selby WS. Microscopic colitis: an underdiagnosed cause of chronic diarrhoea--the clue is in the biopsies. Intern Med J 2003; 33:305-9. [PMID: 12823676 DOI: 10.1046/j.1445-5994.2003.00355.x] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
Microscopic forms of colitis (collagenous colitis and lymphocytic colitis) are uncommon but important causes of chronic diarrhoea that are often overlooked. The clinical features of these disorders are similar, and they are more common in middle-aged females, although the female predominance is greater in collagenous colitis. Although their cause is unclear, both are associated with a variety of autoimmune diseases. Colonoscopy and barium enema are typically normal, so that the diagnosis depends on the demonstration of characteristic changes on histopathological examination of colorectal biopsies. These should be taken in all patients undergoing colonoscopy for the investigation of chronic diarrhoea. There are no large controlled trials of therapy available. Treatment is empirical, generally using the same agents as for inflammatory bowel -disease. Assessment of therapy is also difficult as spontaneous remissions occur often.
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Affiliation(s)
- C S Pokorny
- Liverpool Hospital, New South Wales, Australia.
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29
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Abstract
Microscopic colitis is a relatively common cause of chronic watery diarrhea, often accompanied by abdominal pain and weight loss. The colonic mucosa appears normal grossly, and the diagnosis is made when there is an intraepithelial lymphocytosis and a mixed inflammatory infiltrate in the lamina propria. The two main subtypes, collagenous and lymphocytic colitis, are similar clinically and histologically, distinguished by the presence or absence of a thickened subepithelial collagen band. Many potential pathophysiological mechanisms have been described, although none have been conclusively proved. There is a paucity of randomized treatment trials in these patients, although a rational approach to therapy often leads to satisfactory control of symptoms.
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Affiliation(s)
- Darrell S Pardi
- Division of Gastroenterology and Hepatology, Mayo Clinic and Foundation, Rochester, Minnesota, USA
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30
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Cindoruk M, Tuncer C, Dursun A, Yetkin I, Karakan T, Cakir N, Soykan I. Increased colonic intraepithelial lymphocytes in patients with Hashimoto's thyroiditis. J Clin Gastroenterol 2002; 34:237-9. [PMID: 11873103 DOI: 10.1097/00004836-200203000-00008] [Citation(s) in RCA: 31] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND Hashimoto's thyroiditis is an autoimmune thyroid disorder. Lymphocytic colitis and collagenous colitis are characterized by diarrhea with normal endoscopic findings. Autoimmune disorders are common in Hashimoto's thyroiditis and lymphocytic colitis. The aim of this study was to investigate the incidence of lymphocytic colitis in patients with Hashimoto's thyroiditis. STUDY Fifty patients with well-documented Hashimoto's thyroiditis were included. Twenty patients with nonulcer dyspepsia served as a control group. Five of 50 patients with Hashimoto's thyroiditis reported intermittent diarrhea, whereas no patients had diarrhea in the control group. All patients and the control group underwent total colonoscopy, and multiple colonoscopic biopsies were performed. RESULTS We found that 40% (20 of 50) of Patients with Hashimoto's thyroiditis had histologic findings consistent with lymphocytic colitis, and one patient in the control group had lymphocytic colitis (p < 0.01). The mean number of intraepithelial lymphocytes was 34.4/100 epithelial cells in these 20 patients, whereas the mean number of intraepithelial lymphocytes was 12.3/100 epithelial cells in the other 30 patients with Hashimoto's thyroiditis (p < 0.05). CONCLUSIONS There was a higher incidence of histologic findings of lymphocytic colitis in patients with Hashimoto's thyroiditis, although most of the patients were clinically asymptomatic. This finding suggests that lymphocytic colitis may have an asymptomatic clinical course and should encourage further clinical investigations to better anticipate the relationship between autoimmune disorders.
