The Nonradiographic Axial Spondyloarthritis, the Radiographic Axial Spondyloarthritis, and Ankylosing Spondylitis: The Tangled Skein of Rheumatology

Abstract

Since 1984 the diagnosis of ankylosing spondylitis (AS) has been based upon the modified New York (mNY) criteria with mandatory presence of radiographic sacroiliitis, without which the diagnosis is not tenable. However, it may take years or decades for radiographic sacroiliitis to develop delaying the diagnosis for long periods. It did not matter in the past because no effective treatment was available. However, with the availability of a highly effective treatment, namely, tumour necrosis factor-α inhibitors (TNFi), the issue of early diagnosis of AS acquired an urgency. The Assessment of SpondyloArthritis International Society (ASAS) classification criteria published in 2009 was a significant step towards this goal. These criteria described an early stage of the disease where sacroiliitis was demonstrable only on MRI but not on standard radiograph. Therefore, this stage of the disease was labelled "nonradiographic axial SpA" (nr-axSpA). But questions have been raised if, in search of early diagnosis, specificity was compromised. The Federal Drug Administration (FDA, USA) withheld approval for the use of TNFi in patients with nr-axSpA because of issues related to the specificity of these criteria. This review attempts to clarify some of these aspects of the nr-axSpA-AS relationship and also tries to answer the question whether ASAS classifiable radiographic axial spondyloarthritis (r-axSpA) term can be interchangeably used with the term AS.

Figure 1

The circles “A,” “B,” and “C” represent (1) the axial spondyloarthritis (axSpA); (2) the peripheral SpA, and (3) the extra-articular manifestations of SpA, respectively. Within the axSpA (circle A) the two subcomponents are “Aa” and “Ab” that represent nonradiographic axSpA (nr-axSpA) and radiographic axSpA (r-axSpA), respectively. Circles “B,” “C,” “D,” “E,” and “F” represent (i) peripheral arthritis of SpA pattern, (ii) extra-articular features, (iii) inflammatory bowel disease-related SpA, (iv) psoriasis-related SpA, and (v) reactive arthritis-related SpA. Patients in circle “A” are often identified as “primary” SpA and those in circles “C,” “D,” or “E” as “secondary” SpA.

Figure 2

Natural history of axial SpA over timeline → from left to right. For details see text.

Figure 3

“nr-axSpA” = nonradiographic axial spondyloarthritis; “r-axSpA” = radiographic axial spondyloarthritis; ASAS = Assessment of SpondyloArthritis International Society; mNY diagnostic criteria = modified New York diagnostic criteria; “AS” = ankylosing spondylitis. mNY = modified New York, ASAS = Assessment of SpondyloArthritis International Society classification criteria; r-axSpA = radiographic axial spondyloarthritis; AS = ankylosing spondylitis. ^∗It is to be noted that mNY are diagnostic criteria [10]. ¹Genetic factors include HLA B27, ERAP-1, and IL23R and certain protein biomarkers include KIR3DL1, Sclerostin, and Dkk-1. ²Intensity of acute phase response is genetically determined, for example, C-reactive protein response.