What Are the Possible Complications of Juvenile Rheumatoid Arthritis?

Patient Presentation
A 6-year-old female came to clinic with > 3 week history of her legs bothering her in the night and swelling of both knees.
The knees had been warm and swollen with intermittent pain unrelieved by ibuprofen.
There was also occasional pain in both ankles.
The past medical history revealed ear infections.
The family history revealed osteoarthritis in grandparents and adult onset diabetes. The family denied other autoimmune or connective tissue disorders.
The review of systems showed decreased appetite but no fever, weight loss, rashes, recent illnesses, travel history or pets.
The pertinent physical exam showed normal vital signs, and weight and height were in the 50-75%. HEENT, cardiac and skin examinations were normal.
Musculoskeletal examination revealed both knees to be swollen with considerable warmth medially but with full range of motion.
The ankles were also bilaterally swollen with mild erythema and tenderness on range of motion.
There was normal range of motion and no synovitis in all other joints.
The laboratory evaluation initially showed a hemoglobin of 10.5 g/dl, hematocrit of 32%, with white blood cell count of 12.2 x 1000/mm2 with 7100 neutrophils.
Liver function and hepatitis screening tests were normal. Erythrocyte sedimentation rate was elevated at 35 mm/hr, anti-nuclear antibody was elevated at 1:80 dilution, and the rheumatoid factor was negative.
Because of the patient’s presentation and laboratory testing, the physician suspected juvenile rheumatoid arthritis. The patient was placed on Naproxyn and referred to a rheumatologist.
Further evaluation and continued symptoms confirmed
a diagnosis of pauciarticular juvenile rheumatoid arthritis.
Over the patient’s clinical course a diagnosis of right-sided anterior uveitis was made and was being treated with prednisolone and Cyclogyl® eye drops.
The patient began treatment with methotrexate and hydroxychloroquin and had improved symptoms 6 weeks later.

Juvenile rheumatoid arthritis (JRA) is a group of diseases which have chronic joint inflammation and an unknown cause.
Chronic synovial inflammation is associated with B cell lymphocyte, T cell lymphocyte and macrophage invasion and release of cytokines, which promote inflammation and sometimes destruction.
Overall, ~10-20 cases/100,000 children occur in the U.S.

The major classifications of JRA by the American College of Rheumatology are based on the clinical course over the first 6 months of illness.

  • Pauciarticular JRA
    • 60% of patients
    • Less than 4 joints, can occur in any joint but often knees and ankles, generally does not occur in hips and generally does not cause destructive arthritis
    • Two types:
      • Type 1, females > males, often patients are preschool age, rare in children > 10 years
      • Type 2, males > females, often patients are 9-11 years old
    • Extraarticular manifestations – uncommon except for uveitis occurs in ~20% of patients
    • Lab tests
      • Antinuclear antibody (ANA) – low titer
      • Rheumatoid factor – generally absent
      • HLA-B27 often present in Type 2
  • Polyarticular JRA
    • 30% of patients
    • More than 5 joints, can occur in any joint but often larger joints with symmetric involvement, generally does not occur in hips, destructive arthritis occurs in > 50% of patients
    • Females > males
    • Ages 2-5 years and 10-18 years
    • Extraarticular manifestations – fever, hepatosplenomegaly and lymphadenopathy, uveitis occurs in ~ 5% of patients
    • Lab tests
      • ANA – low titer in younger age group
      • Rheumatoid factor – common in older age group
  • Systemic-onset (also known as Still’s disease)
    • 10% of patients
    • Number of joints is variable with any joint possibly involved including hips, destructive arthritis occurs in > 50% of patients
    • Extraarticular manifestations – fever, hepatosplenomegaly, lymphadenopathy, polyserositis, rash, uveitis is rare
    • Lab tests
      • ANA – generally absent
      • Rheumatoid factor – rare

Evaluation for possible JRA includes:

