Comorbidities in Spondyloarthritis

  • Abhijeet Danve
  • Siba P. RaychaudhuriEmail author
Comorbidities (E Husni, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Comorbidities

Opinion statement

Spondyloarthritides (SpA) are a group of immune-mediated inflammatory diseases that affect the axial and peripheral skeleton as well as the skin, eye, and gut. Patients with SpA are at increased risk of developing certain comorbidities which may have adverse impacts on health outcomes and management of and may be associated with increased health care costs. Rheumatologists should be aware of comorbid conditions associated in order to provide comprehensive care to SpA patients. Common comorbidities include gastroduodenal ulcers, cardiovascular diseases including hypertension, myocardial infarction, and stroke, osteoporosis and vertebral fractures, sleep apnea, and lung disease.


Ankylosing spondylitis Spondyloarthritis Comorbidity 


Compliance with ethical standards

Conflict of interest

Dr. Abhijeet Danve declares no conflict of interest.

Dr. Siba Raychaudhuri declares no conflict of interest.

Human and animal rights and informed consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Source and grants


References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    •• Raychaudhuri SP, Deodhar A. The classification and diagnostic criteria of ankylosing spondylitis. J Autoimmun. 2014;48–49:128–33. Provides detailed review of the spectrum of spondyloarthritis, including descriptions of non-radiographic axial spondyloarthritis.CrossRefPubMedGoogle Scholar
  2. 2.
    Feinstein AR. The pre-therapeutic classification of co-morbidity in chronic disease. J Chronic Dis. 1970;23(7):455–68.CrossRefPubMedGoogle Scholar
  3. 3.
    • Kang JH, Chen YH, Lin HC. Comorbidity profiles among patients with ankylosing spondylitis: a nationwide population-based study. Ann Rheum Dis. 2010;69(6):1165–8. Here, the authors have studied the prevalence and risk of comorbidities in patients with ankylosing spondylitis compared with the general population.CrossRefPubMedGoogle Scholar
  4. 4.
    Bremander A, Petersson IF, Bergman S, Englund M. Population-based estimates of common comorbidities and cardiovascular disease in ankylosing spondylitis. Arthritis Care Res (Hoboken). 2011;63(4):550–6.CrossRefGoogle Scholar
  5. 5.
    • Molto A, Etcheto A, van der Heijde D, et al. Prevalence of comorbidities and evaluation of their screening in spondyloarthritis: results of the international cross-sectional ASAS-COMOSPA Study. Ann Rheum Dis. 2016;75(6):1016–23. This study informs about comorbidities in axSpA across multiple countries in different human races.CrossRefPubMedGoogle Scholar
  6. 6.
    Mathieu S, Gossec L, Dougados M, Soubrier M. Cardiovascular profile in ankylosing spondylitis: a systematic review and meta-analysis. Arthritis Care Res (Hoboken). 2011;63(4):557–63.CrossRefGoogle Scholar
  7. 7.
    Papadakis JA, Sidiropoulos PI, Karvounaris SA, et al. High prevalence of metabolic syndrome and cardiovascular risk factors in men with ankylosing spondylitis on anti-TNFalpha treatment: correlation with disease activity. Clin Exp Rheumatol. 2009;27(2):292–8.PubMedGoogle Scholar
  8. 8.
    •• Sherer Y, Shoenfeld Y. Mechanisms of disease: atherosclerosis in autoimmune diseases. Nat Clin Pract Rheumatol. 2006;2(2):99–106. Here, the authors have reviewed how autoimmune factors such as autoreactive lymphocytes or autoantibodies contribute to atherosclerosis in autoimmune rheumatic conditions.CrossRefPubMedGoogle Scholar
  9. 9.
    Bergfeldt L. HLA-B27-associated cardiac disease. Ann Intern Med. 1997;127(8 Pt 1):621–9.CrossRefPubMedGoogle Scholar
  10. 10.
    Peters MJ, van der Horst-Bruinsma IE, Dijkmans BA, Nurmohamed MT. Cardiovascular risk profile of patients with spondylarthropathies, particularly ankylosing spondylitis and psoriatic arthritis. Semin Arthritis Rheum. 2004;34(3):585–92.CrossRefPubMedGoogle Scholar
