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Aranda Rubio Y, Pallardo Rodil B, Gómez Pavón FJ. [Lymphocytic colitis associated with duloxetine]. Rev Esp Geriatr Gerontol 2025; 60:101561. [PMID: 39378643 DOI: 10.1016/j.regg.2024.101561] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2024] [Accepted: 08/14/2024] [Indexed: 10/10/2024]
Affiliation(s)
- Yanira Aranda Rubio
- F.E.A. Servicio de Geriatría, Hospital Universitario Central de la Cruz Roja, San José y Santa Adela, Madrid, España; Universidad Alfonso X El Sabio, Madrid, España.
| | - Beatriz Pallardo Rodil
- F.E.A. Servicio de Geriatría, Hospital Universitario Central de la Cruz Roja, San José y Santa Adela, Madrid, España; Universidad Alfonso X El Sabio, Madrid, España
| | - Francisco Javier Gómez Pavón
- F.E.A. Servicio de Geriatría, Hospital Universitario Central de la Cruz Roja, San José y Santa Adela, Madrid, España; Universidad Alfonso X El Sabio, Madrid, España
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Bergman D, Roelstraete B, Sun J, Ebrahimi F, Butwicka A, Pardi DS, Ludvigsson JF. Psychiatric Disorders Among 5,800 Patients With Microscopic Colitis: A Nationwide Population-Based Matched Cohort Study. Am J Gastroenterol 2024; 119:2516-2525. [PMID: 38994845 DOI: 10.14309/ajg.0000000000002955] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/04/2023] [Accepted: 06/17/2024] [Indexed: 07/13/2024]
Abstract
INTRODUCTION Microscopic colitis (MC) is an inflammatory condition of the large intestine. Primarily diagnosed in middle-aged and older adults, the incidence of the disease has increased markedly during the past few decades. While MC is associated with a reduced quality of life, large-scale studies on the association with future psychiatric disorders are lacking. METHODS We conducted a nationwide matched cohort study in Sweden from 2006 to 2021. Through a nationwide histopathology database (the Epidemiology Strengthened by histoPathology Reports in Sweden study), we identified 5,816 patients with a colorectal biopsy consistent with MC. These patients were matched with 21,509 reference individuals from the general population all of whom with no previous record of psychiatric disorders. RESULTS From 2006 to 2021, 519 patients with MC (median age 64.4 years [interquartile range = 49.5-73.3]) and 1,313 reference individuals were diagnosed with psychiatric disorders (9.9 vs 6.5 events per 1,000 person-years), corresponding to 1 extra case of psychiatric disorder in 29 patients with MC over 10 years. After adjustments, the hazard ratio for psychiatric disorders was 1.57 (95% confidence interval = 1.42-1.74). We found significantly elevated estimates up to 10 years after MC diagnosis and a trend toward higher risk with increasing age. Specifically, we observed increased risks for unipolar depression, anxiety disorders, stress-related disorders, substance abuse, and suicide attempts. In sibling-controlled analysis, the adjusted hazard ratio was 1.76 (95% confidence interval = 1.44-2.15). DISCUSSION Patients with MC are at increased risk of incident psychiatric disorders compared with the general population.
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Affiliation(s)
- David Bergman
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
| | - Bjorn Roelstraete
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
| | - Jiangwei Sun
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
| | - Fahim Ebrahimi
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
- Department of Gastroenterology and Hepatology, Clarunis University Center for Gastrointestinal and Liver Diseases, Basel, Switzerland
| | - Agnieszka Butwicka
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
- Akershus University Hospital, Lørenskog, Division of Mental Health Services, R&D Department, Norway
- Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
- Department of Biostatistics and Translational Medicine, Medical University of Lodz, Lodz, Poland
| | - Darrell S Pardi
- Inflammatory Bowel Disease Clinic, Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, Minnesota, USA
| | - Jonas F Ludvigsson
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
- Department of Pediatrics, Orebro University Hospital, Orebro, Sweden
- Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York, USA
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Abdel-Razeq R, Boustany A, Onwuzo S, Saleh M, Gupta R, Zeid HKA, Onwuzo CN, Farhat D, Najjar M, El Alayli A, Asaad I. PROTON-PUMP INHIBITORS ARE ASSOCIATED WITH AN INCREASED RISK OF MICROSCOPIC COLITIS: A POPULATION-BASED STUDY AND REVIEW OF THE LITERATURE. ARQUIVOS DE GASTROENTEROLOGIA 2024; 61:e24053. [PMID: 39442126 DOI: 10.1590/s0004-2803.24612024-053] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/04/2024] [Accepted: 07/24/2024] [Indexed: 10/25/2024]
Abstract
BACKGROUND •The study evaluated the risk of developing microscopic colitis and its subtypes in patients on PPI therapy. BACKGROUND •Using a large multicenter database, a retrospective cohort analysis was conducted, excluding patients with autoimmune diseases, and adjusting for confounders. BACKGROUND •An increased risk of developing microscopic colitis was associated with female gender, smoking, and the use of PPI, SSRI, and NSAIDs. BACKGROUND •The use of PPI represented the highest odds of developing microscopic colitis. BACKGROUND Microscopic colitis is a relatively new diagnosis that was first described in the 1980s. Patients usually present with chronic watery and non-bloody diarrhea and are typically characterized by an unremarkable gross appearance of the colon on lower endoscopy while having evidence of lymphocytic infiltration of the lamina propria and the epithelium on histology. Two subtypes have been described in the literature: Collagenous colitis, with marked thickening of the subepithelial layer, and Lymphocytic colitis. Multiple risk factors such as female gender, older age and celiac disease have been associated with this entity. A few studies have found an association between microscopic colitis and proton-pump inhibitor (PPI). The aim of our study was to evaluate the risk of developing microscopic colitis and its subtypes for patients who are on PPI therapy. METHODS A validated multicenter and research platform database of more than 360 hospitals from 26 different healthcare systems across the United States from 1999 to September 2022 was utilized to construct this study. Patients aged 18 years and above were included. Individuals who have been diagnosed with any autoimmune disease have been excluded. A multivariate regression analysis was performed to assess risk of developing microscopic, lymphocytic, and collagenous colitis by accounting for potential confounders including female gender, smoking history, and the use of proton pump inhibitor, nonsteroidal anti-inflammatory drugs, and selective serotonin receptor inhibitors. A two-sided P value <0.05 was considered as statistically significant, and all statistical analyses were performed using R version 4.0.2 (R Foundation for Statistical Computing, Vienna, Austria, 2008). RESULTS 78,256,749 individuals were screened in the database and 69,315,150 were selected in the final analysis after accounting for inclusion and exclusion criteria. The baseline characteristics of patients with microscopic, lymphocytic, and collagenous colitis is seen in table 1. Using a multivariate regression analysis, the risk of developing microscopic, lymphocytic, and collagenous colitis was calculated and illustrated in table 2. DISCUSSION Our study showed that the risk of microscopic colitis, lymphocytic colitis and collagenous colitis was higher in females and smokers. Although medications like SSRI and NSAIDs showed a positive correlation with colitis, the highest likelihood of developing this disease was associated with PPIs. Lansoprazole has been documented to be associated with microscopic colitis as it is believed to inhibit colonic proton pumps, and subsequently promote diarrhea and inflammation. Interestingly, the prevalence of lymphocytic colitis and collagenous colitis was similar in the cohort of patients treated with PPIs, indicating no specific predisposition to either subtype. This study further confirms the risk factors associated with microscopic colitis. It can help guide physicians to recognize and eliminate these risk factors prior to initiating treatment for this disease. Future studies can focus on identifying the incidence of microscopic colitis with the different types of PPIs in the market.
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Affiliation(s)
| | - Antoine Boustany
- Division of Gastroenterology, Department of Internal Medicine, University of Florida College of Medicine, Jacksonville, FL, USA
| | - Somtochukwu Onwuzo
- Department of Gastroenterology, Allegheny General Hospital, Pittsburgh, PA, USA
| | - Mustafa Saleh
- Department of Medicine, Division of Hematology and Oncology, American University of Beirut Medical Center, Beirut, Lebanon
- Lebanese University, Faculty of Medical Sciences, Beirut, Lebanon
| | - Riya Gupta
- Kasturba Medical College, Mangalore, India
| | | | - Chidera N Onwuzo
- Department of Medicine & Surgery, General Hospital Lagos Island, Lagos, Nigeria
| | - David Farhat
- Department of Surgery, Johns Hopkins University, School of Medicine, Baltimore, Maryland, USA
| | - Mimi Najjar
- The Sydney Kimmel Comprehensive Cancer Center, Johns Hopkins University, School of Medicine, Baltimore, Maryland, USA
| | - Abdallah El Alayli
- Department of Medicine, Saint Louis University, St. Louis, Missouri, USA
| | - Imad Asaad
- Department of Gastroenterology, Firelands Health, Sandusky, OH, USA
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Feakins RM. Inflammatory disorders of the large intestine. MORSON AND DAWSON'S GASTROINTESTINAL PATHOLOGY 2024:709-857. [DOI: 10.1002/9781119423195.ch35] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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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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Tome J, Tariq R, Chelf CJ, Khanna S, Pardi DS. Effectiveness of Bile Acid Sequestrants in Microscopic Colitis and Utility of Bile Acid Testing: A Systematic Review and Meta-analysis. Am J Gastroenterol 2024; 119:1792-1799. [PMID: 38864509 DOI: 10.14309/ajg.0000000000002886] [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] [Received: 03/02/2024] [Accepted: 06/07/2024] [Indexed: 06/13/2024]
Abstract
INTRODUCTION Bile acid sequestrants (BAS) are an option for microscopic colitis (MC) refractory or intolerant to budesonide. There are inconsistent data on the prevalence of bile acid malabsorption (BAM) and utility of bile acid testing in MC. The aim of this systematic review and meta-analysis was to evaluate these outcomes. METHODS A systematic search of randomized control trials and observational studies of adults with MC treated with BAS was conducted using MEDLINE, Embase, Cochrane, and Scopus from inception to January 22, 2024. Data were extracted on (i) prevalence of BAM, (ii) clinical response and adverse events, and (iii) recurrence after BAS discontinuation. Data were pooled using random-effects models to determine weighted pooled estimates and 95% confidence intervals (CIs). RESULTS We included 23 studies (1 randomized control trial, 22 observational), with 1,011 patients with MC assessed for BAM and 771 treated with BAS. The pooled prevalence of BAM was 34% (95% CI 0.26-0.42, I2 = 81%). The pooled response rate with BAS induction for all patients with MC, irrespective of BAM, was 62% (95% CI 0.55-0.70, I2 = 71%). There was a higher pooled response rate in patients with BAM compared with those without BAM ( P < 0.0001). The pooled rate of BAS-related adverse effects was 9% (95% CI 0.05-0.14, I2 = 58%). DISCUSSION One-third of patients with MC had BAM, and almost two-thirds of all patients responded to BAS with limited side effects. Patients with MC and BAM were more likely to respond to therapy, supporting the value of bile acid testing.
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Affiliation(s)
- June Tome
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
| | - Raseen Tariq
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
| | - Cynthia J Chelf
- Mayo Clinic Libraries, Mayo Clinic, Rochester, Minnesota, USA
| | - Sahil Khanna
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
| | - Darrell S Pardi
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
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Tome J, Tariq R, Hassett LC, Khanna S, Pardi DS. Effectiveness and Safety Profile of Budesonide Maintenance in Microscopic Colitis: A Systematic Review and Meta-Analysis. Inflamm Bowel Dis 2024; 30:1178-1188. [PMID: 37589651 DOI: 10.1093/ibd/izad178] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/20/2023] [Indexed: 08/18/2023]
Abstract
BACKGROUND Microscopic colitis (MC) is a common cause of chronic diarrhea. Randomized controlled trials (RCTs) have demonstrated the efficacy of budesonide treatment for MC. However, relapse is frequent after discontinuation of budesonide, and data on maintenance therapy are limited. We performed a systematic review and meta-analysis evaluating these outcomes in clinical trials and real-world settings. METHODS A systematic search was performed on October 31, 2022, of Medline, Embase, Cochrane, and Scopus. Case series, case-control, cohort studies, and RCTs of adults with MC were included. Data were pooled using random effects models to calculate weighted pooled estimates and 95% confidence intervals. Heterogeneity was assessed using the I2 statistic. RESULTS We included 35 studies (11 RCTs, 24 observational studies) with 1657 MC patients treated with budesonide induction and 146 for maintenance. The overall pooled clinical remission rate with budesonide treatment was similar between RCTs and observational studies. The pooled remission rate with budesonide maintenance therapy was 84% (95% CI, 0.60-1.00; I2 = 91%). After budesonide discontinuation, the pooled relapse rate was 53% (95% CI, 0.42-0.63; I2 = 76%). On maintenance therapy, no differences were noted in adverse events (eg, metabolic bone disease, hypertension, hyperglycemia, cataracts/glaucoma) in those on budesonide vs placebo or other noncorticosteroid medications for MC (P = .9). CONCLUSIONS Budesonide is an effective maintenance treatment for MC. There is a high risk of recurrence after budesonide discontinuation, but long-term use at the lowest effective dose appears to be relatively safe and have limited adverse effects.
