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  • 1. Amcoff, Karin
    et al.
    Joossens, Marie
    Pierik, Marie J.
    Jonkers, Daisy
    Bohr, Johan
    Joossens, Sofie
    Romberg-Camps, Marielle
    Nyhlin, Nils
    Wickbom, Anna K.
    Rutgeerts, Paul J.
    Tysk, Curt
    Bodin, Lennart
    Colombel, Jean-Frederic
    Vermeire, Severine
    Halfvarson, Jonas
    Örebro University, School of Medicine, Örebro University, Sweden.
    Influence of genetics in the expression of serological markers in twins with IBD2012In: Gastroenterology, ISSN 0016-5085, E-ISSN 1528-0012, Vol. 142, no 5, p. S881-S881Article in journal (Other academic)
  • 2.
    Amcoff, Karin
    et al.
    Department of Gastroenterology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Joossens, Marie
    Department of Microbiology and Immunology, Rega Institute, Katholieke Universiteit, Leuven,Belgium; VIB Center for the Biology of Disease, Leuven, Belgium; Microbiology Unit, Faculty of Sciences and Bioengineering Sciences, Vrije Universiteit, Brussels, Belgium.
    Pierik, Marie J.
    Gastroenterology, University Hospital Maastricht, Maastricht, The Netherlands.
    Jonkers, Daisy
    Gastroenterology, University Hospital Maastricht, Maastricht, The Netherlands.
    Bohr, Johan
    Örebro University, School of Health Sciences. Department of Gastroenterology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Joossens, Sofie
    Gastroenterology, Catholic University of Leuven (KUL), Leuven, Belgium.
    Romberg-Camps, Mariëlle
    Department of Gastroenterology-Hepatology, Zuyderland Medical Center, Sittard, Netherlands.
    Nyhlin, Nils
    Örebro University, School of Medical Sciences. Department of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Wickbom, Anna
    Örebro University, School of Medical Sciences. Department of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Rutgeerts, Paul J.
    Department of Gastroenterology, University Hospital Gasthuisberg, Leuven, Belgium.
    Tysk, Curt
    Department of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Bodin, Lennart
    Institute of Environmental Medicine, Unit of Intervention and Implementation Research, Karolinska Institute, Stockholm, Sweden.
    Colombel, Jean-Frederic
    Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York NY, USA.
    Vermeire, Severine
    Department of Gastroenterology, University Hospital Gasthuisberg, Leuven, Belgium.
    Halfvarson, Jonas
    Örebro University, School of Medical Sciences. Department of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Concordance in Anti-OmpC and Anti-I2 Indicate the Influence of Genetic Predisposition: Results of a European Study of Twins with Crohn's Disease2016In: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 10, no 6, p. 695-702Article in journal (Refereed)
    Abstract [en]

    Background and Aims: An adaptive immunological response to microbial antigens has been observed in Crohn's disease (CD). Intriguingly, this serological response precedes the diagnosis in some patients and has also been observed in healthy relatives. We aimed to determine whether genetic factors are implicated in this response in a CD twin cohort.

    Methods: In total, 82 twin pairs (Leuven n = 13, Maastricht n = 8, Örebro n = 61) took part: 81 pairs with CD (concordant monozygotic n = 16, discordant monozygotic n = 22, concordant dizygotic n = 3, discordant dizygotic n = 40) and 1 monozygotic pair with both CD and ulcerative colitis. Serology for Pseudomonas fluorescens-related protein (anti-I2), Escherichia coli outer membrane porin C (anti-OmpC), CBir1flagellin (anti-CBir1) and antibodies to oligomannan (anti-Saccharomyces cerevisiae antibody [ASCA]) was determined by standardized enzyme-linked immunoassay.

    Results: All markers were more often present in CD twins than in their healthy twin siblings. Using the intraclass correlation coefficient (ICC), agreements in concentrations of anti-OmpC and anti-I2 were observed in discordant monozygotic but not in discordant dizygotic twin pairs with CD (anti-OmpC, ICC 0.80 and -0.02, respectively) and (anti-I2, ICC 0.56 and 0.05, respectively). In contrast, no agreements were found in anti-CBir, immunoglobulin (Ig) G ASCA and ASCA IgA.

    Conclusions: We show that anti-I2 and anti-CBir1 statuses have specificity for CD and confirm previous reported specificities for anti-OmpC and ASCA. Based on quantitative analyses and observed ICCs, genetics seems to predispose to the anti-OmpC and anti-I2 response but less to ASCA and anti-CBir1 responses.

  • 3.
    Bohr, Johan
    et al.
    Örebro University, School of Health Sciences. Örebro University Hospital. Division of Gastroenterology, Department of Medicine, Örebro University Hospital, Örebro, Sweden.
    Wickbom, Anna
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Division of Gastroenterology, Department of Medicine, Örebro University Hospital, Örebro, Sweden.
    Hegedus, Agnes
    Department of Laboratory Medicine/Pathology, Örebro University Hospital, Örebro, Sweden.
    Nyhlin, Nils
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Division of Gastroenterology, Department of Medicine, Örebro University Hospital, Örebro, Sweden.
    Hultgren-Hörnquist, Elisabeth
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Tysk, Curt
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital. Division of Gastroenterology, Department of Medicine, Örebro University Hospital, Örebro, Sweden.
    Diagnosis and management of microscopic colitis: Current perspectives2014In: Clinical and Experimental Gastroenterology, ISSN 1178-7023, E-ISSN 1178-7023, Vol. 7, p. 273-284Article, review/survey (Refereed)
    Abstract [en]

    Collagenous colitis and lymphocytic colitis, together constituting microscopic colitis, are common causes of chronic diarrhea. They are characterized clinically by chronic nonbloody diarrhea and a macroscopically normal colonic mucosa where characteristic histopathological findings are seen. Previously considered rare, they now have emerged as common disorders that need to be considered in the investigation of the patient with chronic diarrhea. The annual incidence of each disorder is five to ten per 100,000 inhabitants, with a peak incidence in 60- to 70-year-old individuals and a predominance of female patients in collagenous colitis. The etiology and pathophysiology are not well understood, and the current view suggests an uncontrolled mucosal immune reaction to various luminal agents in predisposed individuals. Clinical symptoms comprise chronic diarrhea, abdominal pain, fatigue, weight loss, and fecal incontinence that may impair the patient's health-related quality of life. An association is reported with other autoimmune disorders, such as celiac disease, thyroid disorders, diabetes mellitus, and arthritis. The best-documented treatment, both short-term and long-term, is budesonide, which induces clinical remission in up to 80% of patients after 8 weeks' treatment. However, after successful budesonide therapy is ended, recurrence of clinical symptoms is common, and the best possible long-term management deserves further study. The long-term prognosis is good, and the risk of complications, including colonic cancer, is low. We present an update of the epidemiology, pathogenesis, diagnosis, and management of microscopic colitis.

