Transcript Slide 1
Seronegative
Spondyloarthropathie
s
Internal Medicine/Pediatrics
Noon conference series
June 1, 2006
Back to basics
The skeleton
Axial skeleton
Skull
Vertebral column
Vertebrae
Sacrum
Coccyx
Ribs
Sternum
Appendicular skeleton
Girdles
Extremities
Back to basics
Articulations
Diarthrosis (moveable)
Synarthrosis (immoveable)
Majority of articulations
Contiguous bones are covered by cartilage, connected
by ligaments, and have an interposing synovial sac
Contiguous bones are in direct contact without
cartilage, syovium, or ligaments
Amphiarthrosis (sort of moveable)
Characteristics of both diarthrosis and synarthrosis
Contiguous surfaces are either:
Connected by fibrocartiganeous disks (vertebral joint)
Covered by fibrocartilage and partial synovium, and attached
by external ligaments (sacroiliac joint)
Back to basics
Enthesis
Enthesis is the site of bony attachment of
Tendon
Ligament
Cartilage
Joint capsule
Fascia
Seronegative
spondyloarthropathies
Comprise these conditions…
Ankylosing spondylitis (the prototype)
Psoriatic arthritis
Reactive arthritis
Formerly called Reiter’s syndrome)
Enteropathic arthritis
Undifferentiated spondyloarthropathy
Mnemonic is PURE-A (sort of like purée)
Why are these diseases classified
together?
Well, because they share these characteristics…
HLA-B27 association
Enthesitis (both juxtaärticular and extraärticular)
Axial skeleton arthritis (generally secondary to
juxtaärticular enthesitis)
Peripheral arthritis (generally a synovitis)
Spondylitis (inflammation of vertebral bodies)
Sacroiliitis (inflammation of sacroiliac joint)
Asymmetric (cf rheumatoid arthritis)
Extraärticular manifestations (besides enthesitis)
Seronegativity
Rheumatoid factor and ANA negative
Why are these diseases classified
together?
HLA-B27 association
Ankylosing spondylitis: 95%
Ethnically matched controls: 8%
Reactive arthritis: 70%
Enteropathic arthritis: 50%
Psoriatic arthritis: 35%
Why are these diseases classified
together?
Enthesitis
Inflammation of an enthesis
Principal pathogenetic mechanism in
spondyloarthropathy
Pathogenesis
CD8 T cells infiltrate entheses
Activated macrophages release cytokines (eg TNF)
Fibroblasts synthesize new collagen (cf rhematoid arthritis!!)
New bone formation results
Clinical
Axial skeleton arthritis (see later)
Enthesopathy at other sites
Calcaneal spurs at plantar fascia insertion
Spurs at Achilles tendon insertion
Manifests as extraärticular or juxtaärticular bony tenderness
Why are these diseases classified
together?
Axial skeleton arthritis
Arises from enthesitis
Includes spondylitis and sacroiliitis
Spondylitis
CD8 T cells invade the junction of the annulus fibrosis and the
vertebral body (an enthesis)
Annulus fibrosis is replaced by bone (syndesmophytosis)
Vertebral bodies assume a square shape, and ultimately a
bamboo spine
Sacroiliitis
CD8 T cells invades the subchondral area at the junction of the
bones and the cartilage (an enthesis)
Cartilage on iliac side is replaced by bone, obliterating the jont
space and hardening the joint
Ankylosing spondylitis
Inflammatory back pain
Inflammatory back pain requires 4 of these 5
criteria (serves as a screening tool for AS)
Young onset ( 40 years)
Morning stiffness ( 30 minutes)
Chronic ( 3 months)
Activity improves the pain (rest does not)
Insidious (not acute)
(mnemonic is YMCA-I)
Diffuse lumbar or gluteal, not focal or radicular
Cf focal pain of disk herniation
Ankylosing spondylitis
Other clinical (besides back pain)
Restriction of lumbar movement
Anterior uveitis (iritis or iridocyclitis) (25%)
Shober’s test – mark the patient’s back at the level of the posterior
iliac spine. Place one finger 5 cm below this mark and a 2nd finger
10 cm above this mark. Patient is instructed to touch his toes. If
the distance between finegrs increases < 5 cm, lumbar flexion is
limited.
