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Nationwide population-based cohort study of celiac disease and risk of Ehlers-Danlos syndrome and joint hypermobility syndrome

  • Author Footnotes
    1 These authors contributed equally to this work.
    Monika Laszkowska
    Footnotes
    1 These authors contributed equally to this work.
    Affiliations
    Celiac Disease Center, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY, USA
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  • Author Footnotes
    1 These authors contributed equally to this work.
    Abhik Roy
    Footnotes
    1 These authors contributed equally to this work.
    Affiliations
    Celiac Disease Center, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY, USA
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  • Benjamin Lebwohl
    Affiliations
    Celiac Disease Center, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY, USA

    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
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  • Peter H.R. Green
    Affiliations
    Celiac Disease Center, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY, USA
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  • Heléne E.K. Sundelin
    Affiliations
    Department of Pediatrics, Linköping, University Hospital, Linköping, Sweden
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  • Jonas F. Ludvigsson
    Correspondence
    Corresponding author at: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, 171 77 Stockholm, Sweden. Tel.: +46 019 6021000; fax: +46 08 31 49 75.
    Affiliations
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden

    Department of Pediatrics, Örebro University Hospital, Örebro, Sweden

    Division of Epidemiology and Public Health, School of Medicine, University of Nottingham, Nottingham, UK
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  • Author Footnotes
    1 These authors contributed equally to this work.

      Abstract

      Background

      Patients with celiac disease (CD) often have articular complaints, and small prior studies suggest an association with Ehlers-Danlos syndrome (EDS)/joint hypermobility syndrome (JHS).

      Aims

      This study examines the risks of EDS/JHS in patients with CD.

      Methods

      This cohort study compared all individuals in Sweden diagnosed with CD based on small intestinal biopsy between 1969–2008 (n = 28,631) to 139,832 matched reference individuals, and to a second reference group undergoing biopsy without having CD (n = 16,104). Rates of EDS/JHS were determined based on diagnostic codes in the Swedish Patient Register. Hazard ratios (HRs) for EDS/JHS were estimated through Cox regression.

      Results

      There are 45 and 148 cases of EDS/JHS in patients with CD and reference individuals, respectively. This corresponds to a 49% increased risk of EDS/JHS in CD (95%CI = 1.07–2.07). The HR for EDS was 2.43 (95%CI = 1.20–4.91) and for JHS 1.34 (95%CI = 0.93–1.95). Compared to reference individuals undergoing intestinal biopsy, CD was not a risk factor for EDS/JHS. A stronger association was seen in patients initially diagnosed with EDS/JHS and subsequently diagnosed with CD (odds ratio = 2.29; 95%CI = 1.21–4.34).

      Conclusions

      Individuals with CD have higher risk of EDS/JHS than the general population, which may be due to surveillance bias or factors intrinsic to celiac development.

      Keywords

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      References

        • Ludvigsson J.F.
        • Green P.H.
        Clinical management of coeliac disease.
        Journal of Internal Medicine. 2011; 269: 560-571
        • Sollid L.M.
        • Thorsby E.
        HLA susceptibility genes in celiac disease: genetic mapping and role in pathogenesis.
        Gastroenterology. 1993; 105: 910-922
        • Elfstrom P.
        • Granath F.
        • Ekstrom Smedby K.
        • et al.
        Risk of lymphoproliferative malignancy in relation to small intestinal histopathology among patients with celiac disease.
        Journal of the National Cancer Institute. 2011; 103: 436-444
        • Elfstrom P.
        • Sundstrom J.
        • Ludvigsson J.F.
        Systematic review with meta-analysis: associations between coeliac disease and type 1 diabetes.
        Alimentary Pharmacology and Therapeutics. 2014; 40: 1123-1132
        • Reilly N.R.
        • Lebwohl B.
        • Hultcrantz R.
        • et al.
        Increased risk of nonalcoholic fatty liver disease after diagnosis of celiac disease.
        Journal of Hepatology. 2015;
        • Conti V.
        • Leone M.C.
        • Casato M.
        • et al.
        High prevalence of gluten sensitivity in a cohort of patients with undifferentiated connective tissue disease.
        European Annals of Allergy and Clinical Immunology. 2015; 47: 54-57
        • Hull R.
        Rheumatoid arthritis and coeliac disease.
        Lancet. 1989; 1: 330
        • Gutierrez-Achury J.
        • Coutinho de Almeida R.
        • Wijmenga C.
        Shared genetics in coeliac disease and other immune-mediated diseases.
        Journal of Internal Medicine. 2011; 269: 591-603
        • Atteno M.
        • Costa L.
        • Tortora R.
        • et al.
        The occurrence of lower limb enthesopathy in coeliac disease patients without clinical signs of articular involvement.
        Rheumatology. 2013; 52: 893-897
        • Lubrano E.
        • Ciacci C.
        • Ames P.R.
        • et al.
        The arthritis of coeliac disease: prevalence and pattern in 200 adult patients.
        British Journal of Rheumatology. 1996; 35: 1314-1318
        • Rodrigo L.
        • Blanco I.
        • Bobes J.
        • et al.
        Remarkable prevalence of coeliac disease in patients with irritable bowel syndrome plus fibromyalgia in comparison with those with isolated irritable bowel syndrome: a case-finding study.
        Arthritis Research and Therapy. 2013; 15: R201
        • Castori M.
        Ehlers-Danlos syndrome, hypermobility type: an underdiagnosed hereditary connective tissue disorder with mucocutaneous, articular, and systemic manifestations.
        ISRN Dermatology. 2012; 2012: 751768
        • Beighton P.
        • De Paepe A.
        • Steinmann B.
        • et al.
        Ehlers-Danlos syndromes: revised nosology, Villefranche, 1997. Ehlers-Danlos National Foundation (USA) and Ehlers-Danlos Support Group (UK).
        American Journal of Medical Genetics. 1998; 77: 31-37
        • Colombi M.
        • Dordoni C.
        • Chiarelli N.
        • et al.
        Differential diagnosis and diagnostic flow chart of joint hypermobility syndrome/Ehlers-Danlos syndrome hypermobility type compared to other heritable connective tissue disorders.
        American Journal of Medical Genetics Part C, Seminars in Medical Genetics. 2015; 169C: 6-22
        • Castori M.
        • Morlino S.
        • Pascolini G.
        • et al.
        Gastrointestinal and nutritional issues in joint hypermobility syndrome/Ehlers-Danlos syndrome, hypermobility type.
        American Journal of Medical Genetics Part C, Seminars in Medical Genetics. 2015; 169C: 54-75
        • Zarate N.
        • Farmer A.D.
        • Grahame R.
        • et al.
        Unexplained gastrointestinal symptoms and joint hypermobility: is connective tissue the missing link.
        Neurogastroenterology and Motility. 2010; 22: 252-278
        • Reilly D.J.
        • Chase J.W.
        • Hutson J.M.
        • et al.
        Connective tissue disorder – a new subgroup of boys with slow transit constipation.
        Journal of Pediatric Surgery. 2008; 43: 1111-1114
        • Arunkalaivanan A.S.
        • Morrison A.
        • Jha S.
        • et al.
        Prevalence of urinary and faecal incontinence among female members of the hypermobility syndrome Association (HMSA).
        Journal of Obstetrics and Gynaecology. 2009; 29: 126-128
        • Vounotrypidis P.
        • Efremidou E.
        • Zezos P.
        • et al.
        Prevalence of joint hypermobility and patterns of articular manifestations in patients with inflammatory bowel disease.
        Gastroenterology Research and Practice. 2009; 2009: 924138
        • Fikree A.
        • Aktar R.
        • Grahame R.
        • et al.
        Functional gastrointestinal disorders are associated with the joint hypermobility syndrome in secondary care: a case-control study.
        Neurogastroenterology and Motility. 2015; 27: 569-579
        • Danese C.
        • Castori M.
        • Celletti C.
        • et al.
        Screening for celiac disease in the joint hypermobility syndrome/Ehlers-Danlos syndrome hypermobility type.
        American Journal of Medical Genetics Part A. 2011; 155A: 2314-2316
      1. Ehlers-Danlos Syndrome, Hypermobility Type. http://www.ncbi.nlm.nih.gov/books/NBK1279/.

