ARTHRITIS, JUVENILE RHEUMATOID

ARTHRITIS, JUVENILE RHEUMATOID - Jason Silva, MD
BASICS
DESCRIPTION
• Most common form of chronic arthritis in children and a major cause of musculoskeletal disability.
• General characteristics
- Age of onset 16 years
- Signs of arthritis
 Joint swelling, decreased range of motion, pain
- >6 weeks of symptoms
• 3 subtypes exist, determined by clinical characteristics seen in 1st 6 months of illness
- Systemic: Occurs in 10-20% of affected children; usually characterized by febrile onset and evanescent rash with multiple physical and laboratory abnormalities
- Polyarticular: Occurs in 30-40% of affected children; multiple (>4) joint involvement and minimal systemic features; large and small joints affected
- Pauciarticular: Occurs in 40-50% of affected children; involvement of 4 joints, usually larger joints, especially of lower extremities; risk for chronic uveitis in young girls and axial skeletal involvement in older boys
• System(s) Affected: Hematologic/lymphatic/ immunologic; Musculoskeletal
• Synonym(s): Juvenile chronic arthritis; Juvenile arthritis; Juvenile idiopathic arthritis; Still disease
GENERAL PREVENTION
No known preventive measures
EPIDEMIOLOGY
• Predominant age: 1-4 years and 9-14 years
• Predominant sex
- Poly/Pauciarticular: Female > Male
- Systemic: Female = Male
Incidence
1/10,000 children
Prevalence
~1/1,000 children
RISK FACTORS
• HLA-B27 in pauciarticular juvenile rheumatoid arthritis increases risk of spondyloarthropathy
• Rheumatoid factor positivity increases risk for severe arthritis in polyarticular JRA
• ANA positivity increases risk for uveitis in pauciarticular and polyarticular JRA
Genetics
• HLA-B27 histocompatibility antigen associated with risk of evolving spondyloarthropathy in older boys with pauciarticular JRA
• Weaker HLA associations exist for other subtypes (HLA-DR5, HLA-DR8, HLA-DR4)
- DR 4: Polyarticular
- DR 5, 8: Pauciarticular
ETIOLOGY
Multifactorial, including
• Abnormal immune response
• Genetic predisposition
• Environmental triggers, possibly infectious
• Immunoglobulin or complement deficiency
ASSOCIATED CONDITIONS
• Other autoimmune disorders
• Increased prevalence of autoimmune thyroiditis, subclinical hypothyroidism, and celiac disease (1)[B]


DIAGNOSIS
SIGNS AND SYMPTOMS
• Systemic
- Arthralgias/arthritis
- Fever: Spiking and remitting, may be >39C
- Rash: Salmon, macular, nonpruritic rash over trunk and extremities
- Chest pain, pericardial friction rub
- Dyspnea
- Fatigue
- Hepatosplenomegaly
- Lymphadenopathy
- Myalgias
- Weight loss
• Polyarticular
- Arthralgia/arthritis
- Growth retardation
- Hand weakness/difficulty writing
- Malaise
- Morning stiffness
- Rheumatoid nodules
- Synovial thickening
- Weight loss
• Pauciarticular
- Abnormal gait
- Eye pain, redness
- Joint swelling
- Leg-length abnormality
- Morning stiffness
- Photophobia
- Flexion contractures
ALERT
Pregnancy Considerations
Unpredictable effect on disease activity
Physical Exam
Atlantoaxial instability/subluxation
TESTS
Lab
• Leukocyte count normal or markedly elevated (systemic), lymphopenia
• Hemoglobin normal or low (especially systemic)
• Platelet count normal or elevated
• Joint-fluid aspiration and analysis helpful in excluding infection
• ANA positive (>1:80): 40% (polyarticular or pauciarticular): increased risk of uveitis in female patients
• Rheumatoid factor positive: 10-15% (usually polyarticular): Poor prognosis
• TSH
• HLA-B27 positive: 70% in pauciarticular boys
• ESR
- Systemic: Always elevated
- Polyarticular: Usually elevated
- Pauciarticular: May be within normal range
• Drugs that may alter lab results
- Anti-inflammatories may alter CBC and ESR.
