Ankylosing Spondylitis Causes and Risk Factors

Experts do not understand exactly why some people get ankylosing spondylitis, but they do know many factors play a role.

Genes and Family History

The clearest risk factors involve inherited genes and family history:

• A gene called HLA-B27 is found in 85% to 95% of people with ankylosing spondylitis, though some estimates are lower. ¹ Brewerton DA, Hart FD, Nicholls A, Caffrey M, James DC, Sturrock RD. Ankylosing spondylitis and HL-A 27. The Lancet. 1973 Apr 28;301(7809):904-7. ^{, 2} Dean LE, Jones GT, Macdonald AG, Downham C, Sturrock RD, Macfarlane GJ. Global prevalence of ankylosing spondylitis. Rheumatology (Oxford). 2014;53(4):650-7. ^{, 3} Clough, JD. The Cleveland Clinic Guide to Arthritis. Kaplan Publishing. New York, NY. 2009 ^{, 4} >Poddubnyy D, Sieper J. Similarities and differences between nonradiographic and radiographic axial spondyloarthritis: a clinical, epidemiological and therapeutic assessment. Curr Opin Rheumatol 2014;26:377-383. As cited in Taurog JD, Chhabra A, Colbert RA. Ankylosing Spondylitis and Axial Spondyloarthritis. N Engl J Med. 2016 Jun 30;374(26):2563-74. doi: 10.1056/NEJMra1406182. Review. PubMed PMID: 27355535. Experts estimate only about 8% of people around the world have this gene. ⁵ J. D. Reveille, "HLA-B27 and the seronegative spondyloarthropathies," American Journal of the Medical Sciences, vol. 316, no. 4, pp. 239–249, 1998. As cited in M. H. Abdelrahman, S. Mahdy, I. A. Khanjar, et al., "Prevalence of HLA-B27 in Patients with Ankylosing Spondylitis in Qatar," International Journal of Rheumatology, vol. 2012, Article ID 860213, 3 pages, 2012. doi:10.1155/2012/860213.
• Not everyone who has HLA-B27 will get AS. Experts estimate people who carry HLA-B27 have a 2% to 10% chance of developing spondyloarthritis. ⁶ Taurog JD, Chhabra A, Colbert RA. Ankylosing Spondylitis and Axial Spondyloarthritis. N Engl J Med. 2016;374(26):2563-74.
• A family history of ankylosing spondylitis is an additional risk factor for developing the disease. For example, a person who inherits HLA-B27 and has a parent with ankylosing spondylitis has about 20% chance of developing AS. ⁷ Genetics Home Reference. Ankylosing spondylitis. https://ghr.nlm.nih.gov/condition/ankylosing-spondylitis#inheritance National Library of Medicine. Published February 7, 2017. Reviewed September 2014. Accessed February 13, 2017.
• Black people who have ankylosing spondylitis are less likely to have the HLA-B27 gene than white people who have the disease. ⁸ Khan MA. Race-Related Differences in HLA Association with Ankylosing Spondylitis and Reiter’s Disease in American Blacks and Whites. Journal of the National Medical Association. 1978;70(1):41-42.
• In addition to HLA-B27, genetic variations in genes ERAP1, IL1A, and IL23R are also linked to ankylosing spondylitis. ⁹ Genetics Home Reference. Ankylosing spondylitis. https://ghr.nlm.nih.gov/condition/ankylosing-spondylitis#inheritance National Library of Medicine. Published February 7, 2017. Reviewed September 2014. Accessed February 13, 2017.

See Understanding the Different Names and Classifications for Spondyloarthritis (SpA)

Exactly how genes and family history affect the risk of ankylosing spondylitis is not known.

Other Risk Factors

In addition to genes and family history, factors that can affect risk include:

Sex. Men are two to three times more likely to get ankylosing spondylitis than women. ¹⁰ Lee W, Reveille JD, Davis JC, Learch TJ, Ward MM, Weisman MH. Are there gender differences in severity of ankylosing spondylitis? Results from the PSOAS cohort. Ann Rheum Dis. 2007;66(5):633-8. Men also tend to have more severe symptoms. Because AS is more common in men, diagnosis in women is often overlooked or missed, especially because women tend to have pain in the neck, hips, and/or peripheral joints instead of the low back.

