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Age at symptom onset in ankylosing spondylitis: is there a gender difference?
  1. Adrian Ciurea1,
  2. Almut Scherer2,
  3. Ulrich Weber3,
  4. Regula Neuenschwander4,
  5. Giorgio Tamborrini5,
  6. Pascale Exer6,
  7. Jürg Bernhard7,
  8. Peter M Villiger8,
  9. Rudolf Kissling3,
  10. Beat A Michel1,
  11. Daniel Stekhoven2
  12. on behalf of the rheumatologists of the Swiss Clinical Quality Management Program for axial spondyloarthritis
  1. 1 Department of Rheumatology, University Hospital, Zurich, Switzerland
  2. 2 Swiss Clinical Quality Management Foundation, Zurich, Switzerland
  3. 3 King Christian 10th Hospital for Rheumatic Diseases, Gråsten, Denmark
  4. 4 University of Zurich, Zurich, Switzerland
  5. 5 Department of Rheumatology, Bethesda Hospital, Basel, Switzerland
  6. 6 Praxis Rheuma-Basel, Basel, Switzerland
  7. 7 Department of Rheumatology and Rehabilitation, Bürgerspital, Solothurn, Switzerland
  8. 8 Department of Rheumatology and Clinical Immunology, Inselspital, Bern, Switzerland
  1. Correspondence to Dr Adrian Ciurea, Department of Rheumatology, University Hospital Zurich, Gloriastrasse 25, Zurich CH-8091, Switzerland; adrian.ciurea{at}usz.ch

https://doi.org/10.1136/annrheumdis-2014-205613

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    The impact of human leukocyte antigen (HLA)-B27 on the age at disease onset in patients with ankylosing spondylitis (AS) has consistently been shown in several cohorts.1–⇓⇓4 A potential gender difference with respect to age at symptom onset remains, however, controversial5–⇓⇓8 as the distribution of HLA-B27 within these populations is not known in all studies. While no sex differences with regard to disease onset were found in several cohorts from Europe,5 ,6 a later disease onset in men was reported in a North American investigation.7 We analysed this issue within the ongoing Swiss Clinical Quality Management cohort of patients with axial spondyloarthritis (axSpA).9 Ethics approval was given by the regional review boards. Informed consent was obtained from all patients.

    From a total of 3046 spondyloarthritis patients recruited until June 2014, 2098 (1294 men, 804 women) were included in this analysis, as they fulfilled the Assessment in SpondyloArthritis International Society (ASAS) classification criteria, with the following minor modifications, as the cohort was initiated before the publication of these criteria.9 First, inflammatory back pain was defined as low back pain and morning stiffness for >3 months, improving with exercise but not relieved by rest. Second, the ASAS criterion ‘good response to non-steroidal anti-inflammatory drugs’ was added to the questionnaire at a later time point.

    Demographic characteristics at inclusion are shown for the global population of axSpA, as well as for the subgroups of AS (radiographic axSpA) and non-radiographic axSpA (nr-axSpA), in patients with available pelvic radiographs (n=1532) (table 1). Male axSpA and AS patients were significantly younger at disease onset (defined as the age at onset of back pain) compared with female patients (26.3±9.3 vs 28.5±10.1 in axSpA and 26.3±9.8 vs 29.3±11.7 in AS, p<0.001), whereas no gender difference was detected in nr-axSpA patients. The median difference between the age at onset in male and female AS patients was 2.7 years (IQR 1.53–4.48; Mann–Whitney U test p<0.001).

    View this table:
    Table 1

    Baseline demographic characteristics of men and women with axial spondyloarthritis (axSpA) and the subgroups of patients, ankylosing spondylitis (AS) and non-radiographic (nr-)axSpA

    HLA-B27 prevalence differed between men and women with AS (83.0% vs 72.1%, p<0.001). However, this observation may not fully account for the gender difference in disease onset in AS patients (figure 1A), as women were on average 1.8 years older than men at the beginning of back pain in the subgroup of HLA-B27-positive patients (Mann–Whitney U test, p<0.001, figure 1B). By contrast, no significant age differences at symptom onset were observed in HLA-B27-negative women and men with AS (mean difference 1.0 year, p=0.69, figure 1B). Further disease precipitating intrinsic or extrinsic factors might be involved. Smoking would be a candidate factor in this regard, as differences in smoking rates paralleled differences in age at symptom onset in the subgroups (table 1). However, the age at disease onset was comparable in smokers and non-smokers with AS (27.3±10.3 vs 26.9±10.7, p=0.39). Although relatively small, the gender difference with regard to symptom onset in AS (mid-twenties in men vs late twenties in women) might be relevant with regard to the choice of profession, career entry and family planning.

    Figure 1
    Figure 1

    Age at symptom onset in women and men with ankylosing spondylitis. (A) Frequency distribution of age at symptom onset. (B) HLA-B27 positivity and age at symptom onset.

    Female patients with AS had a slightly longer mean diagnostic delay than male patients: 6.4±7.3 versus 5.3±6.4 years, p=0.05 (table 1), confirming previous analyses.5 ,6 The lower percentage of HLA-B27 positivity in women might have contributed to this effect.2

    A limitation of our study, as well as of previous investigations, is the possibility of recall bias with regard to the age at onset of the disease. Whether different inclusion criteria and/or different definitions of disease onset used in the literature might explain the discrepant findings remains unclear.

    In conclusion, HLA-B27-positive women with AS had a later onset of back pain than men.

    Acknowledgments

    We thank all rheumatologists and patients for participation, the members of the SCQM axSpA scientific board for helpful discussions, and the entire SCQM staff for data management and support. A list of rheumatology offices and hospitals that are contributing to the SCQM registries can be found online (http://www.scqm.ch/institutions).

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    Footnotes

    • Contributors AC and DS designed the study. All investigators substantially contributed to the acquisition, analysis or interpretation of data. AC wrote the article and all coauthors revised the manuscript critically for important intellectual content. All authors finally approved the version to be published.

    • Funding This study was supported by a grant from the “Stiftung für Rheumaforschung” and by a grant from Abbvie AG. The SCQM Foundation was financially supported by the Swiss Society of Rheumatology, the Balgrist Foundation, the ARCO Foundation and by Abbvie, Bristol-Myers-Squibb, Merck Sharp & Dohme, Pfizer, Roche and UCB. Publication of this article was not contingent upon approval by the study sponsors.

    • Competing interests AC has received consulting and/or speaking fees from Abbvie, Merck Sharp & Dohme, Pfizer and UCB. UW has received honoraria from Abbvie for being a workshop convenor of the International Course of MRI in Spondyloarthritis and for contributing to a slide kit on spondyloarthritis. PE has received speaking fees from Abbvie.

    • Patient consent Obtained.

    • Ethics approval Ethics committee Kanton Zurich.

    • Provenance and peer review Not commissioned; externally peer reviewed.