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El Hage Chehade N, Ghoneim S, Shah S, Pardi DS, Farraye FA, Francis FF, Hashash JG. Efficacy and Safety of Vedolizumab and Tumor Necrosis Factor Inhibitors in the Treatment of Steroid-refractory Microscopic Colitis: A Systematic Review and Meta-analysis. J Clin Gastroenterol 2024; 58:789-799. [PMID: 37668427 DOI: 10.1097/mcg.0000000000001914] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/31/2023] [Accepted: 07/20/2023] [Indexed: 09/06/2023]
Abstract
BACKGROUND Tumor necrosis factor (TNF-α) inhibitors and the α4β7 integrin antagonist, vedolizumab, have been investigated as treatment options for patients with steroid-refractory microscopic colitis. AIMS To evaluate the benefit of vedolizumab and TNF-α inhibitors in patients with steroid-refractory microscopic colitis. METHODS Retrospective studies and case series involving patients with steroid-refractory MC who either received vedolizumab, adalimumab, or infliximab were eligible for inclusion. Pooled proportional meta-analyses were used to calculate the rate of clinical remission at induction, clinical response, maintenance of remission, histologic remission, and overall medication related adverse effects. Statistical analysis was performed in R using the metafor and meta packages. RESULTS A total of 14 studies involving 164 patients were included. Pooled analysis showed a clinical remission rate of 63.5% [95% CI (0.483; 0.776), I 2 =43% P =0.08], 57.8% [95% CI (0.3895; 0.7571), I 2 =0%, P =0.7541], and 39.3% [95% CI (0.0814; 0.7492), I 2 =66%, P =0.02] for vedolizumab, infliximab, and adalimumab, respectively. The maintenance of remission rates were 65.9% [95% CI (0.389; 0.889), I 2 =67%, P =0.02], 45.3% [95% CI (0.1479; 0.7747), I 2 =0%, P =0.36] and 32.5% [95% CI (0.000; 0.8508), I 2 =53%, P =0.14] in patients who received vedolizumab, infliximab, and adalimumab, respectively. Rate of biological-related adverse events warranting discontinuation of therapy was 12.2%, 32.9%, and 23.0% for the vedolizumab, infliximab, and adalimumab groups, respectively. CONCLUSION Vedolizumab and anti-TNF-α agents demonstrated a clinical benefit in the treatment of steroid-refractory microscopic colitis and with a tolerable safety profile. Future randomized controlled trials are needed to compare vedolizumab with TNF-α inhibitors and examine treatment effect on patients' quality of life.
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Affiliation(s)
- Nabil El Hage Chehade
- Department of Internal Medicine, MetroHealth Medical Center, Case Western Reserve University, Cleveland, OH
| | - Sara Ghoneim
- Division of Gastroenterology and Hepatology, University of Nebraska Medical Center, Omaha, NE
| | - Sagar Shah
- Department of Internal Medicine, Ronald Reagan Medical Center, University of California Los Angeles, Los Angeles, CA
| | - Darrell S Pardi
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN
| | - Francis A Farraye
- Inflammatory Bowel Disease Center, Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, FL
| | - Fadi F Francis
- Division of Gastroenterology and Hepatology, American University of Beirut, Beirut, Lebanon
- Division of Gastroenterology, Hepatology, and Nutrition, University of Pittsburgh, Pittsburgh, PA
| | - Jana G Hashash
- Inflammatory Bowel Disease Center, Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, FL
- Division of Gastroenterology and Hepatology, American University of Beirut, Beirut, Lebanon
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González IA, Conrad M, Weinbrom S, Patel T, Kelsen JR, Russo P. Clinicopathologic Characterization of Lymphocytic Colitis in the Pediatric Population. Pediatr Dev Pathol 2024; 27:156-168. [PMID: 38160439 PMCID: PMC11972057 DOI: 10.1177/10935266231215117] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/03/2024]
Abstract
BACKGROUND Lymphocytic colitis (LC) in the pediatric population has been associated with immune dysregulation. METHODS Single-center retrospective study of pediatric LC. RESULTS 50 patients (35 female, 70%) with a median age of 12 years at diagnosis (interquartile range: 5.7-15.8) of LC were identified. At presentation, 11 patients (22%) had malnutrition, 16 (32%) had a known underlying immune dysregulation, 4 (8%) had celiac disease (CD), and none had a diagnosis of inflammatory bowel disease. The most common medications prior to diagnosis were non-steroidal anti-inflammatory drugs, proton pump inhibitor, and selective serotonin reuptake inhibitors (10% each). Colonic biopsies showed a median number of intraepithelial lymphocytes (IELs)/100 epithelial cells of 48 (range: 25-85), and only 10% of cases had neutrophilic cryptitis. Upper gastrointestinal tract findings included lymphocytic esophagitis (4%), and duodenal IELs without and with villous blunting (9% each) (n: 47). Ten patients (23%) had increased IELs in the terminal ileum (n: 43). Treatments including 5-ASA, budesonide, prednisone, and gluten-free diet improved symptoms in <50% of patients (n: 42), and all follow-up colonoscopies showed persistent LC (n: 13). CONCLUSION Our study supports the association of LC with immune-mediated conditions, most commonly celiac disease. Symptomatic improvement was seen in <50% of patients with none of the patients with repeat colonoscopy showing histologic improvement.
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Affiliation(s)
- Iván A. González
- Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Maire Conrad
- Department of Gastroenterology, Hepatology and Nutrition, Children’s Hospital of Philadelphia, PA, USA
| | - Sarah Weinbrom
- Department of Gastroenterology, Hepatology and Nutrition, Children’s Hospital of Philadelphia, PA, USA
| | - Trusha Patel
- Department of Gastroenterology, Hepatology and Nutrition, Children’s Hospital of Philadelphia, PA, USA
| | - Judith R. Kelsen
- Department of Gastroenterology, Hepatology and Nutrition, Children’s Hospital of Philadelphia, PA, USA
| | - Pierre Russo
- Department of Pathology and Laboratory Medicine, Children’s Hospital of Philadelphia, PA, USA
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Enwerem NY, Yen EF. The colitis may be microscopic, but the diarrhea is not: update on the treatment of microscopic colitis and immune checkpoint inhibitor colitis. Curr Opin Gastroenterol 2024; 40:50-59. [PMID: 37874119 DOI: 10.1097/mog.0000000000000986] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/25/2023]
Abstract
PURPOSE OF REVIEW Microscopic colitis is an inflammatory disease of the colon that presents as watery diarrhea with minimal to normal endoscopic changes on colonoscopy. It encompasses two common subtypes, lymphocytic colitis and collagenous colitis, which are both treated similarly.Immune checkpoint inhibitor colitis is among the most common immune-related adverse events. Endoscopic and histological findings range from normal colonic mucosa to inflammatory bowel like changes. This review article provides update in treatment and management of microscopic colitis and immune checkpoint inhibitor colitis (ICPi colitis). RECENT FINDINGS Recent studies on microscopic colitis have focused on the successful use of immunomodulators such as biologics for treatment of budesonide refractory microscopic colitis cases. Microscopic colitis does not confer an added risk for colorectal cancer.With the increasing usage of immunotherapy agents, immune checkpoint inhibitor colitis is becoming more common. ICPi colitis can be successfully managed with steroids, with treatment stepped up to biologics for moderate to severe cases or for mild cases that do not respond to steroids. Immunotherapy agents can be carefully re-introduced in mild cases, after treatment of ICPi colitis. SUMMARY Biologics can be used to treat budesonide refractory microscopic colitis. ICPi colitis can be managed with steroids and biologics in moderate to severe cases.
