title: Atopic dermatitis is associated with an increased risk for rheumatoid arthritis and inflammatory bowel disease, and a decreased risk for type 1 diabetes.
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.
  
  
  OBJECTIVE
  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.affiliation: 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.
authors.forename: Jochen
authors.initials: J
authors.lastname: Schmitt
authors.affiliation: Center for Evidence-based Healthcare, Medizinische Fakultät Carl Gustav Carus, TU Dresden, Dresden, Germany.
authors.forename: Kristin
authors.initials: K
authors.lastname: Schwarz
authors.affiliation: Department of Dermatology, Venereology and Allergy, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.
authors.forename: Hansjörg
authors.initials: H
authors.lastname: Baurecht
authors.affiliation: Department of Dermatology, Venereology and Allergy, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.
authors.forename: Melanie
authors.initials: M
authors.lastname: Hotze
authors.affiliation: Department of Dermatology, Venereology and Allergy, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.
authors.forename: Regina
authors.initials: R
authors.lastname: Fölster-Holst
authors.affiliation: Department of Dermatology, Venereology and Allergy, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.
authors.forename: Elke
authors.initials: E
authors.lastname: Rodríguez
authors.affiliation: Max-Delbrück-Centrum for Molecular Medicine, Berlin-Buch, Berlin, Germany; Pediatric Allergy, Experimental and Clinical Research Center, Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Young A E
authors.initials: YAE
authors.lastname: Lee
authors.affiliation: Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany.
authors.forename: Andre
authors.initials: A
authors.lastname: Franke
authors.affiliation: 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.
authors.forename: Frauke
authors.initials: F
authors.lastname: Degenhardt
authors.affiliation: Institute of Epidemiology and PopGen Biobank, University Hospital Schleswig-Holstein, Kiel, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Lieb
authors.affiliation: Institute of Genetic Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Gieger
authors.affiliation: Department of Pediatric Pneumology and Allergy, University Children's Hospital Regensburg (KUNO), Regensburg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Kabesch
authors.affiliation: Institute of Human Genetics, University of Bonn, Bonn, Germany; Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany.
authors.forename: Markus M
authors.initials: MM
authors.lastname: Nöthen
authors.affiliation: 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.
authors.forename: Alan D
authors.initials: AD
authors.lastname: Irvine
authors.affiliation: 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.
authors.forename: W H Irwin
authors.initials: WHI
authors.lastname: McLean
authors.affiliation: Center for Evidence-based Healthcare, Medizinische Fakultät Carl Gustav Carus, TU Dresden, Dresden, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Deckert
authors.affiliation: Center for Evidence-based Healthcare, Medizinische Fakultät Carl Gustav Carus, TU Dresden, Dresden, Germany.
authors.forename: Victoria
authors.initials: V
authors.lastname: Stephan
authors.affiliation: Department of Medicine III, Medizinische Fakultät Carl Gustav Carus, TU Dresden, Dresden, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Schwarz
authors.affiliation: Department of Medicine III, Medizinische Fakultät Carl Gustav Carus, TU Dresden, Dresden, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Aringer
authors.affiliation: Department of Dermatology and Allergy, University of Bonn Medical Center, Bonn, Germany.
authors.forename: Natalija
authors.initials: N
authors.lastname: Novak
authors.affiliation: Department of Dermatology, Venereology and Allergy, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Weidinger
mesh_terms: D000293:Adolescent; D000328:Adult; D001172:Arthritis, Rheumatoid / Q000453:epidemiology*; D002648:Child; D002675:Child, Preschool; D003876:Dermatitis, Atopic / Q000453:epidemiology*; D003922:Diabetes Mellitus, Type 1 / Q000453:epidemiology*; D005260:Female; D005858:Germany / Q000453:epidemiology; D006801:Humans; D015994:Incidence; D007223:Infant; D007231:Infant, Newborn; D015212:Inflammatory Bowel Diseases / Q000453:epidemiology*; D008297:Male; D016017:Odds Ratio; D015995:Prevalence; D012307:Risk Factors; D055815:Young Adult
keywords: Atopic dermatitis; cohort study; epidemiology; inflammatory bowel disease; rheumatoid arthritis; type 1 diabetes