1. Overview of Juvenile Idiopathic Arthritis
Pediatric Rheumatology
Red Team Resident
Teaching Series

2. Juvenile Idiopathic Arthritis
One of the more common chronic childhood diseases
almost as common as childhood-onset diabetes mellitus
at least 4 times more common than sickle cell disease or cystic fibrosis
at least 10 times more common than leukemia, hemophilia, chronic renal failure, or muscular dystrophy

3. Differential Diagnosis for JIA
Acute (within 72 hours)
Infection: Septic arthritis, Rheumatic fever
Malignancy: Leukemia, Neuroblastoma
Toxic Synovitis
Blood disorders: Hemophilia, Sickle Crisis (dactylitis)
Trauma
Chronic (more than 4 weeks)
Infection: TB, Lyme disease, Parvovirus, Rubella
Pigmented villonodular synovitis (PVNS)
Other rheumatic diseases (SLE, Sarcoid, vasculitis)

4. CRITERIA FOR THE DIAGNOSIS OF JUVENILE IDIOPATHIC ARTHRITIS
Age of onset < 16 years
Arthritis (swelling or effusion, limitation of motion, tenderness or pain on motion, and/or increased heat) in one or more joints
Duration of disease 6 weeks or longer
Onset type defined by type of disease in the first 6 months: Polyarticular: 5 or more inflamed joints Oligoarticular: < 5 inflamed joints Systemic arthritis: Characteristic fever
Exclusion of other forms of arthritis

5. Juvenile Arthritis Breakdown
Oligoarticular JIA (50-60%)
Polyarticular JIA (30-35%)
Systemic JIA (5-10%)
Enthesitis Related Arthritides (5-15%)
Juvenile Ankylosing Spondylitis
Reactive Arthritis
IBD associated arthritis
Juvenile Psoriatic Arthritis
ILAR (International League of Associations for Rheumatology) Classification of JIA

6. Case History #1
2 yo girl presents with a 4 week history of limping. Mom notices she wants to be carried out of bed in morning and cannot fully straighten her right leg. But by the afternoon she is running around. ROS: No fevers. No rash. No recent illnesses. PE: normal vitals, right leg with swelling, limitation of motion and pain on passive motion and right ankle with swelling Labs: Normal CBC, ESR 25, ANA positive

8. Oligoarticular JIA Fewer than 5 joints Peak onset between 2-4 years
Tends to affect larger joints and lower extremities
Asymmetric joint involvement
Peak onset between 2-4 years
One knee is the most common presentation (50%)
Highest risk of uveitis among the JIA types
Girls:Boys - 3:1
Labs may be normal or mild elevation of acute phase reactants
ANA positive (<1:640) in 65-85%
Rheumatoid Factor usually negative
Ankle or wrist arthritis and symmetric arthritis predictive of erosions

9. Uveitis Up to 21% of oligoarticular and 10% of polyarticular patients
ANA positive JIA patients are at higher risk of uveitis
Highest risk of uveitis: ANA+ young girls with oligoarticular disease
Usually asymptomatic
Can occur anytime

10. Uveitis - Complications
cataracts
glaucoma
visual impairment, including blindness
posterior synechiae
band keratopathy

11. Case History #2
14 yo girl presents with hand and feet pain over 6 weeks. It is difficult for her to write in school and run during her basketball practices. She feels that her hands are more stiff in the mornings. ROS: Fatigue. Occasional low grade fevers. No rash. No recent illnesses PE: normal vitals, MSK – bilateral wrists, MCPs, PIPs, knees, ankles, and feet swollen and tender to palpation Labs: WBC 7K, Hgb 12, Plt 500 K, ESR 51, ANA negative, RF positive, anti CCP antibody positive

13. Polyarticular JIA 5 or more joints involved Age of onset: biphasic
Girls:Boys – up to 5:1
Usually symmetric joints involving the large and small joints
Can see boutonnière and swan neck deformities
Rheumatoid Factor positive patients onset in late childhood or adolescence
rheumatoid nodules (5-10%)
early erosive disease
chronic course persisting into adulthood
Can see systemic symptoms of mild fever, fatigue

14. Poly JIA – Laboratory Usually have elevated acute phase reactants
Rheumatoid Factor (RF)
Associated with worse prognosis
Anti Cyclic Citrullinated Peptide antibodies (anti-CCP antibodies)
up to 75% of children with RF+ poly JIA have positive anti CCP antibodies

15. Case History #3
10 yo boy presents with 2 weeks of high spiking fevers (>103), rash, joint pains, and body aches. When the fever is down, he feels fine.
ROS: positive for chest pain, headaches, sore throat
PE: T 38.0 HR 120 BP 120/75
HEENT- cervical LAD
Skin- salmon colored evanescent rash on arms/legs
Lungs- crackles at bases
MSK – bilateral shoulders, elbows, wrist, hips, and knees swollen and painful on movement
Labs: Infectious evaluation negative; PPD neg; ESR 105 WBC 25K Hgb 10 Plt 800K AST 60 ALT 75 ANA negative
Radiology: CXR shows bilateral pleural effusions

17. Keobner phenomenom

18. Systemic Juvenile Idiopathic Arthritis (SJIA)
Girls:Boys - 1:1
Peak age of onset is variable
Characteristic features: fever 39°C or higher for >2 weeks and salmon colored rash
Arthritis joint involvement variable or may be just arthralgias
Child looks ill during fever, but well when afebrile
Other features include carditis, pleuritis, pneumonitis, CNS, anemia, DIC, “macrophage activation syndrome”
Rash in 80% of patients
Labs: Elevated ESR, CRP, WBC, Platelets, Ferritin, d-dimers, AST, and ALT. Anemia, low Albumin, ANA and RF negative
Uveitis is rare
Prognosis guarded

19. SJIA Quotidian Fever Curve
Fever occurs on a once to twice daily basis, usually during the same time of day each day, spiking to approximately the same temperature each time. The temperature will often become hypothermic after a fever, prior to return to a normal temperature.