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Affiliation(s)
- June Tome
- Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA
| | - Raseen Tariq
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| | | | - Sahil Khanna
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| | - Darrell S Pardi
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
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Raju SA, Rawcliffe ME, Bowker-Howell FJ, Shiha MG, Kaur KE, Griffin J, Cross SS, Sanders DS. Coeliac Disease and Microscopic Colitis: The Largest Study Assessing Prognosis and Risk of Hospital Admission. Nutrients 2024; 16:2081. [PMID: 38999829 PMCID: PMC11243059 DOI: 10.3390/nu16132081] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2024] [Revised: 06/21/2024] [Accepted: 06/25/2024] [Indexed: 07/14/2024] Open
Abstract
Microscopic colitis (MC) and coeliac disease (CD) are common associated gastrointestinal conditions. We present the largest study assessing hospitalisation in patients with MC and the effect of a concomitant diagnosis of CD. Data were retrospectively collected between January 2007 and December 2021 from all patients diagnosed with MC and compared to a database of patients with only CD. In total, 892 patients with MC (65% female, median age 65 years (IQR: 54-74 years) were identified, with 6.4% admitted to hospital due to a flare of MC. Patients admitted were older (76 vs. 65 years, p < 0.001) and presented with diarrhoea (87.7%), abdominal pain (26.3%), and acute kidney injury (17.5%). Treatment was given in 75.9% of patients, including intravenous fluids (39.5%), steroids (20.9%), and loperamide (16.3%). Concomitant CD was diagnosed in 3.3% of patients and diagnosed before MC (57 versus 64 years, p < 0.001). Patients with both conditions were diagnosed with CD later than patients with only CD (57 years versus 44 years, p < 0.001). In conclusion, older patients are at a higher risk of hospitalisation due to MC, and this is seen in patients with a concomitant diagnosis of CD too. Patients with MC are diagnosed with CD later than those without.
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Affiliation(s)
- Suneil A Raju
- Academic Unit of Gastroenterology, Sheffield Teaching Hospitals National Health Service Foundation Trust, Sheffield S102JF, UK
- Division of Clinical Medicine, School of Medicine and Population Health, University of Sheffield, Sheffield S102RX, UK
| | - Megan E Rawcliffe
- Academic Unit of Gastroenterology, Sheffield Teaching Hospitals National Health Service Foundation Trust, Sheffield S102JF, UK
- Division of Clinical Medicine, School of Medicine and Population Health, University of Sheffield, Sheffield S102RX, UK
| | - Freya J Bowker-Howell
- Academic Unit of Gastroenterology, Sheffield Teaching Hospitals National Health Service Foundation Trust, Sheffield S102JF, UK
- Division of Clinical Medicine, School of Medicine and Population Health, University of Sheffield, Sheffield S102RX, UK
| | - Mohamed G Shiha
- Academic Unit of Gastroenterology, Sheffield Teaching Hospitals National Health Service Foundation Trust, Sheffield S102JF, UK
- Division of Clinical Medicine, School of Medicine and Population Health, University of Sheffield, Sheffield S102RX, UK
| | - Kamaldeep E Kaur
- Academic Unit of Gastroenterology, Sheffield Teaching Hospitals National Health Service Foundation Trust, Sheffield S102JF, UK
- Division of Clinical Medicine, School of Medicine and Population Health, University of Sheffield, Sheffield S102RX, UK
| | - Jonathan Griffin
- Division of Clinical Medicine, School of Medicine and Population Health, University of Sheffield, Sheffield S102RX, UK
| | - Simon S Cross
- Division of Clinical Medicine, School of Medicine and Population Health, University of Sheffield, Sheffield S102RX, UK
| | - David S Sanders
- Academic Unit of Gastroenterology, Sheffield Teaching Hospitals National Health Service Foundation Trust, Sheffield S102JF, UK
- Division of Clinical Medicine, School of Medicine and Population Health, University of Sheffield, Sheffield S102RX, UK
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Bjurström O, Karling P. The association between drugs and repeated treatment with budesonide in patients with microscopic colitis: a retrospective observational study. Therap Adv Gastroenterol 2024; 17:17562848241240640. [PMID: 38510459 PMCID: PMC10953108 DOI: 10.1177/17562848241240640] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/03/2023] [Accepted: 03/01/2024] [Indexed: 03/22/2024] Open
Abstract
Background Smoking and the use of non-steroidal anti-inflammatory drugs (NSAIDs) acetylsalicylic acid (ASA), proton pump inhibitors (PPIs), serotonin reuptake inhibitors (SSRIs), and statins have been associated with microscopic colitis (MC). Objectives We investigated whether these factors were associated with repeated budesonide treatments in patients diagnosed with MC. Design Retrospective observational study. Methods All patients with a histologically verified diagnosis of MC at our clinic between the years 2006 and 2022 were identified. Baseline factors and drugs prescribed before and after diagnosis were registered. The influence of risk factors on the odds of having a prescription of oral budesonide and the odds of having a second course of budesonide was studied. Results Patients with MC (n = 183) with a mean age of 62.3 years [standard deviation (SD): 13.3 years] were followed for a median of 5 years (25th-75th percentile 4-10 years) after diagnosis. In all, 138 patients (75%) had at least one prescription of budesonide after diagnosis, and 90 patients (49%) had at least one clinical relapse treated with budesonide. Patients who had been prescribed NSAIDs within 1 year before clinical relapse had higher odds for clinical relapse [odds ratio (OR): 3.70, 95% confidence interval (CI): 1.06-12.9] but there was no increased risk for clinical relapse for the use of ASA (OR: 0.99, 95% CI: 0.39-2.90), PPIs (OR: 1.09, 95% CI: 0.45-2.63), SSRI (OR: 1.41, 95% CI: 0.82-2.44), or statins (OR: 0.83, 95% CI: 0.35-1.99). No association was seen between being a smoker and/or being prescribed NSAID, ASA, PPI, SSRI, and statins at baseline and the odds of having a prescription of oral budesonide within 1 year after diagnosis. Conclusion The risk of being prescribed a second course of budesonide is associated with receiving a prescription of NSAIDs but not with the use of ASA, PPIs, SSRIs, and statins.
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Affiliation(s)
- Oliver Bjurström
- Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden
| | - Pontus Karling
- Department of Public Health and Clinical Medicine, Umeå University, Umeå, 901 87, Sweden
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Gallo A, Pellegrino S, Pero E, Agnitelli MC, Parlangeli C, Landi F, Montalto M. Main Disorders of Gastrointestinal Tract in Older People: An Overview. GASTROINTESTINAL DISORDERS 2024; 6:313-336. [DOI: 10.3390/gidisord6010022] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/02/2025] Open
Abstract
From a physiological standpoint, aging is a progressive reduction in each organ system’s capacity to maintain homeostasis in the face of illness or stressors. With advancing age, gastrointestinal (GI) symptoms and signs may increase, not only due to the aging processes but also to the superimposed effects of comorbidities, which can badly affect digestive functions (i.e., diabetes, malignancy, etc.) and environmental exposure. In general, gastrointestinal symptoms in older people more often underlie organic pathologies, while GI functional disorders are less frequently diagnosed in this age group. Moreover, gastrointestinal disease can also present in a nuanced and atypical manner, making the diagnostic hypothesis and, consequently, the correct diagnosis and therapy more challenging. In addition, with reference to this age group, the clinical implications of gastrointestinal pathologies can be more severe due to a decreased physiologic reserve, with a higher risk for malnutrition resulting in falls, depression, social isolation, and a deterioration of functional status. In this review, we focused on the most frequent GI tract disorders, highlighting the main age-related changes, their epidemiological, pathophysiological and clinical implications, and any differences with younger patients.
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Affiliation(s)
- Antonella Gallo
- Department of Geriatrics, Orthopedics and Rheumatology, Fondazione Policlinico Universitario “A. Gemelli”, IRCCS, 00168 Rome, Italy
| | - Simona Pellegrino
- Department of Geriatrics, Orthopedics and Rheumatology, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
| | - Erika Pero
- Department of Geriatrics, Orthopedics and Rheumatology, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
| | - Maria Chiara Agnitelli
- Department of Geriatrics, Orthopedics and Rheumatology, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
| | - Caterina Parlangeli
- Department of Geriatrics, Orthopedics and Rheumatology, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
| | - Francesco Landi
- Department of Geriatrics, Orthopedics and Rheumatology, Fondazione Policlinico Universitario “A. Gemelli”, IRCCS, 00168 Rome, Italy
- Department of Geriatrics, Orthopedics and Rheumatology, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
| | - Massimo Montalto
- Department of Geriatrics, Orthopedics and Rheumatology, Fondazione Policlinico Universitario “A. Gemelli”, IRCCS, 00168 Rome, Italy
- Department of Geriatrics, Orthopedics and Rheumatology, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
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Jordi SBU, Misselwitz B. Refining the Concept of Microscopic Colitis: HLA Signatures Discriminating Collagenous and Lymphocytic Colitis. J Crohns Colitis 2024; 18:339-340. [PMID: 38174741 DOI: 10.1093/ecco-jcc/jjad211] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/05/2024]
Affiliation(s)
- Sebastian Bruno Ulrich Jordi
- Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
- Department for Biomedical Research, University of Bern, Bern, Switzerland
| | - Benjamin Misselwitz
- Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
- Department for Biomedical Research, University of Bern, Bern, Switzerland
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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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13
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Nielsen OH, Pardi DS. Diagnosis and Pharmacological Management of Microscopic Colitis in Geriatric Care. Drugs Aging 2024; 41:113-123. [PMID: 38231321 PMCID: PMC10869377 DOI: 10.1007/s40266-023-01094-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/28/2023] [Indexed: 01/18/2024]
Abstract
Microscopic colitis, a diagnosis under the umbrella term of inflammatory bowel disease, is a prevalent cause of watery diarrhea, often with symptoms of urgency and bloating, typically observed in older adults aged ≥ 60 years. Its incidence has been reported to exceed those of ulcerative colitis and Crohn's disease in some geographical areas. Although nonpathognomonic endoscopic abnormalities, including changes of the vascular mucosal pattern; mucosal erythema; edema; nodularity; or mucosal defects, e.g., "cat scratches" have been reported, a colonoscopy is typically macroscopically normal. As reliable biomarkers are unavailable, colonoscopy using random biopsies from various parts of the colon is compulsory. Based on the histological examination under a microscope, the disease is divided into collagenous (with a thickened subepithelial collagenous band) and lymphocytic (with intraepithelial lymphocytosis) colitis, although incomplete forms exist. In routine clinical settings, the disease has a high risk of being misdiagnosed as irritable bowel syndrome or even overlooked. Therefore, healthcare providers should be familiar with clinical features and rational management strategies. A 6-8-week oral budesonide treatment course (9 mg/day) is considered the first-line therapy, but patients often experience relapse when discontinued, or might become intolerant, dependent, or even fail to respond. Consequently, other therapeutic options (e.g., bismuth subsalicylate, biologics, loperamide, bile acid sequestrants, and thiopurines) recommended by available guidelines may be prescribed. Herein, clinically meaningful data is provided based on the latest evidence that may aid in reaching a diagnosis and establishing rational therapy in geriatric care to control symptoms and enhance the quality of life for those affected.
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Affiliation(s)
- Ole Haagen Nielsen
- Department of Gastroenterology D112, Herlev Hospital, University of Copenhagen, Borgmester Ib Juuls Vej 1, 2730, Herlev, Denmark.
| | - Darrell S Pardi
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
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14
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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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15
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Mourelle-Sanmartín P, Sedano-Gómez GE, Malfeito-Jiménez R. Carbamazepine as an inducing factor of older adult microscopic colitis. Rev Esp Geriatr Gerontol 2023; 58:101385. [PMID: 37633224 DOI: 10.1016/j.regg.2023.101385] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2023] [Revised: 06/07/2023] [Accepted: 07/04/2023] [Indexed: 08/28/2023]
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16
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Tome J, Sehgal K, Kamboj AK, Harmsen WS, Khanna S, Pardi DS. Bile Acid Sequestrants in Microscopic Colitis: Clinical Outcomes and Utility of Bile Acid Testing. Clin Gastroenterol Hepatol 2023; 21:3125-3131.e2. [PMID: 37172800 DOI: 10.1016/j.cgh.2023.04.031] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/23/2023] [Revised: 04/18/2023] [Accepted: 04/22/2023] [Indexed: 05/15/2023]
Abstract
BACKGROUND & AIMS Bile acid sequestrants (BAS) may be a treatment in microscopic colitis (MC), but efficacy data are limited. We evaluated the effectiveness of BAS in MC and assessed the utility of bile acid testing to predict response. METHODS Adults with MC treated with BAS (2010-2020) at Mayo Clinic were identified. Bile acid malabsorption was defined by elevated serum 7⍺-hydroxy-4-cholesten-3-one or by fecal testing using previously validated cutoffs. Response was defined at 12 ± 4 weeks after BAS initiation as: complete (resolution of diarrhea), partial (≥50% improvement in diarrhea), nonresponse (<50% improvement), and intolerance (discontinuation due to side effects). Logistic regression was used to identify predictors of response to BAS. RESULTS We identified 282 patients (median age, 59 years [range, 20-87 years]; 88.3% women) with median follow-up of 4.5 years (range, 0.4-9.1 years). Patients were treated with the following BAS: 64.9% cholestyramine, 21.6% colesevelam, and 13.5% colestipol. Clinical outcomes were: 49.3% complete response, 16.3% partial response, 24.8% nonresponse, and 9.6% intolerance. There were no differences in outcomes between those on BAS alone or BAS combined with other medications (P = .98). The dose of BAS was not associated with response (P = .51). Bile acid testing was done in 31.9% of patients, and 56.7% were positive. No predictors of response to BAS were identified. After BAS discontinuation, 41.6% had recurrence at a median of 21 weeks (range, 1-172 weeks). CONCLUSION In one of the largest cohorts evaluating BAS treatment in MC, nearly two-thirds had a partial or complete response. Additional research is needed to determine the role of BAS and bile acid malabsorption in MC.
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Affiliation(s)
- June Tome
- Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota
| | - Kanika Sehgal
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Amrit K Kamboj
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - William S Harmsen
- Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota
| | - Sahil Khanna
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Darrell S Pardi
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota.
