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Pathogenesis of spondyloarthritis

David T Yu, MD
Astrid van Tubergen, MD, PhD
Section Editor
Joachim Sieper, MD
Deputy Editor
Paul L Romain, MD


The term spondyloarthritis (SpA, formerly spondyloarthropathy) refers to a group of disorders that includes ankylosing spondylitis (AS), nonradiographic axial SpA (nr-axSpA), undifferentiated spondyloarthritis (USpA), reactive arthritis, and the arthritis and spondylitis that may accompany psoriasis and inflammatory bowel diseases (IBD). SpA can also be differentiated into axial and peripheral SpA, depending upon the predominant regions of involvement. Axial SpA includes both AS and nr-axSpA, based upon the presence or absence, respectively, of abnormalities of the sacroiliac joints on plain radiography.

This topic review will focus primarily on the pathogenesis of AS, regarding which the most is known. The pathogenesis of each of the other members of the SpA family, especially nr-axSpA, is probably closely related to that of AS [1]. The clinical manifestations, diagnosis, and treatment of AS are presented separately. (See "Clinical manifestations of axial spondyloarthritis (ankylosing spondylitis and nonradiographic axial spondyloarthritis) in adults" and "Diagnosis and differential diagnosis of axial spondyloarthritis (ankylosing spondylitis and nonradiographic axial spondyloarthritis) in adults" and "Assessment and treatment of ankylosing spondylitis in adults".)

The clinical aspects of the other types of SpA are also presented in detail elsewhere, as is SpA in children. (See "Clinical manifestations of axial spondyloarthritis (ankylosing spondylitis and nonradiographic axial spondyloarthritis) in adults" and "Clinical manifestations and diagnosis of peripheral spondyloarthritis in adults" and "Reactive arthritis" and "Clinical manifestations and diagnosis of psoriatic arthritis" and "Clinical manifestations and diagnosis of arthritis associated with inflammatory bowel disease and other gastrointestinal diseases" and "Spondyloarthritis in children".)


Several elements are important in the pathogenesis of spondyloarthritis (SpA), a group of diseases with diverse clinical manifestations, which involve several different structures. These elements include interactions in the context of a particular genetic background between the gut microbiome, innate lymphoid cells, and the anatomic structures that are disease targets. Those structures include, for axial SpA, the entheses along the axial skeleton, and for peripheral SpA, the peripheral joints. At the sites of pathology, the major mediators are tumor necrosis factor (TNF)-alpha and interleukin (IL)-17 and IL-17A. (See 'Proinflammatory mediators validated by clinical observations' below and 'The gut microbiome, gut mucosa, and IL-23' below.)

The largest single genetic contribution is from the gene for human leukocyte antigen (HLA)-B27, but the presence of HLA-B27 is not absolutely essential. Moreover, non-HLA genes and others are also involved. (See 'Genetic factors' below.)

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Literature review current through: Nov 2017. | This topic last updated: Dec 13, 2017.
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