1. Dr. Naeem Jagani

3.  These are a group of clinical disorders that
share certain clinical features ,a predilection
to cause inflammation at enthesis and have
an association with HLA-B27 allele.
 These include: 1) Ankylosing spodylitis
2) Reactive arthritis (Reiter’s
syndrome)
3) Psoriatic arthritis & spondylitis
4) Enteropathic S & A ( IBD )
5) Juvenile onset SA
6) Undifferentiated SA

4.  The estimated prevalence is 0.2% to 1.2%
 Among adults with chronic low back pain:
prevalence is about 5%

5.  Greek: “ankylos” = bent
“spondylos” = spinal vertebra
 Chronic inflammatory disease of axial
skeleton causing back pain and progressive
stiffness
 Periph jts & extra- articular tissue may also
be involved
 Peak age 20-30 years
 Three times more prevalent in men

6.  Strong link between AS and HLA-B27
 Gene on Chr 6; therefore autosomal
transmission
 Relative Risk if 1st degree relative with AS:
16 to 94
 Twin studies concordance of AS: 63% for
identical twins
 90% of risk estimated to be genetic
 Only small percentage of HLA-B27 individuals
in population suffer from a SpA (3-8% of
Americans HLA-B27 positive), suggesting that
other genetic and environmental factors may
play a role

7.  AS and HLA-B27 – strong association
 Ethnic and racial variability in presence and
expression of HLA-B27
7
HLA-B27
positive
AS and HLA-
B27 positive
Western European
Whites
8% 90%
African Americans 2% to 4% 48%

8.  Major histocompatability complex (MHC) class I allele
(antigen presenting cells)
 Presents peptides from intracellular
pathogens( arthritogenic peptide) for recognition by
T-cell receptors of CD8+ T cells (recognise epitope)
(Autoimmunity to cartilage proteoglycan aggrecan);
sharing of Pg epitopespossible explanation for
pathological sites of AS
 Pathogenic link between HLA-B27 and AS elusive
despite association of over 30 years
 HLA B271) may function @ level of thymus by
allowing selection of arthritogenic T cells
2) peptide binding cleft of HLA B27 mol.
That is able to bind a unique arthritis causing peptide
3)Molecular mimicry theory
4) Receptor theory(peptide well presented
by B27)

9.  Characterized by chronic inflammation
and progressive ankylosis
 Commonly accepted that inflammation is
driving force for structural damage in AS
 Current research shows that tumor
necrosis factor (TNF) is important
cytokine contributing to inflammation in
AS.

10.  Hallmark of
structural
abnormality in AS is
bony ankylosis.
 No molecular
explanation for
ankylosis.

11.  Stimulation of endothelial cells to express adhesion
molecules
 Recruitment of white blood cells in inflamed
synovium and skin
 Induction of inflammatory cytokine production
(e.g., IL-1, IL-6)
 Stimulation of synovial cells to release
collagenases
 Induction of bone and cartilage resorption
 Stimulation of fibroblast proliferation
11

12. 12
Bone
Erosions
Macrophages
Endothelium
Synoviocytes
↑ Proinflammatory cytokines
↑ Chemokines
↑ Adhesion molecules
↑ Metalloproteinase synthesis
Articular
Cartilage
Degradation
Increased Cell
Infiltration
Increased
Inflammation
Osteoclast
progenitors
↑ RANKL expression
TNF

13.  Poorly documented in literature
 Variable severity of symptoms and radiographic progression
 Slow speed of disease progression
 Until recently, lack of validated outcome measure
 No motivation to study AS until Anti-TNFs arrived on scene
 Average age of onset: 25 years
 Mean time between diagnosis and onset of
symptoms: 8.6 years
 Average age of retirement 39.4 years
Mean disease duration at retirement: 10.8 years
AS cause of work cessation: 96%
.

14.  Inflammatory back pain
 Onset before age 40 years
 Insidious onset
 Improvement with exercise
 No improvement with rest
 Pain at night (with improvement upon arising)
 Patient has a 25% probability of having ankylosing spondylitis if
four of five of the above symptoms are present, assuming a 5%
prevalence of AS among patients with chronic low back pain.
.

15.  Chronic & progressive form of seronegative
arthritis with axial skeleton predominance
 Affects 0.1-0.2% of the population
 90-95% of patients are HLA-B27 positive
 7% of general population is positive, only 1% of
positives will develop ankylosing spondylitis
 Male:female 4-10:1

16.  Starts with sacroiliac joints
 begins with sclerosis, eventually get ankylosis
 Progresses to include facet joints, spine, iliac
crest, ischial tuberosity, greater trochanter,
hips, patella, calcaneus, glenohumeral joints
 peripheral joint involvement in 30%

17.  Enthesopathy - calcification & ossification of
ligaments, tendons, joint capsules at
insertion into bone
 Erosion of subligamentous bone due to
inflammatory response
 Marrow oedema
 Fusion of interspinous ligament
 Dagger sign

19.  IN SPINE : inflammatory granulation tissue @ junctn of
annulus fibrosus of disc cartilage & margin of vertebral
bone, the outer annular fibres erode & eventually replaced
by bone forming bony ‘syndesmophytes’ which grow by
enchondral ossification bridging adjacent vertebral
bodies BAMBOO spine
 Resorption of vertebral endplates(@ disk margin)
‘squaring of vertebrae’…….also diffuse osteoporosis
 Soft tissue findings are new bone formation in outer layers
of annulus fibrosis as well as chronic synovitis and capsular
fibrosis
 Peripheral Jts : Synovial hyperplasia, lymphoid infiltration
& pannus but lacks the exuberant synovial villi, fibrin
deposits & plasma cell accumulations of RA. Central
cartilagenous erosions caused by proliferation of
subchondral granulation tissue are common in AS but rare
in RA.

21.  Patients usually present with low back pain
and stiffness, which improves with activity
 Decreased range of motion in lumbar spine
 Thoraco-cervical kyphosis (late)
 One-third of patients will have acute,
unilateral uveitis

22.  Pseudoarthrosis (Anderson lesion), cervical
spine fracture, C1-C2 subluxation, cauda
equina syndrome
 Peripheral joint ankylosis
 Restrictive lung disease, upper lobe fibrosis
 Aortic root dilation (20%) & murmur (2%)