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Abstract
Microscopic colitis (MC) is a chronic inflammatory disease that affects the older population. Its clinical presentation includes a variety of gastrointestinal manifestations. The main symptom is chronic watery, nonbloody diarrhea. The disease has a female predominance. The diagnosis might be challenging since the symptoms are similar to other differential diagnoses, such as celiac disease, irritable bowel syndrome, Crohn's disease, bacterial overgrowth, and infectious colitis. The golden diagnostic tool for diagnosis is performing colonoscopy to obtain the colonic biopsy, which demonstrates the characteristic histological evidence needed for diagnosis. The treatment starts with an accurate diagnosis and trial of any possible offending medications. Alternatively, there are many medications, such as bismuth or budesonide, which are very effective in treating this disease. The primary objective of this detailed review is to enhance knowledge and understanding of this condition among healthcare providers to guide them with detailed information regarding epidemiology, clinical presentation, diagnosis, and appropriate management. In the assessment of individuals presenting with persistent chronic diarrhea, it is essential for healthcare providers to consider MC as a probable differential diagnosis.
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Affiliation(s)
- Khalid I AlHussaini
- Department of Internal Medicine, Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh, SAU
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18
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Songtanin B, Chen JN, Nugent K. Microscopic Colitis: Pathogenesis and Diagnosis. J Clin Med 2023; 12:4442. [PMID: 37445477 DOI: 10.3390/jcm12134442] [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: 05/08/2023] [Revised: 06/26/2023] [Accepted: 06/29/2023] [Indexed: 07/15/2023] Open
Abstract
Microscopic colitis is a type of inflammatory bowel disease and is classified as either collagenous colitis or lymphocytic colitis. The typical presentation is chronic watery diarrhea. The disease occurs more frequently in women aged 60-65 years and is increasing in incidence. The pathophysiology of microscopic colitis remains poorly understood and has not been well-described with possible several pathogeneses. To date, the diagnosis of microscopic colitis depends on histological tissue obtained during colonoscopy. Other non-invasive biomarkers, such as inflammatory markers and fecal biomarkers, have been studied in microscopic colitis, but the results remains inconclusive. The approach to chronic diarrhea is important and being able to differentiate chronic diarrhea in patients with microscopic colitis from other diseases, such as inflammatory bowel disease, functional diarrhea, and malignancy, by using non-invasive biomarkers would facilitate patient management. The management of microscopic colitis should be based on each individual's underlying pathogenesis and involves budesonide, bile acid sequestrants, or immunosuppressive drugs in refractory cases. Cigarette smoking and certain medications, especially proton pump inhibitors, should be eliminated, when possible, after the diagnosis is made.
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Affiliation(s)
- Busara Songtanin
- Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA
| | - Jason N Chen
- School of Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA
| | - Kenneth Nugent
- Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA
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19
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Djembissi Fotso A, Arvanitakis M, Salame M, Gallez J, Lakis A. What do we know today about drug-induced microscopic colitis? A case of lymphocytic colitis on olmesartan. Acta Gastroenterol Belg 2023; 86:474-480. [PMID: 37814563 DOI: 10.51821/86.3.11361] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/11/2023]
Abstract
Microscopic colitis is part of the differential diagnosis of chronic watery diarrhea. Colonoscopy discloses a normal looking mucosa, therefore its diagnosis is based on histology of colonic biopsies. Two main phenotypes are distinguished: collagenous colitis and lymphocytic colitis. A third entity, incomplete microscopic colitis or unspecified microscopic colitis has been reported in the literature. It affects preferentially women over 60 years of age and its association with certain drugs is increasingly established. In case of suspected drug-induced microscopic colitis, identification of the responsible drug is a key to management. After discontinuation of the suspected drug, the gold standard of treatment is budesonide both for induction and for maintenance in case of clinical relapse, as is often the case after discontinuation. Therapy with immunomodulators, biologics, or surgery is reserved for refractory forms of microscopic colitis after multidisciplinary consultation. Through the clinical case of colitis on olmesartan, we will review the latest recommendations on drug-induced microscopic colitis.
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Affiliation(s)
- A Djembissi Fotso
- Department of Gastroenterology, Centre Hospitalier Régional de la Haute Senne, Soignies, Belgium
- Department of Gastroenterology, Erasme Hospital, Université Libres de Bruxelles (ULB), Brussels, Belgium
| | - M Arvanitakis
- Department of Gastroenterology, Erasme Hospital, Université Libres de Bruxelles (ULB), Brussels, Belgium
| | - M Salame
- Department of Gastroenterology, Centre Hospitalier Régional de la Haute Senne, Soignies, Belgium
| | - J Gallez
- Department of Gastroenterology, Centre Hospitalier Régional de la Haute Senne, Soignies, Belgium
| | - A Lakis
- Department of Gastroenterology, Centre Hospitalier Régional de la Haute Senne, Soignies, Belgium
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20
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Larsson JK, Clarkson S, Sjoberg K. Regional differences in the incidence of lymphocytic and collagenous colitis over time. Scand J Gastroenterol 2023; 58:1445-1452. [PMID: 37599473 DOI: 10.1080/00365521.2023.2248536] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/19/2023] [Revised: 07/07/2023] [Accepted: 08/11/2023] [Indexed: 08/22/2023]
Abstract
BACKGROUND In microscopic colitis (MC), the incidence has increased over the last decades. The aim of the present study was to determine the incidence of lymphocytic (LC) and collagenous colitis (CC) in the county Skåne (Scania), southern Sweden, during the period 2010-20 with focus both on the temporal and spatial variations. METHODS The MC diagnosis was retrieved from the biopsy registries at the Departments of Pathology. Established diagnostic criteria (increased lymphocyte count, inflammation in lamina propria and in CC a collagen band) were used for diagnosis. Age, gender, date for diagnosis and municipality of residence were retrieved for all patients. RESULTS In total 1985 patients could be identified with a mean age of 62.9 years (SD 15.7) whereof 1415 were women. The incidence for CC was stable with a total age-standardized rate (ASR) per 100 000 person-years of 6.34, (range 4.6-8.1). In LC the ASR was 7.90 (range 1.7-15.2) but increased markedly 2015-20 reaching 15.2 in 2019. Also, the northwest part of the region showed significantly higher ASR:s of LC during the last part of the decade in comparation to the whole region. CONCLUSIONS The incidence of CC was stable during the period while LC differed substantially in a way that indicates that it most probably must be two different disease entities. In LC, in view of the marked and rapid increase, although no definitive explanation could be found, causative environmental factors could be contemplated, why further studies are indicated.
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Affiliation(s)
- Johanna Kristina Larsson
- Department of Clinical Sciences, Lund University, Malmö, Sweden
- Department of Gastroenterology and Nutrition, Skåne University Hospital, Malmö, Sweden
| | | | - Klas Sjoberg
- Department of Clinical Sciences, Lund University, Malmö, Sweden
- Department of Gastroenterology and Nutrition, Skåne University Hospital, Malmö, Sweden
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21
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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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22
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Songtanin B, Kahathuduwa C, Nugent K. Fecal calprotectin level in microscopic colitis: a systematic review and meta-analysis. Proc AMIA Symp 2023; 36:641-646. [PMID: 37614849 PMCID: PMC10444001 DOI: 10.1080/08998280.2023.2223950] [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: 02/09/2023] [Revised: 04/04/2023] [Accepted: 06/07/2023] [Indexed: 08/25/2023] Open
Abstract
Background There are no specific biomarkers for microscopic colitis (MC), and the diagnosis depends on histopathological tissue obtained during colonoscopy. Studies on the role of fecal calprotectin (FCP) in MC are limited. A literature search of PubMed, Embase, and Scopus was conducted from each database's inception through September 2022. Methods A DerSimonian-Liard random-effects meta-analysis was performed to examine the standardized mean difference (SMD) in FCP levels between patients with MC and control patients with chronic diarrhea. Results Six studies with 96 active MC patients and 200 controls were included in the meta-analysis. Random effects meta-analysis revealed that FCP was significantly and moderately elevated in patients with MC compared to the control group (SMD = 0.6 [95% CI 0.3, 1.0], P = 0.001). Imputing one effect size confirmed the observation that FCP is significantly higher in patients with MC than control subjects with chronic diarrhea (SMD = 0.5 [95% CI 0.2, 0.9], P = 0.004). Study heterogeneity between the SMDs was not significant (I2 = 41%, P = 0.1). Conclusion These results indicate that FCP levels in patients with chronic diarrhea can help identify patients with MC. More studies with serial measurements of FCP would provide a better understanding of its utility in MC.
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Affiliation(s)
- Busara Songtanin
- Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, Texas, USA
| | - Chanaka Kahathuduwa
- Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, Texas, USA
| | - Kenneth Nugent
- Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, Texas, USA
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23
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DiGiacomo DV, Roelstraete B, Hammarström L, Farmer JR, Khalili H, Ludvigsson JF. Predominant Antibody Deficiency and Risk of Microscopic Colitis: a Nationwide Case-Control Study in Sweden. J Clin Immunol 2023:10.1007/s10875-023-01499-3. [PMID: 37162615 DOI: 10.1007/s10875-023-01499-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2023] [Accepted: 04/21/2023] [Indexed: 05/11/2023]
Abstract
PURPOSE : Predominant antibody deficiency (PAD) disorders, including common variable immunodeficiency (CVID), have been linked to increased risk of gastrointestinal infections and inflammatory bowel diseases. However, there are limited data on the relationship between PAD, specifically CVID, and risk of microscopic colitis (MC). METHODS We performed a nationwide case-control study of Swedish adults with MC diagnosed between 1997 and 2017 (n = 13,651). Data on biopsy-verified MC were retrieved from all of Sweden's pathology departments through the Epidemiology Strengthened by histoPathology Reports in Sweden (ESPRESSO) study. We defined predominant antibody deficiency using International Union of Immunologic Societies (IUIS) phenotypic classification. Individuals with MC were matched to population controls by age, sex, calendar year, and county. We used logistic regression to estimate adjusted odds ratios (aORs) and 95% confidence intervals (CIs). RESULTS The prevalence of PAD in MC was 0.4% as compared to 0.05% in controls. After adjustment for potential confounders, this corresponded to an aOR of 7.29 (95%CI 4.64-11.63). The magnitude of the association was higher for CVID (aOR 21.01, 95% 5.48-137.44) compared to other antibody deficiencies (aOR 6.16, 95% CI 3.79-10.14). In exploratory analyses, the association between PAD and MC was particularly strong among males (aOR 31.73, 95% CI 10.82-135.04). CONCLUSION In this population-based study, predominant antibody deficiency was associated with increased risk of MC, particularly among males. Clinicians who encounter these patients should consider a detailed infectious history and screening for antibody deficiency.
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Affiliation(s)
- Daniel V DiGiacomo
- Clinical and Translational Epidemiology Unit, Mongan Institute, Massachusetts General Hospital, Boston, MA, USA
- Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - Bjorn Roelstraete
- Sachs' Children and Youth Hospital, Stockholm South General Hospital, Stockholm, Sweden
| | - Lennart Hammarström
- Division of Clinical Immunology and Transfusion Medicine, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden
| | - Jocelyn R Farmer
- Division of Allergy and Inflammation, Beth Israel Lahey Health, Harvard Medical School, Boston, MA, USA
| | - Hamed Khalili
- Clinical and Translational Epidemiology Unit, Mongan Institute, Massachusetts General Hospital, Boston, MA, USA.
- Division of Gastroenterology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
- Division of Clinical Epidemiology, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
| | - Jonas F Ludvigsson
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
- Department of Pediatrics, Orebro University Hospital, Orebro, Sweden
- Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY, USA
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24
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Bergman D, Khalili H, Lebwohl B, Roelstraete B, Green PHR, Ludvigsson JF. Celiac disease and risk of microscopic colitis: A nationwide population-based matched cohort study. United European Gastroenterol J 2023; 11:189-201. [PMID: 36939488 PMCID: PMC10039793 DOI: 10.1002/ueg2.12374] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/24/2022] [Accepted: 02/09/2023] [Indexed: 03/21/2023] Open
Abstract
BACKGROUND An association has been reported between celiac disease (CD) and microscopic colitis (MC). However, large, population-based cohort studies are rare. OBJECTIVE To systematically examine the association between CD and MC in a large, nationwide cohort. METHODS We conducted a nationwide population-based matched cohort study in Sweden of 45,138 patients with biopsy-verified CD (diagnosed in 1990-2016), 223,149 reference individuals, and 51,449 siblings of CD patients. Data on CD and MC were obtained from all (n = 28) pathology departments in Sweden. Adjusted hazard ratios (aHRs) were calculated using Cox regression. RESULTS During follow-up, 452 CD patients and 197 reference individuals received an MC diagnosis (86.1 vs. 7.5 per 100,000 person-years). This difference corresponded to an aHR of 11.6 (95% confidence interval [CI] = 9.8-13.8) or eight extra MC cases in 1000 CD patients followed up for 10 years. Although the risk of MC was highest during the first year of follow-up (aHR 35.2; 95% CI = 20.1-61.6), it remained elevated even after 10 years (aHR 8.1; 95% CI = 6.0-10.9). Examining MC subtypes lymphocytic colitis (LC) and collagenous colitis (CC) separately, the aHR was 12.4 (95% CI = 10.0-15.3) for LC and 10.2 (95% CI = 7.7-13.6) for CC. MC was also more common before CD (adjusted odds ratio [aOR] = 52.7; 95% CI = 31.4-88.4). Compared to siblings, risk estimates decreased but remained elevated (CD and later MC: HR = 6.2; CD and earlier MC: aOR = 7.9). CONCLUSION Our study demonstrated a very strong association of MC with CD with an increased risk of future and previous MC in CD patients. The magnitude of the associations underscores the need to consider the concomitance of these diagnoses in cases in which gastrointestinal symptoms persist or recur despite a gluten-free diet or conventional MC treatment. The comparatively lower risk estimates in sibling comparisons suggest that shared genetic and early environmental factors may contribute to the association between CD and MC.
