The SpA concept encompasses patients with phenotypic features such as inflammatory bowel disease, dactylitis, and psoriasis that are largely distinct from those seen in other inflammatory arthropathies such as rheumatoid arthritis. At one end of the spectrum lies AS, the prototypic form of SpA in which sufficient damage has accumulated in one or both sacroiliac joints to be evident on plain radiographs (erosions, sclerosis, and/or ankylosis). Individuals with these abnormalities together with additional clinical criteria that reflect axial involvement will meet modified New York criteria and can be classified as having AS. However, delays of 8–11 years between the onset of symptoms and a diagnosis are not uncommon in both adults [3
] and children [4
]. Patients with clinical features of SpA who fail to meet criteria for AS can often be classified as undifferentiated SpA by applying either European Spondyloarthropathy Study Group (ESSG) [5
] or Amor [6
] criteria. However, undifferentiated SpA is not simply an early presentation of AS; long-term outcome studies suggest that more than 40% of patients with undifferentiated SpA may not develop AS even after 10 years of follow-up [7
]. This has underscored the importance of recognizing early forms of AS involving the axial skeleton, but in a preradiographic stage when definite sacroiliitis is not apparent on plain radiographs [2
In an effort to identify characteristics that might distinguish individuals with nonradiographic disease from those with AS, Rudwaleit et al.
•] examined a large group from the German Spondyloarthritis Inception Cohort (GESPIC). Patients were required to have a clinical diagnosis of axial SpA by the treating rheumatologist. (Note that this designation was made prior to the publication of criteria for axial SpA as discussed below.) Classification of AS was based on the modified New York criteria, whereas axial SpA was defined by a modified version of the ESSG criteria for undifferentiated SpA, and the absence of definite radiographic sacroiliitis. The ESSG modification incorporated HLA-B27, acute anterior uveitis, and dactylitis as minor criteria that could accompany the major criterion of inflammatory back pain (IBP).
There were remarkably few differences between the group with early AS (n = 236) and those with axial SpA (n = 226). Notably, the presence of HLA-B27 and the frequency of arthritis, enthesitis, uveitis, and IBP were the same. Measures of disease activity such as the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), morning stiffness, fatigue, and night pain were also the same. HLA-B27 was associated with a younger age at disease onset in both groups. However, male sex and an elevated C reactive protein (CRP) were associated with radiographic sacroiliitis (odds ratios of 2.38 and 1.85, respectively) and the presence of syndesmophytes, whereas no such relationship was found for HLA-B27. This study suggests that obtaining plain radiographs in patients with signs and symptoms of AS such as IBP, enthesitis, arthritis, uveitis, HLA-B27, and an elevated BASDAI does not provide definitive classification if the radiographs are negative. Indeed, individuals with nonradiographic axial SpA have many of the same clinical features, emphasizing that radiographic confirmation of AS in the sacroiliac joints should not be used as a criterion in defining patients with axial involvement.
Although the AS cohort included individuals with up to 10 years of disease (vs. <=5 years for the axial SpA cohort), a subanalysis of AS patients with less than or equal to 5 years of disease resulted in similar findings. The current study suggests that elevated CRP may be a marker for the evolution of nonradiographic axial SpA to AS. Interestingly, three cytokines strongly correlated with CRP elevations are interleukins (IL)-6, IL-1, and IL-17 [9
], two of which (IL-6 and IL-17) have been implicated in AS pathogenesis [10
], including evidence for IL-6 overexpression in inflamed sacroiliac joints [11
] and in serum where it correlates with CRP and with disease activity [10
]. It will be of interest to learn whether neutralizing these cytokines is beneficial in axial SpA and AS