Ankylosing Spondylitis Flashcards
What is the epidemiology, pathology, and pathogenesis of ankylosing spondylitis (AS)?
Inflammatory disorder primarily affecting the axial skeleton, with peripheral joints and extraarticular surfaces frequently involved
Epidemiology
- 0.5-1% of population
- 2nd/3rd decade; M:F 2-3:1
- 90% with AS are HLA-B27 +ve. Baseline population ~7%
- ~5% of those with HLA-B27 have AS; 10-30% with HLA-B27 who are a first degree relative of AS proband have AS
Pathogenesis
- HLA B allele main role is antigen presentation to CD8+
- Dramatic response to TNF blockade implies central role
- Recent evidence implicates IL23-17 pathway
Pathology
- Sacroiliitis often the earliest manifestation: macrophages, T-cells, plasma cells, osteoclasts
- Eroded joint replaced by fibrocartilage regeneration and ossification, which can obliterate the joint
- Inflammation of paravertebral connective tissue at junction of annulus fibrosis and vertebral bone results in syndesmophyte formation and ultimately bridged vertebral bodies
- Others: diffuse osteoporosis, erosion of vertebral bodies at disc margin, squaring of vertebrae, destruction of disc-bone border
Bamboo spine (see image)
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peripheral synovitis: marked vascularity, lining layer hyperplasia, lymphoid infiltration, pannus formation.
- central cartilagenous erosions from proliferation of subchondral granulation tissue
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enthesitis: inflammation of fibrocartilagenous enthesis is characteristic of all spondyloarthropathies
- associated with erosive lesions that eventually ossify
How is ankyklosing spondylitis (AS) diagnosed? What are the features that differentiate mechanical back pain from inflammatory?
Inflammatory back pain features
Chronic pain with >=4 of the following:
- onset <40yrs
- insidious
- improvement with exercise
- no improvement with rest
- pain at night with no improvement on getting up
Others
- morning stiffness >30mins
Quite specific
- alternating buttock pain
- awakening from back pain only in the 2nd half of the night
How is ankylosing spondylitis (AS) treated? How is disease progress measure clinically?
All regimens require an exercise program designed to maintain posture and range of motion
NSAIDs are first line
- reduce pain and tenderness, increase mobility, slow radiographic progression (particualrly in high risk)
Anti-TNFa
- infliximab, etanercept, adalimumab, golimumab
- use in definite diagnosis, active disease inadequately responsive to >=2 different NSAIDs
- rapid and sustained reduction in all clinical and laboratory measurement of disease activity
- ~50% achieve >=50% reduction in severity index
- BMD increases within 24 weeks of therapy
- Alters radiographic progression if started early
- Good response in: younger, shorter disease, higher inflammatory markers, lower baseline disability
DMARDs
- sulfasalazine of benefit in peripheral arthritis phenotype. Try before TNFa in these
- methotrexate of no benefit
- glucocorticoids of no benefit
Secukinumab (anti IL-17) approved by PBS recently
- both for TNFi naive and non-responders
- works for enthesitis and dactylitis
- no TB/MS risk
Anterior uveitis
- local glucocorticoids
- mydriatic agents
- anti-TNFa reduce but don’t remove attacks
Progress
- loss of height
- limitation of chest expansion or spinal flexion
- occiput-wall distance
What are the laboratory and radiologic manifestations of ankylosing spondylitis?
- *Laboratory (nothing diagnostic)**
- HLA-B27 in 90%*
- ESR/CRP ofte*n but not always elevated
- May have RF/anti-CCP/ANA, but not usually
- serum matrix metalloproteinase 3 levels correlate with disease activity
Radiographic
- Symmetric sacroiliitis is eventually present on xray (may take years)
- look for erosions, sclerosis, and ankylosis and the anteroinferior half (bottom third on AP pelvic xray)
- 0 = normal
- 1 = suspicious
- 2 = early sacroiliitis: minor sclerosis, limited erosions, joint space narrowing
- 3 = definite sacroiliitis: severe sclerosis, clear erosions, joint space pseudowidening, some ankylosis
- 4 = advanced sacroiliitis: ankylosis and fusion
- MRI increasingly used due to improved sensitivity (T2 or T1 with contrast)
What’s the most specific clinical finding in ankylosing spondylitis? Predictors of radiographic progression?
Most specific finding is loss of spinal mobility
- limitation of anterior or lateral flexion/extension of the lumber spine or chest expansion
- normal chest expansion >=5cm; normal lateral bend >10cm
- Modified Schober = marks at lumbosacral junction and 10cm above. Maximal bend forward from standing. >=5cm increase = normal; <4cm = decreased
Predictors of progression in non-radiographic axial spondyloarthritis
- Spine: existing syndesmophytes, high inflammatory markers, smoking
- SIJ: baseline sacroiliitis, baseline inflammatory change on MRI, elevated CRP
The big 3 predictors are syndesmophytes, CRP, and smoking
- all 3 +ve 55% progress at 2yrs
- all 3 -ve 4% progress at 2yrs
Ank. Spond - case classification:
Lower back pain > 3 months and < 45 years old
Don’t need sacroilitis on imaging for diagnosis now!
Treatment of Ankylosing Spondylitis:
Ankylosing spondylitis is associated with which valvular defect?
Aortic Regurgitation