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Affiliation(s)
- David Bergman
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
| | - Hamed Khalili
- Massachusetts General Hospital, Crohn's and Colitis Center and Harvard Medical School, Boston, Massachusetts, USA
- Division of Clinical Epidemiology, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden
| | - Benjamin Lebwohl
- Department of Medicine, Celiac Disease Center at Columbia University Medical Center, New York, New York, USA
| | - Bjorn Roelstraete
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
| | - Peter H R Green
- Departments of Medicine and Surgical Pathology, Columbia University College of Physicians and Surgeons, New York, New York, USA
| | - Jonas F Ludvigsson
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
- Department of Pediatrics, Orebro University Hospital, Orebro, Sweden
- Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York, USA
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25
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Colonocyte keratin 7 is expressed de novo in inflammatory bowel diseases and associated with pathological changes and drug-resistance. Sci Rep 2022; 12:22213. [PMID: 36564440 PMCID: PMC9789078 DOI: 10.1038/s41598-022-26603-2] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2022] [Accepted: 12/16/2022] [Indexed: 12/24/2022] Open
Abstract
The clinical course of IBD, characterized by relapses and remissions, is difficult to predict. Initial diagnosis can be challenging, and novel disease markers are needed. Keratin 7 (K7) is a cytoskeletal intermediate filament protein not expressed in the colonic epithelium but has been reported in IBD-associated colorectal tumors. Our aim was to analyze whether K7 is expressed in chronic colonic inflammatory diseases and evaluate its potential as a novel biomarker. K7 was analyzed in two patient cohorts using immunohistochemistry-stained colon samples and single-cell quantitative digital pathology methods. K7 was correlated to pathological changes and clinical patient characteristics. Our data shows that K7 is expressed de novo in the colonic epithelium of ulcerative colitis and Crohn's disease IBD patients, but not in collagenous or lymphocytic colitis. K7 mRNA expression was significantly increased in colons of IBD patients compared to controls when assessed in publicly available datasets. While K7 increased in areas with inflammatory activity, it was not expressed in specific crypt compartments and did not correlate with neutrophils or stool calprotectin. K7 was increased in areas proximal to pathological alterations and was most pronounced in drug-resistant ulcerative colitis. In conclusion, colonic epithelial K7 is neo-expressed selectively in IBD patients and could be investigated for its potential as a disease biomarker.
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Boivineau G, Zallot C, Zerbib F, Plastaras L, Amiot A, Boivineau L, Koch S, Peyrin-Biroulet L, Vuitton L. Biologic Therapy for Budesonide-refractory, -dependent or -intolerant Microscopic Colitis: a Multicentre Cohort Study from the GETAID. J Crohns Colitis 2022; 16:1816-1824. [PMID: 35793161 DOI: 10.1093/ecco-jcc/jjac089] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND Budesonide remains the backbone therapy for microscopic colitis [MC]; however, relapses are frequent, and some patients are intolerant or dependent. Anti-TNF therapy is increasingly used to treat these patients, but available evidence is still limited. The aim of this study was to evaluate the effectiveness and safety of anti-TNF therapy in MC patients failing budesonide. METHODS In a multicentre retrospective cohort study, budesonide-refractory, -dependent, or -intolerant MC patients treated with anti-TNF agents were included. Clinical remission was defined as fewer than three bowel movements per day, and clinical response was defined as an improvement in stool frequency of at least 50%. RESULTS Fourteen patients were included. Median age was 58.5 years, median disease duration was 25 months, and median follow-up was 29.5 months. Seven patients were treated with infliximab [IFX], and seven with adalimumab. Clinical remission without steroids at 12 weeks was reached in 5/14 [35.7%] patients; all of these received IFX. Clinical response at 12 and 52 weeks, was obtained in 9/14 [64.3%] and 7/14 [50%] patients, respectively. Five patients switched to another anti-TNF agent. When considering both first- and second-line anti-TNF therapies, 7 [50%] patients were in clinical remission at Week 52. Mild to moderate adverse events were reported in six ptients. Two patients were treated with vedolizumab, of whom one had clinical response; one patient treated with ustekinumab had no response. CONCLUSIONS This is the first multicentre cohort study showing that half of patients treated with anti-TNF therapy for MC achieved clinical remission in case of budesonide failure.
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Affiliation(s)
- Grégoire Boivineau
- Gastroenterology Department, Besançon University Hospital, Besançon, France
| | - Camille Zallot
- Department of Gastroenterology, University of Lorraine, CHRU-Nancy, France
| | - Franck Zerbib
- Gastroenterology Department, Bordeaux University Hospital, Centre Medico-chirurgical Magellan, Hôpital Haut-Lévêque, Bordeaux, France
| | | | - Aurélien Amiot
- Department of Gastroenterology, Hopitaux Universitaires Bicêtre, AP-HP, Universite Paris Est Creteil, INSERM UMR1018, Le Kremlin Bicêtre, France
| | - Lucile Boivineau
- Hepatogastroenterology Department, Montpellier University Hospital, Montpellier, France
| | - Stéphane Koch
- Gastroenterology Department, Besançon University Hospital, Besançon, France
| | | | - Lucine Vuitton
- Gastroenterology Department, Besançon University Hospital, Besançon, France.,Department of Gastroenterology and UMR 1098, University Hospital of Besançon, University Bourgogne-Franche-Comté, Besançon, France
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27
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Boks M, Lilja M, Widerström M, Karling P, Lindam A, Eriksson A, Sjöström M. Increased incidence of late-onset inflammatory bowel disease and microscopic colitis after a Cryptosporidium hominis outbreak. Scand J Gastroenterol 2022; 57:1443-1449. [PMID: 35802626 DOI: 10.1080/00365521.2022.2094722] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVES In 2010, 27,000 inhabitants (45% of the population) of Östersund, Sweden, contracted clinical cryptosporidiosis after drinking water contaminated with Cryptosporidium hominis. After the outbreak, local physicians perceived that the incidence of inflammatory bowel disease (IBD), including ulcerative colitis (UC), Crohn's disease (CD), and IBD-unclassified, and microscopic colitis (MC) increased. This study assessed whether this perception was correct. MATERIALS AND METHODS This observational study included adult patients (≥18 years old) from the local health care region who were diagnosed with pathology-confirmed IBD or MC during 2006-2019. We collected and validated the diagnosis, date of diagnosis, age at diagnosis, and sex from the Swedish quality register SWIBREG and electronic patient records. Population data were collected from Statistics Sweden. The incidences for 2006-2010 (pre-outbreak) and 2011-2019 (post-outbreak) were evaluated by negative binomial regression analysis and presented as incidence rate ratios (IRRs). Data were analyzed for IBD, for UC and CD separately, and MC. RESULTS During the study period, we identified 410 patients with new onset IBD and 155 new cases of MC. Overall, we found a trend toward an increased incidence of IBD post-outbreak (IRR 1.39, confidence interval (CI) 0.99-1.94). In individuals ≥40 years old, the post-outbreak incidence significantly increased for IBD (IRR 1.69, CI 1.13-2.51) and CD (IRR 2.23, CI 1.08-4.62). Post-outbreak incidence of MC increased 6-fold in all age groups (IRR 6.43, CI 2.78-14.87). CONCLUSIONS The incidence of late-onset IBD and MC increased after the Cryptosporidium outbreak. Cryptosporidiosis may be an environmental risk factor for IBD and MC.
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Affiliation(s)
- Marije Boks
- Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden
| | - Mikael Lilja
- Department of Public Health and Clinical Medicine, Unit of Research, Education and Development - Östersund, Umeå University, Umeå, Sweden
| | | | - Pontus Karling
- Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden
| | - Anna Lindam
- Department of Public Health and Clinical Medicine, Unit of Research, Education and Development - Östersund, Umeå University, Umeå, Sweden
| | - Axel Eriksson
- Department of Clinical Microbiology, Umeå University, Umeå, Sweden
| | - Malin Sjöström
- Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden
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Vernia F, Tatti T, Necozione S, Capannolo A, Cesaro N, Magistroni M, Valvano M, Pompili S, Sferra R, Vetuschi A, Latella G. Is mastocytic colitis a specific clinical-pathological entity? Eur J Histochem 2022; 66:3499. [PMID: 36440694 PMCID: PMC9761410 DOI: 10.4081/ejh.2022.3499] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2022] [Accepted: 11/10/2022] [Indexed: 12/23/2022] Open
Abstract
The number of intestinal mast cells (MC) is increased in several types of colitis, but the mucosa of patients with chronic non-bloody diarrhea has not been studied. The current study sought to determine the relationship between MC counts and degranulation and the severity of symptoms in patients with chronic loose stools. Following a negative laboratory workup for the most common causes of chronic diarrhea, patients with chronic non-bloody loose stools were included in the study. Patients with macroscopic evidence of inflammation or organic disease were excluded after endoscopy with biopsies. Biopsies from the 179 patients in the study were stained with hematoxylin and eosin and anti-CD117 c-kit antibodies. Immunohistochemistry was used to assess the degree of MC degranulation. Out of the 179 patients, 128 had normal histologic findings suggestive of irritable bowel syndrome and were used as controls. Twenty-four presented with abnormally high MC counts (≥40 MC x HPF), 23 with ≥20 intraepithelial lymphocytes x HPF suggesting lymphocytic colitis, and 4 had both (≥40 MC and ≥20 intraepithelial lymphocytes x HPF). In the patients with high MC counts, figures were significantly higher in the right colon versus the left colon (p=0.016), but degranulation did not differ in the right versus the left colon (p=0.125). No age or sex-related difference was observed (p=0.527 and p=0.859 respectively). The prevalence of abdominal pain and bloating did not differ in the three groups (p=0.959 and p=0.140, respectively). Patients with lymphocytic colitis (p=0.008) and those with high MC counts (p=0.025) had significantly higher evacuation rates compared to controls. There was no difference between these two groups (p=0.831). Mast cell degranulation was not associated with the number of evacuations, abdominal pain, or bloating (p=0.51; p=0.41; p=0.42, respectively). The finding that a significantly higher number of evacuations was linked to increased MC in the colonic mucosa of a subset of patients with otherwise normal laboratory and endoscopic findings suggests that "mastocytic colitis" may be a new clinical-pathological entity responsible for chronic non-bloody diarrhea. Prospective studies with a larger number of patients, as well as endoscopic and histological follow-up, are needed to confirm this hypothesis.
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Affiliation(s)
- Filippo Vernia
- Gastroenterology Unit, Department of Life, Health and Environmental Sciences, University of L’Aquila,*These authors contributed equally to this work
| | - Tiziana Tatti
- Pathology Unit, S. Salvatore Academic Hospital, L'Aquila,*These authors contributed equally to this work
| | - Stefano Necozione
- Epidemiology Unit, Department of Life, Health and Environmental Sciences, University of L'Aquila
| | - Annalisa Capannolo
- Diagnostic and Surgical Endoscopy Unit, San Salvatore Academic Hospital, L'Aquila
| | - Nicola Cesaro
- Gastroenterology Unit, Department of Life, Health and Environmental Sciences, University of L’Aquila
| | - Marco Magistroni
- Gastroenterology Unit, Department of Life, Health and Environmental Sciences, University of L’Aquila
| | - Marco Valvano
- Gastroenterology Unit, Department of Life, Health and Environmental Sciences, University of L’Aquila
| | - Simona Pompili
- Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, Italy
| | - Roberta Sferra
- Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, Italy
| | - Antonella Vetuschi
- Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, Italy
| | - Giovanni Latella
- Gastroenterology Unit, Department of Life, Health and Environmental Sciences, University of L’Aquila,*These authors contributed equally to this work
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Varelas AI, Fürst S, Langner C. Mixed lymphocytic and collagenous inflammation of the entire gastrointestinal tract under therapy with serotonin and norepinephrine reuptake inhibitors. Virchows Arch 2022; 481:779-783. [PMID: 35655103 PMCID: PMC9636289 DOI: 10.1007/s00428-022-03351-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2022] [Revised: 04/27/2022] [Accepted: 05/23/2022] [Indexed: 01/01/2023]
Abstract
Drug-induced injury to the gastrointestinal tract has gained growing significance in recent years, and the list of causative medications keeps expanding. Herein, we present the case of a 45-year-old female with major depressive disorder treated with two serotonin and norepinephrine reuptake inhibitors (venlafaxine and duloxetine). She developed nausea and weight loss. Endoscopic evaluation of the upper and lower gastrointestinal tract rendered grossly normal mucosa in all segments. Histological examination, however, revealed lymphocytic esophagitis, collagenous gastritis, celiac disease-like intraepithelial lymphocytosis of the duodenum, and incomplete collagenous colitis. Gastrointestinal side effects of psychoactive drugs are largely underrecognized. This is the first report of a mixed lymphocytic and collagenous pattern of injury affecting esophagus, stomach, duodenum, and colon triggered by combined treatment with venlafaxine and duloxetine. In patients with unclear symptoms, obtaining biopsies from mucosa that is normal upon endoscopic inspection may render decisive clues for clinical management.
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Affiliation(s)
- Ana I Varelas
- Department of Pathology, Portuguese Institute of Oncology, Porto, Portugal
- Diagnostic and Research Institute of Pathology, Diagnostic and Research Centre for Molecular BioMedicine, Medical University of Graz, Neue Stiftingtalstraße 6, 8010, Graz, Austria
| | - Stefan Fürst
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Medical University of Graz, Graz, Austria
| | - Cord Langner
- Diagnostic and Research Institute of Pathology, Diagnostic and Research Centre for Molecular BioMedicine, Medical University of Graz, Neue Stiftingtalstraße 6, 8010, Graz, Austria.
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Takedomi H, Sakata Y, Tomonaga M, Naruse N, Yukimoto T, Akutagawa T, Tsuruoka N, Shimoda R, Kido S, Esaki M. Collagenous Colitis Possibly Associated with Dipeptidyl Peptidase-4 Inhibitor. Intern Med 2022; 61:2731-2734. [PMID: 35135927 PMCID: PMC9556224 DOI: 10.2169/internalmedicine.9040-21] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/07/2023] Open
Abstract
A 60-year-old man with type 2 diabetes mellitus treated with a dipeptidyl peptidase-4 (DPP-4) inhibitor was referred to our hospital because of his refractory watery diarrhea. Ileocolonoscopy revealed increased capillary growth, fine granular mucosa, and longitudinal mucosal tears mainly in the left side of the colon. A bioptic examination revealed thickened subepithelial collagen bands, thus confirming the diagnosis of collagenous colitis. Systemic steroid therapy was initiated, but his symptoms recurred when tapering the steroid. However, withdrawal of the DPP-4 inhibitor was successful even after the cessation of steroid therapy. We therefore considered his collagenous colitis to have been caused by the DPP-4 inhibitor.