  • 4.
    Borssen, Åsa Danielsson
    et al.
    Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden.
    Marschall, Hanns-Ulrich
    Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden.
    Bergquist, Annika
    Department of Medicine, Section of Hepatology and Gastroenterology, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
    Rorsman, Fredrik
    Department of Medical Sciences, Section of Gastroenterology and Hepatology, Uppsala University, Uppsala, Sweden.
    Weiland, Ola
    Department of Medicine, Division of Infectious Diseases, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
    Kechagias, Stergios
    Department of Gastroenterology and Hepatology, University Hospital, Linköping, Sweden; Department of Medical and Health Sciences, Linköping University, Linköping, Sweden.
    Nyhlin, Nils
    Örebro University, School of Medical Sciences. Department of Gastroenterology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Verbaan, Hans
    Department of Clinical Sciences, Gastroenterology Division, Lund University, University Hospital Skane, Malmö, Sweden.
    Nilsson, Emma
    Department of Clinical Sciences, Gastroenterology Division, Lund University, University Hospital Skane, Lund, Sweden.
    Werner, Mårten
    Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden.
    Epidemiology and causes of death in a Swedish cohort of patients with autoimmune hepatitis2017In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 52, no 9, p. 1022-1028Article in journal (Refereed)
    Abstract [en]

    Background: Epidemiological studies of autoimmune hepatitis (AIH) show varying figures on prevalence and incidence, and data on the long-term prognosis are scarce.

    Objective: To investigate the epidemiology, long-term prognosis and causes of death in a Swedish AIH cohort.

    Material and methods: Data collected from 634 AIH patients were matched to the Cause of Death Registry, and survival analyses were made. Prevalence and incidence were calculated for university hospitals with full coverage of cases and compared to the County of Vasterbotten in Northern Sweden.

    Results: AIH point prevalence was 17.3/100,000 inhabitants in 2009, and the yearly incidence 1990-2009 was 1.2/100,000 inhabitants and year. The time between diagnosis and end of follow-up, liver transplantation or death was in median 11.3 years (range 0-51.5 years). Men were diagnosed earlier (p<.001) and died younger than women (p=.002). No gender differences were found concerning transplant-free, overall survival and liver-related death. Cirrhosis at diagnosis was linked to an inferior survival (p<.001). Liver-related death was the most common cause of death (32.7%). The relative survival started to diverge from the general population 4 years after diagnosis but a distinct decline was not observed until after more than 10 years.

    Conclusions: Long-term survival was reduced in patients with AIH. No gender difference regarding prognosis was seen but men died younger, probably as a result of earlier onset of disease. Cirrhosis at diagnosis was a risk factor for poor prognosis and the overall risk of liver-related death was increased.

  • 5.
    Borssén, Åsa D.
    et al.
    Department of Public Health and Clinical Medicine, Umeå University, Norrlands Universitetssjukhus, Umeå, Sweden.
    Palmqvist, Richard
    Department of Medical Biosciences, Pathology, Umeå University, Umeå, Sweden.
    Kechagias, Stergios
    Department of Gastroenterology and Hepatology, Department of Medical and Health Sciences, Linköping University, Linköping, Sweden.
    Marschall, Hanns-Ulrich
    Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Bergquist, Annika
    Department of Medicine, Section of Hepatology and Gastroenterology, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
    Rorsman, Fredrik
    Department of Medical Sciences, Section of Gastroenterology and Hepatology, Uppsala University, Uppsala, Sweden.
    Weiland, Ola
    Division of Infectious Diseases, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
    Verbaan, Hans
    Department of Clinical Sciences, Lund University, University Hospital Skåne, Malmö, Sweden.
    Nyhlin, Nils
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Nilsson, Emma
    Department of Clinical Sciences, Lund University, University Hospital Skåne, Malmö, Sweden.
    Werner, Marten
    Department of Public Health and Clinical Medicine, Umeå University, Norrlands Universitetssjukhus, Umeå, Sweden.
    Histological improvement of liver fibrosis in well-treated patients with autoimmune hepatitis: A cohort study2017In: Medicine (Baltimore, Md.), ISSN 0025-7974, E-ISSN 1536-5964, Vol. 96, no 34, article id e7708Article in journal (Refereed)
    Abstract [en]

    Autoimmune hepatitis (AIH) is a chronic autoimmune liver disease that if left untreated may lead to the development of cirrhosis. Previous studies on AIH patients have suggested that fibrosis and even cirrhosis can be reversed by medical treatment. The aim of this study was to evaluate the efficacy of medical treatment for protection of developing fibrosis and cirrhosis.

    A total of 258 liver biopsies from 101 patients (72 women, 29 men) were analyzed by a single pathologist and classified according to the Ishak grading (inflammation) and staging (fibrosis) system. Liver histology was stratified according to the temporal changes of fibrosis stage (increased, decreased, or stable), and groups were compared.

    Complete or partial response to medical treatment was 94.9%. Reduction of fibrosis stage from the first to the last biopsy was seen in 63 patients (62.4%). We found an association between a reduction in the fibrosis stage and continuous glucocorticoid medication, as well as lowered scores of inflammation at last biopsy. Twenty-one patients had cirrhosis (Ishak stage 6) at least in one of the previous biopsies, but only 5 patients at the last biopsy.

    Histological improvement is common in AIH patients that respond to medical treatment, and a reduction or stabilization of fibrosis stage occurs in about 2/3 of such patients.

  • 6.
    Eriksson, Carl
    et al.
    Örebro University, School of Medical Sciences.
    Henriksson, Ida
    Department of Gastroenterology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Brus, Ole
    Örebro University, School of Medical Sciences.
    Zhulina, Yaroslava
    Örebro University, School of Medical Sciences. Örebro University Hospital.
    Nyhlin, Nils
    Örebro University, School of Medical Sciences. Örebro University Hospital.
    Tysk, Curt
    Department of Gastroenterology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Montgomery, Scott
    Örebro University, School of Medical Sciences. Karolinska Institutet, Stockholm, Sweden; University College London, London, United Kingdom.
    Incidence, prevalence, and clinical outcome of anaemia in inflammatory bowel disease: A population-based cohort studyManuscript (preprint) (Other academic)
  • 7.
    Eriksson, Carl
    et al.
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Gastroenterology.
    Henriksson, Ida
    Department of Gastroenterology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Brus, Ole
    Örebro University, School of Medical Sciences.
    Zhulina, Yaroslava
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Gastroenterology.
    Nyhlin, Nils
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Gastroenterology.
    Tysk, Curt
    Department of Gastroenterology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Montgomery, Scott
    Örebro University, School of Medical Sciences. Clinical Epidemiology Unit, Department of Medicine, Karolinska Institutet, Stockholm, Sweden; Department of Epidemiology and Public Health, University College London, London, UK.
    Halfvarson, Jonas
    Örebro University, School of Medical Sciences. Department of Gastroenterology.
    Incidence, prevalence and clinical outcome of anaemia in inflammatory bowel disease: a population-based cohort study2018In: Alimentary Pharmacology and Therapeutics, ISSN 0269-2813, E-ISSN 1365-2036, Vol. 48, no 6, p. 638-645Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The incidence and short-term outcome of anaemia in inflammatory bowel disease (IBD) are largely unknown.