  11. 11.
    Coxib and Traditional NSAID Trialists’ (CNT) Collaboration, Bhala N, Emberson J, et al. Vascular and upper gastrointestinal effects of non-steroidal anti-inflammatory drugs: meta-analyses of individual participant data from randomised trials. Lancet. 2013;382(9894):769–79.CrossRefGoogle Scholar
  12. 12.
    Haroon NN, Paterson JM, Li P, Inman RD, Haroon N. Patients with ankylosing spondylitis have increased cardiovascular and cerebrovascular mortality: a population-based study. Ann Intern Med. 2015;163(6):409–16.CrossRefPubMedGoogle Scholar
  13. 13.
    Eriksson JK, Jacobsson L, Bengtsson K, Askling J. Is ankylosing spondylitis a risk factor for cardiovascular disease, and how do these risks compare with those in rheumatoid arthritis? Ann Rheum Dis. 2016. doi: 10.1136/annrheumdis-2016-209315.PubMedGoogle Scholar
  14. 14.
    Chou CH, Lin MC, Peng CL, et al. A nationwide population-based retrospective cohort study: increased risk of acute coronary syndrome in patients with ankylosing spondylitis. Scand J Rheumatol. 2014;43(2):132–6.CrossRefPubMedGoogle Scholar
  15. 15.
    Peters MJ, Visman I, Nielen MM, et al. Ankylosing spondylitis: a risk factor for myocardial infarction? Ann Rheum Dis. 2010;69(3):579–81.CrossRefPubMedGoogle Scholar
  16. 16.
    •• Mathieu S, Pereira B, Soubrier M. Cardiovascular events in ankylosing spondylitis: an updated meta-analysis. Semin Arthritis Rheum. 2015;44(5):551–5. Excellent meta-analysis about risk of stroke and MI in AS.CrossRefPubMedGoogle Scholar
  17. 17.
    Szabo SM, Levy AR, Rao SR, et al. Increased risk of cardiovascular and cerebrovascular diseases in individuals with ankylosing spondylitis: a population-based study. Arthritis Rheum. 2011;63(11):3294–304.CrossRefPubMedGoogle Scholar
  18. 18.
    Brophy S, Cooksey R, Atkinson M, et al. No increased rate of acute myocardial infarction or stroke among patients with ankylosing spondylitis—a retrospective cohort study using routine data. Semin Arthritis Rheum. 2012;42(2):140–5.CrossRefPubMedGoogle Scholar
  19. 19.
    Essers I, Stolwijk C, Boonen A, et al. Ankylosing spondylitis and risk of ischaemic heart disease: a population-based cohort study. Ann Rheum Dis. 2016;75(1):203–9.CrossRefPubMedGoogle Scholar
  20. 20.
    Lin CW, Huang YP, Chiu YH, Ho YT, Pan SL. Increased risk of ischemic stroke in young patients with ankylosing spondylitis: a population-based longitudinal follow-up study. PLoS One. 2014;9(4):e94027.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Keller JJ, Hsu JL, Lin SM, et al. Increased risk of stroke among patients with ankylosing spondylitis: a population-based matched-cohort study. Rheumatol Int. 2014;34(2):255–63.CrossRefPubMedGoogle Scholar
  22. 22.
    Gupta N, Saigal R, Goyal L, Agrawal A, Bhargava R, Agrawal A. Carotid intima media thickness as a marker of atherosclerosis in ankylosing spondylitis. Int J Rheumatol. 2014;2014:839135.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Ersozlu Bozkirli ED, Bozkirli E, Yucel AE. Effects of infliximab treatment in terms of cardiovascular risk and insulin resistance in ankylosing spondylitis patients. Mod Rheumatol. 2014;24(2):335–9.CrossRefPubMedGoogle Scholar
  24. 24.
    Wasko MC, Hsia EC, Kirkham B, et al. Effect of golimumab on carotid atherosclerotic disease measures and cardiovascular events in inflammatory arthritides. J Clin Rheumatol. 2014;20(1):1–10.CrossRefPubMedGoogle Scholar
  25. 25.
    Calin A. Osteoporosis and ankylosing spondylitis. Br J Rheumatol. 1991;30(4):318–9.Google Scholar
  26. 26.
    Klingberg E, Lorentzon M, Mellstrom D, et al. Osteoporosis in ankylosing spondylitis—prevalence, risk factors and methods of assessment. Arthritis Res Ther. 2012;14(3):R108.CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Reid DM, Nicoll JJ, Kennedy NS, Smith MA, Tothill P, Nuki G. Bone mass in ankylosing spondylitis. J Rheumatol. 1986;13(5):932–5.PubMedGoogle Scholar