Acute eye pain
Increased lacrimation
Photophobia
Blurred vision
Aortitis with fibrosis
Aortic insufficiency
Third degree heart block (5%)
Ankylosing spondylitis
Radiographic evaluation
Sacroiliac joints
Grade 0
Normal
Grade 1
Suspicious changes
Grade 2
Minimal abnormality – small localized areas with
erosion or sclerosis without alterations in joint width
Grade 3
Unequivocal abnormality – moderate or advanced
sacroiliitis with 1 of the following: erosions,
sclerosis, widening, narrowing, or partial ankylosis
Grade 4
Severe abnormality – total ankylosis
Ossification of SI joint space
Bamboo spine
Ankylosing spondylitis
Modified New York Diagnostic Criteria
Low back pain 3 months improved by exercise and not
relieved by rest
Limitation of lumbar spine in sagittal and frontal planes
Chest expansion reduction relative to normal values
corrected for age and sex (costovertebral ankylosis,
25%)
Radiographic criteria of sacroiliitis
Bilateral grade 2-4 OR
Unilateral grade 3-4
Ankylosing spondylitis is defined by the presence of either
radiographic criterion PLUS any clinical criterion
Reactive arthritis
Interesting historical backdrop
In 1916, Hans Reiter reported Reiter’s syndrome:
a triad of nongonococcal urethritis, conjunctivitis,
and arthritis that occurred in a young German
officer following an episode of bloody dysentery
Subseqently, more cases were reported following
enteric infections OR venereally acquired
genitourinary infections.
In 1967, the term reactive arthritis was applied to
similar cases following Yersinia gastroenteritis
The two terms should be considered synonomous
The term reactive arthritis is increasingly preferred
Reactive arthritis
Pathogenesis
Clinical syndrome triggered by specific etiologic
agents in a genetically susceptible host
Follows 1-4 weeks after a
Urogenital infection (affects principally men)
Usually C. trachomatis
Enteric infection (affects both genddrs equally)
Salmonella
Shigella
Campylobacter
Yersinia
Reactive arthritis
Clinical
Peripheral arthritis
Asymmetric additive oligoarthritis (usually)
Synovitis
Warm
Edematous
Tender
Pain with active or passive movement
Usually lower extremity joints (knee, ankle, subtalar)
Conjunctivitis
Reactive arthritis
Clinical
Nongonococcal urethritis
Occurs in postenteric or postvenereal disease
When present, is usally the first symptom
In men
Mild dysuria
Mucopurulent urethral discharge
May present as prostatitis or epididymitis
In women
When it occurs in postvenereal disease, C. trachomatis is
often the etiology
Dysuria
Purulent vaginitis or cervicitis with vaginal discharge
Asymptomatic urethritis often features sterile pyuria
Reactive arthritis
Clinical (continued)
Keratoderma blenorrhagica
A papulosquamous skin rash
Comprises vesicles that become hyperkeratotic,
forming crusts before disappearing
Palms/soles
Penis (causing circinate balanitis
Oral ulcers (ususally shallow and painless)
Inflammatory back pain (50% of patients)
Enthesitis (40%)
Dactylitis (40%)
Anterior uveitis (20% of patients)
Reactive arthritis
Keratoderma blenorrhagica
Reactive arthritis
Evaluation
Synovial fluid analysis
Pleocytosis (5 000 to 50 000 WBC/mcL) with
polymorphonuclear cell predominance
Protein levels
Glucose normal
Cf reduced glucose level in true septic arthritis
Gram stain and culture are sterile
Urethral or cervical smears in patients with
clinical urethritis
C. trachomatis
N. gonorrhoeae
Enteropathic Arthritis
Clinical
Affects 10-20% of patients with inflammatory
bowel disease (IBD)
Peripheral arthritis affects 10-20% of IBD
patients
Generally affects knees, ankles, and feet
Always indicates active IBD
Radiographic axial arthritis affects 10% of IBD
patients
Frequently asymptomatic
Independent of bowel inflammation
Why are these diseases classified
together?
Treatment
Nonsteroidal antiinflammatory agents
Disease modifying anti-rheumatic drugs
(DMARDs)
Methotrexate: inhibits recruitment of CD4 and CD8 T
cells
Tumor necrosis factor antagonists
Indamethacin
Infliximab: a monoclonal antibody that binds to TNF and
inhibits binding of TNF to its receptor
Etanercept: similar emchanism to infliximab
For axial arthritis, exercises to maintain posture
and flexibility