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Affiliation(s)
- Hironobu Takedomi
- Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, Saga University, Japan
| | - Yasuhisa Sakata
- Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, Saga University, Japan
| | - Michito Tomonaga
- Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, Saga University, Japan
| | - Naomi Naruse
- Department of Endoscopic Diagnostics and Therapeutics, Saga University Hospital, Japan
| | - Takahiro Yukimoto
- Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, Saga University, Japan
| | - Takashi Akutagawa
- Department of Endoscopic Diagnostics and Therapeutics, Saga University Hospital, Japan
| | - Nanae Tsuruoka
- Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, Saga University, Japan
| | - Ryo Shimoda
- Department of Endoscopic Diagnostics and Therapeutics, Saga University Hospital, Japan
| | - Shinichi Kido
- Department of Pathology and Microbiology, Faculty of Medicine, Saga University, Japan
| | - Motohiro Esaki
- Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, Saga University, Japan
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Celiac Disease Is Associated with Microscopic Colitis in Refractory Cases in Adults: A Systematic Review and Meta-Analysis of Observational Studies. Dig Dis Sci 2022; 67:3529-3542. [PMID: 34448981 DOI: 10.1007/s10620-021-07232-7] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/25/2021] [Accepted: 08/16/2021] [Indexed: 01/03/2023]
Abstract
BACKGROUND Microscopic colitis and Celiac disease have been shown to occur concomitantly, but their relationship has yet to be systematically evaluated. Some patients with refractory microscopic colitis may have simultaneous celiac disease, and the converse is also true. AIMS We performed a systematic review and meta-analysis of observational studies to assess the prevalence and possible association between these two conditions. METHODS PubMed, Embase, Cochrane, Web of Science, SciELO, and CINAHL Plus were systematically searched through January 26, 2021, to include relevant observational studies assessing the prevalence of microscopic colitis in celiac disease population or vice versa. DerSimonian-Laird approach using random effects was used to pool data and compare outcomes. Pooled prevalence, 95% confidence interval (CI), and p values (where applicable) were calculated. RESULTS Five studies (with 2589 patients, age range 39.5-52 years and females 66.6%) and 21 studies (with 7186 patients, age range 46.4-65.8 years and females 76.3%) were included assessing the prevalence of microscopic colitis in refractory celiac disease and celiac disease in refractory microscopic colitis cohort. The overall prevalence was 4.5% (2.6-6.3%) and 6.7% (5.2-8.1%), respectively. Five studies showed higher odds of celiac disease diagnosis in the refractory microscopic colitis population compared to the control group (OR 8.12, CI 4.92-13.41, p < 0.001). CONCLUSION Celiac disease and microscopic colitis are concomitantly prevalent in a subset of population with either refractory diagnosis. Clinicians should explore alternate diagnosis when one condition has been appropriately treated and patients continue to have refractory symptoms.
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Nielsen OH, Fernandez-Banares F, Sato T, Pardi DS. Microscopic colitis: Etiopathology, diagnosis, and rational management. eLife 2022; 11:e79397. [PMID: 35913459 PMCID: PMC9342949 DOI: 10.7554/elife.79397] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2022] [Accepted: 07/19/2022] [Indexed: 01/09/2023] Open
Abstract
Microscopic colitis is an inflammatory bowel disease divided into two subtypes: collagenous colitis and lymphocytic colitis. With an increasing incidence of microscopic colitis exceeding those of ulcerative and Crohn's disease among elderly people in some countries, microscopic colitis is a debilitating life experience. Therefore, physicians should be familiar with its clinical features and management strategies because the disease deserves the same attention as the classical inflammatory bowel diseases. Here, state-of-the-art knowledge of microscopic colitis is provided from a global perspective with reference to etiopathology and how to establish the diagnosis with the overall aim to create awareness and improve rational management in clinical practice. The immune system and a dysregulated immune response seem to play a key role combined with risk factors (e.g. cigarette smoking) in genetically predisposed individuals. The symptoms are characterized by recurrent or chronic nonbloody, watery diarrhea, urgency, weight loss, and a female preponderance. As biomarkers are absent, the diagnosis relies on colonoscopy with a histological assessment of biopsy specimens from all parts of the colon. Although the disease is not associated with a risk of colorectal cancer, a recent nationwide, population-based cohort study found an increased risk of lymphoma and lung cancer. Budesonide is the first-line therapy for management, whereas immunomodulatory drugs (including biologics) and drugs with antidiarrheal properties may be indicated in those failing, dependent, or intolerant to budesonide. In microscopic colitis induced by checkpoint inhibitors, a drug class used increasingly for a wide range of malignancies, a more aggressive therapeutic approach with biologics introduced early seems reasonable. However, particular attention needs to be drawn to the existence of incomplete forms of microscopic colitis with the risk of being overlooked in routine clinical settings.
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Affiliation(s)
- Ole Haagen Nielsen
- Department of Gastroenterology, Herlev Hospital, University of CopenhagenHerlevDenmark
| | - Fernando Fernandez-Banares
- Department of Gastroenterology, Hospital Universitari Mutua TerrassaBarcelonaSpain
- Centro de Investigación Biomédica en Red de enfermedades hepáticas y digestivasCIBERehdSpain
| | - Toshiro Sato
- Department of Gastroenterology, Keio University School of MedicineTokyoJapan
| | - Darrell S Pardi
- Division of Gastroenterology and Hepatology, Mayo ClinicRochesterUnited States
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Fedor I, Zold E, Barta Z. Microscopic colitis in older adults: impact, diagnosis, and management. Ther Adv Chronic Dis 2022; 13:20406223221102821. [PMID: 35813189 PMCID: PMC9260565 DOI: 10.1177/20406223221102821] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2021] [Accepted: 04/28/2022] [Indexed: 11/18/2022] Open
Abstract
Microscopic colitis (comprising lymphocytic and collagenous colitis, albeit an incomplete variant is gaining recognition as well) is a chronic, immune-mediated inflammatory state of the lower gastrointestinal tract (colon). The diagnosis requires diagnostic colonoscopy with characteristic histopathological findings. They have a propensity to present in senior populations (above 60 years of age), particularly women - who are approximately 2.5-3 times more likely to develop microscopic colitis. Preexisting other immune-inflammatory diseases are also shown to predispose patients for the development of microscopic colitis. The classic presentation is profuse watery diarrhea, often during the night or early morning hours. Fecal incontinence and abdominal pain are frequent as well. Thus, the disease impacts patients' quality of life and well-being. The first described cases date back to the seventies and eighties of the twentieth century, thereby they can be considered fairly recently discovered disease states. Our understanding of the disease and its pathophysiology is still incomplete. Although there is a lack of unified recommendation for treatment, most clinicians prefer the use of budesonide, and most published guidelines regard this locally acting glucocorticoid as the therapy of choice. In our article, we aimed for a brief, noncomprehensive overview of the clinical significance, diagnosis, and management of microscopic colitis.
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Affiliation(s)
- Istvan Fedor
- Department of Public Health and Epidemiology,
Faculty of Medicine, University of Debrecen, Kassai Street 26., Debrecen
4012, Hungary
- Department of Clinical Immunology, Doctoral
School of Clinical Immunology and Allergology, Institute of Internal
Medicine, Faculty of Medicine, University of Debrecen, Moricz Zs. Street
22., Debrecen 4004, Hungary
| | - Eva Zold
- Department of Clinical Immunology, Doctoral
School of Clinical Immunology and Allergology, Institute of Internal
Medicine, Faculty of Medicine, University of Debrecen, Debrecen,
Hungary
| | - Zsolt Barta
- GI Unit, Department of Infectology, Doctoral
School of Clinical Immunology and Allergology, Faculty of Medicine,
University of Debrecen, Debrecen, Hungary
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Savarino E, Zingone F, Barberio B, Marasco G, Akyuz F, Akpinar H, Barboi O, Bodini G, Bor S, Chiarioni G, Cristian G, Corsetti M, Di Sabatino A, Dimitriu AM, Drug V, Dumitrascu DL, Ford AC, Hauser G, Nakov R, Patel N, Pohl D, Sfarti C, Serra J, Simrén M, Suciu A, Tack J, Toruner M, Walters J, Cremon C, Barbara G. Functional bowel disorders with diarrhoea: Clinical guidelines of the United European Gastroenterology and European Society for Neurogastroenterology and Motility. United European Gastroenterol J 2022; 10:556-584. [PMID: 35695704 PMCID: PMC9278595 DOI: 10.1002/ueg2.12259] [Citation(s) in RCA: 70] [Impact Index Per Article: 23.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/21/2022] [Accepted: 05/20/2022] [Indexed: 11/23/2022] Open
Abstract
Irritable bowel syndrome with diarrhoea (IBS‐D) and functional diarrhoea (FDr) are the two major functional bowel disorders characterized by diarrhoea. In spite of their high prevalence, IBS‐D and FDr are associated with major uncertainties, especially regarding their optimal diagnostic work‐up and management. A Delphi consensus was performed with experts from 10 European countries who conducted a literature summary and voting process on 31 statements. Quality of evidence was evaluated using the grading of recommendations, assessment, development, and evaluation criteria. Consensus (defined as >80% agreement) was reached for all the statements. The panel agreed with the potential overlapping of IBS‐D and FDr. In terms of diagnosis, the consensus supports a symptom‐based approach also with the exclusion of alarm symptoms, recommending the evaluation of full blood count, C‐reactive protein, serology for coeliac disease, and faecal calprotectin, and consideration of diagnosing bile acid diarrhoea. Colonoscopy with random biopsies in both the right and left colon is recommended in patients older than 50 years and in presence of alarm features. Regarding treatment, a strong consensus was achieved for the use of a diet low fermentable oligo‐, di‐, monosaccharides and polyols, gut‐directed psychological therapies, rifaximin, loperamide, and eluxadoline. A weak or conditional recommendation was achieved for antispasmodics, probiotics, tryciclic antidepressants, bile acid sequestrants, 5‐hydroxytryptamine‐3 antagonists (i.e. alosetron, ondansetron, or ramosetron). A multinational group of European experts summarized the current state of consensus on the definition, diagnosis, and management of IBS‐D and FDr.
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Affiliation(s)
- Edoardo Savarino
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
| | - Fabiana Zingone
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
| | - Brigida Barberio
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
| | - Giovanni Marasco
- Division of Internal Medicine, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.,Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Filiz Akyuz
- Department of Gastroenterology, İstanbul University İstanbul School of Medicine, İstanbul, Turkey
| | - Hale Akpinar
- Department of Internal Medicine, Dokuz Eylül University School of Medicine, Izmir, Turkey
| | - Oana Barboi
- Department of Gastroenterology, 'Grigore T. Popa' University of Medicine and Pharmacy, Iasi, Romania.,Institute of Gastroenterology and Hepatology, 'Saint Spiridon' Hospital, Iasi, Romania
| | - Giorgia Bodini
- Gastrointestinal Unit, Department of Internal Medicine, University of Genoa, Genoa, Italy
| | - Serhat Bor
- Division of Gastroenterology, Ege University School of Medicine, Izmir, Turkey
| | | | - Gheorghe Cristian
- Fundeni Clinical Institute Center of Gastroenterology and Hepatology, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
| | - Maura Corsetti
- National Institute for Health Research, Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust, Nottingham, UK.,Nottingham Digestive Diseases Centre, School of Medicine, University of Nottingham, Nottingham, UK
| | - Antonio Di Sabatino
- First Department of Internal Medicine, IRCCS San Matteo Hospital Foundation, University of Pavia, Pavia, Italy
| | - Anca Mirela Dimitriu
- Center of Gastroenterology and Hepatology, Fundeni Clinical Institute, University of Medicine and Pharmacy, Bucharest, Romania
| | - Vasile Drug
- Department of Gastroenterology, 'Grigore T. Popa' University of Medicine and Pharmacy, Iasi, Romania.,Institute of Gastroenterology and Hepatology, 'Saint Spiridon' Hospital, Iasi, Romania
| | - Dan L Dumitrascu
- 2nd Department of Internal Medicine, 'Iuliu Hatieganu' University of Medicine and Farmacy, Cluj-Napoca, Romania
| | - Alexander C Ford
- Leeds Gastroenterology Institute, Leeds Teaching Hospitals NHS Trust, Leeds, UK.,Leeds Institute of Medical Research at St. James's Sciences, University of Leeds, Leeds, UK
| | - Goran Hauser
- Department of Gastroenterology, Clinical Hospital Center Rijeka, Faculty of Medicine, University of Rijeka, Rijeka, Croatia
| | - Radislav Nakov
- Department of Gastroenterology, Tsaritsa Yoanna University Hospital, Medical University of Sofia, Sofia, Bulgaria
| | - Nisha Patel
- Imperial College Healthcare NHS Trust, Institute of Global Health Innovation, St Mary's Hospital Campus, London, UK
| | - Daniel Pohl
- Department of Gastroenterology, University Hospital Zurich, Zurich, Switzerland
| | - Cătălin Sfarti
- Department of Gastroenterology, 'Grigore T. Popa' University of Medicine and Pharmacy, Iasi, Romania.,Institute of Gastroenterology and Hepatology, 'Saint Spiridon' Hospital, Iasi, Romania
| | - Jordi Serra
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Badalona, Spain.,Digestive System Research Unit, University Hospital Vall d'Hebron, Barcelona, Spain.,Department of Medicine, Autonomous University of Barcelona, Badalona, Spain
| | - Magnus Simrén
- Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Alina Suciu
- Center of Gastroenterology and Hepatology, Fundeni Clinical Institute, University of Medicine and Pharmacy, Bucharest, Romania
| | - Jan Tack
- Translational Research Center for Gastrointestinal Disorders, University of Leuven, Leuven, Belgium
| | - Murat Toruner
- Department of Gastroenterology, Ankara University School of Medicine, Ankara, Turkey
| | - Julian Walters
- Division of Digestive Diseases, Department of Metabolism, Digestion, and Reproduction, Faculty of Medicine, Imperial College London, London, UK.,Department of Gastroenterology, Division of Medicine and Integrated Care, Imperial College Healthcare NHS Trust, London, UK
| | - Cesare Cremon
- Division of Internal Medicine, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.,Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Giovanni Barbara
- Division of Internal Medicine, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.,Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
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35
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Hertz S, Durack J, Kirk KF, Nielsen HL, Lin DL, Fadrosh D, Lynch K, Piceno Y, Thorlacius-Ussing O, Nielsen H, Lynch SV. Microscopic Colitis Patients Possess a Perturbed and Inflammatory Gut Microbiota. Dig Dis Sci 2022; 67:2433-2443. [PMID: 34059992 DOI: 10.1007/s10620-021-07045-8] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/23/2020] [Accepted: 05/08/2021] [Indexed: 12/12/2022]
Abstract
BACKGROUND Microscopic colitis (MC), an inflammatory disease of the colon, is characterized by chronic non-bloody diarrhea with characteristic inflammation and for some, collagen deposits in mucosal biopsies. The etiology of MC is unclear, although previous findings implicate luminal factors and thus the gut microbiome. However, the relationships between fecal microbiota and MC are relatively unexplored. METHODS Stool microbiota of MC (n = 15) and healthy controls (HC; n = 21) were assessed by 16S rRNA V4 amplicon sequencing and analysis performed in QIIME. Gut microbiota functions were predicted using Piphillin and inflammatory potential assessed using an in vitro HT29 colonocyte cell assay. RESULTS MC patient fecal microbiota were less diverse (Faiths index; p < 0.01) and compositionally distinct (PERMANOVA, weighted UniFrac, R2 = 0.08, p = 0.02) compared with HC subjects. MC microbiota were significantly depleted of members of the Clostridiales, enriched for Prevotella and more likely to be dominated by this genus (Chi2 = 0.03). Predicted pathways enriched in MC microbiota included those related to biosynthesis of antimicrobials, and sphingolipids, to glycan degradation, host defense evasion, and Th17 cell differentiation and activation. In vitro, exposure of cultured colonocytes to cell-free products of MC patient feces indicates reduced gene expression of IL-1B and occludin and increased GPR119 and the lymphocyte chemoattractant CCL20. CONCLUSION MC gut microbiota are distinct from HC and characterized by lower bacterial diversity and Prevotella enrichment and distinct predicted functional pathways. Limited in vitro experiments indicate that compared with cell-free products from healthy fecal microbiota, MC microbiota induce distinct responses when co-cultured with epithelial cells, implicating microbiota perturbation in MC-associated mucosal dysfunction.