    AIM: To determine the incidence, prevalence and clinical outcome of anaemia in terms of resolution of anaemia within 12 months. We also planned to assess risk factors for anaemia in IBD.

    METHODS: A random sample of 342 patients was obtained from the population-based IBD cohort of Örebro University Hospital, Sweden, consisting of 1405 patients diagnosed between 1963 and 2010. Haemoglobin measurements recorded from 1 January 2011 to 31 December 2013 were extracted from the Clinical Chemistry data system.

    RESULTS: In Crohn's disease, the incidence rate of anaemia was 19.3 (95% CI: 15.4-23.7) per 100 person-years and the prevalence was 28.7% (CI: 22.0-36.2), compared with 12.9 (CI: 9.8-16.5) and 16.5% (CI: 11.2-22.9) for ulcerative colitis. Crohn's disease was associated with an increased incidence (OR = 1.60; CI: 1.02-2.51) and prevalence of anaemia (OR = 2.04; CI: 1.20-3.46) compared to ulcerative colitis. Stricturing disease phenotype in Crohn's disease (HR = 2.59; CI: 1.00-6.79) and extensive disease in ulcerative colitis (HR = 2.40; CI: 1.10-5.36) were associated with an increased risk of anaemia. Despite a higher probability of receiving specific therapy within 3 months from the diagnosis of anaemia, Crohn's disease patients had a worse outcome in terms of resolution of anaemia within 12 months (56% vs 75%; P = 0.03).

    CONCLUSIONS: Anaemia is a common manifestation of IBD even beyond the first years after the diagnosis of IBD. Crohn's disease is associated with both an increased risk and a worse outcome.

  • 8.
    Fransén, Karin
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Franzén, Petra
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Magnuson, Anders
    Örebro University Hospital, Örebro, Sweden.
    Elmabsout, Ali
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Nyhlin, Nils
    Örebro University Hospital.
    Wickbom, Anna
    Örebro University Hospital, Örebro, Sweden.
    Curman, Bengt
    Örebro University Hospital, Örebro, Sweden.
    Törkvist, Leif
    Karolinska University Hospital, Stockholm, Sweden.
    D'Amato, Mauro
    Karolinska University Hospital, Stockholm, Sweden.
    Bohr, Johan
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital.
    Tysk, Curt
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital.
    Sirsjö, Allan
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Halfvarson, Jonas
    Örebro University, School of Medicine, Örebro University, Sweden. Örebro University Hospital.
    Polymorphism in the retinoic acid metabolizing enzyme CYP26B1 and the development of Crohn's disease2013In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 8, p. e72739-Article in journal (Refereed)
    Abstract [en]

    Several studies suggest that Vitamin A may be involved in the pathogenesis of inflammatory bowel disease (IBD), but the mechanism is still unknown. Cytochrome P450 26 B1 (CYP26B1) is involved in the degradation of retinoic acid and the polymorphism rs2241057 has an elevated catabolic function of retinoic acid, why we hypothesized that the rs2241057 polymorphism may affect the risk of Crohn's disease (CD) and Ulcerative Colitis (UC). DNA from 1378 IBD patients, divided into 871 patients with CD and 507 with UC, and 1205 healthy controls collected at Örebro University Hospital and Karolinska University Hospital were analyzed for the CYP26B1 rs2241057 polymorphism with TaqMan® SNP Genotyping Assay followed by allelic discrimination analysis. A higher frequency of patients homozygous for the major (T) allele was associated with CD but not UC compared to the frequency found in healthy controls. A significant association between the major allele and non-stricturing, non-penetrating phenotype was evident for CD. However, the observed associations reached borderline significance only, after correcting for multiple testing. We suggest that homozygous carriers of the major (T) allele, relative to homozygous carriers of the minor (C) allele, of the CYP26B1 polymorphism rs2241057 may have an increased risk for the development of CD, which possibly may be due to elevated levels of retinoic acid. Our data may support the role of Vitamin A in the pathophysiology of CD, but the exact mechanisms remain to be elucidated.

  • 9.
    Giannakopoulos, Georgios
    et al.
    Division of Gastroenterology, Department of Gastroenterology, Dermatology and Rheumatology, Karolinska University Hospital, Stockholm, Sweden.
    Verbaan, Hans
    Department of Medicine, Skåne University Hospital, Malmö, Sweden.
    Friis-Liby, Inga-Lill
    Department of Medicine, Sahlgren’s University Hospital, Göteborg, Sweden.
    Sangfelt, Per
    Department of Medicine, Akademiska Hospital, Uppsala, Sweden.
    Nyhlin, Nils
    Örebro University, School of Medical Sciences. Örebro University Hospital.
    Almer, Sven
    Division of Gastroenterology, Department of Gastroenterology, Dermatology and Rheumatology, Karolinska University Hospital, Stockholm, Sweden; Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden.
    Mycophenolate mofetil treatment in patients with autoimmune hepatitis failing standard therapy with prednisolone and azathioprine2019In: Digestive and Liver Disease, ISSN 1590-8658, E-ISSN 1878-3562, Vol. 51, no 2, p. 253-257Article in journal (Refereed)
    Abstract [en]

    Background: Data on rescue treatment of autoimmune hepatitis in patients that fail standard treatment are sparse.

    Aims: To report our long-term experience with mycophenolate mofetil.

    Methods: Retrospective study in 22 patients with autoimmune hepatitis who failed azathioprine and prednisolone due to adverse events (n = 14, 64%), lack of remission (n = 5, 23%) or a combination (n=3, 13%).

    Results: Mycophenolate mofetil was started at a dose of 20 mg/kg/day and increased to a maximum of 3 g/day. Follow-up was 0-6 months in 7 patients; more than 12 months in 15 (68%) and more than 24 months in 10. Normal aminotransferase levels were obtained (n = 3) or maintained (n = 7) in 10 patients (45%) after three to 30 weeks. 12 patients (55%) were withdrawn during the first 6 months, due to adverse events. Three patients were switched to cyclosporine and one underwent liver transplantation. Successful treatment with mycophenolate mofetil continued in 10 patients (45%) for a median of 71 months (range 20-124). Of these, one stopped prednisolone, five have a prednisolone dose <5 mg daily and four patients 5-10 mg.