Age. Ankylosing spondylitis is usually diagnosed in people in their teens, 20s and 30s. Ninety-five percent of patients are diagnosed before the age of 46. ¹¹ Dean LE, Jones GT, Macdonald AG, Downham C, Sturrock RD, Macfarlane GJ. Global prevalence of ankylosing spondylitis. Rheumatology (Oxford). 2014;53(4):650-7. ^{, 12} Ankylosing Spondylitis. https://www.hopkinsarthritis.org/arthritis-info/ankylosing-spondylitis/ Last updated October 10, 2012. Accessed December 15, 2016. It is possible for children to be diagnosed: 15% of people with ankylosing spondylitis are diagnosed before age 15. ¹³ Colbert RA. Classification of juvenile spondyloarthritis: enthesitis-related arthri- tis and beyond. Nat Rev Rheumatol 2010; 6:477-85. As cited in Taurog JD, Chhabra A, Colbert RA. Ankylosing Spondylitis and Axial Spondyloarthritis. N Engl J Med. 2016 Jun 30;374(26):2563-74. doi: 10.1056/NEJMra1406182. Review. PubMed PMID: 27355535.

See 5 Unusual Ankylosing Spondylitis Symptoms

Related diseases. Past or present history of verified Crohn’s disease, ulcerative colitis, or psoriasis increases the likelihood of developing axial spondyloarthitis. ¹⁴ Taurog JD, Chhabra A, Colbert RA. Ankylosing Spondylitis and Axial Spondyloarthritis. N Engl J Med. 2016;374(26):2563-74.

Bacteria. Everyone has bacteria that live in their intestines, and these bacteria—collectively called gut microbiota—are thought to be involved in the development and regulation of the immune system. ⁵ J. D. Reveille, "HLA-B27 and the seronegative spondyloarthropathies," American Journal of the Medical Sciences, vol. 316, no. 4, pp. 239–249, 1998. As cited in M. H. Abdelrahman, S. Mahdy, I. A. Khanjar, et al., "Prevalence of HLA-B27 in Patients with Ankylosing Spondylitis in Qatar," International Journal of Rheumatology, vol. 2012, Article ID 860213, 3 pages, 2012. doi:10.1155/2012/860213. Many scientists believe that gut microbiota influence the development of ankylosing spondylitis. ¹⁶ Rashid T, Wilson C, Ebringer A. The link between ankylosing spondylitis, Crohn's disease, Klebsiella, and starch consumption. Clin Dev Immunol. 2013;2013:872632. ^{, 17} Ciccia F, Guggino G, Rizzo A, et al. Dysbiosis and zonulin upregulation alter gut epithelial and vascular barriers in patients with ankylosing spondylitis. Ann Rheum Dis. 2017; ^{, 18} Rosenbaum JT, Davey MP. Time for a gut check: evidence for the hypothesis that HLA-B27 predisposes to ankylosing spondylitis by altering the microbiome. Arthritis Rheum. 2011;63(11):3195-8. ^{, 19} Yang L, Wang L, Wang X, Xian CJ, Lu H. A Possible Role of Intestinal Microbiota in the Pathogenesis of Ankylosing Spondylitis. Int J Mol Sci. 2016;17(12) ^{, 20} Gill T, Asquith M, Rosenbaum JT, Colbert RA. The intestinal microbiome in spondyloarthritis. Curr Opin Rheumatol. 2015;27(4):319-25. While there is growing evidence for this connection, scientists are still learning about it.

Just because someone has risk factors for ankylosing spondylitis does not guarantee he or she will develop the disease.

See Development and Progression of Ankylosing Spondylitis.

These complications are quite rare and are generally only seen in the most severe cases of ankylosing spondylitis.