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Affiliation(s)
- Mehmet Cindoruk
- Department of Gastroenterology, Gazi University Medical School, Ankara, Turkey
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Abstract
Microscopic colitis is an umbrella term used to include two idiopathic inflammatory bowel disorders that present with chronic watery diarrhea, normal endoscopic findings and characteristic inflammatory changes on histology. Collagenous colitis and lymphocytic colitis are distinguished by the presence of a thickened subepithelial collagen table. It is likely that they are a spectrum of one disease, but this is yet to be proven. The majority of cases tend to undergo spontaneous remission within a few years of onset, and their clinical course is benign, with no increase in risk of colorectal cancer. Sufficient evidence exists to suggest that microscopic colitis occurs as a response to one or more luminal antigens. A variety of medications have been reported in the treatment of this condition, but only colloidal bismuth and budesonide have thus far been shown to be effective in randomized controlled trials.
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Affiliation(s)
- Peter Tagkalidis
- Department of Gastroenterology, The Royal Melbourne Hospital, The University of Melbourne, Melbourne, Australia.
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Abstract
Collagenous and lymphocytic colitis are atypical colitides that should be considered in elderly patients with unexplained diarrhea. The lack of natural history data and apparent underreporting of these disorders have made the determination of true incidence difficult. Better insight into the pathogenesis and heightened awareness of these conditions will lead to earlier diagnosis and more effective treatment.
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Affiliation(s)
- Kevin A Waschke
- Division of Gastroenterology, Department of Pathology, McGill University Health Center, Montreal, Quebec, Canada
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Ben Soussan E, Savoye G, Lemoine F, Ducastelle P, Colin R. Azathioprine as a treatment of refractory lymphocytic colitis. Eur J Gastroenterol Hepatol 2001; 13:457-8. [PMID: 11338080 DOI: 10.1097/00042737-200104000-00027] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
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Fine KD, Do K, Schulte K, Ogunji F, Guerra R, Osowski L, McCormack J. High prevalence of celiac sprue-like HLA-DQ genes and enteropathy in patients with the microscopic colitis syndrome. Am J Gastroenterol 2000; 95:1974-82. [PMID: 10950045 DOI: 10.1111/j.1572-0241.2000.02255.x] [Citation(s) in RCA: 111] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVE Celiac sprue is associated with specific HLA-DQ genes (mainly DQ2). Because there are epidemiological and histopathological similarities between celiac sprue and microscopic colitis, we hypothesized that these syndrome may share an HLA genetic predisposition and pathogenesis. METHODS The HLA-DQ genes of 25 patients with celiac sprue, 53 patients with the microscopic colitis syndrome, and 429 normal controls were typed and compared. Serum was analyzed for antigliadin and antiendomysial antibodies. Small intestinal biopsies were analyzed for signs of histopathology. RESULTS HLA-DQ2 or DQ1,3 (the latter as DQ1,7,DQ1,8, or DQ1,9) were seen more frequently in both patient groups relative to controls. In patients with the microscopic colitis syndrome, serological tests for celiac sprue were weakly positive in 17%; mild inflammation of the small intestine without villous atrophy was present in 43%, and inflammation plus partial or subtotal villous atrophy was present in 27%. CONCLUSIONS A shared set of predisposing HLA-DQ genes account for the epidemiological overlap of celiac sprue and microscopic colitis. Mild to moderate mononuclear cell inflammation of the small intestine, often accompanied by partial or subtotal villous atrophy, is frequent in patients with the microscopic colitis syndrome. Although further studies will be necessary to determine if this enteropathy is induced by dietary gluten, we speculate that the small intestinal but not colonic histopathology in patients with microscopic colitis is caused by immunological gluten sensitivity.