    Conclusion: Approximately one of two patients with autoimmune hepatitis that fail standard treatment benefit from long-term maintenance with mycophenolate mofetil, especially those with previous intolerance to thiopurines, where mycophenolate mofetil is effective in two thirds. (C) 2018 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

  • 10.
    Gunaltay, Sezin
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Kumawat, Ashok Kumar
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Institute of Infection, College of Medical, Veterinary & Life Sciences, University of Glasgow, Glasgow, United Kingdom.
    Nyhlin, Nils
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital.
    Bohr, Johan
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital.
    Tysk, Curt
    Örebro University Hospital. Division of Gastroenterology, Department of Medicine, Örebro University, Örebro, Sweden.
    Hultgren, Olof
    Örebro University Hospital.
    Hultgren-Hörnquist, Elisabeth
    Örebro University, School of Medicine, Örebro University, Sweden.
    Enhanced levels of chemokines and their receptors in the colon of microscopic colitis patients indicate mixed immune cell recruitment2015In: Mediators of Inflammation, ISSN 0962-9351, E-ISSN 1466-1861, article id 132458Article in journal (Refereed)
    Abstract [en]

    Microscopic colitis (MC), comprising collagenous colitis (CC) and lymphocytic colitis (LC), is a common cause of chronic diarrhea. Various immune cell infiltrations in the epithelium and lamina propria are seen in MC immunopathology. We compared gene and protein expressions of different immune cell attracting chemokines and their receptors in colon biopsies from MC patients in active disease or histopathological remission (CC/LC-HR) with controls, using qRT-PCR and Luminex, respectively. CC and LC patients with active disease demonstrated a mixed chemokine profile with significantly enhanced gene and/or protein expressions of the chemokines CCL2, CCL3, CCL4, CCL5, CCL7, CCL22, CXCL8, CXCL9, CXCL10, CXCL11, and CX(3)CL1 and the receptors CCR2, CCR3, CCR4, CXCR1, CXCR2, and CX(3)CR1. Enhanced chemokine/chemokine receptor gene and protein levels in LC-HR patients were similar to LC patients, whereas CC-HR patients demonstrated almost normalized levels. These findings expand the current understanding of the involvement of various immune cells in MC immunopathology and endorse chemokines as potential diagnostic markers as well as therapeutic candidates. Moreover, this study further supports the hypothesis that CC and LC are two different entities due to differences in their immunoregulatory responses.

  • 11.
    Gunaltay, Sezin
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Nyhlin, Nils
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Kumawat, Ashok
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Bohr, Johan
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Tysk, Curt
    Örebro University Hospital, Örebro, Sweden.
    Hultgren, Olof
    Örebro University, School of Medicine, Örebro University, Sweden.
    Hultgren-Hörnquist, Elisabeth
    Örebro University, School of Medicine, Örebro University, Sweden.
    Increased expression of T cell recruiting chemokines in the colonic mucosa of microscopic colitis patients2013In: Immunology, ISSN 0019-2805, E-ISSN 1365-2567, Vol. 140, p. 135-135Article in journal (Other academic)
  • 12.
    Gunaltay, Sezin
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Nyhlin, Nils
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Kumawat, Ashok
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Tysk, Curt
    Örebro University Hospital, Örebro, Sweden.
    Bohr, Johan
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Hultgren, Olof
    Örebro University, School of Medicine, Örebro University, Sweden.
    Hultgren-Hörnquist, Elisabeth
    Örebro University, School of Medicine, Örebro University, Sweden.
    IL-1/TLR signaling inhibitors in microscopic and ulcerative colitis: Immunopathogenic markers of active disease and remission2013In: Immunology, ISSN 0019-2805, E-ISSN 1365-2567, Vol. 140, p. 167-167Article in journal (Other academic)
  • 13.
    Gunaltay, Sezin
    et al.
    Örebro University, School of Medical Sciences. Nutrition-Gut-Brain Interactions Research Centre, Örebro University, Örebro, Sweden.
    Repsilber, Dirk
    Örebro University, School of Medical Sciences. Nutrition-Gut-Brain Interactions Research Centre, Örebro University, Örebro, Sweden.
    Helenius, Gisela
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Pathology, Örebro University Hospital, Örebro, Sweden.
    Nyhlin, Nils
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Medicine, Div. of Gastroenterol., Örebro University Hospital, Örebro, Sweden.
    Bohr, Johan
    Department of Medicine, Div of Gastroenterol, Örebro Univ Hosp, Örebro, Sweden; Fac of Med and Hlth, Örebro Univ, Örebro, Sweden.
    Hultgren, Olof
    Örebro University, School of Medical Sciences. Department of Microbiology and Immunology, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Hultgren Hörnquist, Elisabeth
    Örebro University, School of Medical Sciences. Nutrition-Gut-Brain Interactions Research Centre, Örebro University, Örebro, Sweden.
    Oligoclonal T-cell Receptor Repertoire in Colonic Biopsies of Patients with Microscopic Colitis and Ulcerative Colitis2017In: Inflammatory Bowel Diseases, ISSN 1078-0998, E-ISSN 1536-4844, Vol. 23, no 6, p. 932-945Article in journal (Refereed)
    Abstract [en]

    Background: Microscopic colitis (MC), comprising collagenous colitis (CC) and lymphocytic colitis (LC), is a type of variation of inflammatory bowel diseases. Local T-cell infiltration in the mucosa plays a major role in MC immunopathology.

    Methods: To understand diversity and clonality of infiltrating T cells, we analyzed the T-cell receptor beta (TCR beta) chains in colonic biopsies of MC, ulcerative colitis (UC), and their remission counterparts (CC/LC-HR [histological remission] or UC-R [remission]) compared with patients with non-inflamed colons using next-generation sequencing.

    Results: Compared with controls and patients with CC, patients with LC had significantly lower diversity with significantly lower evenness and richness in TCRVb-Jb gene segments. Similarly, patients with LC-HR had lower diversity because of significantly lower TCRVb-Jb clone richness. Patients with UC and UC-R showed significantly higher diversity and richness. Univariate and multivariate analyses were performed to identify TCRVb-Jb gene segments differentiating disease types from controls or their remission counterparts. Patients with LC were discriminated from controls by 12 clones and from patients with CC by 8 clones. Neither univariate nor multivariate analyses showed significance for patients with CC or CC-HR compared with controls. Patients with UC and UC-R had 16 and 14 discriminating clones, respectively, compared with controls.

    Conclusions: Altogether, patients with MC and UC showed an oligoclonal TCRb distribution. TCRVb-Jb clone types and their diversity were distinctive between patients with CC and LC, as well as for patients with UC, suggesting different pathophysiological mechanisms according to disease type and stage. This study suggests that CC and LC are different entities because of differences in immunoregulatory responses, as mirrored by their T-cell repertoire.

