Seronegative Spondyloarthropathies Internal Medicine/Pediatrics Noon conference series June 1, 2006

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Seronegative Spondyloarthropathies Internal
Medicine/PediatricsNoon conference seriesJune
1, 2006
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Back to basics

• The skeleton

• Axial skeleton
• Skull
• Vertebral column
• Vertebrae
• Sacrum
• Coccyx
• Ribs
• Sternum
• Appendicular skeleton
• Girdles
• Extremities

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Back to basics

• Articulations

• Diarthrosis (moveable)
• Majority of articulations
• Contiguous bones are covered by cartilage,
  connected by ligaments, and have an interposing
  synovial sac
• Synarthrosis (immoveable)
• 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)

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Back to basics

• Enthesis

• Enthesis is the site of bony attachment of
• Tendon
• Ligament
• Cartilage
• Joint capsule
• Fascia

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Seronegative spondyloarthropathies

• Comprise these conditions

• Ankylosing spondylitis (the prototype)
• Psoriatic arthritis
• Reactive arthritis
• Formerly called Reiters syndrome)
• Enteropathic arthritis
• Undifferentiated spondyloarthropathy
• Mnemonic is PURE-A (sort of like purée)

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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)
• Spondylitis (inflammation of vertebral bodies)
• Sacroiliitis (inflammation of sacroiliac joint)
• Peripheral arthritis (generally a synovitis)
• Asymmetric (cf rheumatoid arthritis)
• Extraärticular manifestations (besides
  enthesitis)
• Seronegativity
• Rheumatoid factor and ANA negative

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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

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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

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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

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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

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Ankylosing spondylitis

• Other clinical (besides back pain)

• Restriction of lumbar movement
• Shobers test mark the patients 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 lt 5 cm, lumbar flexion is limited.
• Anterior uveitis (iritis or iridocyclitis) (25)
• Acute eye pain
• Increased lacrimation
• Photophobia
• Blurred vision
• Aortitis with fibrosis
• Aortic insufficiency
• Third degree heart block (5)

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Ankylosing spondylitis

• Radiographic evaluation

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Ossification of SI joint space
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Bamboo spine
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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

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Reactive arthritis

• Interesting historical backdrop

• In 1916, Hans Reiter reported Reiters 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

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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

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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

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Reactive arthritis

• Clinical

• Nongonococcal urethritis
• Occurs in postenteric or postvenereal disease
• When it occurs in postvenereal disease, C.
  trachomatis is often the etiology
• When present, is usally the first symptom
• In men
• Mild dysuria
• Mucopurulent urethral discharge
• May present as prostatitis or epididymitis
• In women
• Dysuria
• Purulent vaginitis or cervicitis with vaginal
  discharge
• Asymptomatic urethritis often features sterile
  pyuria

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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)

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Reactive arthritis

• Keratoderma blenorrhagica

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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

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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

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Why are these diseases classified together?

• Treatment

• Nonsteroidal antiinflammatory agents
• Indamethacin
• Disease modifying anti-rheumatic drugs (DMARDs)
• Methotrexate inhibits recruitment of CD4 and CD8
  T cells
• Tumor necrosis factor antagonists
• 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