Dr. Naeem Jagani

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

The estimated prevalence is 0.2% to 1.2%

Among adults with chronic low back pain: prevalence is about 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

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

AS and HLA-B27 – strong association Ethnic and racial variability in presence and

expression of HLA-B27

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HLA-B27 positive

AS and HLA-B27 positive

Western European Whites

8% 90%

African Americans 2% to 4% 48%

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 epitopespossible 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)

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.

Hallmark of structural abnormality in AS is bony ankylosis.

No molecular explanation for ankylosis.

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

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Bone Erosions

Macrophages

Endothelium

Synoviocytes

Proinflammatory cytokines Chemokines

Adhesion molecules

Metalloproteinase synthesis

ArticularCartilage

Degradation

Increased Cell Infiltration

Increased Inflammation

Osteoclast progenitors

RANKL expression

TNF

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 yearsAS cause of work cessation: 96%

.

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..

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

Starts with sacroiliac jointsbegins with sclerosis, eventually get

ankylosis Progresses to include facet joints, spine,

iliac crest, ischial tuberosity, greater trochanter, hips, patella, calcaneus, glenohumeral jointsperipheral joint involvement in 30%

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

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.

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

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%)