  • 14.
    Göranzon, C.
    et al.
    Department of Medicine, Division of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Kumawat, Ashok Kumar
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Hultgren-Hörnqvist, Elisabeth
    Örebro University, School of Medicine, Örebro University, Sweden.
    Tysk, Curt
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital. Department of Medicine, Division of Gastroenterology, Örebro University Hospital, Region Örebro County, Örebro, Sweden.
    Eriksson, S.
    Department of Pathology, Örebro University Hospital, Örebro, Sweden.
    Bohr, Johan
    School of Health and Medical Sciences, Örebro University, Örebro, Sweden; Department of Medicine, Division of Gastroenterology, Örebro University Hospital, Region Örebro County, Örebro, Sweden.
    Nyhlin, Nils
    Örebro University Hospital. Department of Medicine, Division of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Immunohistochemical characterization of lymphocytes in microscopic colitis2013In: Journal of Crohn's and Colitis, ISSN 1197-4982, Vol. 7, no 10, p. e434-e442Article in journal (Refereed)
    Abstract [en]

    Background and Aims: Microscopic colitis (MC), encompassing the subgroups collagenous colitis (CC) and lymphocytic colitis (LC), is characterized by macroscopically normal or near-normal colonic mucosa, and an increased number of intraepithelial lymphocytes (IELs) and mononuclear cell infiltration in the underlying lamina propria (LP), in addition to an increased collagen layer in CC. This study aimed to characterize the inflammatory cells involved in mucosal inflammation, using immunohistochemistry.

    Methods Paraffin-embedded biopsies from 23 untreated patients with MC (CC = 13, LC = 10) and 17 controls were stained with antibodies against CD3, CD4, CD8, CD20, CD30, Foxp3, CD45RO and Ki67. Computerized image analysis was used to calculate areas of stained lymphocytes in the surface and crypt epithelia as well as in the LP.

    Results In CC and LC, an increase of predominantly CD8+ lymphocytes was seen in both the epithelium and the lamina propria, whereas a decreased amount of CD4+ lymphocytes was found in the lamina propria. CD45RO+ and Foxp3+ cells were more abundant in all areas in both patient groups compared to controls, as were CD20+ areas, although more scarce. Ki67+ areas were only more abundant in the epithelium, whereas CD30+ areas were more abundant in the lamina propria of both patient groups compared to controls.

    Conclusions This study confirms an increased amount of CD8+ lymphocytes in the epithelium. Lymphocytic proliferation and activation markers were more abundant, whereas a decreased amount of CD4+ lymphocytes was seen in the LP. Further studies are needed to reveal the underlying mechanism(s).

  • 15.
    Günaltay, Sezin
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Nyhlin, Nils
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital. Department of Medicine, Division of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Kumawat, Ashok Kumar
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Tysk, Curt
    Örebro University Hospital. Department of Medicine, Division of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Bohr, Johan
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital. Department of Medicine, Division of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Hultgren, Olof
    Örebro University, School of Medicine, Örebro University, Sweden. Örebro University Hospital. Department of Microbiology and Immunology, Örebro University Hospital, Örebro, Sweden.
    Hultgren-Hörnquist, Elisabeth
    Örebro University, School of Medicine, Örebro University, Sweden.
    Differential expression of interleukin-1/Toll-like receptor signaling regulators in microscopic and ulcerative colitis2014In: World Journal of Gastroenterology, ISSN 1007-9327, E-ISSN 2219-2840, Vol. 20, no 34, p. 12249-12259Article in journal (Refereed)
    Abstract [en]

    AIM: To investigate Toll-like receptor (TLR) signaling regulators in microscopic and ulcerative colitis patients.

    METHODS: Total RNA and microRNA were isolated from fresh frozen colonic biopsies of non-inflamed controls and patients with active or in-remission collagenous colitis (CC), lymphocytic colitis (LC), or ulcerative colitis (UC). We compared expressions of interleukin-1 receptor-associated kinase (IRAK)-2, IRAK-M, interleukin (IL)-37, microRNA (miR)-146a, miR-155, and miR-21 using quantitative real time reverse transcription polymerase chain reaction.

    RESULTS: IRAK-M expression was increased in LC patients with active disease in histopathological remission (LC-HR; P = 0.02) and UC patients (P = 0.01), but no differences in IRAK-2 expression were detected compared to controls. miR-146a, -155 and -21 expressions were increased in LC-HR (P = 0.04, 0.07, and 0.004) and UC (P = 0.02, 0.04 and 0.03) patients. miR-146a and miR-21 expressions were significantly enhanced in UC patients compared to UC remission (UC-R; P = 0.01 and 0.04). Likewise, active CC patients showed significantly increased expression of miR-155 (P = 0.003) and miR-21 (P = 0.006). IL-37 expression was decreased in both CC (P = 0.03) and LC (P = 0.04) patients with a similar trend in UC patients but not statistically significant, whilst it was increased in UC-R patients compared to controls (P = 0.02) and active UC (P = 0.001).

    CONCLUSION: The identification of differentially expressed miRNAs, IL-37, and IRAK-M suggests different pathophysiologic mechanisms in various disease stages in LC, CC, and UC. (C) 2014 Baishideng Publishing Group Inc. All rights reserved.

  • 16.
    Günaltay, Sezin
    et al.
    Örebro University, School of Medical Sciences.
    Repsilber, Dirk
    Örebro University, School of Medical Sciences.
    Helenius, Gisela
    Örebro University, School of Medical Sciences.
    Nyhlin, Nils
    Örebro University, School of Medical Sciences.
    Bohr, Johan
    Örebro University, School of Health Sciences.
    Hultgren-Hörnquist, Elisabeth
    Örebro University, School of Medical Sciences.
    Oligoclonal T cell receptor repertoire in colonic biopsies of microscopic and ulcerative colitis patientsManuscript (preprint) (Other academic)
  • 17.
    Kumawat, Ashok Kumar
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Nyhlin, Nils
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital. Department of Medicine, Division of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Wickbom, Anna
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Medicine, Division of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Tysk, Curt
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital. Department of Medicine, Division of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Bohr, Johan
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital. Department of Medicine, Division of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Hultgren, Olof
    Örebro University Hospital. Department of Microbiology and Immunology, Örebro University Hospital, Örebro, Sweden.
    Hultgren-Hörnquist, Elisabeth
    Örebro University, School of Medicine, Örebro University, Sweden.
    An In Vitro Model to Evaluate the Impact of the Soluble Factors from the Colonic Mucosa of Collagenous Colitis Patients on T Cells: Enhanced Production of IL-17A and IL-10 from Peripheral CD4(+) T Cells2014In: Mediators of Inflammation, ISSN 0962-9351, E-ISSN 1466-1861, article id 879843Article in journal (Refereed)
    Abstract [en]

    Soluble factors from intestinal mucosal cells contribute to immune homeostasis in the gut. We have established an in vitro model to investigate the regulatory role of soluble factors from inflamed intestinal mucosa of collagenous colitis (CC) patients in the differentiation of T cells. Peripheral blood CD4(+) T cells from healthy donors were polyclonally activated in the presence of conditioned medium (CM) generated from denuded biopsies (DNB) or isolated lamina propria mononuclear cells (LPMCs) from mucosal biopsies from CC patients compared to noninflamed controls, to determine proliferation and secretion of cytokines involved in T-cell differentiation. Compared to controls, we observed significantly increased production of the proinflammatory cytokines IFN-gamma, IL-17A, IL-6, and IL-1 beta and the anti-inflammatory cytokines IL-4 and IL-10 in the presence of CC-DNB-CM. The most pronounced effect of CC-LPMC-CM on peripheral CD4(+) T cells was a trend towards increased production of IL-17A and IL-10. A trend towards reduced inhibition of T-cell proliferation was noted in the presence of CC-DNB-CM. In conclusion, our in vitro model reveals implications of soluble factors from CC colonic mucosa on peripheral T cells, enhancing their production of both pro-and anti-inflammatory cytokines.