        • Ludvigsson J.F.
        • Andersson E.
        • Ekbom A.
        • et al.
        External review and validation of the Swedish national inpatient register.
        BMC Public Health. 2011; 11: 450
        • Ludvigsson J.F.
        • Otterblad-Olausson P.
        • Pettersson B.U.
        • et al.
        The Swedish personal identity number: possibilities and pitfalls in healthcare and medical research.
        European Journal of Epidemiology. 2009; 24: 659-667
        • Ludvigsson J.F.
        • Brandt L.
        • Montgomery S.M.
        • et al.
        Validation study of villous atrophy and small intestinal inflammation in Swedish biopsy registers.
        BMC Gastroenterology. 2009; 9: 19
        • Ludvigsson J.F.
        • Montgomery S.M.
        • Ekbom A.
        • et al.
        Small-intestinal histopathology and mortality risk in celiac disease.
        JAMA. 2009; 302: 1171-1178
        • Ludvigsson J.F.
        • Brandt L.
        • Montgomery S.M.
        Symptoms and signs in individuals with serology positive for celiac disease but normal mucosa.
        BMC Gastroenterology. 2009; 9: 57
        • Olen O.
        • Bihagen E.
        • Rasmussen F.
        • et al.
        Socioeconomic position and education in patients with coeliac disease.
        Digestive and Liver Disease. 2012;
      2. http://www.skyscape.com/products/products.cgi?id=246.

        • Waldenlind K.
        • Eriksson J.K.
        • Grewin B.
        • et al.
        Validation of the rheumatoid arthritis diagnosis in the Swedish National Patient Register: a cohort study from Stockholm County.
        BMC Musculoskeletal Disorders. 2014; 15: 432
        • Shirley E.D.
        • Demaio M.
        • Bodurtha J.
        Ehlers-Danlos syndrome in orthopaedics: etiology, diagnosis, and treatment implications.
        Sports Health. 2012; 4: 394-403
        • Scher D.L.
        • Owens B.D.
        • Sturdivant R.X.
        • et al.
        Incidence of joint hypermobility syndrome in a military population: impact of gender and race.
        Clinical Orthopaedics and Related Research. 2010; 468: 1790-1795
        • Hoffman G.S.
        • Filie J.D.
        • Schumacher Jr., H.R.
        • et al.
        Intractable vasculitis, resorptive osteolysis, and immunity to type I collagen in type VIII Ehlers-Danlos syndrome.
        Arthritis and Rheumatism. 1991; 34: 1466-1475
        • Dieterich W.
        • Esslinger B.
        • Trapp D.
        • et al.
        Cross linking to tissue transglutaminase and collagen favours gliadin toxicity in coeliac disease.
        Gut. 2006; 55: 478-484
        • Zhao X.
        • Johnson R.L.
        Collagenous sprue: a rare, severe small-bowel malabsorptive disorder.
        Archives of Pathology and Laboratory Medicine. 2011; 135: 803-809