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Affiliation(s)
- K D Fine
- Intestinal Health Institute, Dallas, Texas, USA
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35
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Cruz-Correa M, Giardiello FM, Bayless TM. Atypical forms of inflammatory bowel disease: microscopic colitis and pouchitis. Curr Opin Gastroenterol 2000; 16:343-8. [PMID: 17031099 DOI: 10.1097/00001574-200007000-00009] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
Three atypical colitides (and enterides) are collagenous colitis, lymphocytic colitis, and ileal pouchitis. Collagenous and lymphocytic colitis are similar inflammatory bowel disorders of unknown cause with symptoms including chronic watery diarrhea, occurring in middle age. Pouchitis is the most significant long-term complication in patients with ileoanal pouch anastomosis. The clinical and histologic features and management of these entities are discussed.
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Affiliation(s)
- M Cruz-Correa
- Division of Gastroenterology, Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
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36
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Tromm A, Griga T, Möllmann HW, May B, Müller KM, Fisseler-Eckhoff A. Budesonide for the treatment of collagenous colitis: first results of a pilot trial. Am J Gastroenterol 1999; 94:1871-5. [PMID: 10406251 DOI: 10.1111/j.1572-0241.1999.01222.x] [Citation(s) in RCA: 39] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVE Collagenous colitis is a chronic watery diarrhea disorder characterized by a subepithelial collagen layer and a lymphoplasmacytic infiltration within the lamina propria. However, no standard treatment has been introduced by controlled clinical trials. Aim of the present pilot trial was to investigate the clinical effects of orally administered budesonide (3 mg t.i.d.) in 7 patients with collagenous colitis. In addition, the histomorphological changes after budesonide treatment were described in a group of 3 patients. METHODS The study was performed as an open label pilot trial. Study end point was the clinical remission of collagenous colitis defined by stool frequency and stool consistency. RESULTS The results indicate a rapid and sustained clinical response in all patients. Stool frequency significantly decreased (p < 0.001) from 10.43 +/- 5.56 per day (4-20 per day) to 3.3 +/- 1.2 (1-5 per day) after 10 days and to 1.86 +/- 0.69 per day (1-3 per day) after 10 wk. Moreover stool consistency changed from watery (6 patients) or soft (1 patient) to soft (1 patient) or solid (6 patients). Clinical improvement was achieved within the first 10 days in all patients and maintained after dose reduction. In 3 patients no diarrhea recurred within 7, 12, or 15 months after treatment with budesonide was terminated. In these patients control biopsies were taken and showed a marked regression of both characteristics, the collagen band and the lymphoplasmacytic infiltration. CONCLUSIONS With respect to the preliminary data from this pilot trial, budesonide with its high topical and low systemic effects seems to be of therapeutic clinical benefit in collagenous colitis. A therapeutic effect could be demonstrated for both therapeutic goals, the clinical response and morphological changes. Further studies on the effects of budesonide on mucosal collagen metabolism and long-term follow-up are warranted.
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Affiliation(s)
- A Tromm
- Department of Gastroenterology and Hepatology and Institute of Pathology, BG-Kliniken Bergmannsheil, University Clinic, Ruhr-University Bochum, Germany
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Abstract
Collangenous colitis is a clinicopathologic syndrome characterized by (1) chronic watery diarrhea and crampy abdominal pain and (2) distinctive colorectal histopathology that includes a subepithelial collagen band, prominent chronic inflammation in the lamina propria, and increased intraepithelial lymphocytes. Lymphocytic colitis has similar clinical features to collangenous colitis, the main symptom being chronic watery diarrhea. Diversion colitis is an inflammatory process that arises in segments of the large intestine that are excluded from the fecal stream. This condition usually occurs in patients with ileostomy or colostomy when a mucous fistula or Hartmann's pouch has been left.