  • 18. Nyhlin, Nils
    et al.
    Bohr, Johan
    Örebro University, School of Health and Medical Sciences.
    Eriksson, Sune
    Tysk, Curt
    Örebro University, School of Health and Medical Sciences.
    Microscopic colitis: a common and an easily overlooked cause of chronic diarrhoea2008In: European journal of internal medicine, ISSN 0953-6205, E-ISSN 1879-0828, Vol. 19, no 3, p. 181-186Article in journal (Refereed)
    Abstract [en]

    Microscopic colitis, comprising collagenous colitis and lymphocytic colitis, is characterised clinically by chronic watery diarrhoea, a macroscopically normal colonic mucosa where diagnostic histopathological features are seen on microscopic examination. The annual incidence of each disorder is 4–6/100,000 inhabitants, with a peak incidence in 60–70 year old individuals and a noticeable female predominance in collagenous colitis. The aetiology is unknown. Abdominal pain, weight loss, fatigue, and faecal incontinence are common symptoms in addition to chronic diarrhoea that impair the health-related quality of life of the patient. There is an association to other autoimmune disorders such as celiac disease, diabetes mellitus, thyroid disorders and arthritis. Budesonide is the best-documented short-term treatment, but the optimal long-term strategy needs further study. The long-term prognosis is good and the risk of complications including colonic cancer is low.

  • 19.
    Nyhlin, Nils
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital. Department of Medicine, Division of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Wickbom, Anna
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Medicine, Division of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Montgomery, Scott M.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital. Clinical Epidemiology Unit, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden; Department of Epidemiology and Public Health, University College London, London, United Kingdom.
    Tysk, Curt
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital. Department of Medicine, Division of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Bohr, Johan
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital. Department of Medicine, Division of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Letter: persisting clinical symptoms in microscopic colitis in remission - authors' reply2014In: Alimentary Pharmacology and Therapeutics, ISSN 0269-2813, E-ISSN 1365-2036, Vol. 40, no 1, p. 118-118Article in journal (Refereed)
  • 20.
    Nyhlin, Nils
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital. Department of Medicine, Division of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Wickbom, Anna
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Medicine, Division of Gastroenterology, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Montgomery, Scott M.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital. Clinical Epidemiology Unit, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
    Tysk, Curt
    Örebro University Hospital. Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Medicine, Division of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Bohr, Johan
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital. Department of Medicine, Division of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Long-term prognosis of clinical symptoms and health-related quality of life in microscopic colitis: a case-control study2014In: Alimentary Pharmacology and Therapeutics, ISSN 0269-2813, E-ISSN 1365-2036, Vol. 39, no 9, p. 963-972Article in journal (Refereed)
    Abstract [en]

    Background: Microscopic colitis, comprising collagenous colitis (CC) and lymphocytic colitis (LC), is a common cause of chronic diarrhoea. The long-term prognosis is not well described.

    Aim: To study outcome of symptoms and health-related quality of life (HRQoL).

    Methods: A case-control study using a postal questionnaire with three population-based controls per patient matched for age, sex and municipality. HRQoL was assessed by the Short Health Scale (SHS). Patients in clinical remission, defined as a mean of <3 stools/day, were evaluated separately (CC; n=72, LC; n=60).

    Results: The study included 212 patients and 627 matched controls. Median disease duration was 5.9 (range 0.5-27) years and 6.4 (0.3-14.8) years for CC and LC respectively. Abdominal pain, fatigue, arthralgia, myalgia, faecal incontinence and nocturnal defecation were significantly more prevalent in CC patients compared with controls. These differences persisted in CC patients in clinical remission with respect to abdominal pain (36% vs. 21%), fatigue (54% vs. 34%), arthralgia (61% vs. 41%) and myalgia (53% vs. 37%). In LC patients, abdominal pain, fatigue, faecal incontinence and nocturnal defecation were more prevalent compared with controls. In LC patients in clinical remission, fatigue was more prevalent compared with controls (54% vs. 37%). These differences were statistically significant (P<0.05). All four HRQoL dimensions (symptom burden, social function, disease-related worry, general well-being) were impaired in patients with active CC and LC.

    Conclusions: Although considered to be in clinical remission, patients with microscopic colitis suffer from persisting symptoms such as abdominal pain, fatigue, arthralgia or myalgia several years after diagnosis.

  • 21.
    Tysk, Curt
    et al.
    Örebro University, School of Health and Medical Sciences.
    Bohr, Johan
    Nyhlin, Nils
    Wickbom, Anna
    Eriksson, Sune
    Diagnosis and management of microscopic colitis2008In: World Journal of Gastroenterology, ISSN 1007-9327, E-ISSN 2219-2840, Vol. 14, no 48, p. 7280-7288Article in journal (Other academic)
    Abstract [en]

    Microscopic colitis, comprising collagenous and lymphocytic colitis, is characterized clinically by chronic watery diarrhea, and a macroscopically normal colonic mucosa where diagnostic histopathological features are seen on microscopic examination. The annual incidence of each disorder is 4-6/100,000 inhabitants, with a peak incidence in 60-70-year-old individuals and a noticeable female predominance for collagenous colitis. The etiology is unknown. Chronic diarrhea, abdominal pain, weight loss, fatigue and fecal incontinence are common symptoms, which impair the health-related quality of life of the patient. There is an association with other autoimmune disorders such as celiac disease, diabetes mellitus, thyroid disorders and arthritis. Budesonide is the best-documented short-term treatment, but the optimal long-term strategy needs further study. The long-term prognosis is good and the risk of complications including colonic cancer is low.