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Affiliation(s)
- Ngozi Y Enwerem
- University of Texas Southwestern Medical Center, Division of Digestive and Liver Diseases
- VA Medical Center, Dallas, Texas
| | - Eugene F Yen
- Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
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Rim DS, Shin JH, Jacoba I, Sharma K, Kim DW. Case report: Exploring teduglutide as a therapeutic option for refractory microscopic colitis: insights and implications. Front Med (Lausanne) 2023; 10:1231565. [PMID: 37649980 PMCID: PMC10462905 DOI: 10.3389/fmed.2023.1231565] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2023] [Accepted: 07/28/2023] [Indexed: 09/01/2023] Open
Abstract
Microscopic colitis is a chronic inflammatory condition of the colon characterized by chronic watery diarrhea, generally with endoscopically normal or nonspecific findings, and can be diagnosed by histopathological examination of colon mucosal biopsies. Some patients experience severe symptoms that do not respond to conventional medical treatment. A glucagon-like peptide-2 (GLP-2) analog, teduglutide, is used in patients with short bowel syndrome (SBS) dependent on parenteral support. In this case report, we describe a patient with microscopic colitis who demonstrated significant symptom improvement following teduglutide treatment.
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Affiliation(s)
- Daniel Sungku Rim
- Department of Medicine, Section of Endocrinology, Diabetes, Nutrition and Weight Management, Boston University Chobanian and Avedisian School of Medicine, Boston, MA, United States
| | - Jeong-Hun Shin
- Department of Medicine, Section of Endocrinology, Diabetes, Nutrition and Weight Management, Boston University Chobanian and Avedisian School of Medicine, Boston, MA, United States
- Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Republic of Korea
| | - Isa Jacoba
- Department of Pathology and Laboratory Medicine, Boston University Chobanian and Avedisian School of Medicine, Boston, MA, United States
| | - Kavita Sharma
- Department of Medicine, Section of Endocrinology, Diabetes, Nutrition and Weight Management, Boston University Chobanian and Avedisian School of Medicine, Boston, MA, United States
| | - Dong Wook Kim
- Department of Medicine, Section of Endocrinology, Diabetes, Nutrition and Weight Management, Boston University Chobanian and Avedisian School of Medicine, Boston, MA, United States
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Rehde A, Hendel SK, Juhl CB, Gubatan J, Nielsen OH. Effectiveness of Non-Budesonide Therapies in Management of Microscopic Colitis: A Systematic Review and Meta-analysis. Drugs 2023:10.1007/s40265-023-01914-4. [PMID: 37358712 DOI: 10.1007/s40265-023-01914-4] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/12/2023] [Indexed: 06/27/2023]
Abstract
BACKGROUND Budesonide is accepted as first-choice therapy for microscopic colitis (MC); however, symptoms often recur and some patients may be dependent, intolerant, or even fail budesonide. We performed a systematic review and meta-analysis to determine the effectiveness of non-budesonide therapies (thiopurines, bismuth subsalicylate [BSS], bile acid sequestrants [BAS], loperamide and biologics) for MC suggested by international guidelines. METHODS We searched the CENTRAL, MEDLINE, and EMBASE databases from their inception to 18 April 2023 for the above-mentioned therapeutics in MC. We pooled the response and remission rates by medication using a random-effects model. RESULTS Twenty-five studies comprising 1475 patients were included in the meta-analysis. Treatment with BSS showed the highest response rate of 75% (95% confidence interval [CI] 0.65-0.83; I2 = 70.12%), with 50% achieving remission of symptoms (95% CI 0.35-0.65; I2 = 71.06%). Treatment with tumor necrosis factor (TNF) inhibitors (infliximab and adalimumab) demonstrated a response rate of 73% (95% CI 0.63-0.83; I2 = 0.00%), with a remission rate of 44% (95% CI 0.32-0.56; I2 = 0.00%). The response rate for those treated with vedolizumab was similar; 73% responded to treatment (95% CI 0.57-0.87; I2 = 35.93%), with a remission rate of 56% (95% CI 0.36-0.75; I2 = 46.30%). Loperamide was associated with response and remission rates of 62% (95% CI 0.43-0.80; I2 = 92.99%) and 14% (95% CI 0.07-0.25), respectively, whereas BAS use was associated with response and remission rates of 60% (95% CI 0.51-0.68; I2 = 61.65%) and 29% (95% CI 0.12-0.55), respectively. Finally, the outcomes for thiopurine use were 49% (95% CI 0.27-0.71; I2 = 81.45%) and 38% (95% CI 0.23-0.54; I2 = 50.05%), respectively DISCUSSION: The present systematic review and meta-analysis provides rates of effectiveness of non-budesonide therapies for MC based on available data in the field. Studies in the meta-analysis showed a large amount of heterogeneity due to the variability in assessing the clinical effects of intervention between the studies caused by differences in the definitions of response or remission rates between the studies included. This may likely result in overestimating the benefit of a treatment. Furthermore, the number of participants and drug dosages varied, and only a few studies applied disease-specific activity indices. Only one randomized controlled trial (RCT) was identified. All other 24 included studies were either case series or (retrospective) cohort studies, which complicated efforts to perform further sensitivity analyses to adjust for potential confounders and risk of bias. In addition, the overall evidence on the effect of these treatment options was judged as low, mostly due to comparability bias and the observational nature of the available studies, which limited statistically robust comparisons of rates of effectiveness of the different non-budesonide agents ranked against each other. However, our observational findings may inform clinicians regarding the most rational selection of non-budesonide therapies to patients with MC. CLINICAL TRIALS REGISTRATION PROSPERO protocol #CRD42020218649.
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Affiliation(s)
- Amalie Rehde
- Department of Gastroenterology D112, The IBD Clinic, Herlev Hospital, University of Copenhagen, Borgmester Ib Juuls Vej 1, 2730, Herlev, Denmark
| | - Sebastian Kjærgaard Hendel
- Department of Gastroenterology D112, The IBD Clinic, Herlev Hospital, University of Copenhagen, Borgmester Ib Juuls Vej 1, 2730, Herlev, Denmark
| | - Carsten Bogh Juhl
- Cochrane Musculoskeletal Group, University of Southern Denmark, Odense, Denmark
- Department of Physiotherapy and Occupational Therapy, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark
| | - John Gubatan
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA, USA
| | - Ole Haagen Nielsen
- Department of Gastroenterology D112, The IBD Clinic, Herlev Hospital, University of Copenhagen, Borgmester Ib Juuls Vej 1, 2730, Herlev, Denmark.
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Khushal S, Oliva-Hemker M. Diagnosis and Management of Microscopic Colitis in Pediatric Patients. Paediatr Drugs 2022; 24:217-233. [PMID: 35501559 DOI: 10.1007/s40272-022-00504-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 03/27/2022] [Indexed: 11/27/2022]
Abstract
Microscopic colitis (MC) is an inflammatory disease of the colon, characterized by chronic watery diarrhea with distinguishing histologic findings despite normal endoscopic appearance of the colonic mucosa. MC is a common cause of diarrhea in older adults, though it has been infrequently reported in children and adolescents. As MC is rare in the pediatric population, and the clinical presentation is non-specific, increased awareness of this disease amongst pediatric clinicians and pathologists is essential for timely diagnosis, which requires performing colonoscopy with biopsy. The etiology of MC is incompletely understood, but current theories in pathogenesis inform management strategies. The goals of management in pediatric MC should be to achieve symptomatic improvement while minimizing adverse effects of treatment. Many patients who achieve clinical response have symptomatic recurrence after discontinuation of initial therapy, and may require maintenance medication therapy to sustain remission. This review aims to summarize the epidemiology and risk factors, clinical features, diagnosis, theories regarding pathogenesis, and suggested management approaches for MC in the pediatric population.
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Affiliation(s)
- Salina Khushal
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Maria Oliva-Hemker
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
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Vuyyuru SK, Kedia S, Sahu P, Ahuja V. Immune-mediated inflammatory diseases of the gastrointestinal tract: Beyond Crohn's disease and ulcerative colitis. JGH Open 2022; 6:100-111. [PMID: 35155819 PMCID: PMC8829105 DOI: 10.1002/jgh3.12706] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2021] [Revised: 12/26/2021] [Accepted: 12/29/2021] [Indexed: 12/17/2022]
Abstract
Immune-mediated inflammatory diseases (IMIDs) are a diverse group of complex inflammatory diseases that result from dysregulated immune pathways and can involve any system of the human body. Inflammatory bowel disease (IBD) is one such disease involving the gastrointestinal (GI) system. With high prevalence in the West and increasing incidence in newly industrialized countries, IBD poses a significant burden on health care. IMIDs of the GI system other than IBD can have similar clinical features, causing diagnostic and therapeutic challenges. Although these disorders share a common pathophysiology, the defects can occur anywhere in the complex network of cytokines, inflammatory mediators, and innate and adaptive systems, leading to unregulated inflammation. Precise knowledge about them will help determine the possible targeted therapy. Thus, it is essential to distinguish these disorders from IBD. This review describes various IMIDs of the GI tract that mimic IBD.
