A great deal of progress has occurred in the past few years in elucidating the causes and designing new treatments for
ankylosing spondylitis and other types of spondyloarthritis. In addition to the
human leukocyte antigen (HLA)-B27 and other major histocompatibility complex (MHC) genes, chromosomal regions and genes elsewhere in the genome are being implicated both in
disease susceptibility and severity. The various ways
HLA-B27 may function in causing spondyloarthritis now are better understood to encompass not only antigen presentation but also other mechanisms, possibly all being operative in pathogenesis (misfolding of the HLA-B27 molecule, impaired intracellular killing of bacteria, and HLA-B27 itself serving as an
autoantigen). Specific enteric and sexually acquired
infections can trigger
reactive arthritis, though no specific microbe has been identified in other forms of spondyloarthritis. Intestinal
inflammation with impairment of the gut:blood barrier may be operative in driving
ankylosing spondylitis and enteropathic
arthritis. A number of treatments have been tried in spondyloarthritis, including older agents such as
methotrexate and
sulfasalazine but also newer drugs such as pamindronate. The recent introduction of
tumor necrosis factor (
TNF) blockers in the treatment of spondyloarthritis has offered the most hope in not only relieving symptoms and signs of both peripheral
arthritis and enthesitis but also
spinal disease, which often has been refractory to other agents. Their high cost and considerable side effect profile, however, have necessitated the establishment of guidelines for their use in these diseases in order to target the patient in whom they are likely to have the most benefit.