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Affiliation(s)
- Sandra Hertz
- Department of Medicine, University of California San Francisco, 513 Parnassus Ave, S357D, Box 0538, San Francisco, CA, 94143, USA. .,Department of Infectious Diseases, Aalborg University Hospital, Mølleparkvej 4, 7th floor, east wing, 9000, Aalborg, Denmark.
| | - Juliana Durack
- Department of Medicine, University of California San Francisco, 513 Parnassus Ave, S357D, Box 0538, San Francisco, CA, 94143, USA
| | - Karina Frahm Kirk
- Department of Infectious Diseases, Aalborg University Hospital, Mølleparkvej 4, 7th floor, east wing, 9000, Aalborg, Denmark
| | - Hans Linde Nielsen
- Department of Clinical Microbiology, Aalborg University Hospital, Mølleparkvej 10, 6th floor, 9000, Aalborg, Denmark.,Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
| | - Din L Lin
- Department of Medicine, University of California San Francisco, 513 Parnassus Ave, S357D, Box 0538, San Francisco, CA, 94143, USA
| | - Douglas Fadrosh
- Department of Medicine, University of California San Francisco, 513 Parnassus Ave, S357D, Box 0538, San Francisco, CA, 94143, USA
| | - Kole Lynch
- Department of Medicine, University of California San Francisco, 513 Parnassus Ave, S357D, Box 0538, San Francisco, CA, 94143, USA
| | - Yvette Piceno
- Department of Medicine, University of California San Francisco, 513 Parnassus Ave, S357D, Box 0538, San Francisco, CA, 94143, USA
| | - Ole Thorlacius-Ussing
- Department of Gastrointestinal Surgery, Aalborg University Hospital, Hobrovej 18-22, 9000, Aalborg, Denmark.,Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
| | - Henrik Nielsen
- Department of Infectious Diseases, Aalborg University Hospital, Mølleparkvej 4, 7th floor, east wing, 9000, Aalborg, Denmark.,Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
| | - Susan V Lynch
- Department of Medicine, University of California San Francisco, 513 Parnassus Ave, S357D, Box 0538, San Francisco, CA, 94143, USA
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36
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Tome J, Sehgal K, Kamboj AK, Harmsen WS, Kammer PP, Loftus EV, Tremaine WJ, Khanna S, Pardi DS. The Epidemiology of Microscopic Colitis in Olmsted County, Minnesota: Population-Based Study From 2011 to 2019. Clin Gastroenterol Hepatol 2022; 20:1085-1094. [PMID: 34216819 PMCID: PMC8716639 DOI: 10.1016/j.cgh.2021.06.027] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/16/2021] [Revised: 06/13/2021] [Accepted: 06/21/2021] [Indexed: 02/06/2023]
Abstract
BACKGROUND & AIMS Epidemiologic studies from Europe and North America have reported an increasing incidence of microscopic colitis (MC) in the late 20th century, followed by a plateau. This population-based study assessed recent incidence trends and the overall prevalence of MC over the past decade. METHODS Residents of Olmsted County, MN, diagnosed with collagenous colitis (CC) or lymphocytic colitis (LC) between January 1, 2011, and December 31, 2019 were identified using the Rochester Epidemiology Project. Clinical variables were abstracted by chart review. Incidence rates were age- and sex-adjusted to the 2010 US population. Associations between incidence and age, sex, and calendar periods were evaluated using Poisson regression analyses. RESULTS A total of 268 incident cases of MC were identified with a median age at diagnosis of 64 years (range, 19-90 y); 207 (77%) were women. The age- and sex-adjusted incidence of MC was 25.8 (95% CI, 22.7-28.9) cases per 100,000 person-years. The incidence of LC was 15.8 (95% CI, 13.4-18.2) and CC was 9.9 (95% CI, 8.1-11.9) per 100,000 person-years. A higher MC incidence was associated with increasing age and female sex (P < .01). There was no significant trend in age- and sex-adjusted incidence rate over the study period (P = .92). On December 31, 2019, the prevalence of MC, LC, and CC (including cases diagnosed before 2011) was 246.2, 146.1, and 100.1 per 100,000 persons, respectively. CONCLUSIONS The incidence of MC and its subtypes was stable between 2011 and 2019, but its prevalence was higher than in previous periods. The incidence of MC continues to be associated with increasing age and female sex.
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Affiliation(s)
- June Tome
- Department of Internal Medicine, Mayo Clinic, Rochester, MN
| | - Kanika Sehgal
- Department of Internal Medicine, Mayo Clinic, Rochester, MN
| | - Amrit K. Kamboj
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN
| | - William S. Harmsen
- Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN
| | | | - Edward V. Loftus
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN
| | | | - Sahil Khanna
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN
| | - Darrell S. Pardi
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN
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37
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Limdi JK. Editorial commentary on the Indian Journal of Gastroenterology-March-April 2022. Indian J Gastroenterol 2022; 41:115-118. [PMID: 35522371 DOI: 10.1007/s12664-022-01261-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Affiliation(s)
- Jimmy K Limdi
- Section of Inflammatory Bowel Diseases, Division of Gastroenterology, Northern Care Alliance NHS Foundation Trust, Manchester, UK.
- University of Manchester, Manchester, UK.
- Manchester Metropolitan University, Manchester, UK.
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38
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Kikuchi H, Sakuraba H, Akemoto Y, Hosoi K, Murai Y, Hoshi K, Fukutoku Y, Asari T, Sawada Y, Hasui K, Tatsuta T, Hiraga H, Chinda D, Mikami T, Fukuda S. Endoscopic and histopathologic features of Anti‐PD‐1‐related collagenous colitis. DEN OPEN 2022; 2:e92. [PMID: 35310729 PMCID: PMC8828179 DOI: 10.1002/deo2.92] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/27/2021] [Revised: 12/01/2021] [Accepted: 12/25/2021] [Indexed: 11/22/2022]
Abstract
Objectives Cancer patients treated with immune checkpoint inhibitors occasionally show persistent diarrhea accompanied by endoscopic features of ulcerative colitis. The endoscopic mucosal inflammation may appear mild in some patients compared to the clinical severity, which can make choosing a treatment challenging. In this study, we evaluated the factors that support the continuation of chemotherapy by assessing the endoscopic and histopathological characteristics of patients who experienced diarrhea after immune checkpoint inhibitor administration. Methods This study included eight patients who were diagnosed with collagenous colitis based on pathological assessments. We retrospectively investigated these patients’ backgrounds, laboratory data, and computed tomography images that were extracted from their medical records. We also summarized their endoscopic and pathologic findings. Results All eight patients were being treated with anti‐programmed cell death‐1/programmed cell death‐ligand 1 therapeutic agents and had a recent history of oral proton pump inhibitor therapy. The anti‐programmed cell death‐1‐related collagenous colitis in these cases was characterized by endoscopically mild mucosal inflammation, high fecal calprotectin levels, and a lower frequency of intestinal wall thickening on computed tomography. Histological assessments showed CD8+ lymphocytes predominantly infiltrating the lamina propria and crypts of the colonic mucosa. Suspending the proton pump inhibitor therapy relieved the patients’ symptoms and allowed the continuation of the anti‐programmed cell death‐1/programmed cell death‐ligand 1 therapy. Conclusions Anti‐programmed cell death‐1‐related collagenous colitis is reversible; appropriate diagnosis of adverse events is crucial for the continuation of immune checkpoint inhibitor therapy.
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Affiliation(s)
- Hidezumi Kikuchi
- Department of Gastroenterology and Hematology Hirosaki University Graduate School of Medicine Aomori Japan
- Department of Community Medicine Hirosaki University Graduate School of Medicine Aomori Japan
| | - Hirotake Sakuraba
- Department of Gastroenterology and Hematology Hirosaki University Graduate School of Medicine Aomori Japan
| | - Yui Akemoto
- Department of Anatomic Pathology Hirosaki University Hospital Aomori Japan
| | - Kazuhiro Hosoi
- Department of Pharmacy Hirosaki University Hospital Aomori Japan
| | - Yasuhisa Murai
- Department of Gastroenterology and Hematology Hirosaki University Graduate School of Medicine Aomori Japan
| | - Kentaro Hoshi
- Department of Gastroenterology and Hematology Hirosaki University Graduate School of Medicine Aomori Japan
| | - Yukari Fukutoku
- Department of Gastroenterology and Hematology Hirosaki University Graduate School of Medicine Aomori Japan
| | - Taka Asari
- Department of Gastroenterology and Hematology Hirosaki University Graduate School of Medicine Aomori Japan
| | - Yohei Sawada
- Department of Gastroenterology and Hematology Hirosaki University Graduate School of Medicine Aomori Japan
| | - Keisuke Hasui
- Department of Gastroenterology and Hematology Hirosaki University Graduate School of Medicine Aomori Japan
| | - Tetsuya Tatsuta
- Department of Gastroenterology and Hematology Hirosaki University Graduate School of Medicine Aomori Japan
| | - Hiroto Hiraga
- Department of Gastroenterology and Hematology Hirosaki University Graduate School of Medicine Aomori Japan
| | - Daisuke Chinda
- Department of Gastroenterology and Hematology Hirosaki University Graduate School of Medicine Aomori Japan
| | - Tatsuya Mikami
- Innovation Center for Health Promotion Hirosaki University Graduate School of Medicine Aomori Japan
| | - Shinsaku Fukuda
- Department of Gastroenterology and Hematology Hirosaki University Graduate School of Medicine Aomori Japan
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Fredrick TW, Ramos GP, Braga Neto MB, Kane S, Faubion WA, Loftus EV, Pardi DS, Pasha SF, Farraye FA, Zhang L, Raffals LE. Clinical Course and Impact of Immune Checkpoint Inhibitor Colitis Resembling Microscopic Colitis. CROHN'S & COLITIS 360 2022; 4:otac008. [PMID: 36777041 PMCID: PMC9802423 DOI: 10.1093/crocol/otac008] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/15/2021] [Indexed: 01/10/2023] Open
Abstract
Background Microscopic colitis (MC) is suspected to result from increased immune activity in gut mucosa. Immune checkpoint inhibitors (ICIs) treat cancer by activating the immune system, and further investigation is needed regarding their role in the development of MC. Methods A retrospective case series investigated cases of endoscopically and histologically confirmed MC developing after administration of ICIs. Clinical notes and medication administration records were reviewed for demographics, symptom duration, and treatment response. Results Nineteen cases of de novo MC were identified, with 95% of cases requiring steroid treatment, 53% presenting with hospitalization, and colitis-related mortality in 1 individual. Symptom onset occurred a median of 160 days after initiation of ICI therapy and 53 days after their most recent dose of therapy. Patients had a median of 125 days of symptoms, and ICI therapy was held in 70% of individuals due for treatment. Conclusions MC can develop after ICI administration, and presents with severe symptoms, often requiring hospitalization and steroid treatment. In certain individuals this can require a prolonged treatment course of steroid therapy or immunomodulators. Individuals developing diarrhea after ICI therapy warrant thorough workup including endoscopy and rapid treatment initiation given the disease severity observed in this series.
