Juvenile Idiopathic Arthritis - Basic Science

summary
- Juvenile Idiopathic Arthritis is a chronic autoimmune inflammatory arthritis lasting greater than 6 weeks in a patient younger than 16 years of age that typically presents with morning joint stiffness and ocular infections.
- Diagnosis is one of exclusion and presence of infection must be ruled out. One of the following must be present to confirm the diagnosis: rash, iridocyclitis, pericarditis, tenosynovitis, intermittent fever, presence of RF, C-spine involvement, morning stiffness.
- Treatment is usually immunomodulating drugs and frequent ophthalmologic exams.

Epidemiology
- Demograpics
  - female > male
- Anatomic location
  - joint involvement ( knee > hand/wrist > ankle > hip > C-spine)

Etiology
- Genetics
  - HLA markers
    
    DR4 associated with polyarticular
    
    DR8, DR5, DR2.1 associated with pauciarticular
  - RF- seropositive in <15%
- Diagnostic criteria
  - a diagnosis of exclusion
    
    must rule out infection
  - one of the following must be present to make diagnosis
    
    rash
    
    presence of RF
    
    iridocyclitis
    
    C-spine involvement
    
    pericarditis
    
    tenosynovitis
    
    intermittent fever
    
    morning stiffness
- Associated conditions
  - C-spine involvement
    
    may lead to kyphosis, facet ankylosis, and atlantoaxial subluxation
  - Ocular involvement
    
    typically consists of iridocyclitis, a type of anterior uveitis
    
    frequently indolent and requires immediate ophthalmologic evaluation for slit lamp examination
    
    can lead to rapid loss of vision if untreated
    
    increase risk with positive ANA titer
  - Stills disease
    
    acute-onset JRA with multiple joint involvement, fever, rash, and splenomegaly
    
    infection must be ruled out
    
    male = female
    
    usually presents at age 5-10 years

                        Classification
                    
                        Onset
                    
                        early onset denotes onset before teens
                    
                        late onset denotes onset during teens or later
                    
                                            Classification of Juvenile Rheumatoid Arthritis
                                        
                                            Polyarticular (30%)
                                        
                                            • Hand/wrist involvement most common
• Deformity is wrist ulnar deviation and flexion with MCP stiffness in extended, swollen & radially deviated digits position
• 60% remission rate
 
                                            • > 5 joints involved
• Small joint involvement (hand, wrist)
• Symmetric findings
• F>M
 
                                            Pauciarticular (50%)(oligoarticular)
                                        
                                            • Most common type
• Early-onset associated with iridiocyclitis in 50% and chronic uveitis
• Obtain ophthalmology consult; requires frequent ophthalmologic exams (q4 mth if ANA+; q6 mth if ANA-)
• Girls are affected four times more often than boys in early-onset
• Peak age 2-3 yrs
• Late-onset seen more frequent in boys
• Typical finding is a limp that improves during the day
• Best prognosis for long term remission (70%)
 
                                            • < 5 joints involved
• Large joint involvement (knees, ankles)
• Asymmetric findings (leg length discrepancy, involved limb ends up LONGER)
• M:F =1:4
• Age 2-3y
                                        
                                            Systemic (20%)
                                        
                                            • Includes Stills disease
• Poorest prognosis
 
                                            • systemic symptoms (rash, fever, multiple joint involvement) anemia, high WBC, elevated ESR, CRP, platelets
• Hepatosplenomegaly, lymphadenopathy, pericarditis
• M=F, age 5-10y

Presentation
- Symptoms
  - morning stiffness and joint pain
  - visual changes
  - fever
- Physical exam
  - rash
  - iridocyclitis (can lead to rapid loss of vision if untreated)

Imaging
- Radiographs
  - often negative at presentation
  - juxta-articular, late osteopenia and joint destruction can be seen if disease progressive
  - obtain flexion-extension neck radiographs to rule out atlantoaxial instability

Studies
- Laboratory
  - rheumatoid factor
    
    RF seropositive in <15%
    
    associated with higher incidence of chronic, active, and progressive disease
    
    often results in more destructive DJD
    
    more likely to progress into adult RA
    
    RF seronegative is more common
  - ANA
    
    ANA positive is diagnostic
  - basic serology
    
    values often normal and are not diagnostic

Treatment
- Nonoperative
  - immunomodulating drugs (DMARDs) and frequent ophthalmologic exams
    
    indications
    
    first line of treatment
    
    medications
    
    DMARDs (disease modifying antirheumatic drugs)
    
    new class of medications that have had significant impact on outcomes
    
    includes but not limited to
    
    etanercept
    
    TNF inhibitor
    
    rituximab
    
    chimeric monoclonal antibody against CD20 on B cell surface
    
    azathioprine
    
    purine synthesis inhibitor
    
    high dose aspirin/NSAIDs
    
    salicylates are now used less frequently secondary to DMARD success
    
    occasionally, gold may be used
    
    intra-articular steroid injections
    
    frequent ophthalmologic exams
    
    slit-lamp examination twice yearly if ANA(-), every 4 months if ANA(+)
    
    progressive iridocyclitis can lead to rapid loss of vision if untreated
- Operative
  - synovectomy
  - epiphysiodesis
    
    indications
    
    LLD (affected leg typically longer in oligoarticular disease)
  - corrective osteotomies
    
    indications
    
    extremity deformity
    
    deferred until skeletal maturitity
  - arthrodesis and arthroplasty
    
    indications
    
    for severe disease

Prognosis
- 50% patients symptoms resolve without sequelae
- 25% are slightly disabled
- 25% have crippling arthritis or blindness
  - best prognosis pauciarticular > polyarticular > systemic

Classification of Juvenile Rheumatoid Arthritis
Polyarticular (30%)	• Hand/wrist involvement most common • Deformity is wrist ulnar deviation and flexion with MCP stiffness in extended, swollen & radially deviated digits position • 60% remission rate	• > 5 joints involved • Small joint involvement (hand, wrist) • Symmetric findings • F>M
Pauciarticular (50%)(oligoarticular)	• Most common type • Early-onset associated with iridiocyclitis in 50% and chronic uveitis • Obtain ophthalmology consult; requires frequent ophthalmologic exams (q4 mth if ANA+; q6 mth if ANA-) • Girls are affected four times more often than boys in early-onset • Peak age 2-3 yrs • Late-onset seen more frequent in boys • Typical finding is a limp that improves during the day • Best prognosis for long term remission (70%)	• < 5 joints involved • Large joint involvement (knees, ankles) • Asymmetric findings (leg length discrepancy, involved limb ends up LONGER) • M:F =1:4 • Age 2-3y
Systemic (20%)	• Includes Stills disease • Poorest prognosis	• systemic symptoms (rash, fever, multiple joint involvement) anemia, high WBC, elevated ESR, CRP, platelets • Hepatosplenomegaly, lymphadenopathy, pericarditis • M=F, age 5-10y