  28. 28.
    Ghozlani I, Ghazi M, Nouijai A, et al. Prevalence and risk factors of osteoporosis and vertebral fractures in patients with ankylosing spondylitis. Bone. 2009;44(5):772–6.CrossRefPubMedGoogle Scholar
  29. 29.
    Klingberg E, Geijer M, Gothlin J, et al. Vertebral fractures in ankylosing spondylitis are associated with lower bone mineral density in both central and peripheral skeleton. J Rheumatol. 2012;39(10):1987–95.CrossRefPubMedGoogle Scholar
  30. 30.
    Montala N, Juanola X, Collantes E, et al. Prevalence of vertebral fractures by semiautomated morphometry in patients with ankylosing spondylitis. J Rheumatol. 2011;38(5):893–7.CrossRefPubMedGoogle Scholar
  31. 31.
    Vosse D, Landewe R, van der Heijde D, van der Linden S, van Staa TP, Geusens P. Ankylosing spondylitis and the risk of fracture: results from a large primary care-based nested case–control study. Ann Rheum Dis. 2009;68(12):1839–42.CrossRefPubMedGoogle Scholar
  32. 32.
    Bessant R, Harris C, Keat A. Audit of the diagnosis, assessment, and treatment of osteoporosis in patients with ankylosing spondylitis. J Rheumatol. 2003;30(4):779–82.PubMedGoogle Scholar
  33. 33.
    Magrey MN, Lewis S, Asim KM. Utility of DXA scanning and risk factors for osteoporosis in ankylosing spondylitis—a prospective study. Semin Arthritis Rheum. 2016;46(1):88–94.CrossRefPubMedGoogle Scholar
  34. 34.
    van der Weijden MA, Claushuis TA, Nazari T, Lems WF, Dijkmans BA, van der Horst-Bruinsma IE. High prevalence of low bone mineral density in patients within 10 years of onset of ankylosing spondylitis: a systematic review. Clin Rheumatol. 2012;31(11):1529–35.CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Carter S, Lories RJ. Osteoporosis: a paradox in ankylosing spondylitis. Curr Osteoporos Rep. 2011;9(3):112–5.CrossRefPubMedGoogle Scholar
  36. 36.
    Capaci K, Hepguler S, Argin M, Tas I. Bone mineral density in mild and advanced ankylosing spondylitis. Yonsei Med J. 2003;44(3):379–84.CrossRefPubMedGoogle Scholar
  37. 37.
    Devogelaer JP, Maldague B, Malghem J, Nagant de Deuxchaisnes C. Appendicular and vertebral bone mass in ankylosing spondylitis. A comparison of plain radiographs with single- and dual-photon absorptiometry and with quantitative computed tomography. Arthritis Rheum. 1992;35(9):1062–7.CrossRefPubMedGoogle Scholar
  38. 38.
    Gratacos J, Collado A, Pons F, et al. Significant loss of bone mass in patients with early, active ankylosing spondylitis: a followup study. Arthritis Rheum. 1999;42(11):2319–24.CrossRefPubMedGoogle Scholar
  39. 39.
    Jun JB, Joo KB, Her MY, et al. Femoral bone mineral density is associated with vertebral fractures in patients with ankylosing spondylitis: a cross-sectional study. J Rheumatol. 2006;33(8):1637–41.PubMedGoogle Scholar
  40. 40.
    Korkosz M, Gasowski J, Grzanka P, et al. Baseline new bone formation does not predict bone loss in ankylosing spondylitis as assessed by quantitative computed tomography (QCT): 10-year follow-up. BMC Musculoskelet Disord. 2011;12:121.Google Scholar
  41. 41.
    • Ward MM, Deodhar A, Akl EA, et al. American College of Rheumatology/Spondylitis Association of America/Spondyloarthritis Research and Treatment Network 2015 recommendations for the treatment of ankylosing spondylitis and nonradiographic axial spondyloarthritis. Arthritis Rheumatol. 2016;68(2):282–98. Recommendations from ACR-SPARTAN-SAA to guide about management of comorbidities.CrossRefPubMedGoogle Scholar
  42. 42.
    Davey-Ranasinghe N, Deodhar A. Osteoporosis and vertebral fractures in ankylosing spondylitis. Curr Opin Rheumatol. 2013;25(4):509–16. This study reviews the risks and underlying causes of osteoporosis and fractures in AS.CrossRefPubMedGoogle Scholar
  43. 43.
    Siu S, Haraoui B, Bissonnette R, et al. Meta-analysis of tumor necrosis factor inhibitors and glucocorticoids on bone density in rheumatoid arthritis and ankylosing spondylitis trials. Arthritis Care Res (Hoboken). 2015;67(6):754–64.CrossRefGoogle Scholar