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Affiliation(s)
- Thomas W Fredrick
- Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota, USA
| | - Guilherme P Ramos
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
| | - Manuel B Braga Neto
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
| | - Sunanda Kane
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
| | - William A Faubion
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
| | - Edward V Loftus
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
| | - Darrell S Pardi
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
| | - Shabana F Pasha
- Division of Gastroenterology and Hepatology, Mayo Clinic, Phoenix, Arizona, USA
| | - Francis A Farraye
- Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, Florida, USA
| | - Lizhi Zhang
- Division of Anatomic Pathology, Mayo Clinic, Rochester, Minnesota, USA
| | - Laura E Raffals
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
- Address correspondence to: Laura E. Raffals, MD, Mayo Clinic, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905, USA ()
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40
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Bislenghi G, Ferrante M, De Hertogh G, Sucameli F, Wolthuis A, Sabino J, Vermeire S, D'Hoore A. Proctocolectomy and ileal pouch-anal anastomosis for the treatment of collagenous colitis. Clin J Gastroenterol 2022; 15:586-591. [PMID: 35220554 DOI: 10.1007/s12328-022-01611-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/02/2021] [Accepted: 02/14/2022] [Indexed: 01/12/2023]
Abstract
The role of surgery for collagenous colitis (CC) is unexplored. Either diverting stoma, subtotal colectomy with ileo-rectal anastomosis, and proctocolectomy with ileal pouch-anal anastomosis (IPAA) have been proposed. However, the optimal surgical strategy still needs to be defined. The aim of this short report is to report our experience with two cases of IPAA for CC. Two patients affected by histologically proven CC with watery diarrhea refractory to several lines of medical treatment underwent a laparoscopic proctocolectomy with IPAA at a tertiary referral hospital for the treatment of Inflammatory Bowel Disease in Belgium. A longer rectal cuff was left in place because of the absence of macroscopic inflammation of the rectal mucosa and the consequent negligible risk of cuffitis. No postoperative complications (90 days) occurred. Definitive pathological examination confirmed the diagnosis of CC. At six months, pouchoscopy revealed no signs of inflammation. One year after surgery, mean Öresland and Pouch Functional Score were 10.5 (8-13) and 11.5 (9-14). Functional outcomes after IPAA for CC were barely satisfactory. A high stool frequency not responding to high doses of anti-diarrheals was observed. This has also previously been reported for CC patients receiving a diverting stoma. Proctocolectomy and IPAA for medical refractory CC leads to acceptable short-term gastrointestinal functional outcomes which seems to be particularly affected by high stool frequency. For this reason, pouch surgery might not be the optimal indication for collagenous colitis.
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Affiliation(s)
- Gabriele Bislenghi
- Department of Abdominal Surgery, University Hospitals Leuven, KU Leuven, Herestraat 49, 3000, Leuven, Belgium.
| | - Marc Ferrante
- Department of Gastroenterology and Hepatology, University Hospitals Leuven, KU Leuven, Herestraat 49, 3000, Leuven, Belgium
| | - Gert De Hertogh
- Department of Morphology and Molecular Pathology, University Hospitals Leuven, KU Leuven, Herestraat 49, 3000, Leuven, Belgium
| | - Francesco Sucameli
- Department of Abdominal Surgery, University Hospitals Leuven, KU Leuven, Herestraat 49, 3000, Leuven, Belgium
| | - Albert Wolthuis
- Department of Abdominal Surgery, University Hospitals Leuven, KU Leuven, Herestraat 49, 3000, Leuven, Belgium
| | - Joao Sabino
- Department of Gastroenterology and Hepatology, University Hospitals Leuven, KU Leuven, Herestraat 49, 3000, Leuven, Belgium
| | - Severine Vermeire
- Department of Gastroenterology and Hepatology, University Hospitals Leuven, KU Leuven, Herestraat 49, 3000, Leuven, Belgium
| | - Andrè D'Hoore
- Department of Abdominal Surgery, University Hospitals Leuven, KU Leuven, Herestraat 49, 3000, Leuven, Belgium
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Weimers P, Vedel Ankersen D, Lophaven SN, Bonderup OK, Münch A, Lynge E, Løkkegaard ECL, Munkholm P, Burisch J. Microscopic Colitis in Denmark: Regional Variations in Risk Factors and Frequency of Endoscopic Procedures. J Crohns Colitis 2022; 16:49-56. [PMID: 34232280 DOI: 10.1093/ecco-jcc/jjab119] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
OBJECTIVE Microscopic colitis [MC], encompassing collagenous colitis [CC] and lymphocytic colitis [LC], is an increasingly prevalent gastrointestinal disease with an unknown aetiology. Previous research has reported significant differences in the incidence of MC within Denmark, with the lowest incidence found in the most populated region [Capital Region of Denmark]. Our aim was to elucidate the causes of these regional differences. DESIGN All incident MC patients [n = 14 302] with a recorded diagnosis of CC [n = 8437] or LC [n = 5865] entered in The Danish Pathology Register between 2001 and 2016 were matched to 10 reference individuals [n = 142 481]. Information regarding drug exposure, including proton pump inhibitors [PPIs], selective serotonin reuptake inhibitors [SSRIs], statins, and nonsteroidal anti-inflammatory drugs [NSAIDs], were retrieved from The Danish National Prescription Registry. Information regarding endoscopy rate, smoking-related diseases, and immune-mediated inflammatory diseases were acquired from The Danish National Patient Registry. RESULTS Smoking, immune-mediated inflammatory diseases, exposure to PPIs, SSRIs, statins, and NSAIDs were significantly associated with MC in all Danish regions. The association between drug exposure and MC was weakest in the Capital Region of Denmark with an odds ratio of 1.8 (95% confidence interval [CI]: 1.61-2.01). The relative risk of undergoing a colonoscopy with biopsy was significantly increased in sex- and age-matched controls in all regions compared with controls from the Capital Region of Denmark, with the greatest risk found in the Region of Southern Denmark, 1.37 [95% CI: 1.26-1.50]. CONCLUSIONS The cause of the regional differences in MC incidence in Denmark seems to be multifactorial, including variations in disease awareness and distribution of risk factors.
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Affiliation(s)
- Petra Weimers
- Department of Gastroenterology, North Zealand University Hospital, Capital Region, Denmark
| | - Dorit Vedel Ankersen
- Department of Gastroenterology, North Zealand University Hospital, Capital Region, Denmark
| | | | - Ole K Bonderup
- Diagnostic centre, Section of Gastroenterology, Silkeborg Hospital, Silkeborg, Denmark
| | - Andreas Münch
- Department of Gastroenterology and Hepatology, Linköping University Hospital, Linköping, Sweden
- Department of Health, Medicine, and Caring Sciences, Linköping University, Linköping, Sweden
| | - Elsebeth Lynge
- Centre for Epidemiological Research, Nykøbing Falster Hospital, University of Copenhagen, Copenhagen, Denmark
| | | | - Pia Munkholm
- Department of Gastroenterology, North Zealand University Hospital, Capital Region, Denmark
| | - Johan Burisch
- Department of Gastroenterology, North Zealand University Hospital, Capital Region, Denmark
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Sandler RS, Keku TO, Woosley JT, Galanko JA, Peery AF. Medication use and microscopic colitis. Aliment Pharmacol Ther 2021; 54:1193-1201. [PMID: 34514632 PMCID: PMC8511165 DOI: 10.1111/apt.16594] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/10/2021] [Revised: 07/08/2021] [Accepted: 08/20/2021] [Indexed: 12/23/2022]
Abstract
BACKGROUND Microscopic colitis is an increasingly common cause of watery diarrhoea. Several classes of medications have been associated with microscopic colitis in prior studies. AIMS To determine the association between the use of previously implicated medications and microscopic colitis. METHODS This was a case-control study of patients referred for elective, outpatient colonoscopy for diarrhoea. Patients were excluded for inflammatory bowel disease, C difficile, or other infectious diarrhoea. Colon biopsies were reviewed by the study pathologist and patients were classified as microscopic colitis cases or non-microscopic colitis controls. RESULTS The study population included 110 microscopic colitis cases and 252 controls. The cases were older, better educated and more likely to be female. Cases reported a greater number of loose, watery, or liquid stools, nocturnal stools, more urgency and weight loss compared to controls. There was no association with proton pump inhibitors (PPIs), adjusted OR (aOR) 0.66, 95% CI 0.38-1.13 or nonsteroidal anti-inflammatory drugs, aOR 0.68, 95% CI 0.40-1.17. Cholecystectomy was less common in cases, aOR 0.33, 95% CI 0.17-0.64, but microscopic colitis cases had more frequent bowel movements following cholecystectomy. CONCLUSION Compared to similar patients with diarrhoea, cases with microscopic colitis were not more likely to have taken previously implicated medications. They had more diarrhoea following cholecystectomy, suggesting that bile may play a role in symptoms or aetiology. We conclude that the appropriate choice of controls is crucial to understanding risk factors for microscopic colitis.
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Affiliation(s)
- Robert S. Sandler
- Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill
- Department of Medicine, University of North Carolina at Chapel Hill
| | - Temitope O. Keku
- Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill
- Department of Medicine, University of North Carolina at Chapel Hill
| | - John T. Woosley
- Department of Pathology, University of North Carolina at Chapel Hill
| | - Joseph A. Galanko
- Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill
- Department of Medicine, University of North Carolina at Chapel Hill
| | - Anne F. Peery
- Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill
- Department of Medicine, University of North Carolina at Chapel Hill
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Oruganti P, Awan R, Ding X, Wesolowski M, Abegunde AT. Epidemiology and Clinical Outcomes of Microscopic Colitis: Preliminary Results From the Loyola University Microscopic Colitis Registry (LUMiCoR). Front Med (Lausanne) 2021; 8:715458. [PMID: 34631738 PMCID: PMC8493955 DOI: 10.3389/fmed.2021.715458] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2021] [Accepted: 07/22/2021] [Indexed: 11/13/2022] Open
Abstract
Microscopic colitis (MC) is a common cause of chronic diarrhea with limited long-term data. We searched the pathology records at our institution from 2008 to 2018 to identify cases of MC. Total sample included patients with either a diagnosis of MC or incomplete MC (MCi).Chart review was performed and data were summarized for descriptive statistics. Logistic regression was used to estimate the unadjusted effects of predictors on MC. A total of 216 patients (88.32% white, 80.56% females, mean age 67.12 +/– 15.79) were studied; 50.00% had CC, 40.28% had LC and 9.72% had MCi. Majority (52.31%) were smokers and 21.84% of females were using some form of hormonal therapy. The odds of LC in reference to CC were significantly higher for those using tricyclic antidepressants (TCAs) (OR: 3.23, 95% C.I: 1.18–8.80, p = 0.02). The odds of smoking, statins, aspirin and beta-blocker use were decreased in MCi in reference to CC (all p < 0.05), 29 (74.35%) patients with unresolved symptoms underwent repeat colonoscopies with biopsies. One case of MCi resolved, 8 (72.73%) out of 11 cases of LC resolved, 2 (18.18%) continued to be LC and 1 (9.09%) transformed to CC, 8 (47.06%) out of 17 cases of CC resolved, 8 (47.06%) continued to be CC and 1 (5.88%) transformed to LC. Majority of patients had CC. TCA use resulted in increased odds of LC in reference to CC. Biopsies from repeat colonoscopies in some patients revealed changes in the pathological diagnoses raising the question of interchangeability of MC (CC to LC and vice versa).
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Affiliation(s)
- Poornima Oruganti
- Department of Internal Medicine, Loyola University Medical Center, Maywood, IL, United States
| | - Rehmat Awan
- Department of Internal Medicine, Loyola University Medical Center, Maywood, IL, United States
| | - Xianzhong Ding
- Department of Pathology, Loyola University Medical Center, Maywood, IL, United States
| | - Michael Wesolowski
- Loyola University Chicago, Clinical Research Office Biostatistics Collaborative Core, Chicago, IL, United States
| | - Ayokunle T Abegunde
- Division of Gastroenterology and Nutrition, Loyola University Medical Center, Maywood, IL, United States
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Mihaly E, Patai Á, Tulassay Z. Controversials of Microscopic Colitis. Front Med (Lausanne) 2021; 8:717438. [PMID: 34712675 PMCID: PMC8546222 DOI: 10.3389/fmed.2021.717438] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2021] [Accepted: 08/11/2021] [Indexed: 11/21/2022] Open
Abstract
Microscopic colitis (MC) has become a disease with increased awareness due to the availability of new data about the pathogenesis, diagnosis and therapy of this disease. The incidence of MC is increasing, reaching the incidence of the inflammatory bowel disease (IBD) in some populations. However, some aspects of MC are still controversial. It is unknown whether the changes of microbiome play a role in the pathogenesis and what is in the background of the different subtypes of disease that can transform into each other. Is there a connection between MC and IBD or why the histological changes do not follow the clinical activity? We do not know what the etiology of the incomplete MC is, and what its natural course is. The association of MC with celiac disease is well-known- is there a common pathogenesis? The MC treatment is budesonide. Its effectiveness is high, but the relapse rate is high, as well. Why would biologics be effective in these cases when budesonide is not? This mini-review makes an attempt to summarize the data about MC and highlight that there are still unanswered questions in the pathogenesis, diagnosis and therapy of the disease, which can initiate further investigations in the future.
