1. Spondyloarthropathies John Imboden MD

2. 23 y.o. woman with low back pain
9 years of low back pain
Spontaneous, insidious onset at age 14
persistent, dull, non-radiating
improved by mild-moderate activity
made worse by inactivity
associated with AM stiffness for >3 hours
Episode of “eye inflammation” age 12
Family History: Unremarkable
Social History: Full-time college student

3. 23 y.o. woman with low back pain
On examination: decreased range of motion of her lumbar spine and decreased chest expansion
She has had some relief with NSAIDs but now her back pain is so severe she has had to cut back on her course load and is uncertain whether she can continue college.
She has seen multiple physicians in the past 9 years but none has been able to make a diagnosis.
What is the likely cause of the back pain?

4. Spondyloarthropathies
Ankylosing spondylitis
Reactive arthritis
Arthritis associated with inflammatory bowel disease (Crohn’s disease and ulcerative colitis)
Arthritis associated with psoriasis
Undifferentiated spondyloarthropathy

5. Spondyloarthropathies: common features
Involvement of the axial skeleton
Asymmetric oligoarthritis of peripheral joints
Enthesitis & dactylitis
Seronegative
negative tests for rheumatoid factor and ANA
Association with HLA-B27

6. Involvement of axial skeleton: sacroiliac joints and all components of spine
Sacroiliitis occurs in 100% cases of ankylosing spondylitis

7. Peripheral arthritis: asymmetric oligoarthritis with predilection for large joints of lower extremities
Peripheral arthritis occurs in the great majority of patients with reactive
arthritis or psoriatic arthritis but in <25% with ankylosing spondylitis

8. Dactylitis: “sausage” digit

9. Enthesitis: inflammation at insertion of Achilles tendon

10. Enthesitis
inflammation and boney proliferation where plantar fascia inserts onto the calcaneus

11. Enthesitis: inflammation where tendon, ligament, or joint capsule attach to bone
Spondyloarthopathy:
- Enthesitis
- Synovitis
T cell and macrophage
Infiltration
Local cytokine production:
IL-1, IL-6, IL-17, TNF-a

13. HLA-B27 and spondyloarthropathies
HLA-B27 in Caucasian populations in US
normal controls 8%
ankylosing spondylitis 90%
reactive arthritis with spondylitis %
psoriatic with spondylitis 50%
IBD with spondylitis 50%

14. HLA polymorphisms and selected autoimmune diseases
Disease HLA marker relative risk
ankylosing spondylitis B
reactive arthritis B
rheumatoid arthritis DR

15. HLA-B27 and risk of spondyloarthropathy
Strongest association between an HLA gene and a rheumatic disease
BUT
HLA-B27 not absolutely required
HLA-B27 not sufficient
<20% of B27+ individuals develop disease

16. HLA-B27 and risk of spondyloarthropathy
Environmental triggers
mucosal inflammation (infection, IBD)
psoriasis
unknown
+ Spondyloarthropathy
Genetic background
HLA-B27
other genes

17. Ankylosing Spondylitis

18. Ankylosing Spondylitis
An inflammatory arthritis with predilection for the axial skeleton
Sacroiliac joints
always involved
bilateral
early in the course of the disease
Spine (cervical, thoracic, lumbar)
variable in severity and extent

19. Ankylosing spondylitis: a genetically determined disease
Family and twin studies: largely a genetic disease
Multiple genes involved: HLA-B27 confers a relative risk of 90 but constitutes only 15-50% of the overall genetic risk
Environmental trigger is essential but ubiquitous

20. Ankylosing Spondylitis
male predominance: M:F, 3:1
age of onset: 15 to 35 years - rarely begins after age 50
usual presenting complaint: low back pain

21. Age of onset of symptoms in AS (Feldkeller et al
Age of onset of symptoms in AS (Feldkeller et al. Rheumatol Int 23: 61, 2003

22. Ankylosing spondylitis: “inflammatory” back pain
insidious in onset
persistent
dull in quality
associated with stiffness
worse in AM or after prolonged inactivity
eased by mild activity

23. Physical examination in ankylosing spondylitis
Tenderness over the sacroiliac joints
Limited range of motion of the spine
Decreased chest expansion
due to inflammation of the costovertebral joints