  44. 44.
    Visvanathan S, van der Heijde D, Deodhar A, et al. Effects of infliximab on markers of inflammation and bone turnover and associations with bone mineral density in patients with ankylosing spondylitis. Ann Rheum Dis. 2009;68(2):175–82.CrossRefPubMedGoogle Scholar
  45. 45.
    Kang KY, Kim IJ, Jung SM, et al. Incidence and predictors of morphometric vertebral fractures in patients with ankylosing spondylitis. Arthritis Res Ther. 2014;16(3):R124.CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Maas F, Spoorenberg A, van der Slik BP, et al. Clinical risk factors for the presence and development of vertebral fractures in patients with ankylosing spondylitis. Arthritis Care Res (Hoboken). 2016. doi: 10.1002/acr.22980.
  47. 47.
    Sivri A, Kilinc S, Gokce-Kutsal Y, Ariyurek M. Bone mineral density in ankylosing spondylitis. Clin Rheumatol. 1996;15(1):51–4.CrossRefPubMedGoogle Scholar
  48. 48.
    Cooper C, Carbone L, Michet CJ, Atkinson EJ, O’Fallon WM, Melton 3rd LJ. Fracture risk in patients with ankylosing spondylitis: a population based study. J Rheumatol. 1994;21(10):1877–82.PubMedGoogle Scholar
  49. 49.
    Einsiedel T, Schmelz A, Arand M, et al. Injuries of the cervical spine in patients with ankylosing spondylitis: experience at two trauma centers. J Neurosurg Spine. 2006;5(1):33–45.CrossRefPubMedGoogle Scholar
  50. 50.
    Thumbikat P, Hariharan RP, Ravichandran G, McClelland MR, Mathew KM. Spinal cord injury in patients with ankylosing spondylitis: a 10-year review. Spine (Phila Pa 1976). 2007;32(26):2989–95.CrossRefGoogle Scholar
  51. 51.
    Westerveld LA, Verlaan JJ, Oner FC. Spinal fractures in patients with ankylosing spinal disorders: a systematic review of the literature on treatment, neurological status and complications. Eur Spine J. 2009;18(2):145–56.CrossRefPubMedGoogle Scholar
  52. 52.
    Sambrook PN, Geusens P. The epidemiology of osteoporosis and fractures in ankylosing spondylitis. Ther Adv Musculoskelet Dis. 2012;4(4):287–92.CrossRefPubMedPubMedCentralGoogle Scholar
  53. 53.
    Kang JH, Lin HC. Obstructive sleep apnea and the risk of autoimmune diseases: a longitudinal population-based study. Sleep Med. 2012;13(6):583–8.CrossRefPubMedGoogle Scholar
  54. 54.
    • Solak O, Fidan F, Dundar U, et al. The prevalence of obstructive sleep apnea syndrome in ankylosing spondylitis patients. Rheumatology (Oxford). 2009;48(4):433–5. An informative study about the association of sleep apnea with AS.CrossRefGoogle Scholar
  55. 55.
    Sung JJ, Kuipers EJ, El-Serag HB. Systematic review: the global incidence and prevalence of peptic ulcer disease. Aliment Pharmacol Ther. 2009;29(9):938–46.CrossRefPubMedGoogle Scholar
  56. 56.
    Wolfe MM, Lichtenstein DR, Singh G. Gastrointestinal toxicity of nonsteroidal antiinflammatory drugs. N Engl J Med. 1999;340(24):1888–99.CrossRefPubMedGoogle Scholar
  57. 57.
    Shen CC, Hu LY, Yang AC, Kuo BI, Chiang YY, Tsai SJ. Risk of psychiatric disorders following ankylosing spondylitis: a nationwide population-based retrospective cohort study. J Rheumatol. 2016;43(3):625–31.CrossRefPubMedGoogle Scholar
  58. 58.
    Barlow JH, Macey SJ, Struthers GR. Gender, depression, and ankylosing spondylitis. Arthritis Care Res. 1993;6(1):45–51.CrossRefPubMedGoogle Scholar
  59. 59.
    Meesters JJ, Bremander A, Bergman S, Petersson IF, Turkiewicz A, Englund M. The risk for depression in patients with ankylosing spondylitis: a population-based cohort study. Arthritis Res Ther. 2014;16(5):418.CrossRefPubMedPubMedCentralGoogle Scholar
  60. 60.
    Hellgren K, Smedby KE, Backlin C, et al. Ankylosing spondylitis, psoriatic arthritis, and risk of malignant lymphoma: a cohort study based on nationwide prospectively recorded data from Sweden. Arthritis Rheumatol. 2014;66(5):1282–90.CrossRefPubMedGoogle Scholar
  61. 61.