  • 22.
    Tysk, Curt
    et al.
    Örebro University, School of Health and Medical Sciences.
    Wickbom, Anna
    Nyhlin, Nils
    Eriksson, Sune
    Bohr, Johan
    Recent advances in diagnosis and treatment of microscopic colitis2011In: Annals of Gastroenterology, ISSN 1108-7471, E-ISSN 1792-7463, Vol. 24, no 4, p. 253-262Article in journal (Other academic)
    Abstract [en]

    Microscopic colitis, comprising collagenous colitis and lymphocytic colitis, is a common cause of chronic diarrhoea. It is characterised clinically by chronic watery diarrhoea and a macroscopically normal colonic mucosa where diagnostic histopathological features are seen on microscopic examination. The annual incidence of each disorder is 4-6/100000 inhabitants, with a peak incidence in individuals 60-70 years old and a noticeable female predominance in collagenous colitis. The aetiology is unknown. Chronic diarrhoea, abdominal pain, weight loss, fatigue, and faecal incontinence are common symptoms that impair the health-related quality of life of the patient. There is an association with other autoimmune disorders, such as celiac disease, thyroid disorders, diabetes mellitus, and arthritis. Budesonide is the best-documented treatment, both short-term and long-term. Recurrence of symptoms is common after withdrawal of successful budesonide therapy, and the optimal long-term treatment strategy needs further study. The long-term prognosis is good, and the risk of complications including colonic cancer is low. We review epidemiology, clinical features, diagnosis and treatment of microscopic colitis,

  • 23.
    Wickbom, Anna
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Bohr, Johan
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital.
    Eriksson, Sune
    Dept Pathology, Örebro Univ Hosp, Örebro, Sweden.
    Udumyan, Ruzan
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Clin Epidemiol & Biostat Unit, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Nyhlin, Nils
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital.
    Tysk, Curt
    Örebro University, School of Health and Medical Sciences. Dept Gastroenterol, Örebro University Hospital, Region Örebro County, Örebro, Sweden.
    Stable Incidence of Collagenous Colitis and Lymphocytic Colitis in Orebro, Sweden, 1999-2008: A Continuous Epidemiologic Study2013In: Inflammatory Bowel Diseases, ISSN 1078-0998, E-ISSN 1536-4844, Vol. 19, no 11, p. 2387-2393Article in journal (Refereed)
    Abstract [en]

    Background: The incidence of microscopic colitis (MC) has increased in several centers, but long-term epidemiologic data are missing. We report an epidemiologic study of collagenous colitis (CC) and lymphocytic colitis (LC) during 1999-2008, as a follow-up of our previous studies 1984-1998. Methods: Population-based study of residents of the catchment area of the hospital, with a new diagnosis of MC between 1999 and 2008. Patients were identified by diagnosis registers of the Departments of Medicine and Pathology. Medical files were reviewed, and colonic biopsies were reevaluated. Results: Collagenous colitis was diagnosed in 96 patients (75 females) and LC in 90 patients (74 females). The mean annual age-standardized incidence (per 100,000 inhabitants) was MC 10.2 (95% confidence interval: 8.7-11.7), CC 5.2 (4.2-6.3), and LC 5.0 (4.0-6.0). Age-specific incidence showed a peak in females older than 70 years. Prevalence (per 100,000 inhabitants) on December 31, 2008, was MC 123 (107.6-140.0), CC 67.7 (56.4-80.6), and LC 55.3 (45.2-67.1). A comparison of current study period with 1993-1998 showed unchanged mean incidence of MC, but a 2-fold increase in women older than 60 years with LC (standardized rate ratios 2.2, [1.2-3.7]) and increased female to male ratio (4.6:1 versus 2.1:1; P = 0.02) in LC. Conclusions: After an initial rise during 1980s and early 1990s, annual incidence of CC and LC has been stable during the last 15 years around 5/100,000 inhabitants for each disorder. The increasing incidence in older women with LC may be related to an increasing proportion of older individuals in the background population and increased colonoscopy frequency in elderly.

  • 24.
    Wickbom, Anna
    et al.
    Örebro University, School of Medical Sciences.
    Bohr, Johan
    Department of Gastroenterology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Nyhlin, Nils
    Örebro University, School of Medical Sciences.
    Eriksson, Anders
    Department of Medicine, Emergency and Geriatrics, Sahlgrenska University Hospital/East Hospital, Gothenburg, Sweden.
    Lapidus, Annika
    Department of Gastroenterology, Ersta Hospital, Stockholm, Sweden.
    Münch, Andreas
    Division of Gastroenterology and Hepatology, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
    Ung, Kjell-Arne
    Department of Internal Medicine, Sahlgrenska University Hospital/Mölndal, Gothenburg.
    Vigren, Lina
    Department of Medicine, Trelleborg Hospital, Trelleborg, Sweden.
    Tysk, Curt
    Department of Gastroenterology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Microscopic colitis in patients with ulcerative colitis or Crohn’s disease: a retrospective observational study and review of the literatureManuscript (preprint) (Other academic)
  • 25.
    Wickbom, Anna
    et al.
    Örebro University, School of Medical Sciences. Department of Gastroenterology, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Bohr, Johan
    Department of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Nyhlin, Nils
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Eriksson, Anders
    Department of Medicine, Emergency and Geriatrics, Sahlgrenska University Hospital East, Gothenburg, Sweden.
    Lapidus, Annika
    Department of Gastroenterology, Ersta Hospital, Stockholm, Sweden.
    Münch, Andreas
    Department of Clinical and Experimental Medicine, Division of Gastroenterology and Hepatology, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
    Ung, Kjell-Arne
    Department of Internal Medicine, Sahlgrenska University Hospital Mölndal, Gothenburg, Sweden.
    Vigren, Lina
    Department of Medicine, Trelleborg Hospital, Trelleborg, Sweden..
    Öst, Åke
    Department of Pathology and Cytology, Aleris Medilab, Täby, Sweden.
    Tysk, Curt
    Department of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Microscopic colitis in patients with ulcerative colitis or Crohn's disease: a retrospective observational study and review of the literature2018In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 53, no 4, p. 410-416Article, review/survey (Refereed)
    Abstract [en]

    OBJECTIVES: Onset of microscopic colitis (MC) in patients with ulcerative colitis (UC) or Crohn's disease (CD), or vice versa, has been reported occasionally but the subject is not well described. We therefore report a retrospective observational study of such patients and review the literature.

    METHODS: Forty-six Swedish gastroenterology clinics were contacted about patients with diagnoses of both inflammatory bowel disease (IBD) and MC. Publications were searched on PubMed.

    RESULTS: We identified 31 patients with onset of MC after a median (range) of 20 (2-52) years after diagnosis of IBD, or vice versa; 21 UC patients developed collagenous colitis (CC) (n = 16) or lymphocytic colitis (LC) (n = 5); nine CD patients developed CC (n = 5) or LC (n = 4); one CC patient developed CD. Of the 21 UC patients, 18 had extensive disease, whereas no consistent phenotype occurred in CD. Literature review revealed 27 comprehensive case reports of patients with diagnoses of both IBD and MC. Thirteen MC patients developed IBD, of which four required colectomy. Fourteen IBD patients later developed MC. There were incomplete clinical data in 115 additional reported patients.