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Affiliation(s)
- Sudheer K Vuyyuru
- Department of GastroenterologyAll India Institute of Medical SciencesNew DelhiIndia
| | - Saurabh Kedia
- Department of GastroenterologyAll India Institute of Medical SciencesNew DelhiIndia
| | - Pabitra Sahu
- Department of GastroenterologyAll India Institute of Medical SciencesNew DelhiIndia
| | - Vineet Ahuja
- Department of GastroenterologyAll India Institute of Medical SciencesNew DelhiIndia
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Abstract
Microscopic colitis (MC) is an inflammatory disease of the large intestine associated with urgent watery diarrhoea. MC may occur in people of all ages, although the disease primarily affects older women. Once believed to be rare, MC is now known to be a common cause of chronic watery diarrhoea in high-income countries, affecting 1 in 115 women and 1 in 286 men during their lifetime in Swedish population-based estimates. An inappropriate immune response to disturbances in the gut microenvironment is implicated in the pathogenesis of MC. Evidence also supports an underlying genetic basis for disease. The diagnosis of MC relies on clinical symptoms and microscopic assessment of colonic biopsy samples. MC is categorized histologically into collagenous colitis, lymphocytic colitis and their incomplete forms. The mainstay of treatment includes the use of budesonide, with or without adjunctive therapies, and withdrawal of offending drugs. Emerging studies suggest a role for biologicals and immunosuppressive therapies for the management of budesonide-refractory or budesonide-dependent disease. MC can have a substantial negative effect on patient quality of life. The outlook for MC includes a better understanding of the immune response, genetics and the microbiome in disease pathogenesis along with progress in disease management through robust clinical trials.
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Affiliation(s)
- Kristin E Burke
- Gastroenterology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
- Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, Boston, MA, USA.
| | - Mauro D'Amato
- Gastrointestinal Genetics Lab, CIC bioGUNE, Basque Research and Technology Alliance (BRTA), Derio, Spain
- Ikerbasque, Basque Foundation for Science, Bilbao, Spain
| | - Siew C Ng
- Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, LK Institute of Health Science, The Chinese University of Hong Kong, Shatin, NT, Hong Kong, China
| | - Darrell S Pardi
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| | - Jonas F Ludvigsson
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
- Department of Paediatrics, Örebro University Hospital, Örebro University, Örebro, Sweden
| | - Hamed Khalili
- Gastroenterology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
- Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, Boston, MA, USA.
- Institute of Environmental Medicine, Nutrition Epidemiology, Karolinska Institutet, Solna, Sweden.
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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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Rojo E, Casanova MJ, Gisbert J. Treatment of microscopic colitis: the role of budesonide and new alternatives for refractory patients. REVISTA ESPANOLA DE ENFERMEDADES DIGESTIVAS 2021; 112:53-58. [PMID: 31880163 DOI: 10.17235/reed.2019.6655/2019] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
Microscopic colitis is a common cause of chronic watery diarrhea with a great impact on patient quality of life. Microscopic colitis includes two histological subtypes: collagenous colitis and lymphocytic colitis. Due to the increasing incidence and awareness of this disease over the last decades, several international guidelines have been recently published. However, there is still significant heterogeneity in the management of these patients, and treatments without solid scientific evidence support are often used in clinical practice. This article reviews the therapeutic role of budesonide in microscopic colitis and summarizes the current evidence regarding other treatments available for this disease, especially for the management of refractory patients. Finally, an updated treatment algorithm is proposed.
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Affiliation(s)
- Eukene Rojo
- Servicio de Aparato Digestivo, Hospital Universitario de La Princesa, España
| | - María José Casanova
- Servicio de Aparato Digestivo, Hospital Universitario de La Princesa, España
| | - Javier Gisbert
- Servicio de Aparato Digestivo, Hospital Universitario de La Princesa, España
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Shor J, Churrango G, Hosseini N, Marshall C. Management of microscopic colitis: challenges and solutions. Clin Exp Gastroenterol 2019; 12:111-120. [PMID: 30881078 PMCID: PMC6398419 DOI: 10.2147/ceg.s165047] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
Microscopic colitis (MC) is a chronic inflammatory bowel disease characterized by nonbloody diarrhea in the setting of normal appearing colonic mucosa. MC has two main subtypes based on histopathologic features, collagenous colitis and lymphocytic colitis. Management of both subtypes is the same, with treatment goal of reducing the number of bowel movements and improving consistency. First-line treatment involves counseling the patient about decreasing their risk factors, like discontinuing smoking and avoiding medications with suspected association such as NSAIDs, proton pump inhibitor, ranitidine, and sertraline. Starting loperamide for immediate symptomatic relief is used as an adjunct to therapy with glucocorticoids. Budesonide is considered first-line treatment for MC given its favorable side effect profile and good efficacy, though relapse rates are high. Systemic glucocorticoids should be reserved to patients unable to take budesonide. In glucocorticoid refractory disease, medications that have been tried include cholestyramine, bismuth salicylate, antibiotics, probiotics, aminosalicylates, immunomodulators, and anti-tumor necrosis factor-alpha inhibitors. More research is needed for the creation of a systematic stepwise approach for relapsing and refractory disease.
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Affiliation(s)
- Julia Shor
- Department of Gastroenterology, University of Massachusetts Medical School, Worcester, MA, USA,
| | - Gustavo Churrango
- Department of Gastroenterology, University of Massachusetts Medical School, Worcester, MA, USA,
| | - Nooshin Hosseini
- Department of Gastroenterology, Mount Sinai Hospital, New York, NY, USA
| | - Christopher Marshall
- Department of Gastroenterology, University of Massachusetts Medical School, Worcester, MA, USA,
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Gentile N, Yen EF. Prevalence, Pathogenesis, Diagnosis, and Management of Microscopic Colitis. Gut Liver 2018; 12:227-235. [PMID: 28669150 PMCID: PMC5945253 DOI: 10.5009/gnl17061] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/09/2017] [Revised: 03/24/2017] [Accepted: 03/24/2017] [Indexed: 12/12/2022] Open
Abstract
Microscopic colitis (MC), which is comprised of lymphocytic colitis and collagenous colitis, is a clinicopathological diagnosis that is commonly encountered in clinical practice during the evaluation and management of chronic diarrhea. With an incidence approaching the incidence of inflammatory bowel disease, physician awareness is necessary, as diagnostic delays result in a poor quality of life and increased health care costs. The physician faces multiple challenges in the diagnosis and management of MC, as these patients frequently relapse after successful treatment. This review article outlines the risk factors associated with MC, the clinical presentation, diagnosis and histologic findings, as well as a proposed treatment algorithm. Prospective studies are required to better understand the natural history and to develop validated histologic endpoints that may be used as end points in future clinical trials and serve to guide patient management.
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Affiliation(s)
- Nicole Gentile
- NorthShore University HealthSystem, University of Chicago, Evanston, IL, USA
| | - Eugene F Yen
- NorthShore University HealthSystem, University of Chicago, Evanston, IL, USA
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Abstract
Targeted immunotherapy has markedly improved the survival of melanoma patients. We report the case of a melanoma patient who developed a collagenous colitis under an anti-PD1 regimen. A 68-year-old woman was treated for a stage IV melanoma. An anti-PD1, pembrolizumab, was introduced after the failure of a first-line therapy with an anti-CTLA4. At cycle 14, pembrolizumab was interrupted because of grade 3 diarrhea. Histologic analysis of colon mucosa showed a thickened apical subepithelial collagen layer with irregular collagen deposition of more than 25 µm thickness. Budesonide 9 mg/day and cholestyramin 8 g/day were then introduced, leading to a decrease in the number of stools to grade 2. Because of the prognosis of the disease, the efficacy of pembrolizumab in this patient and the lack of other efficient treatments, pembrolizumab was restarted, with no worsening of the diarrhea after a follow-up of 8 weeks. In the era of immunotherapy, a new type of drug-induced colitis has emerged because of monoclonal antibodies targeting immune checkpoints such as CTLA-4 and PD1. Gastrointestinal tract immune-mediated adverse effects are now well described with ipilimumab. To the best of our knowledge, this is the first report of a collagenous colitis in a patient treated with pembrolizumab, thus suggesting a new mechanism of toxicity. Classically, collagenous colitis first-line treatment is based on discontinuation of the suspected treatment. However, there may be a strong benefit to maintaining an anti-PD1 regimen in our patients. In this case, symptomatic management associated with budesonide and cholestyramin enabled continuation of pembrolizumab.
