The spondyloarthritides are a group of overlapping disorders that share certain clinical features and genetic associations. These disorders include ankylosing spondylitis, reactive arthritis, psoriatic arthritis and spondylitis, enteropathic arthritis and spondylitis, juvenile-onset spondyloarthritis (SpA), and undifferentiated SpA. The similarities in clinical manifestations and genetic predisposition suggest that these disorders share pathogenic mechanisms.
Ankylosing spondylitis (AS) is an inflammatory disorder of unknown cause that primarily affects the axial skeleton; peripheral joints and extraarticular structures are also frequently involved. The disease usually begins in the second or third decade; male to female prevalence is between 2:1 and 3:1. The term axial spondyloarthritis, coming into common use, includes early or mild forms that do not meet classical criteria for AS.
AS shows a striking correlation with the histocompatibility antigen HLA-B27 and occurs worldwide roughly in proportion to the prevalence of B27 (Chap. 315). In North American whites, the prevalence of B27 is 7%, whereas it is 90% in patients with AS, independent of disease severity.
In population surveys, AS is present in 1–6% of adults inheriting B27, whereas the prevalence is 10–30% among B27+ adult first-degree relatives of AS probands. Concordance rate in identical twins is about 65%. Susceptibility to AS is determined largely by genetic factors, with B27 comprising up to one-half of the genetic component. Other HLA-linked genes may also contribute to susceptibility to AS. Genome-wide single-nucleotide polymorphism (SNP) analysis has identified additional susceptibility alleles in the genes encoding ERAP1 (chromosome 5q15) and IL-23R (chromosome 1p31.3). The genes encoding TNFSF15, TNFSF1A, STAT3, ANTXR2, and IL1R2, and at least six other chromosomal regions have also been implicated.
The sites of axial inflammation in AS are inaccessible to routine biopsy and are rarely approached surgically. Knowledge of the axial histopathology is therefore based mostly on advanced cases. Sacroiliitis is often the earliest manifestations of AS. Synovitis, pannus, myxoid marrow, subchondral granulation tissue and marrow edema, enthesitis, and chondroid differentiation are found. Macrophages, T cells, and osteoclasts are prevalent. Eventually the eroded joint margins are gradually replaced by fibrocartilage regeneration and then by ossification. The joint may become totally obliterated.
In the spine, there is inflammatory granulation tissue at the junction of annulus fibrosis and vertebral bone. The outer annular fibers are eroded and eventually replaced by bone, forming the beginning of a syndesmophyte, which then grows by continued endochondral ossification, ultimately bridging the adjacent vertebral bodies. Ascending progression of this process leads to the “bamboo spine.” Other lesions in the spine include diffuse osteoporosis, erosion of vertebral bodies at the disk margin, “squaring” or “barreling” of vertebrae, and inflammation and destruction of the disk-bone border. Inflammatory arthritis of the apophyseal joints is common, with erosion of cartilage by pannus, often followed by bony ankylosis. Bone mineral density is diminished in the spine and proximal femur early in the course of the ...