Information Technology Reference
In-Depth Information
3In
fl
ammatory Arthritis
3.1 Ankylosing Spondylitis
3.1.1 De
nition and Occurrence
Ankylosing Spondylitis (AS, from the Greek ankylos,fused;spondylos, vertebrae; -itis,
in
ammation) is the prototypic disease of the seronegative spondyloarthritis family, a
group of in
fl
ammatory spinal arthritis that includes AS, psoriatic arthritis, reactive
arthritis, spondyloarthritis associated with in
fl
ammatory bowel disease, and undif-
ferentiated spondyloarthritis. In contrast to rheumatoid arthritis, patients with sero-
negative spondyloarthritis usually do not produce autoantibodies, such as rheumatoid
factor or anti-cyclic citrullinated protein (anti-CCP) antibody, and therefore are
termed
fl
AS primarily involves the axial skeleton, including the spine
and sacroiliac joints, with features of chronic in
“
seronegative.
”
ammation and new bone formation.
The sacroiliac joints are the connections between the lower end of the spine (sacrum)
and the pelvis.
Genetic factors are important in the susceptibility to AS. Early study of AS in
1970s discovered an association with a gene called human leukocyte antigen B27
(HLA-B27) [
37
]. It is estimated that 85
fl
90 % of patients with AS have HLA-B27,
compared to under 10 % of the general population [
38
]. Among those who have
HLA-B27, AS is more common among those with a close relative who also has AS
than in those without any close relative with AS [
39
]. This indicates other genetic
factors are involved in the pathogenesis of AS. Recent genome-wide association
studies have advanced our understanding of the genetic basis of AS. More than
20 genes, e.g. ERAP1, IL-23R, KIF21B, etc., and a few intergenic regions, e.g.
2p15 on chromosome 2, are now identi
-
42
].
Substantial evidence suggests environmental factors trigger the onset of AS in
people with certain genetic background, a theory well supported by the study of
HLA-B27 transgenic rats. These rats develop arthritis and gut
ed to be associated with AS [
40
-
ammation,
resembling human HLA-B27 associated diseases. Interestingly, they are protected
from the disease if raised in germ-free conditions [
43
].
Chronic inflammation of the entheses and new bone formation are two cardinal
features of AS. Entheses are the sites where tendons or ligaments insert into bones.
Immunohistologic staining of entheses from the sacroiliac joints [
44
] and the foot
ligaments [
45
] of patients with AS showed in
in
fl
fl
ammatory cell in
ltration at these
sites. In addition to enthesitis, in
ammation occurs in bone (osteitis) and synovium
(synovitis), and can cause pain and swelling.
New bone formation is a slow and insidious process, with new skeletal tissues
formed in connection with, but extending outside the original bone [
46
]. Bony
growths originating from the ligament insertions of the spine are called syn-
desmophytes, while those originating from the entheses in the extremities are called
enthesophytes. Growth of syndesmophytes starts at the thoracolumbar junction,
gradually involves other spinal areas, and may eventually lead to bridging of
fl