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Singh S, Loo LEJ, Watters C, Ahmed S. Collagenous panenteritis: a rare cause of chronic diarrhoea. Frontline Gastroenterol 2017; 8:232-235. [PMID: 29067147 PMCID: PMC5641846 DOI: 10.1136/flgastro-2016-100760] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2016] [Revised: 12/27/2016] [Accepted: 01/01/2017] [Indexed: 02/04/2023] Open
Abstract
Collagenous panenteritis is a rare inflammatory condition that causes profound diarrhoea and weight loss. There has only been a handful of cases reported in the literature. We report this rare case and the diagnostic difficulties encountered in securing the diagnosis. A 59-year-old woman presented with an 8-month history of diarrhoea and weight loss on a background of a family history of coeliac disease. Her presentation was complicated with acute kidney injury secondary to prerenal losses. Repeated gastroscopies and colonoscopies along with biopsies were inconclusive. It was not until histology of biopsies taken at endoscopies were reviewed that a diagnosis of collagenous panenteritis was secured. Her management revolved around combination of budesonide, gluten-free diet and antidiarrhoeals, which has achieved clinical remission.
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15
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Fernandez-Bañares F, Piqueras M, Guagnozzi D, Robles V, Ruiz-Cerulla A, Casanova MJ, Gisbert JP, Busquets D, Arguedas Y, Pérez-Aisa A, Fernández-Salazar L, Lucendo AJ. Collagenous colitis: Requirement for high-dose budesonide as maintenance treatment. Dig Liver Dis 2017; 49:973-977. [PMID: 28457904 DOI: 10.1016/j.dld.2017.03.026] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/20/2016] [Revised: 03/20/2017] [Accepted: 03/31/2017] [Indexed: 12/11/2022]
Abstract
BACKGROUND Controlled studies show high efficacy of budesonide in inducing short-term clinical remission in collagenous colitis (CC), but relapses are common after its withdrawal. AIM To evaluate the need for high-dose budesonide (≥6mg/d) to maintain clinical remission in CC. METHODS Analysis of a multicentre retrospective cohort of 75 patients with CC (62.3±1.5years; 85% women) treated with budesonide in a clinical practice setting between 2013 and 2015. Frequency of budesonide (9mg/d) refractoriness and safety, and the need for high-dose budesonide to maintain clinical remission, were evaluated. Drugs used as budesonide-sparing, including azathioprine and mercaptopurine, were recorded. Logistic regression analysis was performed to evaluate the risk factors associated with the need for high-dose budesonide (≥6mg/d) to maintain clinical remission. RESULTS Budesonide induced clinical remission in 92% of patients, with good tolerance. Fourteen of 68 patients (21%; 95% CI, 13-32%) needed high-dose budesonide to maintain remission. Only intake of NSAIDs at diagnosis (OR, 8.6; 95% CI, 1.6-44) was associated with the need for high-dose budesonide in the multivariate analysis. TREATMENT with thiopurines was effective in 5 out of 6 patients (83%; 95% CI, 44-97%), allowing for withdrawal from or a dose decrease of budesonide. CONCLUSIONS One fifth of CC patients, especially those with NSAID intake at diagnosis, require high-dose budesonide (≥6mg/d) to maintain clinical remission. In this setting, thiopurines might be effective as budesonide-sparing drugs.
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Affiliation(s)
- Fernando Fernandez-Bañares
- University Hospital Mutua Terrassa; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas.
| | - Marta Piqueras
- Consorci Sanitari Terrassa, Department of Gastroenterology, Terrassa, Spain
| | - Danila Guagnozzi
- Hospital Vall d'Hebron, Department of Gastroenterology, Barcelona, Spain
| | - Virginia Robles
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas; Hospital Vall d'Hebron, Department of Gastroenterology, Barcelona, Spain
| | | | - María José Casanova
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas; University Hospital La Princesa
| | - Javier P Gisbert
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas; University Hospital La Princesa
| | | | - Yolanda Arguedas
- Hospital San Jorge, Department of Gastroenterology, Huesca, Spain
| | | | | | - Alfredo J Lucendo
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas; Hospital General of Tomelloso
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16
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Chande N, Al Yatama N, Bhanji T, Nguyen TM, McDonald JWD, MacDonald JK, Cochrane IBD Group. 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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17
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Cotter TG, Kamboj AK, Hicks SB, Tremaine WJ, Loftus EV, Pardi DS. Immune modulator therapy for microscopic colitis in a case series of 73 patients. Aliment Pharmacol Ther 2017; 46:169-174. [PMID: 28488312 DOI: 10.1111/apt.14133] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2017] [Revised: 03/16/2017] [Accepted: 04/14/2017] [Indexed: 12/11/2022]
Abstract
BACKGROUND Microscopic colitis (MC) is a common cause of chronic diarrhoea. Various treatment options have been described, but there are limited data describing outcomes of corticosteroid-sparing treatments. AIM To evaluate the outcomes of patients with active MC treated with immune modulators. METHODS All patients seen at Mayo Clinic, Rochester between January 1, 1997 and November 30, 2016 with a histological diagnosis of MC were identified. Patients treated with an immune modulator of interest were selected and clinical outcomes recorded. RESULTS Seventy-three MC patients (50 collagenous colitis and 23 lymphocytic colitis) with a median disease duration of 24 months (range, 7-60) were included. The indications for treatment were budesonide-refractoriness in 66%, budesonide dependence in 29%, and budesonide intolerance in 5%. Median age was 51.8 years (range, 43.4-63.1) and 61 (84%) were female. Thiopurines were used in 49 patients (67%) for a median of 4 months (range, 1.5-15). Complete and partial response occurred in 43% and 22% respectively. Adverse effects resulting in therapy cessation occurred in 17 patients (35%). Twelve patients (16%) were treated with methotrexate for a median of 14 months (3-18.8). Complete and partial response occurred in 58% and 17%, respectively. Anti-TNF therapy was used in 10 patients (14%) for a median of 4 months (range, 2.3-5.5). Complete response occurred in four patients and partial response in four patients. CONCLUSIONS The majority of patients with active MC responded to thiopurines, methotrexate, or anti-TNF therapy. Larger controlled studies are required to confirm the efficacy and safety of these medications in MC.
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Affiliation(s)
- T G Cotter
- Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA
| | - A K Kamboj
- Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA
| | - S B Hicks
- Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA
| | - W J Tremaine
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| | - E V Loftus
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| | - D S Pardi
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
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18
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Abstract
PURPOSE OF REVIEW Microscopic colitis is a common cause of chronic watery diarrhea, particularly in the elderly. The accompanying symptoms, which include abdominal pain and fatigue, can markedly impair patients' quality of life. Diagnosis is based upon characteristic histologic findings of the colonic mucosa. This review focuses on the current approach to evaluation and management of patients with microscopic colitis. RECENT FINDINGS Although the incidence of microscopic colitis has been increasing over time, recent epidemiological studies show stabilization at 21.0-24.7 cases per 100,000 person-years. Recent research has further expanded our knowledge of the underlying pathophysiology and emphasized the entity of drug-induced microscopic colitis and the association with celiac disease. Two recent randomized studies have confirmed the effectiveness of oral budesonide for both induction and maintenance treatment of microscopic colitis and is now endorsed by the American Gastroenterological Association as first-line treatment. The incidence of microscopic colitis has stabilized at just over 20 cases per 100,000 person-years. Celiac disease and drug-induced microscopic colitis should be considered in all patients diagnosed with microscopic colitis. There are a number of treatments available for patients with microscopic colitis; however, budesonide is the only option well studied in controlled trials and is effective for both induction and maintenance treatment.