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Affiliation(s)
- F M Giardiello
- Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine (FMG), Baltimore, Maryland, USA
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38
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Affiliation(s)
- A Thomson
- Department of Gastroenterology, St. Michael's Hospital, Toronto, and the University of Toronto, Canada
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39
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Moayyedi P, O'Mahony S, Jackson P, Lynch DA, Dixon MF, Axon AT. Small intestine in lymphocytic and collagenous colitis: mucosal morphology, permeability, and secretory immunity to gliadin. J Clin Pathol 1997; 50:527-9. [PMID: 9378824 PMCID: PMC500002 DOI: 10.1136/jcp.50.6.527] [Citation(s) in RCA: 21] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
There is a recognised association between the "microscopic" forms of colitis and coeliac disease. There are a variety of subtle small intestinal changes in patients with "latent" gluten sensitivity, namely high intraepithelial lymphocyte (IEL) counts, abnormal mucosal permeability, and high levels of secretory IgA and IgM antibody to gliadin. These changes have hitherto not been investigated in microscopic colitis. Nine patients (four collagenous, five lymphocytic colitis) with normal villous architecture were studied. Small intestinal biopsies were obtained by Crosby capsule; small intestinal fluid was aspirated via the capsule. IEL counts were expressed per 100 epithelial cells, and intestinal IgA and IgM antigliadin antibody levels were measured by ELISA. Small intestinal permeability was measured by the lactulose:mannitol differential sugar permeability test. IEL counts were normal in all cases, median 17, range 7-30. Intestinal antigliadin antibodies were measured in six cases and were significantly elevated in two patients (both IgA and IgM). Intestinal permeability was measured in eight cases and was abnormal in two and borderline in one. These abnormalities did not overlap: four of nine patients had evidence of abnormal small intestinal function. Subclinical small intestinal disease is common in the two main forms of microscopic colitis.
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Affiliation(s)
- P Moayyedi
- Department of Gastroenterology, Leeds General Infirmary, United Kingdom
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40
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Abstract
INTRODUCTION Collagenous colitis is a rare disease of unknown etiology that primarily affects middle-aged women. It presents with chronic watery diarrhea and thickening of the subepithelial collagen layer of the colonic mucosa in the absence of endoscopic abnormalities. PURPOSE This study was undertaken to review the current literature on clinical course, pathology, diagnosis, and current management of collagenous colitis. RESULTS Collagenous colitis is an inflammatory disease of the colon, clinically characterized by a waxing and waning course of watery diarrhea, an inflammatory infiltration of the colonic mucosa, and a thickening of the subepithelial collagen layer. Its pathogenesis remains unclear, but there is evidence for an inflammatory process triggered possibly by an uncommon luminal agent. Diagnosis is established by colonic biopsies; in the setting of normal colonic mucosa, the disorder is primarily managed medically with virtually no role for surgery. CONCLUSIONS Pathogenesis of collagenous colitis remains unclear. Current data favor an inflammatory etiology, possibly involving an initiating luminal insult. Guidelines for diagnosis are being established, and medical treatment options are variably effective in the majority of cases. Very unusual refractory cases may benefit from surgical management.
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Affiliation(s)
- I A Halaby
- Department of Surgery, St. Louis University School of Medicine, Missouri, USA
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41
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Bowling TE, Price AB, al-Adnani M, Fairclough PD, Menzies-Gow N, Silk DB. Interchange between collagenous and lymphocytic colitis in severe disease with autoimmune associations requiring colectomy: a case report. Gut 1996; 38:788-91. [PMID: 8707130 PMCID: PMC1383166 DOI: 10.1136/gut.38.5.788] [Citation(s) in RCA: 35] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
BACKGROUND Collagenous colitis and lymphocytic colitis present with a similar clinical picture. Whether these conditions are separate entities or whether they represent different pathological stages of the same condition is an unresolved issue. PATIENT This is a case of collagenous colitis following a fulminant course in which a colectomy was necessary. In the operative specimen the thickened collagen plate, which had been present only two weeks preoperatively had been lost and the pathology was of a lymphocytic colitis. Six months postoperatively this patient developed a CREST syndrome and primary biliary cirrhosis. CONCLUSIONS This case shows the lability of the collagen plate and the common ground between collagenous and lymphocytic colitis, and presents evidence that these two conditions are different manifestations of the same disease. It also describes for the first time an association between collagenous colitis and CREST syndrome and primary biliary cirrhosis.
