Spondyloarthropathies
John Imboden MD
23 y.o. woman with low back
pain
• 9 years of low back pain
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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
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?
Spondyloarthropathies
• Ankylosing spondylitis
• Reactive arthritis
• Arthritis associated with inflammatory
bowel disease (Crohn’s disease and
ulcerative colitis)
• Arthritis associated with psoriasis
• Undifferentiated spondyloarthropathy
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
Involvement of axial skeleton:
sacroiliac joints and all components of spine
Sacroiliitis occurs in 100% cases of ankylosing spondylitis
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
Dactylitis: “sausage” digit
Enthesitis:
inflammation at insertion of Achilles tendon
Enthesitis
inflammation and boney proliferation where plantar fascia
inserts onto the calcaneus
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
HLA-B27 and
spondyloarthropathies
HLA-B27 in Caucasian populations in US
– normal controls
– ankylosing spondylitis
– reactive arthritis
with spondylitis
– psoriatic with spondylitis
– IBD with spondylitis
8%
90%
60-80%
50%
50%
HLA polymorphisms and
selected autoimmune diseases
Disease
ankylosing spondylitis
reactive arthritis
rheumatoid arthritis
HLA marker
B27
B27
DR4
relative risk
90
40
5
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
HLA-B27 and risk of
spondyloarthropathy
Environmental triggers
mucosal inflammation (infection, IBD)
psoriasis
unknown
+
Genetic background
HLA-B27
other genes
Spondyloarthropathy
Ankylosing Spondylitis
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
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 1550% of the overall genetic risk
• Environmental trigger is essential but
ubiquitous
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
Age of onset of symptoms in AS
(Feldkeller et al. Rheumatol Int 23: 61, 2003
Ankylosing spondylitis:
“inflammatory” back pain
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insidious in onset
persistent
dull in quality
associated with stiffness
worse in AM or after prolonged inactivity
eased by mild activity
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
Ankylosing spondylitis
Involvement of
cervical spine:
Inability to touch
occiput to wall
Involvement of
lumbar spine:
Failure to
reverse lumbar
lordosis during
flexion
Sacroiliac joints: normal
Sacroiliac joints:
ankylosing spondyltitis
Late ankylosing spondylitis:
sacroiliitis
Progression of ankylosing spondylitis: lumbar spine
facet “squared-off”
disease
vertebrae
syndesmophytes
Ankylosing spondylitis:
syndesmophytes and fusion of lumbar spine
Spinal complications of AS:
- loss of motion
- osteopenia
- increased risk of fracture
- C1-C2 subluxation
Ankylosing spondylitis
spine fused in flexion
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
Anterior Uveitis:
inflammation of the iris and ciliary body
Anterior uveitis
ocular pain, photophobia, red eye
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
23 y.o. woman with low back
pain
Key features:
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Age of onset: 14
Quality of the back pain: inflammatory
Past history of ocular inflammation
Decreased L spine motion and chest expansion
23 y.o. woman with low back
pain
• Radiograph: bilateral sacroiliitis
• Diagnosis: ankylosing spondylitis
• Started on anti-TNF therapy
– AM stiffness 180 min
– Chest expansion 2 cm
– Returned to college full time
0 min
4.5 cm
Ankylosing spondylitis: therapy
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physical therapy to maintain erect posture
NSAIDs
avoid use of systemic corticosteroids
Anti-tumor necrosis factor therapy
– Symptomatic improvement in axial skeleton
disease
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
Reactive Arthritis
chronic
arthritis
GI/GU
infection
1 -4 wks
reactive
arthritis (1-4%)
months
can be “idiopathic”
resolution
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
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
Reactive arthritis:
extraarticular manifestations
• eye:
– conjunctivitis: usually mild
– anterior uveitis
• mucous membranes and skin:
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urethritis
oral ulcers (painless)
keratoderma blenorrhagica
circinate balanitis
nail changes
Reactive Arthritis: Mouth Ulcers
Reactive arthritis: keratoderma
Psoriatic arthritis
• Peripheral arthritis
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Develops in 5-7% of patients with psoriasis
Oligoarthritis, monarthritis
Polyarthritis
Arthritis mutilans
• Spondylitis
– Develops in 20% with peripheral arthritis
Psoriatic arthritis: polyarthritis
Psoriatic arthritis: DIP involvement
Inflammation of DIP
joint
Nail pitting
Psoriatic arthritis: spondylitis
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