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19
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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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20
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Abstract
Collagenous colitis (CC) is an increasingly recognized cause of chronic inflammatory bowel disease characterized by watery non-bloody diarrhea. As a lesser studied inflammatory bowel disease, many aspects of the CC's natural history are poorly understood. This review discusses strategies to optimally manage CC. The goal of therapy is to induce clinical remission, <3 stools a day or <1 watery stool a day with subsequent improved quality of life (QOL). Antidiarrheal can be used as monotherapy or with other medications to control diarrhea. Budesonide therapy has revolutionized treatment and is superior to prednisone, however, the treatment is associated with high-relapse rates and the management of refractory disease is challenging. Ongoing trials will address the safety and efficacy of low-dose maintenance therapy. For those with refractory disease, case reports and case series support the role of biologic agents. Diversion of the fecal stream normalizes colonic mucosal changes and ileostomy may be considered where anti-tumor necrosis factor (TNF)-α agents are contraindicated. Underlying celiac disease, bile salt diarrhea, and associated thyroid dysfunction should be ruled out. The author recommends smoking cessation as well as avoidance of nonsteroidal anti-inflammatories as well as other associated medications.
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21
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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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22
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Nguyen GC, Smalley WE, Vege SS, Carrasco-Labra A. American Gastroenterological Association Institute Guideline on the Medical Management of Microscopic Colitis. Gastroenterology 2016; 150:242-6; quiz e17-8. [PMID: 26584605 DOI: 10.1053/j.gastro.2015.11.008] [Citation(s) in RCA: 90] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Affiliation(s)
- Geoffrey C Nguyen
- Mount Sinai Hospital Centre for Inflammatory Bowel Disease, University of Toronto, Toronto, Ontario, Canada
| | - Walter E Smalley
- Division of Gastroenterology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee
| | - Santhi Swaroop Vege
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Alonso Carrasco-Labra
- McMaster University, Hamilton, Ontario, Canada; Evidence-Based Dentistry Unit, Faculty of Dentistry, Universidad de Chile, Santiago, Chile
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23
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Jauregui-Amezaga A, Vermeire S, Geboes K. Contemporary methods for the diagnosis and treatment of microscopic colitis. Expert Rev Gastroenterol Hepatol 2016; 10:47-61. [PMID: 26470823 DOI: 10.1586/17474124.2016.1096197] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Microscopic colitis is a common cause of chronic diarrhea. It is characterized by non-bloody watery diarrhea with macroscopically normal colonic mucosa. Its specific histological characteristics confirm the diagnosis. Two distinct histological forms can be identified, namely, collagenous colitis and lymphocytic colitis. In collagenous colitis, a thick colonic subepithelial collagenous deposit can be observed, whereas in lymphocytic colitis, a pronounced intraepithelial lymphocytic inflammation in the absence of a thickened collagen band can be identified. Microscopic colitis occurs more frequently in elderly females and its etiology is believed to be multifactorial, although smoking and consumption of several drugs have been identified as risks factors for the development of the disease. The treatment is based on avoiding the risks factors and administration of oral budesonide.
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Affiliation(s)
| | | | - Karel Geboes
- b 2 University Hospitals Leuven, Pathology, Leuven, Belgium
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24
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Park T, Cave D, Marshall C. Microscopic colitis: A review of etiology, treatment and refractory disease. World J Gastroenterol 2015; 21:8804-8810. [PMID: 26269669 PMCID: PMC4528022 DOI: 10.3748/wjg.v21.i29.8804] [Citation(s) in RCA: 58] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/14/2015] [Revised: 06/09/2015] [Accepted: 06/16/2015] [Indexed: 02/06/2023] Open
Abstract
Microscopic colitis is a common cause of chronic, nonbloody diarrhea. Microscopic colitis is more common in women than men and usually affects patients in their sixth and seventh decade. This article reviews the etiology and medical management of microscopic colitis. The etiology of microscopic colitis is unknown, but it is associated with autoimmune disorders, such as celiac disease, polyarthritis, and thyroid disorders. Smoking has been identified as a risk factor of microscopic colitis. Exposure to medications, such as non-steroidal anti-inflammatory drugs, proton pump inhibitors, and selective serotonin reuptake inhibitors, is suspected to play a role in microscopic colitis, although their direct causal relationship has not been proven. Multiple medications, including corticosteroids, anti-diarrheals, cholestyramine, bismuth, 5-aminosalicylates, and immunomodulators, have been used to treat microscopic colitis with variable response rates. Budesonide is effective in inducing and maintaining clinical remission but relapse rate is as high as 82% when budesonide is discontinued. There is limited data on management of steroid-dependent microscopic colitis or refractory microscopic colitis. Immunomodulators seem to have low response rate 0%-56% for patients with refractory microscopic colitis. Response rate 66%-100% was observed for use of anti-tumor necrosis factor (TNF) therapy for refractory microscopic colitis. Anti-TNF and diverting ileostomy may be an option in severe or refractory microscopic colitis.
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25
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Abstract
Microscopic colitis (MC) is the common denominator for lymphocytic and collagenous colitis (CC). It is now recognized as a relatively frequent cause of diarrhea that equals the prevalence of inflammatory bowel disease. Patients are typically middle-aged women, but disease may occur at every age. Patients with MC report watery, non-bloody diarrhea in the absence of endoscopic and radiologic abnormalities. Lymphocytic colitis is characterized by an increased number of intraepithelial lymphocytes, and CC by a thickened subepithelial collagen band, whereas in both an increased mononuclear infiltration of the lamina propria is found. The pathogenesis of MC is largely unknown, but may relate to autoimmunity, adverse reactions to drugs or (bacterial) toxins, and abnormal collagen metabolism in the case of CC. Budesonide is so far the only drug that has proven efficacy in randomized controlled trials both for the induction and maintenance of remission. Patients who are nonresponsive, dependent or who experience side effects on budesonide may benefit from thiopurine or anti-TNF treatment, but these options are still experimental. The long-term prognosis of MC is good; it does not appear to predispose to malignancies and can in some cases be self-limiting. Further research and randomized clinical trials are required to expand our understanding of the natural course and the pathogenesis of MC.
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26
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Münch A, Langner C. Microscopic colitis: clinical and pathologic perspectives. Clin Gastroenterol Hepatol 2015; 13:228-36. [PMID: 24407107 DOI: 10.1016/j.cgh.2013.12.026] [Citation(s) in RCA: 51] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2013] [Revised: 12/19/2013] [Accepted: 12/19/2013] [Indexed: 02/07/2023]
Abstract
Microscopic colitis is a chronic inflammatory bowel disease characterized by chronic nonbloody diarrhea and specific histopathology features. Active disease, defined as 3 or more stools or 1 or more watery stools per day, significantly reduces quality of life. Epidemiologic studies have found the incidence and prevalence of microscopic colitis to be comparable with those of Crohn's disease and ulcerative colitis. Nevertheless, microscopic colitis is still under-recognized in clinical practice-most health care workers know little about its etiology and pathophysiology. Furthermore, there are many challenges to the diagnosis and treatment of patients. We review the epidemiologic and clinical features of this disorder and discuss its pathogenesis. We also outline the criteria for histopathologic evaluation of microscopic colitis, recently published by the European Consensus on Inflammatory Bowel Disease, and discuss a treatment algorithm created by the European Microscopic Colitis Group. Treatment options for patients with budesonide-refractory disease are discussed.