20. Macrophage Activation Syndrome
Concern for Macrophage Activation Syndrome (MAS) (consumptive process) AKA secondary HLH
High risk in patients with Systemic JIA
Presents with hemorrhagic syndrome, HSM, LAD, fever
See drop in ESR, Platelets, WBC
Coagulopathy – increased PT/PTT, ↑LFTs, elevated d-dimers, ↓fibrinogen, DIC consumption like picture but also due to liver dysfunction
High triglycerides, LDH, FERRITIN (usu > 10,000)
Mental status changes and seizures
Can be life threatening
Also reported with: Polyarticular JIA, SLE, MCTD, JDM, Kawasaki’s, sarcoid

21. Case History #4
16 yo boy presents with lower back pain and bilateral heel pain that affects his basketball playing. He is also complaining of a red painful eye
ROS: positive for fatigue, some weight loss
PE: normal vitals
HEENT – erythematous conjunctiva and sclera
MSK – bilateral ankle swelling, heel tenderness, SI joint pain on palpation, and decreased lumbar flexion
Labs: CBC normal ESR 50 ANA negative, RF negative, HLA-B27 positive

22. *Can have all or only some of the characteristics
Enthesitis Related Arthritis (ERA)/Seronegative Enthesitis Arthritis (SEA)/ Spondyloarthropathies
Refers to a group of rheumatic diseases that includes:
Joints of axial skeleton
Entheses
Psoriasis
Inflammatory bowel disease
Infections
*Can have all or only some of the characteristics

23. ERA/ Spondyloarthropathy
HLA- B27 associated
RF and ANA negative
Adult form: inflammatory low back pain
Juvenile form:
≤16 years old onset
Asymmetric arthritis, usually lower extremities
Peripheral enthesitis
Age of onset – late childhood and adolescence
Boys>Girls
Arthritis – Axial joint involvement
Enthesitis
Iritis – red painful photophobic eye, usually unilateral

24. Enthesial evaluation

25. Iritis: Acute onset of a red, often painful eye

26. Case History #5
4 yo girl presents with a 3 week history of a swollen toe. No history of preceding trauma.
ROS: benign
PE: normal vitals
Skin – dry scaly patches on hands and abnormal nails
MSK – swollen left 3rd toe
Labs: CBC normal, ESR 30, ANA positive

28. Juvenile Psoriatic Arthritis
Psoriasis affects 1-3% of general population and 20-30% of those patients have associated arthritis
Preceded, accompanied, or followed by psoriasis
Half don’t manifest psoriasis until after joint presentation
Age of onset for arthritis 7 to 11 years, with psoriasis between 9 to 13 years – preschool years and middle to late childhood
Slightly more common in girls; M:F of 1:2.5.
Eye
Asymptomatic uveitis % and assoc with +ANA
Symptomatic uveitis - rare in kids and assoc with +HLA-B27
Arthritis
Dactylitis - implies underlying tendinitis (aka sausage digit)
Can be aggressive and damaging
Scattered, asymmetric oligoarthritis of large and small joints, most commonly knee, finger (but DIP is rare), toes.
Pitting of the nails seen in 75% of children with disease.

29. Juvenile Arthritis Therapy
Start with nonsteroidal antiinflammatory drugs (NSAIDS)
If significant synovitis involving multiple joints persists for 3-6 months, or radiologic evidence of destructive disease is present consider initiation of DMARD (disease modifying antirheumatic drug). Methotrexate and sulfasalazine are most commonly used DMARDs.
If significant synovitis persists despite DMARD consider adding biologic agent (TNF inhibitors, Tocilizumab, Abatacept).
Steroids - Never proven to be disease modifying
Moderate to high doses used for systemic JIA and severe uveitis (>1 mg/kg/day)
Low doses for polyarticular JIA and ankylosing spondylitis (5-15 mg/day)
Intraarticular steroid injections

30. Juvenile Arthritis Prognosis
Oligoarticular JIA - Overall better outcome with less damage
many will go into remission but subset of children will develop a polyarticular course
20-30% will get uveitis with the sequelae of blindness if unrecognized and untreated
Polyarticular JIA – Guarded outcome with potential damage
prognosis worse if RF+, small joint or hip involvement, or erosive disease
patients who had not gone into remission by age 16 are likely to have chronic course
Systemic JIA – Guarded outcome
50% will recover without problems
Significant morbidity and mortality can occur with macrophage activation syndrome

31. Important Points to Remember
Arthritis in children can be a symptom of a more systemic process (non rheumatologic and rheumatologic) OR a disease entity itself
ANA is only helpful for helping to determine uveitis risk
Rheumatoid Factor (RF) ONLY important in older children with > 4 joint involvement
Don’t forget the eyes
Toe swelling: think psoriatic arthritis
One knee swelling: think Lyme arthritis
Any child < 5 years of age with hip or back pain: be cautious!
JIA pain is more insidious and less acute
Very rare to have musculoskeletal sprain resulting in acute swelling in children < 3 years of age
Xrays are important to rule out fracture or malignancies; not diagnostic of arthritis