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A positive Helicobacter pylori test is associated with low spondylarthritis incidence in a Danish historical cohort study

  • Lars E. BartelsEmail author
  • Alma B. Pedersen
  • Nickolaj R. Kristensen
  • Hendrik Vilstrup
  • Kristian Stengaard-Pedersen
  • Jens F. Dahlerup
Cohort Studies
  • 13 Downloads

Abstract

Ankylosing spondylitis (AS) and undifferentiated spondylarthritis (uSpA) are related inflammatory diseases affecting the spine and joints with infections among possible etiological factors. Helicobacter pylori (H. pylori) may affect the development of inflammatory diseases. Thus, we hypothesized that H. pylori infection affects AS and uSpA development. This cohort study was performed in Denmark with 56,000 patients from primary health care centers who were enrolled when a UBT was performed. They were followed for a median time of 8 years. From nationwide administrative registries, we extracted personal, diagnostic, and treatment information. Prevalence at time of UBT was studied on enrollment using logistic regression and incidence in the follow-up time of 8 years after UBT was studied using Cox regression, comparing H. pylori positive and H. pylori negative patients and adjusting for confounding variables. The prevalence of AS at the time of the UBT was higher among H. pylori positive individuals (OR = 2.00, CI 1.17–3.41), but likely to be linked to confounding as trends disappeared when stratifying for country of birth. The incidence of AS after UBT was lower for individuals who were previously H. pylori positive (OR = 0.23, CI 0.06–0.93). A similar phenomenon was observed for uSpA. As a novel finding, after UBT, the previously H. pylori infected individuals had lower risk of developing AS and uSpA compared to non-infected. This finding may be caused by etiological effects of previous H. pylori infection or unknown confounders. This suggests that H. pylori may somehow be positively involved in the pathogenesis of AS and uSpA.

Keywords

Helicobacter pylori Ankylosing spondylitis Spondylarthritis Epidemiology 

Notes

Acknowledgements

The study was arranged by the author group. The H. pylori database was mainly constructed by Jens F. Dahlerup and Hendrik Vilstrup. Alma B. Pedersen and Nickolaj R. Kristensen performed most data analysis. Kristian Stengaard-Pedersen participated significantly in data interpretation. As the lead author Lars Erik Bartels wrote the body of the manuscript and all the authors contributed to and approved the final version of the manuscript.

Funding

The data supporting the main conclusion has not been presented before. The project was funded by The Danish Rheumatism Association, Health Research Fund of Central Denmark Region, Program for Clinical Research Infrastructure (PROCRIN), and Clara Hansens Foundation.

Compliance with ethical standards

Conflict of interest

All authors declare no support from any organization for the submitted work; no financial relationships with any organizations that might have an interest in the submitted work in the previous three years; and no other relationships or activities that could appear to have influenced the submitted work.