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Affiliation(s)
- Emese Mihaly
- Gastroenterology Unit, Department of Internal Medicine and Hematology, Semmelweis University, Budapest, Hungary
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45
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Graziano EJ, Vaughn BP, Wang Q, Chow LS, Campbell JP. Microscopic Colitis Is Not an Independent Risk Factor for Low Bone Density. Dig Dis Sci 2021; 66:3542-3547. [PMID: 33063187 DOI: 10.1007/s10620-020-06651-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2020] [Accepted: 10/01/2020] [Indexed: 12/09/2022]
Abstract
BACKGROUND Microscopic colitis (MC) is a subtype of inflammatory bowel disease (IBD) with overlapping risk factors for low bone density (LBD). While LBD is a known complication of IBD, its association with MC is not well-established. AIMS Assess the prevalence of LBD in MC compared to control populations, and evaluate if MC predicts LBD when controlling for confounders. METHODS Retrospective, observational case control study of adult patients with pathologically confirmed MC from 2005 to 2015. Bone density measurements were abstracted from dual-energy X-ray absorptiometry (DEXA) reports, and bone density was classified using T-score: normal (T ≥ - 1.0), osteopenia (- 1.0 > T > -2.5) or osteoporosis (T ≤ - 2.5). Demographics, disease, medication history and LBD risk factors were obtained from chart review. Prevalence of LBD was compared to national and local controls. A matched control cohort to MC patients without prior diagnosis of LBD was analyzed with logistic regression to assess the relationship of MC to LBD. RESULTS One hundred and eighteen patients with MC were identified. Osteopenia in women with MC was more prevalent compared to national controls (67% vs. 49%, p = 0.0004), and LBD was more prevalent in MC patients compared to local controls (82% vs. 55%, p < 0.0001). In MC patients without prior diagnosis of LBD matched to controls, there was a higher prevalence of osteopenia (53.2% vs. 36.7%, p = 0.04). However, after controlling for confounders, MC was not associated with LBD (OR 0.83, 95% CI 0.22, 3.16, p = 0.8). CONCLUSIONS While LBD was more prevalent in MC patients compared to control populations, with adjustment for key confounders (including BMI, steroids, smoking, vitamin D and calcium use), MC was not an independent predictor of LBD.
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Affiliation(s)
- Elliot J Graziano
- Department of Internal Medicine, University of Minnesota, 420 Delaware Street SE MMC 284, Minneapolis, MN, 55455, USA.
| | - Byron P Vaughn
- Inflammatory Bowel Disease Program, Division of Gastroenterology, Hepatology and Nutrition, University of Minnesota, Minneapolis, MN, USA
| | - Qi Wang
- Clinical and Translational Science Institute, University of Minnesota, Minneapolis, MN, USA
| | - Lisa S Chow
- Division of Diabetes, Endocrinology and Metabolism, University of Minnesota, Minneapolis, MN, USA
| | - James P Campbell
- Division of Gastroenterology, Hepatology and Nutrition, University of Minnesota, Minneapolis, MN, USA
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46
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Increasing Incidence of Microscopic Colitis in a Population-Based Cohort Study in Switzerland. Clin Gastroenterol Hepatol 2021; 19:2205-2206. [PMID: 33065310 DOI: 10.1016/j.cgh.2020.10.015] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/11/2020] [Revised: 10/08/2020] [Accepted: 10/09/2020] [Indexed: 02/07/2023]
Abstract
Microscopic colitis (MC) is a chronic inflammatory disease of the colon that presents with chronic, nonbloody watery diarrhea and only few or no endoscopic abnormalities. Histologic examination discriminates lymphocytic colitis (LyC; presence of ≥20 intraepithelial lymphocytes per 100 surface epithelial cells) and collagenous colitis (CC; colonic subepithelial collagen band >10 μm in diameter).1,2 MC not otherwise specified describes a subgroup of patients who do not fulfill the diagnostic criteria for either CC or LyC.1,2 Population-based epidemiologic data regarding MC are scarce. We aimed to evaluate the clinical presentation at diagnosis, incidence, and prevalence of MC in Cantons of Vaud and Fribourg, Switzerland.
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47
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Niccum B, Casey K, Burke K, Lopes EW, Lochhead P, Ananthakrishnan A, Richter JM, Ludvigsson JF, Chan AT, Khalili H. Alcohol Consumption is Associated With An Increased Risk of Microscopic Colitis: Results From 2 Prospective US Cohort Studies. Inflamm Bowel Dis 2021; 28:1151-1159. [PMID: 34473269 PMCID: PMC9340522 DOI: 10.1093/ibd/izab220] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/23/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND No dietary factors have yet been shown to conclusively impact the incidence of microscopic colitis (MC). Here, we sought to examine the relationship between alcohol intake and the risk of MC. METHODS We conducted a prospective cohort study of 209,902 participants (age range, 28.5-66.7 years) enrolled in the Nurses' Health Study (NHS) and Nurses' Health Study II (NHSII). Validated data on alcohol consumption were collected at baseline in 1986 in the NHS and 1991 in the NHSII and updated every 4 years. Diagnoses of MC were confirmed via review of histopathology data. We used Cox proportional hazards modeling to estimate adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs). RESULTS Through 2016 in the NHS and 2017 in the NHSII, we confirmed 352 incident cases of MC over 4,994,324 person-years. Higher alcohol consumption was associated with an increased risk of MC (Ptrend < .001). Compared to non-users, the aHRs of MC were 1.20 (95% CI, 0.86-1.67) for consumers of 0.1-4.9 g/day of alcohol, 1.90 (95% CI, 1.34-2.71) for consumers of 5-14.9 g/day, and 2.31 (95% CI, 1.54-3.46) for consumers of ≥15 g/day. The associations were consistent across the histologic subtypes of collagenous and lymphocytic colitis (Pheterogeneity = .523). When stratified by alcohol type, the risk according to every 2 servings/week appeared to be strongest with consumption of wine (aHR, 1.08; 95% CI, 1.04-1.12) as compared to beer (aHR, 1.01; 95% CI, 0.91-1.12) or liquor (aHR, 1.00; 95% CI, 0.92-1.09). CONCLUSIONS Alcohol consumption was associated with an increased risk of MC. Further studies are needed to determine the mechanism underlying these associations, as well as the impact of reducing alcohol intake in patients with MC.
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Affiliation(s)
- Blake Niccum
- Department of Internal Medicine, Massachusetts General Hospital, Boston, MA, USA
| | - Kevin Casey
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - Kristin Burke
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA,Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, Boston, MA, USA
| | - Emily W Lopes
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA,Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, Boston, MA, USA
| | - Paul Lochhead
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA,Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, Boston, MA, USA
| | - Ashwin Ananthakrishnan
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA,Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, Boston, MA, USA
| | - James M Richter
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA,Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, Boston, MA, USA
| | - Jonas F Ludvigsson
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden,Department of Pediatrics, Orebro University Hospital, Orebro, Sweden,Division of Epidemiology and Public Health, School of Medicine, University of Nottingham, UK,Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY, USA
| | - Andrew T Chan
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA,Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, Boston, MA, USA
| | - Hamed Khalili
- Address correspondence to: Hamed Khalili, MD, MPH, Massachusetts General Hospital, Clinical Translational Epidemiology Unit, 100 Cambridge Street, 16 Floor, Boston, MA 02114, USA ()
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Salvo EM, Ferko NC, Cash SB, Gonzalez A, Kahrilas PJ. Umbrella review of 42 systematic reviews with meta-analyses: the safety of proton pump inhibitors. Aliment Pharmacol Ther 2021; 54:129-143. [PMID: 34114655 DOI: 10.1111/apt.16407] [Citation(s) in RCA: 41] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/17/2020] [Revised: 09/04/2020] [Accepted: 04/30/2021] [Indexed: 12/13/2022]
Abstract
BACKGROUND Proton pump inhibitors (PPIs) are widely used to treat and prevent acid-related disorders. Despite high efficacy, PPI safety has been increasingly scrutinised. However, no comprehensive review summarising investigations of various adverse events is available. AIMS To perform an umbrella review to comprehensively assess associations between adverse events and PPI use. METHODS In accordance with PRISMA, an umbrella review of systematic reviews with meta-analyses was conducted. PubMed and EMBASE were searched from 2015 to July 2019. AMSTAR 2 and GRADE were used to assess quality and certainty of evidence. Author-reported quality assessments were also reviewed. RESULTS Forty-two systematic reviews with meta-analyses, supported predominantly by observational evidence, were included. The most comprehensive studies reported statistically significant associations with PPI use for several outcomes, including: fractures (eg, hip; RR = 1.20; 95% CI = 1.14-1.28; n = 2 103 800), kidney disease (eg, acute kidney injury; RR = 1.61; 95% CI = 1.16-2.22; n = 2 396 640), infections (eg, Clostridioides difficile; OR = 1.99; 95% CI = 1.73-2.30; n = 356 683), gastric cancer (OR = 2.50; 95% CI = 1.74-3.85; n = 943 070) and gastrointestinal events (eg, fundic gland polyps; OR = 2.46; 95% CI = 1.42-4.27; n = 40 218). No associations with non-gastric cancers, or neurological disease were concluded, with conflicting evidence for cardiovascular outcomes. Certainty based on GRADE was very low for most outcomes. CONCLUSIONS This review identified several published associations between PPIs and adverse outcomes, however, further investigation is needed to understand their clinical significance and the likelihood of causal relationship. If higher quality evidence is generated substantiating the potential risks, it may be necessary for clinicians to consider alternative treatment strategies, especially when PPI efficacy is suboptimal.
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Affiliation(s)
- Elizabeth M Salvo
- Value & Evidence Division, Marketing and Market Access, EVERSANA, Burlington, ON, Canada
| | - Nicole C Ferko
- Value & Evidence Division, Marketing and Market Access, EVERSANA, Burlington, ON, Canada
| | - Sarah B Cash
- Value & Evidence Division, Marketing and Market Access, EVERSANA, Burlington, ON, Canada
| | - Ailish Gonzalez
- Health Economics and Market Access, Ethicon Inc, Somerville, NJ, USA
| | - Peter J Kahrilas
- Feinberg School of Medicine at Northwestern University, Chicago, IL, USA
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49
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Olsen LM, Engel PJH, Goudkade D, Villanacci V, Thagaard J, Walbech JS, Bohr J, Kupcinskas J, Verhaegh B, Münch A, Guagnozzi D, Fernández-Bañares F, Munck LK, Fiehn AMK. Histological disease activity in patients with microscopic colitis is not related to clinical disease activity or long-term prognosis. Aliment Pharmacol Ther 2021; 54:43-52. [PMID: 34018208 DOI: 10.1111/apt.16381] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/09/2021] [Revised: 03/02/2021] [Accepted: 04/07/2021] [Indexed: 12/21/2022]
Abstract
BACKGROUND Microscopic colitis (MC) is a common cause of chronic watery diarrhea. Biopsies with characteristic histological features are crucial for establishing the diagnosis. The two main subtypes are collagenous colitis (CC) and lymphocytic colitis (LC) but incomplete forms exist. The disease course remains unpredictable varying from spontaneous remission to a relapsing course. AIM To identify possible histological predictors of course of disease. METHODS Sixty patients from the European prospective MC registry (PRO-MC Collaboration) were included. Digitised histological slides stained with CD3 and Van Gieson were available for all patients. Total cell density and proportion of CD3 positive lymphocytes in lamina propria and surface epithelium were estimated by automated image analysis, and measurement of the subepithelial collagenous band was performed. Histopathological features were correlated to the number of daily stools and daily watery stools at time of endoscopy and at baseline as well as the clinical disease course (quiescent, achieved remission after treatment, relapsing or chronic active) at 1-year follow-up. RESULTS Neither total cell density in lamina propria, proportion of CD3 positive lymphocytes in lamina propria or surface epithelium, or thickness of collagenous band showed significant correlation to the number of daily stools or daily watery stools at any point of time. None of the assessed histological parameters at initial diagnosis were able to predict clinical disease course at 1-year follow-up. CONCLUSIONS Our data indicate that the evaluated histological parameters were neither markers of disease activity at the time of diagnosis nor predictors of disease course.
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50
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Grant RK, Brindle WM, Robertson AJ, Robertson AR, Jones GR, Kirkwood KJ, Fineron PW, Arnott IDR. Incidence of collagenous colitis in NHS Lothian: a population-based study. Frontline Gastroenterol 2021; 13:218-224. [PMID: 35493619 PMCID: PMC8996100 DOI: 10.1136/flgastro-2020-101745] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/25/2020] [Accepted: 05/28/2021] [Indexed: 02/04/2023] Open
Abstract
OBJECTIVE Increases in incidence of collagenous colitis (CC) have been documented across Europe; however, previous data from NHS Lothian (1998-2003) demonstrated this to be a low-prevalence area. We aimed to assess incidence of CC in NHS Lothian over time by comparing a more recent cohort (2013-2018) with our existing cohort. METHODS All histologically confirmed diagnoses of CC between 2013 and 2018 were obtained from the NHS Lothian colorectal pathology department (Western General Hospital, Edinburgh). Case record review was performed to obtain relevant demographic and clinical data. Data were also collected regarding the availability of colonoscopy in NHS Lothian. RESULTS 224 cases of CC were diagnosed between 2013 and 2018, compared with 25 between 1998 and 2003. Mean annual incidence rose from 0.5/100 000 population to 4.3/100 000 population. Incidence in females ≥60 years old rose from 2.3/100 000 population to 22.4/100 000 population (p<0.001). The total number of colonoscopies performed increased by 179.1% from 15 262 (1998-2003) to 42 600 (2013-2018), with the number of CC cases per 1000 colonoscopies performed rising from 1.7 to 5.3 (p<0.001). CONCLUSION We describe the increasing incidence of CC in Southeast Scotland, with temporal trends comparable to other European countries. The increase is particularly marked in older females and parallels increasing numbers of colonoscopies being performed.
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Affiliation(s)
- Rebecca K Grant
- The Edinburgh IBD Unit, Western General Hospital, Edinburgh, UK
| | | | - Andrew J Robertson
- The Centre for Liver and Digestive Disorders, Royal Infirmary of Edinburgh, Edinburgh, UK
| | | | | | | | - Paul W Fineron
- Department of Pathology, Western General Hospital, Edinburgh, UK
| | - Ian D R Arnott
- The Edinburgh IBD Unit, Western General Hospital, Edinburgh, UK
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