Is the current ASAS expert definition of a positive family history useful in identifying axial spondyloarthritis? Results from the SPACE and DESIR cohorts

Zineb Ez-Zaitouni, Andrea Hilkens, Laure Gossec, Inger Jorid Berg, Robert Landewé, Roberta Ramonda, Maxime Dougados, Désirée van der Heijde, Floris van Gaalen

The Assessment of SpondyloArthritis international Society (ASAS) definition of a positive family history (PFH) of spondyloarthritis (SpA) includes the following diseases in first- or second-degree relatives: ankylosing spondylitis (AS), acute anterior uveitis (AAU), reactive arthritis (ReA), inflammatory bowel disease (IBD), and psoriasis. However, it is not known if a PFH for each of these diseases contributes to making a diagnosis of axSpA, sacroiliitis on imaging, or fulfilling the ASAS criteria in patients presenting with chronic back pain (CBP). Therefore, the aim of this study was to assess which SpA diseases in family members are associated with human leukocyte antigen B27 (HLA-B27) and axial spondyloarthritis (axSpA) in CBP patients. CBP patients suspected of axSpA from the SPACE (n = 438) and the DESIR (n = 647) cohort were asked about the presence of SpA diseases in first- or second-degree relatives (AS, AAU, ReA, IBD, and psoriasis). The associations between a PFH and HLA-B27, sacroiliitis on imaging (magnetic resonance imaging (MRI) or radiographs), axSpA diagnosis, and ASAS classification in CBP patients were assessed. In the SPACE and the DESIR cohort, a PFH of AS (odds ratio (OR) 5.9 (95% confidence interval (CI) 3.5-9.9), and OR 3.3 (95% CI 2.1-5.2)) and a PFH of AAU (OR 9.8 (95% CI 3.3-28.9) and OR 21.6 (95% CI 2.9-160.1)) were significantly associated with presence of HLA-B27. Furthermore, in both cohorts a PFH of AS and a PFH of AAU were positively associated with fulfilment of the ASAS criteria, but not with sacroiliitis on imaging. In SPACE but not in DESIR a PFH of AAU was positively associated with axSpA diagnosis. In both cohorts a PFH of ReA, IBD, or psoriasis was not positively associated with HLA-B27 positivity, sacroiliitis on imaging, axSpA diagnosis, or meeting the ASAS criteria for axSpA. In our cohorts, a PFH of AS or AAU is useful for case-finding of axSpA as this is correlated with HLA-B27 carriership. However, as a PFH of ReA, IBD, or psoriasis does not contribute to identifying axSpA in CBP patients, these data suggest that the widely used ASAS definition of a PFH of SpA should be updated. Trial registration number, NCT01648907 . Registered on 20 July 2012.