Jochen Schmitt1, Kristin Schwarz2, Hansjörg Baurecht3, Melanie Hotze3, Regina Fölster-Holst3, Elke Rodríguez3, Young A E Lee4, Andre Franke5, Frauke Degenhardt6, Wolfgang Lieb7, Christian Gieger8, Michael Kabesch9, Markus M Nöthen10, Alan D Irvine11, W H Irwin McLean12, Stefanie Deckert2, Victoria Stephan2, Peter Schwarz13, Martin Aringer13, Natalija Novak14, Stephan Weidinger3. 1. Center for Evidence-based Healthcare, Medizinische Fakultät Carl Gustav Carus, TU Dresden, Dresden, Germany; University Allergy Center, TU Dresden, Dresden, Germany. Electronic address: jochen.schmitt@uniklinikum-dresden.de. 2. Center for Evidence-based Healthcare, Medizinische Fakultät Carl Gustav Carus, TU Dresden, Dresden, Germany. 3. Department of Dermatology, Venereology and Allergy, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany. 4. Max-Delbrück-Centrum for Molecular Medicine, Berlin-Buch, Berlin, Germany; Pediatric Allergy, Experimental and Clinical Research Center, Universitätsmedizin Berlin, Berlin, Germany. 5. Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany. 6. Department of Dermatology, Venereology and Allergy, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany; Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany. 7. Institute of Epidemiology and PopGen Biobank, University Hospital Schleswig-Holstein, Kiel, Germany. 8. Institute of Genetic Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany. 9. Department of Pediatric Pneumology and Allergy, University Children's Hospital Regensburg (KUNO), Regensburg, Germany. 10. Institute of Human Genetics, University of Bonn, Bonn, Germany; Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany. 11. Department of Paediatric Dermatology, Our Lady's Children's Hospital, Crumlin, Dublin, Ireland; National Children's Research Centre, Dublin, Ireland; Department of Clinical Medicine, Trinity College Dublin, Dublin, Ireland. 12. Dermatology and Genetic Medicine, Division of Molecular Medicine, College of Life Sciences and College of Medicine, Dentistry and Nursing, University of Dundee, Dundee, United Kingdom. 13. Department of Medicine III, Medizinische Fakultät Carl Gustav Carus, TU Dresden, Dresden, Germany. 14. Department of Dermatology and Allergy, University of Bonn Medical Center, Bonn, Germany.
Abstract
BACKGROUND: Atopic dermatitis (AD) is characterized by epidermal barrier failure and immune-mediated inflammation. Evidence on AD as a potential risk factor for inflammatory comorbidities is scarce. OBJECTIVES: We sought to test the hypothesis that prevalent AD is a risk factor for incident rheumatoid arthritis (RA) and inflammatory bowel disease (IBD; Crohn disease [CD], ulcerative colitis [UC]) and is inversely related to type 1 diabetes (T1D) and to investigate established RA, IBD, and T1D susceptibility loci in AD. METHODS: This cohort study used data from German National Health Insurance beneficiaries aged 40 years or younger (n = 655,815) from 2005 through 2011. Prevalent AD in the period 2005 to 2006 was defined as primary exposure, and incident RA, IBD, and T1D in the period 2007 to 2011 were defined as primary outcomes. Risk ratios were calculated with generalized linear models. Established RA, IBD, and T1D loci were explored in high-density genotyping data from 2,425 cases with AD and 5,449 controls. RESULTS: Patients with AD (n = 49,847) were at increased risk for incident RA (risk ratio [RR], 1.72; 95% CI, 1.25-2.37) and/or IBD (CD: RR, 1.34; 95% CI, 1.11-1.61; UC: RR, 1.25; 95% CI, 1.03-1.53). After adjusting for health care utilization, there was a nominally significant inverse effect on T1D risk (RR, 0.72; 95% CI, 0.53-0.998). There was no disproportionate occurrence of known RA, CD, UC, or T1D risk alleles in AD. CONCLUSIONS: AD is a risk factor for the development of RA and IBD. This excess comorbidity cannot be attributed to major known IBD and RA genetic risk factors.