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Affiliation(s)
- Andreas Münch
- Division of Gastroenterology and Hepatology, Department of Clinical and Experimental Medicine, Faculty of Health Science, Linköpings University, Linköping, Sweden.
| | - Cord Langner
- Institute of Pathology, Medical University of Graz, Graz, Austria
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27
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Abstract
The literature review gives the present-day views of the definition, etiology, pathogenesis, diagnosis, and treatment of microscopic colitis (MC). In the present view, MC is an inflammatory bowel disease of unknown etiology, which is characterized by chronic watery diarrhea, no macroscopic signs of large bowel involvement in the presence of specific pathomorphological changes. There are two major forms of MC, which are similar in its clinical picture, yet, heterogeneous in histological criteria: collagenous colitis (CC) and lymphocytic colitis (LC). As of now, the prevalence of MC is about 100 cases per 100,000 population, which is similar with that in other inflammatory bowel diseases, such as ulcerative colitis and Crohn's disease. MC generally prevails in women aged over 50 years. The etiology and pathogenesis of MC have not fully investigated. Watery diarrhea is as a predominant pathognomonic symptom in all the patients with MC. The major histological criterion for the diagnosis of CC is subepithelial collagen lining thickening (more than 10 pm) and that for LC is higher intraepithelial lymphocyte counts (more than 20 intraepithelial lymphocytes/100 epitheliocytes). The topical glucocorticosteroid budesonide is currently the only agent, the efficacy of which has been proven in both inducing and maintaining remission in patients with MC in many clinical trials.
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Affiliation(s)
- I V Maev
- A.I. Evdokimov Moscow State University of Medicine and Dentistry, Ministry of Health of Russia, Moscow, Russia
| | - Yu A Kucheryavyi
- A.I. Evdokimov Moscow State University of Medicine and Dentistry, Ministry of Health of Russia, Moscow, Russia
| | - D N Andreev
- A.I. Evdokimov Moscow State University of Medicine and Dentistry, Ministry of Health of Russia, Moscow, Russia
| | - S V Cheremushkin
- A.I. Evdokimov Moscow State University of Medicine and Dentistry, Ministry of Health of Russia, Moscow, Russia
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Farrukh A, Mayberry JF. Microscopic colitis: a review. Colorectal Dis 2014; 16:957-64. [PMID: 25039699 DOI: 10.1111/codi.12716] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/25/2014] [Accepted: 05/17/2014] [Indexed: 12/14/2022]
Abstract
AIM In recent years, microscopic colitis has been increasingly diagnosed. This review was carried out to evaluate demographic factors for microscopic colitis and to perform a systematic assessment of available treatment options. METHOD Relevant publications up to December 2013 were identified following searches of PubMed and Google Scholar using the key words 'microscopic colitis', 'collagenous colitis' and 'lymphocytic colitis'. Two-hundred and forty-eight articles were identified. RESULTS The term microscopic colitis includes lymphocytic colitis and collagenous colitis. Both have common clinical symptoms but are well defined histopathologically. The clinical course is usually benign, but serious complications, including death, may occur. A peak incidence from 60 to 70 years of age with a female preponderance is observed. Although most cases are idiopathic, associations with autoimmune disorders, such as coeliac disease and hypothyroidism, as well as with exposure to nonsteroidal anti-inflammatory drugs and proton-pump inhibitors, have been observed. The incidence and prevalence of microscopic colitis is rising and good-quality epidemiological research is needed. Treatment is currently largely based on anecdotal evidence and on results from limited clinical trials of budesonide. Long-term follow-up of these patients is not well established. CONCLUSION The review synthesizes work on the definition of microscopic colitis and the relationship between collagenous and lymphocytic colitis. It reviews the international epidemiology and work on aetiology. In addition, it critically considers the efficacy of a range of treatments.
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Affiliation(s)
- A Farrukh
- Digestive Disease Centre, University Hospitals of Leicester, Leicester, UK
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Bohr J, Wickbom A, Hegedus A, Nyhlin N, Hultgren Hörnquist E, Tysk C. Diagnosis and management of microscopic colitis: current perspectives. Clin Exp Gastroenterol 2014; 7:273-84. [PMID: 25170275 PMCID: PMC4144984 DOI: 10.2147/ceg.s63905] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
Collagenous colitis and lymphocytic colitis, together constituting microscopic colitis, are common causes of chronic diarrhea. They are characterized clinically by chronic nonbloody diarrhea and a macroscopically normal colonic mucosa where characteristic histopathological findings are seen. Previously considered rare, they now have emerged as common disorders that need to be considered in the investigation of the patient with chronic diarrhea. The annual incidence of each disorder is five to ten per 100,000 inhabitants, with a peak incidence in 60- to 70-year-old individuals and a predominance of female patients in collagenous colitis. The etiology and pathophysiology are not well understood, and the current view suggests an uncontrolled mucosal immune reaction to various luminal agents in predisposed individuals. Clinical symptoms comprise chronic diarrhea, abdominal pain, fatigue, weight loss, and fecal incontinence that may impair the patient's health-related quality of life. An association is reported with other autoimmune disorders, such as celiac disease, thyroid disorders, diabetes mellitus, and arthritis. The best-documented treatment, both short-term and long-term, is budesonide, which induces clinical remission in up to 80% of patients after 8 weeks' treatment. However, after successful budesonide therapy is ended, recurrence of clinical symptoms is common, and the best possible long-term management deserves further study. The long-term prognosis is good, and the risk of complications, including colonic cancer, is low. We present an update of the epidemiology, pathogenesis, diagnosis, and management of microscopic colitis.
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Affiliation(s)
- Johan Bohr
- Division of Gastroenterology, Department of Medicine, Örebro University Hospital, Örebro, Sweden
- School of Health and Medical Sciences, Örebro University, Örebro, Sweden
| | - Anna Wickbom
- Division of Gastroenterology, Department of Medicine, Örebro University Hospital, Örebro, Sweden
- School of Health and Medical Sciences, Örebro University, Örebro, Sweden
| | - Agnes Hegedus
- Department of Laboratory Medicine/Pathology, Örebro University Hospital, Örebro, Sweden
| | - Nils Nyhlin
- Division of Gastroenterology, Department of Medicine, Örebro University Hospital, Örebro, Sweden
- School of Health and Medical Sciences, Örebro University, Örebro, Sweden
| | | | - Curt Tysk
- Division of Gastroenterology, Department of Medicine, Örebro University Hospital, Örebro, Sweden
- School of Health and Medical Sciences, Örebro University, Örebro, Sweden
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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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Münch A, Bohr J, Vigren L, Tysk C, Ström M. Lack of effect of methotrexate in budesonide-refractory collagenous colitis. Clin Exp Gastroenterol 2013; 6:149-52. [PMID: 24039441 PMCID: PMC3770495 DOI: 10.2147/ceg.s48201] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/27/2023] Open
Abstract
Background In most cases, collagenous colitis can be treated effectively with budesonide. However, some patients develop side effects or have chronic symptoms refractory to budesonide. This paper reports an open case series of patients intolerant or refractory to budesonide who were treated with methotrexate (MTX). Methods and patients Nine patients (seven women) with a median (range) age of 62 (44–77) years were studied. Bowel movements were registered during 1 week prior to baseline and after 6 and 12 weeks’ treatment, enabling calculation of the mean bowel movements/day. All patients underwent colonoscopy with biopsies before inclusion to confirm diagnosis. Open treatment with MTX was given 15 mg subcutaneously weekly for 6 weeks and was increased to 25 mg for a further 6 weeks if symptoms were unresponsive to the first 6 weeks’ treatment. The endpoint was clinical remission, which was defined as a mean <3 stools/day and mean <1 watery stool/day/week at Week 12. The Short Health Scale was used at baseline and Week 12 to assess health-related quality of life. Results Five patients fulfilled the treatment according to the protocol and four patients discontinued the study after 3–6 weeks because of adverse events. No patient achieved clinical remission at Week 12. The mean stool frequency/day at baseline was 6.0 stools/day, thereof 5.4 watery stools/day and after 12 weeks treatment 6.4 stools/day, thereof 5.7 watery/day. No patient appreciated an improvement of health-related quality of life. Conclusion Short-term treatment with MTX had no clinical effect in collagenous colitis patients intolerant or refractory to budesonide. Alternative therapies should be investigated in these patients.
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Affiliation(s)
- Andreas Münch
- Division of Gastroenterology and Hepatology, Department of Clinical and Experimental Medicine, Faculty of Health science, Linköping University, Linköping
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Abstract
The treatment of microscopic colitis is mainly based on the use of budesonide, the only drug found effective in controlled clinical trials. After an initial course at a dose of 9 mg daily, however, most patients relapse when the drug is discontinued, hence a maintenance therapy at doses of 6 mg daily or lower is necessary. In order to avoid steroid dependence and drug toxicity different pharmacological agents should be considered as an alternative to indefinite long-term budesonide treatment. Evidence-based guidelines are currently lacking due to the lack of conclusive data concerning the use of either immunosuppressive or anti-tumor necrosis factor agents. For the time being in clinical practice the skilled physician should therefore tailor long term management of microscopic colitis on the single patient.