24. Ankylosing spondylitis
Involvement of cervical spine:
Inability to touch occiput to wall
Involvement of lumbar spine:
Failure to reverse lumbar lordosis during flexion

25. Sacroiliac joints: normal

26. Sacroiliac joints: ankylosing spondyltitis

27. Late ankylosing spondylitis: sacroiliitis

28. Progression of ankylosing spondylitis: lumbar spine
facet “squared-off” syndesmophytes
disease vertebrae

29. Ankylosing spondylitis: syndesmophytes and fusion of lumbar spine
Spinal complications of AS:
loss of motion
osteopenia
increased risk of fracture
- C1-C2 subluxation

30. Ankylosing spondylitis
spine fused in flexion

31. Ankylosing spondylitis: extraarticular manifestations
common: anterior uveitis (20-40%)
Associated with HLA-B27
- GI inflammation (subclinical)
uncommon/rare: aortitis (3% after 15 years)
- apical fibrosis of the lung

32. Anterior Uveitis: inflammation of the iris and ciliary body

33. Anterior uveitis ocular pain, photophobia, red eye

34. Ankylosing spondylitis: diagnosis
Diagnosis is best secured by combination of inflammatory low back pain plus radiographic evidence of sacroiliitis
But plain radiographs may fail to reveal changes for years
MRI of SI joints
HLA-B27 testing
Average delay in diagnosis: 8 years

35. 23 y.o. woman with low back pain
Key features:
Age of onset: 14
Quality of the back pain: inflammatory
Past history of ocular inflammation
Decreased L spine motion and chest expansion

36. 23 y.o. woman with low back pain
Radiograph: bilateral sacroiliitis
Diagnosis: ankylosing spondylitis
Started on anti-TNF therapy
AM stiffness 180 min min
Chest expansion 2 cm cm
Returned to college full time

37. Ankylosing spondylitis: therapy
physical therapy to maintain erect posture
NSAIDs
avoid use of systemic corticosteroids
Anti-tumor necrosis factor therapy
Symptomatic improvement in axial skeleton disease

38. Reactive arthritis
arthritis triggered by GU or GI infections in which the inciting organism cannot be cultured from involved joints
genitourinary infections: Chlamydia trachomatis
enteric infections: Shigella Salmonella Yersinia Campylobacter

39. Reactive Arthritis can be “idiopathic” resolution chronic arthritis
GI/GU 1 -4 wks reactive
infection arthritis (1-4%)
months
can be “idiopathic” resolution

40. Reactive Arthritis
Cultures of synovial fluid and synovial tissue are sterile
Bacterial antigens can be detected in synovial tissue, even years after the onset of arthritis
No evidence of viable organisms
Antibiotics:
No proven benefit for enteric forms

41. Reactive arthritis: general features
M:F, 5:1
often, at onset,constitutional symptoms with prominent weight loss, fatigue, & malaise
peripheral arthritis > axial arthritis
asymmetric oligoarthritis
lower extremity predominance
enthesitis (heel pain is common)
extraarticular disease

42. Reactive arthritis: extraarticular manifestations
eye:
conjunctivitis: usually mild
anterior uveitis
mucous membranes and skin:
urethritis
oral ulcers (painless)
keratoderma blenorrhagica
circinate balanitis
nail changes

43. Reactive Arthritis: Mouth Ulcers

44. Reactive arthritis: keratoderma

45. Psoriatic arthritis Peripheral arthritis Spondylitis
Develops in 5-7% of patients with psoriasis
Oligoarthritis, monarthritis
Polyarthritis
Arthritis mutilans
Spondylitis
Develops in 20% with peripheral arthritis

46. Psoriatic arthritis: polyarthritis

47. Psoriatic arthritis: DIP involvement
Inflammation of DIP
joint
Nail pitting

48. Psoriatic arthritis: spondylitis

49. Spondyloarthropathies: key points
Shared features
Why we group the spondyloarthropathies
How the spondyloarthropathies differ from RA
Major clinical manifestations of ankylosing spondylitis and reactive arthritis
Recognize clinical presentations of these diseases
Importance of HLA-B27 as a risk factor