    •• Hellgren K, Dreyer L, Arkema EV, et al. Cancer risk in patients with spondyloarthritis treated with TNF inhibitors: a collaborative study from the ARTIS and DANBIO registers. Ann Rheum Dis. 2017;76:105–11. Excellent study about malignancy risk in AS.Google Scholar
  62. 62.
    Fouque-Aubert A, Jette-Paulin L, Combescure C, Basch A, Tebib J, Gossec L. Serious infections in patients with ankylosing spondylitis with and without TNF blockers: a systematic review and meta-analysis of randomised placebo-controlled trials. Ann Rheum Dis. 2010;69(10):1756–61.CrossRefPubMedGoogle Scholar
  63. 63.
    Wallis D, Thavaneswaran A, Haroon N, Ayearst R, Inman R. Infection risk in ankylosing spondylitis: results from a longitudinal observational cohort. Arthritis Rheum. 2013;65:1507.Google Scholar
  64. 64.
    Listing J, Strangfeld A, Kary S, et al. Infections in patients with rheumatoid arthritis treated with biologic agents. Arthritis Rheum. 2005;52(11):3403–12.CrossRefPubMedGoogle Scholar
  65. 65.
    Kanathur N, Lee-Chiong T. Pulmonary manifestations of ankylosing spondylitis. Clin Chest Med. 2010;31(3):547–54.CrossRefPubMedGoogle Scholar
  66. 66.
    El Maghraoui A, Dehhaoui M. Prevalence and characteristics of lung involvement on high resolution computed tomography in patients with ankylosing spondylitis: a systematic review. Pulm Med. 2012;2012:965956.CrossRefPubMedPubMedCentralGoogle Scholar
  67. 67.
    Lee CC, Lee SH, Chang IJ, et al. Spontaneous pneumothorax associated with ankylosing spondylitis. Rheumatology (Oxford). 2005;44(12):1538–41.CrossRefGoogle Scholar
  68. 68.
    Berdal G, Halvorsen S, van der Heijde D, Mowe M, Dagfinrud H. Restrictive pulmonary function is more prevalent in patients with ankylosing spondylitis than in matched population controls and is associated with impaired spinal mobility: a comparative study. Arthritis Res Ther. 2012;14(1):R19.CrossRefPubMedPubMedCentralGoogle Scholar
  69. 69.
    Jakobsen AK, Jacobsson LT, Patschan O, Askling J, Kristensen LE. Is nephrolithiasis an unrecognized extra-articular manifestation in ankylosing spondylitis? A prospective population-based Swedish national cohort study with matched general population comparator subjects. PLoS One. 2014;9(11):e113602.CrossRefPubMedPubMedCentralGoogle Scholar
  70. 70.
    Strobel ES, Fritschka E. Renal diseases in ankylosing spondylitis: review of the literature illustrated by case reports. Clin Rheumatol. 1998;17(6):524–30.CrossRefPubMedGoogle Scholar
  71. 71.
    Donmez S, Pamuk ON, Pamuk GE, Aydogdu E, Inman R. Secondary amyloidosis in ankylosing spondylitis. Rheumatol Int. 2013;33(7):1725–9.CrossRefPubMedGoogle Scholar
  72. 72.
    Levy AR, Szabo SM, Rao SR, Cifaldi M, Maksymowych WP. Estimating the occurrence of renal complications among persons with ankylosing spondylitis. Arthritis Care Res (Hoboken). 2014;66(3):440–5.CrossRefGoogle Scholar
  73. 73.
    •• Farber EM, Raychaudhuri SP. Concept of total care: a third dimension in the treatment of psoriasis. Cutis. 1997;59:35–9. Here, the authors have provided their original idea about the concept of total care for chronic inflammatory diseases, keeping psoriasis as the disease model.PubMedGoogle Scholar
  74. 74.
    • Raychaudhuri SP. Comorbidities of psoriatic arthritis—metabolic syndrome and prevention: a report from the GRAPPA 2010 annual meeting. J Rheumatol. 2012;39:437–40. This article provides the concept of total care for the treatment of comorbidities in psoriatic arthritis by rheumatologists in their day-to-day practice.Google Scholar

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© Springer International Publishing AG (outside the USA) 2017

Authors and Affiliations

  1. 1.Yale New Haven HospitalYale University School of MedicineNew HavenUSA
  2. 2.Rheumatology and ImmunologyVA Sacramento Medical CenterMatherUSA
  3. 3.Rheumatology, Allergy & Clinical Immunology, School of MedicineUC DavisDavisUSA

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