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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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35
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Storr MA. Microscopic colitis: epidemiology, pathophysiology, diagnosis and current management-an update 2013. ISRN GASTROENTEROLOGY 2013; 2013:352718. [PMID: 23691336 PMCID: PMC3654232 DOI: 10.1155/2013/352718] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 03/10/2013] [Accepted: 03/28/2013] [Indexed: 12/14/2022]
Abstract
Microscopic colitis is a common cause of chronic diarrhea. Over the last years the incidence and the prevalence of microscopic colitis are rising and this rise is largely attributed to a rising awareness, and concomitantly an increasing number of diagnoses are made. Patients with microscopic colitis report watery, nonbloody diarrhea of chronic, intermittent, or chronic recurrent course. Following an unremarkable physical examination the diagnosis of microscopic colitis is made by colonoscopy, which shows essentially a normal colonic mucosa. Biopsies taken during the colonoscopy procedure will then finally establish the correct diagnosis. Histological workup can then confirm a diagnosis of microscopic colitis and can distinguish the two distinct histological forms, namely, collagenous colitis 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, though this may change in future. Depending on the patients age and gender 10-30% of patients investigated for chronic diarrhea will be diagnosed with microscopic colitis if biopsies are taken. Microscopic colitis is most common in older patients, especially in female patients and is frequently associated with autoimmune disorders and the consumption of several drugs. This review summarizes the present knowledge of the epidemiology, the pathophysiology, and the diagnosis of microscopic colitis and discusses the former and the present treatment options.
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Affiliation(s)
- Martin Alexander Storr
- Division of Gastroenterology, Department of Medicine, Ludwig Maximilians University of Munich, Campus Grosshadern, Marchioninistr 15, 81377 Munich, Germany
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Münch A, Fernandez-Banares F, Munck LK. Azathioprine and mercaptopurine in the management of patients with chronic, active microscopic colitis. Aliment Pharmacol Ther 2013; 37:795-8. [PMID: 23432370 DOI: 10.1111/apt.12261] [Citation(s) in RCA: 44] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/20/2013] [Revised: 01/30/2013] [Accepted: 02/03/2013] [Indexed: 12/12/2022]
Abstract
BACKGROUND Microscopic colitis (MC) is a common chronic diarrhoeal disease, and remission can be induced with budesonide. However, diarrhoea relapses frequently when budesonide is tapered and a few patients become budesonide intolerant. AIM To examine retrospectively the effect of azathioprine (AZA) and mercaptopurine (MP) in patients with chronic, active MC. METHODS/PATIENTS Data on all MC patients who received AZA or MP in the years 1997-2011 at three centres representing three countries were pooled for analysis. The indications for thiopurine therapy were frequent relapses after short-term treatment (N = 26), budesonide dependency on 6 mg (N = 15) and budesonide intolerance (N = 5). The response to thiopurine treatment was defined as clinical remission, intolerance or nonresponse. RESULTS Forty-six MC patients (32 CC and 14 LC), 32 female; median age 59 years (range: 36-83) with a median disease duration of 3 years (range: 0.5-18) were included. Thirteen patients (28%) achieved long-term clinical remission on AZA therapy. AZA failed in 31 patients (67%) due to intolerance and in 2 patients (4%) because of nonresponse. Thirteen of 31 AZA-intolerant patients were switched to MP and 6 patients (46%) obtained clinical remission. Thus, the overall response rate to thiopurines was 19/46 (41%). The main side effects were nausea/vomiting and abnormally elevated liver enzymes. CONCLUSIONS In this retrospective case series, the majority of chronic, active MC patients were intolerant to AZA leading to cessation of treatment. However, further studies are needed to explore the efficacy, acceptance, tolerance and safety of MP in patients with chronic, active MC refractory to budesonide.
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Affiliation(s)
- A Münch
- Division of Gastroenterology and Hepatology, Department of Clinical and Experimental Medicine, Faculty of Health Science, Linköpings University, Linköping, Sweden.
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37
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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: 31] [Impact Index Per Article: 2.4] [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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38
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Yen EF, Pardi DS. Non-IBD colitides (eosinophilic, microscopic). Best Pract Res Clin Gastroenterol 2012; 26:611-22. [PMID: 23384806 DOI: 10.1016/j.bpg.2012.11.012] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/01/2012] [Revised: 11/07/2012] [Accepted: 11/09/2012] [Indexed: 01/31/2023]
Abstract
Microscopic colitis includes the terms lymphocytic colitis and collagenous colitis, and is a common cause of chronic diarrhoea in older adults. The incidence of microscopic colitis has increased over time and has reached levels comparable to other forms of inflammatory bowel disease. In this chapter, an updated review on the epidemiology, diagnosis and treatment of microscopic colitis has been provided. There is limited data available about eosinophilic colitis, which is the least common of the eosinophilic GI disorders. It is important to rule out the secondary causes of colonic eosinophilia in patients with suspected eosinophilic colitis.
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MESH Headings
- Chronic Disease
- Colitis, Collagenous/complications
- Colitis, Collagenous/diagnosis
- Colitis, Collagenous/epidemiology
- Colitis, Collagenous/therapy
- Colitis, Lymphocytic/complications
- Colitis, Lymphocytic/diagnosis
- Colitis, Lymphocytic/epidemiology
- Colitis, Lymphocytic/therapy
- Colitis, Microscopic/complications
- Colitis, Microscopic/diagnosis
- Colitis, Microscopic/epidemiology
- Colitis, Microscopic/therapy
- Diarrhea/epidemiology
- Diarrhea/etiology
- Humans
- Incidence
- Inflammatory Bowel Diseases/complications
- Irritable Bowel Syndrome/complications
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Affiliation(s)
- Eugene F Yen
- Division of Gastroenterology, University of Chicago, Pritzker School of Medicine, NorthShore University HealthSystem, Evanston, IL, USA.
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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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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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41
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Abstract
Microscopic colitis is a common cause of chronic diarrhea in predominantly older adults. Incidence rates of microscopic colitis (including lymphocytic and collagenous colitis) have increased over time to levels comparable to other forms of inflammatory bowel disease. The possibility of drug-induced microscopic colitis is an important consideration when evaluating these patients, although this concept requires further investigation. There are few controlled treatment trials in microscopic colitis, with much of the data on treatment coming from retrospective studies. In patients with microscopic colitis, a systematic approach to therapy often leads to satisfactory control of symptoms. In this review, we will provide an updated assessment of the epidemiology, diagnosis, and treatment of microscopic colitis.
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Affiliation(s)
- Eugene F Yen
- Division of Gastroenterology, University of Chicago Pritzker School of Medicine, NorthShore University HealthSystem, 2650 Ridge Avenue, Suite G221, Evanston, IL 60201, USA.
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Abstract
PURPOSE OF REVIEW A variety of diseases cause symptomatic inflammation of the colon. The epidemiology, clinical features, and/or endoscopic appearance of these conditions are distinct and histologic findings are often definitive. RECENT FINDINGS Recent literature adds to our understanding of the epidemiology and treatment of these disorders. SUMMARY Microscopic colitis, ischemic colitis, eosinophilic colitis, and drug-induced colitis, all cause diarrhea, often with abdominal pain, due to inflammation of the colon. Careful consideration of the clinical features and colonic mucosal biopsies usually lead to the correct diagnosis and appropriate therapy.
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Affiliation(s)
- Darrell S Pardi
- Division of Gastroenterology and Hepatology, Inflammatory Bowel Disease Clinic, Mayo Clinic College of Medicine, Rochester, Minnesota, USA.