References

  1. 1.
    Sieper J, Poddubnyy D (2017) Axial spondyloarthritis. Lancet 390:73–84CrossRefGoogle Scholar
  2. 2.
    Costello ME, Ciccia F, Willner D, Warrington N, Robinson PC, Gardiner B et al (2015) Brief report: intestinal dysbiosis in Ankylosing Spondylitis. Arthritis Rheumatol 67:686–691CrossRefGoogle Scholar
  3. 3.
    Yang L, Wang L, Wang X, Xian CJ, Lu H (2016) A possible role of intestinal microbiota in the pathogenesis of Ankylosing Spondylitis. Int J Mol Sci.  https://doi.org/10.3390/ijms17122126 CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Karreman MC, Luime JJ, Hazes JM, Weel AE (2016) The prevalence and incidence of axial and peripheral spondyloarthritis in inflammatory bowel disease: a systematic review and meta-analysis. J Crohns Colitis 11(5):631–642Google Scholar
  5. 5.
    Orchard TR, Holt H, Bradbury L, Hammersma J, McNally E, Jewell DP et al (2009) The prevalence, clinical features and association of HLA-B27 in sacroiliitis associated with established Crohn’s disease. Aliment Pharmacol Ther 29:193–197CrossRefGoogle Scholar
  6. 6.
    Ossum AM, Palm O, Lunder AK, Cvancarova M, Banitalebi H, Negard A et al (2018) Ankylosing spondylitis and axial spondyloarthritis in patients with long-term inflammatory bowel disease: results from 20 years of Follow-up in the IBSEN study. J Crohns Colitis 12:96–104CrossRefGoogle Scholar
  7. 7.
    Sonnenberg A, Genta RM (2012) Low prevalence of Helicobacter pylori infection among patients with inflammatory bowel disease. Aliment Pharmacol Ther 35:469–476CrossRefGoogle Scholar
  8. 8.
    Bartels LE, Jepsen P, Christensen LA, Gerdes LU, Vilstrup H, Dahlerup JF (2016) Diagnosis of Helicobacter pylori infection is associated with lower prevalence and subsequent incidence of Crohn’s disease. J Crohns Colitis 10(4):443–448CrossRefGoogle Scholar
  9. 9.
    Franceschi F, Zuccala G, Roccarina D, Gasbarrini A (2014) Clinical effects of Helicobacter pylori outside the stomach. Nat Rev Gastroenterol Hepatol 11(4):234–242CrossRefGoogle Scholar
  10. 10.
    Dahlerup S, Andersen RC, Nielsen BS, Schjodt I, Christensen LA, Gerdes LU et al (2011) First-time urea breath tests performed at home by 36,629 patients: a study of Helicobacter pylori prevalence in primary care. Helicobacter 16:468–474CrossRefGoogle Scholar
  11. 11.
    Brown LM (2000) Helicobacter pylori: epidemiology and routes of transmission. Epidemiol Rev 22:283–297CrossRefGoogle Scholar
  12. 12.
    Calvet X, Ramirez Lazaro MJ, Lehours P, Megraud F (2013) Diagnosis and epidemiology of Helicobacter pylori infection. Helicobacter 18(Suppl 1):5–11CrossRefGoogle Scholar
  13. 13.
    Lehours P, Yilmaz O (2007) Epidemiology of Helicobacter pylori infection. Helicobacter 12(Suppl 1):1–3CrossRefGoogle Scholar
  14. 14.
    Suerbaum S, Michetti P (2002) Helicobacter pylori infection. N Engl J Med 347:1175–1186CrossRefGoogle Scholar
  15. 15.
    Bytzer P, Dahlerup JF, Eriksen JR, Jarbol DE, Rosenstock S, Wildt S et al (2011) Diagnosis and treatment of Helicobacter pylori infection. Dan Med Bull 58:C4271PubMedGoogle Scholar
  16. 16.
    Hasni S, Ippolito A, Illei GG (2011) Helicobacter pylori and autoimmune diseases. Oral Dis 17:621–627CrossRefGoogle Scholar
  17. 17.
    Schmidt M, Pedersen L, Sorensen HT (2014) The Danish Civil Registration System as a tool in epidemiology. Eur J Epidemiol 29:541–549CrossRefGoogle Scholar
  18. 18.
    Schmidt M, Schmidt SA, Sandegaard JL, Ehrenstein V, Pedersen L, Sorensen HT (2015) The Danish National Patient Registry: a review of content, data quality, and research potential. Clin Epidemiol 7:449–490CrossRefGoogle Scholar
  19. 19.
    Johannesdottir SA, Horvath-Puho E, Ehrenstein V, Schmidt M, Pedersen L, Sorensen HT (2012) Existing data sources for clinical epidemiology: The Danish National database of reimbursed prescriptions. Clin Epidemiol 4:303–313CrossRefGoogle Scholar
  20. 20.
    Charlson ME, Pompei P, Ales KL, MacKenzie CR (1987) A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis 40:373–383CrossRefGoogle Scholar
  21. 21.