    CONCLUSIONS: Altogether 173 patients with occurrence of both IBD and MC were found. The most common finding in our patients was onset of CC in a patient with UC. Although these are likely random associations of two different disorders, MC should be considered in the patient with UC or CD if there is onset of chronic watery diarrhoea without endoscopic relapse of IBD.

  • 26.
    Wickbom, Anna
    et al.
    Örebro University, School of Medical Sciences. Örebro University Hospital. Division of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Nyhlin, Nils
    Örebro University, School of Medical Sciences. Örebro University Hospital. Division of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Montgomery, Scott M.
    Örebro University, School of Medical Sciences. Örebro University Hospital. Division of Gastroenterology, Örebro University Hospital, Örebro, Sweden; Clinical Epidemiology Unit, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden; Department of Epidemiology and Public Health, University College London, London, United Kingdom.
    Bohr, Johan
    Örebro University Hospital. School of Medical Sciences, Örebro University, Örebro, Sweden; Division of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Tysk, Curt
    Örebro University Hospital. School of Medical Sciences, Örebro University, Örebro, Sweden; Division of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Family history, comorbidity, smoking and other risk factors in microscopic colitis: a case-control study2017In: European Journal of Gastroenterology and Hepathology, ISSN 0954-691X, E-ISSN 1473-5687, Vol. 29, no 5, p. 587-594Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: Data on heredity, risk factors and comorbidity in microscopic colitis, encompassing collagenous colitis (CC) and lymphocytic colitis (LC), are limited.

    AIM: The aim was to carry out a case-control study of family history, childhood circumstances, educational level, marital status, smoking and comorbidity in microscopic colitis.

    METHODS: A postal questionnaire was sent in 2008-2009 to microscopic colitis patients resident in Sweden and three population-based controls per patient, matched for age, sex and municipality.

    RESULTS: Some 212 patients and 627 controls participated in the study. There was an association with a family history of microscopic colitis in both CC [odds ratio (OR): 10.3; 95% confidence interval (CI): 2.1-50.4, P=0.004] and LC (OR not estimated, P=0.008). Current smoking was associated with CC [OR: 4.7; 95% CI: 2.4-9.2, P<0.001) and LC (OR: 3.2; 95% CI: 1.6-6.7, P=0.002). The median age at diagnosis was around 10 years earlier in ever-smokers compared with never-smokers.CC was associated with a history of ulcerative colitis (UC) (OR: 8.7, 95% CI: 2.2-33.7, P=0.002), thyroid disease (OR: 2.3; 95% CI: 1.1-4.5, P=0.02), coeliac disease (OR: 13.1; 95% CI: 2.7-62.7, P=0.001), rheumatic disease (OR 1.9; 95% CI: 1.0-3.5, P=0.042) and previous appendicectomy (OR: 2.2; 95% CI: 1.3-3.8, P=0.003), and LC with UC (OR: 6.8; 95% CI: 1.7-28.0, P=0.008), thyroid disease (OR: 2.4; 95% CI: 1.1-5.4, P=0.037) and coeliac disease (OR: 8.7; 95% CI: 2.8-26.7, P<0.001).

    CONCLUSION: Association with a family history of microscopic colitis indicates that familial factors may be important. The association with a history of UC should be studied further as it may present new insights into the pathogenesis of microscopic colitis and UC.

  • 27.
    Zhulina, Yaroslava
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Internal Medicine, Division of Gastroenterology, Örebro University Hospital, Region Örebro County, Örebro, Sweden.
    Hahn-Strömberg, Victoria
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Pathology, Örebro University Hospital, Örebro, Sweden; Department of Clinical Medicine, Örebro University, Örebro, Sweden.
    Shamikh, Alia
    Department of Pathology, Örebro University Hospital, Örebro, Sweden; Department of Clinical Medicine, Örebro University, Örebro, Sweden.
    Peterson, Christer G. B.
    Department of Medical Sciences, Clinical Chemistry, Uppsala University, Uppsala, Sweden.
    Gustavsson, Anders
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Internal Medicine, Division of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Nyhlin, Nils
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Internal Medicine, Division of Gastroenterology, Örebro University Hospital, Region Örebro County, Örebro, Sweden.
    Wickbom, Anna
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Internal Medicine, Division of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Bohr, Johan
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Internal Medicine, Division of Gastroenterology, Örebro University Hospital, Region Örebro County, Örebro, Sweden.
    Bodin, Lennart
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Institute of Environmental Medicine, Unit of Intervention and Implementation Research, Karolinska Institute, Stockholm, Sweden.
    Tysk, Curt
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Internal Medicine, Division of Gastroenterology, Örebro University Hospital, Region Örebro County, Örebro, Sweden.
    Carlson, Marie
    Department of Medical Sciences, Gastroenterology Research Group, Uppsala University, Uppsala, Sweden.
    Halfvarson, Jonas
    Örebro University, School of Medicine, Örebro University, Sweden. Department of Internal Medicine, Division of Gastroenterology, Örebro University Hospital, Region Örebro County, Örebro, Sweden.
    Subclinical Inflammation with Increased Neutrophil Activity in Healthy Twin Siblings Reflect Environmental Influence in the Pathogenesis of Inflammatory Bowel Disease2013In: Inflammatory Bowel Diseases, ISSN 1078-0998, E-ISSN 1536-4844, Vol. 19, no 8, p. 1725-1731Article in journal (Refereed)
    Abstract [en]

    Background: The mechanisms behind increased fecal calprotectin (FC) in healthy relatives of patients with inflammatory bowel disease (IBD) are unknown. Our aims were to explore if there is a subclinical inflammation with increased neutrophil activity in healthy twin siblings in discordant twin pairs with IBD and to assess the influence of genetics in this context.

    Methods: Nuclear factor kappa B (NF-B) and neutrophil activity, based on myeloperoxidase (MPO) and FC, were analyzed in healthy twin siblings in discordant twin pairs with IBD and compared with healthy controls. NF-B and MPO were assessed by immunohistochemistry and FC by enzyme-linked immunosorbent assay.

    Results: In total, 33 of 34 healthy twin siblings were histologically normal. Increased NF-B was more often observed in healthy twin siblings in discordant twin pairs with Crohn's disease (13/18 [73%]) and with ulcerative colitis (12/16 [75%]) than in healthy controls (8/45 [18%]). MPO was more often increased in healthy twin siblings in discordant pairs with Crohn's disease (12/18 [67%]) than in healthy controls (11/45 [24%]) and FC more often in healthy twin siblings in discordant pairs with ulcerative colitis (14/21 [67%]) than in healthy controls (6/31 [19%]). Interestingly, the observed differences remained when healthy monozygotic and dizygotic twin siblings were analyzed separately.

    Conclusions:We observed increased NF-B, MPO, and FC in healthy twins in both monozygotic and dizygotic discordant pairs with IBD. These novel findings speak for an ongoing subclinical inflammation with increased neutrophil activity in healthy first-degree relatives.

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