Ankylosing spondylitis risk factors: a systematic literature review

Clin Rheumatol. 2021 Aug;40(8):3079-3093. doi: 10.1007/s10067-021-05679-7. Epub 2021 Mar 22.


Radiographic axial spondyloarthritis (also known as ankylosing spondylitis [AS]) is a chronic immune-mediated arthritis characterized by inflammation of the axial skeleton, peripheral joints, and entheses. It is estimated that 1 in every 200 people are affected by AS, making it an important healthcare and socioeconomic issue. In this review, we aim to explore the current understanding of AS risk factors and provide a comprehensive update. Multiple search strings were used to identify articles of interest published in PubMed between January 1, 2013, and February 1, 2021. On the basis of the literature review and analysis, we present up-to-date information on the risk factors of developing AS and our viewpoints on disease onset and progression. Multiple genetic and nongenetic risk factors have been suggested in the onset of AS. HLA-B27 is known to have a strong association with the disease, but other genes have been implicated in disease development. Aside from genetics, other factors are thought to be involved; up to 70% of patients with AS have subclinical intestinal inflammation, suggesting that the origin of the disease may be in the gut. The exact mechanism by which AS onset begins is most likely complex and multifactorial. Key Points • It remains unclear how interactions between genes, microbes, mechanical stress, gender, and other environmental and lifestyle factors predispose patients to the development of ankylosing spondylitis (AS). • The exact mechanisms of AS are complex and multifactorial which will require much future research • Recognizing the risk factors, as well as understanding gene-environment interactions, may offer valuable insights into the etiology of AS and have important implications for diagnosis and treatment strategies.

Keywords: Ankylosing spondylitis; Genetics; HLA-B27; Pathogenesis; Radiographic axial spondyloarthritis; Risk factors.

Publication types

  • Systematic Review

MeSH terms

  • HLA-B27 Antigen / genetics
  • Humans
  • Inflammation
  • Risk Factors
  • Spondylarthritis*
  • Spondylitis, Ankylosing* / epidemiology
  • Spondylitis, Ankylosing* / genetics


  • HLA-B27 Antigen