In their recent review, Baeten et al address the question of whether the spondyloarthritides (SpA), because of phenotypic diversity, represent a panel of distinct albeit related conditions or whether SpA is a single multifaceted disorder ([1]). The authors propose that a disease or condition is primarily defined by its pathophysiology, rather than by its phenotypic presentation. They note that the available evidence suggests that there is a common pathophysiologic foundation for SpA as a whole, thereby supporting the concept that SpA is a single disease with a heterogeneous phenotype. Further, Baeten and colleagues note that emerging data from immunopathology studies and clinical trials suggest that axial SpA and peripheral SpA may be driven by slightly different mechanisms, thereby supporting the current clinical classification ([2-4]) according to the predominant rheumatic manifestations of axial and peripheral disease (as proposed by the Assessment of SpondyloArthritis international Society [ASAS]).

In contrast, in a recent viewpoint article, Robinson et al note that there is compelling evidence indicating that axial SpA and ankylosing spondylitis (AS) are different, although overlapping, entities associated with different prognoses, demographics, genetics, and responses to treatment ([5]). They further argue that use of the new ASAS classification criteria for axial SpA results in substantially increased heterogeneity of the disease group and poor characterization of the natural history of the disease. Additionally, recently developed classification criteria for psoriatic arthritis that does not fit into one disease concept ([6, 7]) support the notion that the availability of accurate classification criteria for defined diseases remains as necessary now as it ever was.

The new ASAS classification criteria and the concept that SpA is a single disease reopen the controversy between splitting and grouping of the disease ([8]). The ASAS classification criteria were developed with the goal of improving sensitivity of criteria for early SpA, especially in patients with non–radiographically evident axial involvement, who are considered at risk of developing AS (as opposed to patients with predominant peripheral involvement, considered to be at low risk of developing AS). Conceptually, the ASAS classification switches from a classification of interrelated nosologic entities to a classification of interrelated clinical manifestations, which presume the disease entity of SpA ([9]) (Figure 1). Most importantly, the pathophysiologic concept of SpA as one disease ignores the obvious differences in the bacterial etiology of reactive arthritis (ReA). The recent description of increased frequency of Chlamydia positivity in synovial tissue from patients with chronic undifferentiated SpA, the growing insight into the etiology of persistent chlamydial infection, and the promising treatment of Chlamydia-induced arthritis with combination antibiotic therapy indicate the necessity of further splitting SpA into different disease entities ([10-13]). Infectious manifestations, such as urethritis/cervicitis or diarrhea, preceding SpA (and especially ReA) are included in the ASAS criteria for peripheral SpA but not directly in the criteria for axial SpA. Future classification sets specifying the infectious triggers might be useful to advance disease-specific diagnostic and treatment studies. Nevertheless, the historical concept and the new classification criteria are overlapping, not exclusive, and can be used for particular purposes. The ASAS criteria provide welcome support for research and clinical trials addressing earlier diagnosis, outcome measurements, and new treatments that cover the whole spectrum of conditions unified as SpA.


Figure 1. Interrelationship between the historical concept of spondyloarthritis (SpA), which grouped together the interrelated nosologic entities, and the Assessment of SpondyloArthritis international Society classification, which presumes the disease entity of SpA.

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In conclusion, the historical concept of interrelated conditions grouped together as a family of distinct diseases is still useful, since our understanding of the common pathophysiologic mechanisms driving SpA is still incomplete, and more importantly, we cannot explain the heterogeneity of infections implicated in some forms of SpA. The subdivision of SpA into defined clinical diagnostic categories, including undifferentiated SpA, is still needed for diagnosis of individual patients, patient education, customized treatment, and prediction of outcome. Further research should establish criteria based on pathogenesis and particularly on the etiologic agents involved in SpA and ReA.

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