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Münch A, Ignatova S, Ström M. Adalimumab in budesonide and methotrexate refractory collagenous colitis. Scand J Gastroenterol 2012; 47:59-63. [PMID: 22149977 DOI: 10.3109/00365521.2011.639079] [Citation(s) in RCA: 86] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
BACKGROUND We described three patients with collagenous colitis (CC) who developed side effects or were refractory to both budesonide and methotrexate and were given adalimumab (ADA) as a third-line treatment. METHOD/PATIENTS Three patients (two women, mean age 45 years and one man, 74 years old) were included. Mean bowel movements per day per week were calculated and stool weight/24 h registered prior to and following ADA treatment. ADA was given in doses 160 mg s.c. (baseline), 80 mg (week 2) and 40 mg (week 4). Sigmoidoscopies with biopsies were performed at baseline and after 6 weeks to examine changes in histology. The Psychological General Well-Being Index (PGWBI) and Short Health Scale (SHS) were used at baseline and after 6 weeks. RESULTS The two female patients tolerated the treatment well. The male patient developed, despite clinical response, side effects (vomiting, abdominal pain) after 80 mg of ADA and the treatment was stopped as side effects reoccurred after rechallenge. The two women were in clinical remission at week 6 and the mean stool frequency per day decreased from mean 11 to 2. Mean stool weight/24 h changed from 600 to 185 g. The quality of life improved drastically in all patients. There were no consistent changes in histology. CONCLUSION ADA seems effective in budesonide and methotrexate refractory CC and can be administrated to selected patients to achieve clinical remission, improve quality of life and possibly avoid colectomy. Further studies for induction and maintenance treatment should be conducted to confirm efficacy and examine safety issues, even in long term.
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Affiliation(s)
- Andreas Münch
- Linköping University Hospital, Clinic of Endocrinology and Gastroenterology, Linköping, Sweden.
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44
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Esteve M, Mahadevan U, Sainz E, Rodriguez E, Salas A, Fernández-Bañares F. Efficacy of anti-TNF therapies in refractory severe microscopic colitis. J Crohns Colitis 2011; 5:612-8. [PMID: 22115383 DOI: 10.1016/j.crohns.2011.05.001] [Citation(s) in RCA: 72] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/22/2011] [Revised: 05/02/2011] [Accepted: 05/02/2011] [Indexed: 12/12/2022]
Abstract
BACKGROUND Refractory microscopic colitis is a rare condition with an unknown rate of occurrence. The efficacy of anti-tumor necrosis factor (TNF) therapy for microscopic colitis has never been reported. Aims 1) To report the frequency of refractory microscopic colitis in the database of the participant hospitals. 2) To describe the therapeutic response to anti-TNF therapy among the refractory cases. METHODS Patients with a histological diagnosis of collagenous colitis and lymphocytic colitis were identified through the Department of Pathology database and the IBD practice database. Patients refractory to medical treatment and with severe symptoms were offered anti-TNF therapy. RESULTS Five of 372 MC patients (1.3%; 95% CI, 0.6 to 3.1) presented with severe symptoms refractory to standard medical therapies. One patient was denied therapy from her insurance carrier. The other 4 received infliximab therapy. The response was excellent after one dose experiencing a 60-90% decrease in bowel movements. Three patients were switched to adalimumab (2 allergic reactions and 1 early loss of response to infliximab). Long-term clinical remission (more than 1 year) was achieved in three cases (2 with adalimumab and 1 with infliximab). One patient on adalimumab had an early loss of response and was referred for colectomy. CONCLUSIONS Microscopic colitis with severe symptoms refractory to standard medical therapy including immunosuppressives is uncommon. In this setting, anti-TNF therapies may be a good option to avoid colectomy.
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Affiliation(s)
- Maria Esteve
- Department of Gastroenterology, Hospital Universitari Mutua Terrassa, Barcelona, Spain
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45
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Abstract
Microscopic colitis is a common cause of chronic diarrhea in predominantly older adults. Incidence rates of microscopic colitis (including lymphocytic and collagenous colitis) have increased over time to levels comparable to other forms of inflammatory bowel disease. The possibility of drug-induced microscopic colitis is an important consideration when evaluating these patients, although this concept requires further investigation. There are few controlled treatment trials in microscopic colitis, with much of the data on treatment coming from retrospective studies. In patients with microscopic colitis, a systematic approach to therapy often leads to satisfactory control of symptoms. In this review, we will provide an updated assessment of the epidemiology, diagnosis, and treatment of microscopic colitis.
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Affiliation(s)
- Eugene F Yen
- Division of Gastroenterology, University of Chicago Pritzker School of Medicine, NorthShore University HealthSystem, 2650 Ridge Avenue, Suite G221, Evanston, IL 60201, USA.
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46
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47
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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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48
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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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49
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El-Matary W, Girgis S, Huynh H, Turner J, Diederichs B. Microscopic colitis in children. Dig Dis Sci 2010; 55:1996-2001. [PMID: 19731020 DOI: 10.1007/s10620-009-0964-4] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2009] [Accepted: 08/20/2009] [Indexed: 01/10/2023]
Abstract
BACKGROUND Microscopic colitis typically presents with chronic watery nonbloody diarrhea with normal endoscopy findings but abnormal inflammatory histopathological findings. As it is mainly a condition of the elderly, pediatric data is scarce. AIMS To describe and characterize children with microscopic colitis. METHODS The pathology database at the University of Alberta Hospital together with the pediatric inflammatory bowel disease database at the Stollery Children's Hospital were both searched from September 1996 to May 2008. Charts of all children under the age of 17 years who fulfilled the diagnostic criteria of microscopic colitis were examined. RESULTS Eleven children (four girls, mean age at diagnosis 11.2 years, +/- 4.4 years) fulfilled the inclusion criteria. The patients were followed up for a mean of 24.8 months (standard deviation, SD 15.2 months). Two patients were on proton pump inhibitors, two had stool organisms, and two had immunodeficiency. All patients had normal endoscopy and colonoscopy on visualization. Five patients were diagnosed with lymphocytic colitis and the rest had nonspecific/eosinophilic microscopic colitis. The majority of children responded to mesalazine. One patient with immunodeficiency was difficult to manage. CONCLUSIONS Microscopic colitis is rare in children. Microscopic eosinophilic colitis is an underdescribed variant of microscopic colitis. The majority of children with microscopic colitis respond well to aminosalicylic acid (5-ASA) medications. Microscopic colitis associated with immunodeficiency can be very challenging to manage. Large multicenter pediatric trials with long-term follow-up are needed to allow investigators to have a better understanding of this rare condition in children.
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Affiliation(s)
- Wael El-Matary
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Stollery Children's Hospital, Faculty of Medicine, University of Alberta, Edmonton, Alberta, Canada.
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Székely H, Pónyai G, Temesvári E, Berczi L, Hársing J, Kárpáti S, Herszényi L, Tulassay Z, Juhász M. Association of collagenous colitis with prurigo nodularis. Eur J Gastroenterol Hepatol 2009; 21:946-951. [PMID: 19398916 DOI: 10.1097/meg.0b013e328321b0e7] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
The etiology and pathogenesis of collagenous colitis (CC) is poorly understood and probably multifactorial; many potential pathophysiological mechanisms have been described, although none have been conclusively proved. Circumstantial evidence suggests that CC appears as an autoimmune response to a luminal or epithelial antigen of unknown origin. Infections and certain drugs (e.g. NSAID, lansoprazole) may act as triggers for an immune-mediated process. CC is characterized clinically by chronic watery, nonbloody diarrhea with normal endoscopic appearance and without radiological abnormalities, but specific microscopic changes in the colon. Histopathology is featured by the presence of a thickened subepithelial collagen band adjacent to the basal membrane. Up to 40% of patients with CC have associated diseases of autoimmune or inflammatory origin, such as thyroid disease, coeliac disease, rheumatoid arthritis, diabetes mellitus, Sjögren's syndrome, CREST syndrome, scleroderma, pernicious anemia, and sarcoidosis. Prurigo nodularis is a chronic condition characterized by intensely pruritic, lichenified, or excoriated papules and nodules of unknown etiology. It is assumed to represent a cutaneous reaction pattern to repeated scrubbing or scratching caused by pruritus. We report a case of CC and prurigo nodularis. To our knowledge, this association has not been reported earlier.
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Affiliation(s)
- Hajnal Székely
- 2nd Department of Internal Medicine, Semmelweis University, Budapest, Hungary
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