  • Laboratory testing
    • ANA
    • Complete blood count with differential – reduction of any and all cell lines may occur
    • Rheumatoid factor
    • Erythrocyte sedimentation rate – generally elevated
    • Alanine aminotransferase – to exclude hepatitis
    • Urinalysis – to exclude infection and nephritis
    • Other tests for systemic JRA
      • Total protein and albumin – increase or decrease with disease progression
      • Fibrinogen and D-dimer – increased with active disease
    • Radiographic evaluation
      • Plain film – for single joints to exclude other causes such as osteomyelitis or septic arthritis
      • Magnetic resonance imaging – with gadolinium injection can show increased inflammation of synovium
      • Computed tomography – to exclude osteoid osteoma as cause of bone pain
  • Other testing
    • Arthrocentesis – to exclude septic arthritis
    • Synovial biopsy – to esclude other diagnoses (e.g. granulomatous arthritis)
    • Echocardiogram – for possible systemic onset JRA with fever, to exclude pericarditis (pericardiocentesis may be needed to treat this), to help make the diagnosis of Kawasaki Disease or Systemic Lupus Erythematosis
    • Dual-Energy X-ray Absorptiometry (DEXA scanning) – to document osteopenia in polyarticular JRA

Pharmacologic treatment mainly includes anti-inflammatory, immunosuppressive, and immunomodulator (e.g. tumor necrosis factor inhibitors, cyclooxygenase-2 inhibitors, etc.) medications. Consultations and co-management may be needed from social work, psychology, school, physical therapy, occupational therapy, surgery, ophthalmology, hematology, and gastroenterology.

Learning Point
Common complications for JRA include:

  • Pauciarticular JRA
    • Knee flexion contractures
    • Leg length discrepencies
    • Uveitis – Screening for uveitis is recommended every 4 months for ANA+ patients and every 6 months for ANA- patients.
  • Polyarticular JRA
    • Cervical spine abnormalities – subluxation, flexion difficulties
    • Skeletal abnormalities – accelerated bone age, narrow joint spaces, joint subluxation, increase in size of epiphyses
  • Systemic-onset JRA
    • Disseminated intravascular coagulation
    • Endarteritis with threatened digital autoamputation
    • Hemolytic anemia
    • Macrophage activation syndrome – all three hematological cell lines become rapidly decreased with massive release of cytokines
    • Pericarditis

Questions for Further Discussion
1. What specific medications are commonly used to treat JRA? What are their side effects?
2. How is uveitis treated?

Related Cases

To Learn More
To view pediatric review articles on this topic from the past year check PubMed.

Information prescriptions for patients can be found at MEDLINEplus for this topic: Juvenile Rheumatoid Arthritis
and at Pediatric Common Questions, Quick Answers for this topic: Juvenile Rheumatoid Arthritis (JRA).

To view current news articles on this topic check Google News.

Miller M. Juvenile Rheumatoid Arthritis. eMedicine.
Available from the Internet at http://www.emedicine.com/ped/topic1749.htm (rev. 1/4/2005, cited 12/12/2005).

Robertson J, Shilkofski N. The Harriet Lane Handbook. 17th. Edit. Mosby Publications: St. Louis. 2005:648-652.

ACGME Competencies Highlighted by Case

  • Patient Care
    1. When interacting with patients and their families, the health care professional communicates effecively and demonstrates caring and respectful behaviors.
    2. Essential and accurate information about the patients is gathered.
    3. Informed decisions about diagnostic and therapeutic interventions based on patient information and preferences, up-to-date scientific evidence, and clinical judgment is made.
    4. Patient management plans are developed and carried out.
    8. Health care services aimed at preventing health problems or maintaining health are provided.
    9. Patient-focused care is provided by working with health care professionals, including those from other disciplines.

  • Medical Knowledge
    10. An investigatory and analytic thinking approach to the clinical situation is demonstrated.
    11. Basic and clinically supportive sciences appropriate to their discipline are known and applied.

  • Practice Based Learning and Improvement
    13. Information about other populations of patients, especially the larger population from which this patient is drawn, is obtained and used.

  • Systems Based Practice
    26. Partnering with health care managers and health care providers to assess, coordinate, and improve health care and how these activities can affect system performance are known.

    Donna M. D’Alessandro, MD
    Associate Professor of Pediatrics, Children’s Hospital of Iowa

    February 20, 2006