BACKGROUND: Atopic dermatitis (AD) is characterized by epidermal barrier failure and immune-mediated inflammation. Evidence on AD as a potential risk factor for inflammatory comorbidities is scarce. OBJECTIVES: We sought to test the hypothesis that prevalent AD is a risk factor for incident rheumatoid arthritis (RA) and inflammatory bowel disease (IBD; Crohn disease [CD], ulcerative colitis [UC]) and is inversely related to type 1 diabetes (T1D) and to investigate established RA, IBD, and T1D susceptibility loci in AD. METHODS: This cohort study used data from German National Health Insurance beneficiaries aged 40 years or younger (n = 655,815) from 2005 through 2011. Prevalent AD in the period 2005 to 2006 was defined as primary exposure, and incident RA, IBD, and T1D in the period 2007 to 2011 were defined as primary outcomes. Risk ratios were calculated with generalized linear models. Established RA, IBD, and T1D loci were explored in high-density genotyping data from 2,425 cases with AD and 5,449 controls. RESULTS: Patients with AD (n = 49,847) were at increased risk for incident RA (risk ratio [RR], 1.72; 95% CI, 1.25-2.37) and/or IBD (CD: RR, 1.34; 95% CI, 1.11-1.61; UC: RR, 1.25; 95% CI, 1.03-1.53). After adjusting for health care utilization, there was a nominally significant inverse effect on T1D risk (RR, 0.72; 95% CI, 0.53-0.998). There was no disproportionate occurrence of known RA, CD, UC, or T1D risk alleles in AD. CONCLUSIONS: AD is a risk factor for the development of RA and IBD. This excess comorbidity cannot be attributed to major known IBD and RA genetic risk factors.
Authors: H Weidner; M Rauner; F Trautmann; J Schmitt; E Balaian; A Mies; S Helas; U Baschant; C Khandanpour; M Bornhäuser; L C Hofbauer; U Platzbecker Journal: Leukemia Date: 2017-01-11 Impact factor: 11.528
Authors: Vanessa L Kronzer; Cynthia S Crowson; Jeffrey A Sparks; Elena Myasoedova; John M Davis Journal: Mayo Clin Proc Date: 2019-11-20 Impact factor: 7.616
Authors: A M Forsea; C Mihai; T Predescu; I Tudose; I Margaritescu; C Giurcaneanu Journal: Acta Endocrinol (Buchar) Date: 2017 Jan-Mar Impact factor: 0.877
Authors: Kevin S O'Connell; Alexey Shadrin; Shahram Bahrami; Olav B Smeland; Francesco Bettella; Oleksandr Frei; Florian Krull; Ragna B Askeland; G Bragi Walters; Katrín Davíðsdóttir; Gyða S Haraldsdóttir; Ólafur Ó Guðmundsson; Hreinn Stefánsson; Chun C Fan; Nils Eiel Steen; Ted Reichborn-Kjennerud; Anders M Dale; Kári Stefánsson; Srdjan Djurovic; Ole A Andreassen Journal: Mol Psychiatry Date: 2019-12-02 Impact factor: 15.992
Authors: Olav B Smeland; Alexey Shadrin; Shahram Bahrami; Iris Broce; Martin Tesli; Oleksandr Frei; Katrine V Wirgenes; Kevin S O'Connell; Florian Krull; Francesco Bettella; Nils Eiel Steen; Leo Sugrue; Yunpeng Wang; Per Svenningsson; Manu Sharma; Lasse Pihlstrøm; Mathias Toft; Michael O'Donovan; Srdjan Djurovic; Rahul Desikan; Anders M Dale; Ole A Andreassen Journal: Biol Psychiatry Date: 2020-02-08 Impact factor: 13.382