Ankylosing spondylitis pathogenesis

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Information about Ankylosing spondylitis pathogenesis
Health & Medicine

Published on March 13, 2014

Author: sitanshubarik

Source: slideshare.net

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 7 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 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)

 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 11

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

 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% .

 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 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%

 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%)

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