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Affiliation(s)
- T E Bowling
- Department of Gastroenterology and Nutrition, Central Middlesex Hospital, London
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42
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Abstract
The incidence and prevalence of collagenous colitis are unknown. An epidemiological study was undertaken between 1984-93. All patients living in the immediate catchment area of Orebro Medical Center Hospital with the diagnosis collagenous colitis were identified. Biopsy specimens classified as unspecific intestinal fibrosis were re-examined to identify cases not correctly diagnosed at first. Medical records were scrutinised and colorectal biopsy specimens re-evaluated. Thirty patients with collagenous colitis were diagnosed during the study period. The female:male ratio was 9:1. The median age at diagnosis was 64 (28-78) years. The prevalence at 31 December 1993, was 15.7/10(5) inhabitants (95% CI; 9.8 to 21.6/10(5)). The mean annual incidence during the period 1984-93 was 1.8/10(5) inhabitants (95% CI; 1.2 to 2.4/10(5)). A peak incidence was found in women 70-79 years old. Collagenous colitis occurs mainly in middle aged women, and the frequency is higher than earlier anticipated. The prevalence and incidence is similar to primary biliary cirrhosis. In women 70-79 years of age, the incidence for collagenous colitis approaches the incidence for ulcerative colitis.
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Affiliation(s)
- J Bohr
- Department of Medicine, Orebro Medical Center Hospital, Sweden
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43
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Abstract
Collagenous colitis and lymphocytic colitis (previously described as microscopic colitis) are two newly recognised forms of colitis. Both have generated much controversy and continue to do so; their aetiology and pathogenesis are unresolved and their association with a variety of immune-related disorders is intriguing. Response to available therapeutic modalities is often disappointing. The possible relationship or overlap between these two conditions remains a controversial issue. The aim of this review is essentially to present an overview of collagenous colitis and lymphocytic colitis and to propose an unifying concept with an adapted terminology.
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Abstract
Collagenous and lymphocytic colitis are newly recognized causes of chronic watery diarrhea that typically affect middle-aged patients. Although endoscopic studies are normal, inflammatory changes and (in the case of collagenous colitis) collagen deposition occur histologically in the colonic mucosa. The pathogenesis of these disorders remains a mystery, but the possible causes are intriguing. Patients may experience spontaneous remissions and relapses, but treatment with sulfasalazine or prednisone is usually effective for patients with distressing symptoms.
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Affiliation(s)
- J M Zeroogian
- Department of Medicine, Beth Israel Hospital, Boston, Massachusetts
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Abstract
We reviewed colorectal biopsies and clinical records from 36 patients with chronic watery diarrhea who had been diagnosed as having microscopic colitis and compared their histologic features with the more detailed and precise criteria for lymphocytic colitis. Published pathologic criteria for lymphocytic colitis were applied to the biopsies and compared. Focal or diffuse nature of the lymphoid infiltrate were noted separately. The focal lymphoid infiltrate was related to lymphoid aggregates in the lamina propria of the mucosa. Eighteen cases had focal lymphoid cell infiltration, and 16 of them had associated diverticula, polyps, or both. Eighteen cases had diffuse lymphoid cell infiltration, and six of them had diverticula or polyps. Results indicate that focal cellular infiltration strongly predicts associated diverticula or polyps. The group with no diverticula or polyps most closely conformed to histologic criteria for lymphocytic colitis (Kruskal-Wallis P < 0.02). We conclude that lymphocytic colitis comprises a well-defined group of cases within the large and less-defined group of microscopic colitis.
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Affiliation(s)
- L R Mills
- Laboratory Service, VA Medical Center, Augusta, Georgia 30904-6285
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