    Dubreuil M, Peloquin C, Zhang Y, Choi HK, Inman RD, Neogi T (2016) Validity of ankylosing spondylitis diagnoses in the health improvement network. Pharmacoepidemiol Drug Saf 25:399–404CrossRefGoogle Scholar
  22. 22.
    Lindstrom U, Exarchou S, Sigurdardottir V, Sundstrom B, Askling J, Eriksson JK et al (2015) Validity of ankylosing spondylitis and undifferentiated spondyloarthritis diagnoses in the Swedish National Patient Register. Scand J Rheumatol 44:369–376CrossRefGoogle Scholar
  23. 23.
    Lynge E, Sandegaard JL, Rebolj M (2011) The Danish National Patient Register. Scand J Public Health 39:30–33CrossRefGoogle Scholar
  24. 24.
    Malfertheiner P, Megraud F, O'Morain CA, Gisbert JP, Kuipers EJ, Axon AT et al (2017) Management of Helicobacter pylori infection-the Maastricht V/Florence consensus report. Gut 66:6–30CrossRefGoogle Scholar
  25. 25.
    Rashid T, Ebringer A, Wilson C (2016) The link between Klebsiella and Ankylosing Spondylitis in worldwide geographical locations. Curr Rheumatol Rev 12:223–231CrossRefGoogle Scholar
  26. 26.
    Jackson L, Britton J, Lewis SA, McKeever TM, Atherton J, Fullerton D et al (2009) A population-based epidemiologic study of Helicobacter pylori infection and its association with systemic inflammation. Helicobacter 14:108–113CrossRefGoogle Scholar
  27. 27.
    Di Leo V, D'Inca R, Bettini MB, Podswiadek M, Punzi L, Mastropaolo G et al (2005) Effect of Helicobacter pylori and eradication therapy on gastrointestinal permeability. Implications for patients with seronegative spondyloarthritis. J Rheumatol 32:295–300PubMedGoogle Scholar
  28. 28.
    Rodrigues IK, Andrigueti M, de Oliveira Gil ID, de Lucca SL, de Andrade KR, Pereira IA et al (2015) An investigation into the relationship between anti-Helicobacter pylori and anti-Saccharomyces cerevisiae antibodies in patients with axial spondyloarthritis and Crohn disease. Rheumatol Int 35:359–366CrossRefGoogle Scholar
  29. 29.
    Vaile JH, Meddings JB, Yacyshyn BR, Russell AS, Maksymowych WP (1999) Bowel permeability and CD45RO expression on circulating CD20+ B cells in patients with ankylosing spondylitis and their relatives. J Rheumatol 26:128–135PubMedGoogle Scholar
  30. 30.
    Martinez-Gonzalez O, Cantero-Hinojosa J, Paule-Sastre P, Gomez-Magan JC, Salvatierra-Rios D (1994) Intestinal permeability in patients with ankylosing spondylitis and their healthy relatives. Br J Rheumatol 33:644–647CrossRefGoogle Scholar
  31. 31.
    Arnold IC, Hitzler I, Muller A (2012) The immunomodulatory properties of Helicobacter pylori confer protection against allergic and chronic inflammatory disorders. Front Cell Infect Microbiol 2:10CrossRefGoogle Scholar
  32. 32.
    He C, Yang Z, Lu N (2016) Imbalance of gastrointestinal microbiota in the pathogenesis of Helicobacter pylori-associated diseases. Helicobacter 21:337–348CrossRefGoogle Scholar
  33. 33.
    Yap TW, Gan HM, Lee YP, Leow AH, Azmi AN, Francois F et al (2016) Helicobacter pylori eradication causes perturbation of the human gut microbiome in young adults. PLoS ONE 11:e0151893CrossRefGoogle Scholar
  34. 34.
    Otasevic L, Zlatanovic G, Stanojevic-Paovic A, Miljkovic-Selimovic B, Dinic M, Djordjevic-Jocic J et al (2007) Helicobacter pylori: an underestimated factor in acute anterior uveitis and spondyloarthropathies? Ophthalmologica 221:6–13CrossRefGoogle Scholar
  35. 35.
    Bae JH, Kim JM (2015) The rate of Helicobacter pylori seropositivity in a group of Korean patients with HLA-B27-associated acute anterior uveitis. PLoS ONE 10:e0123924CrossRefGoogle Scholar
  36. 36.
    Bartels LE, Pedersen AB, Kristensen NR, Jepsen P, Vilstrup H, Stengaard-Pedersen K et al (2018) Helicobacter pylori infection is not associated with rheumatoid arthritis. Scand J Rheumatol 48:24–31CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of RheumatologyAarhus University HospitalAarhus NDenmark
  2. 2.Department of Clinical EpidemiologyAarhus University HospitalAarhus NDenmark
  3. 3.Department of Hepatology and GastroenterologyAarhus University HospitalAarhus NDenmark

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