- Anticonvulsants, antiarrhythmics may increase ANA
• Disorders that may alter lab results: Hemoglobinopathies may alter ESR.
Imaging
• Radiograph of affected joint(s)
• Early radiographic changes
- Soft-tissue swelling
- Periosteal reaction
- Juxta-articular demineralization
• Later changes include
- Joint-space loss
- Articular surface erosions
- Subchondral cyst formation
- Sclerosis
- Joint fusion
• Echocardiography (pericarditis)
• Radionuclide scans (infection, malignancy)
• CT, MRI helpful in identifying early erosions
Diagnostic Procedures/Surgery
• Synovial biopsy occasionally indicated
• Arthrocentesis
Pathological Findings
Synovium shows hyperplasia of synovial cells, hyperemia, and infiltration of small lymphocytes and mononuclear cells.
DIFFERENTIAL DIAGNOSIS
• Other rheumatic diseases, especially SLE and dermatomyositis
• Atypical bacterial or viral infections
- Septic arthritis, osteomyelitis
• Hemoglobinopathies
• Malignancy: Leukemia
• Vasculitis
• Rheumatic fever
• Lyme disease
• Postinfectious arthritis
• Musculoskeletal
- Legg-Calve-Perthes, toxic synovitis
• Pain syndromes
TREATMENT
GENERAL MEASURES
• Treatment goal: Control active disease and extra-articular manifestations to maintain musculoskeletal function as normal as possible.
• Outpatient care except for initial diagnostic workup of systemic juvenile rheumatoid arthritis disease and complications for all subtypes
• Patients require regular (every 4 months in young patients with pauciarticular disease) ophthalmic exams to uncover asymptomatic eye disease, at least for 1st 3 years.
• Moist heat, sleeping bag, or electric blanket to relieve morning stiffness
• Splints for contractures
Diet
Regular diet with special attention to adequate calcium, iron, protein, and caloric intake
Activity
• Full activity as tolerated
• Regular school; may need modified physical education program
SPECIAL THERAPY
Physical Therapy
• Include daily home exercise program, required for joints with limited motion.
• Orthotics for support
MEDICATION (DRUGS)
First Line
• NSAIDs adequate in ~50% of patients, symptoms often improve within days, full efficacy 2-3 months
• Average of 2 or 3 trials needed to determine most effective drug for an individual patient; change NSAID if no clinical response within 3 weeks of initiating treatment
• Drugs for children include
- Ibuprofen (Motrin, Advil, Nuprin): 30-40 mg/kg/d, divided q.i.d.
- Naproxen (Naprosyn, Aleve): 10-20 mg/kg/d divided b.i.d.
- Tolmetin sodium: 15-30 mg/kg/d; t.i.d. or q.i.d.
• Contraindications to NSAIDs: Known allergies
• Precautions: May worsen a bleeding diathesis; use caution with all NSAIDs in renal insufficiency and hypovolemic states
• Significant possible interactions: NSAIDs may lower serum levels of digitalis and anticonvulsants and blunt the effect of loop diuretics. NSAIDs may increase serum methotrexate levels.
Second Line
• 30-40% of patients will require addition of disease-modifying antirheumatic drugs, including methotrexate, sulfasalazine, antimalarials, leflunomide
• Methotrexate: Standard dose 8-12.5 mg/m2/wk
• Plateau of efficacy reached with parenteral administration of 15 mg/m2/wk; further increase in dosage is not associated with any additional therapeutic benefit (2)[B]
• Other agents
- Corticosteroids for serious cardiac involvement or unresponsive uveitis
- Intra-articular corticosteroids
- Etanercept (Enbrel)
- Immune globulin intravenously
- Cyclosporine (Neoral)
• Alternative drugs
- Other NSAIDs
- Salicylates: Avoid salicylate therapy during serious viral illness or varicella exposure secondary to risk of Reye syndrome
- Analgesics for pain control
SURGERY
• Total hip and/or knee replacement may be needed for severe disease.
• Soft tissue release, if splinting, traction unsuccessful
• Limb length or angular deformity corrections
• Synovectomy is rarely performed.
ALERT
Pediatric Considerations
Behavioral and compliance problems frequent in toddlers and teenagers
FOLLOW-UP
DISPOSITION
Admission Criteria
• Patient loses ambulatory ability
• Signs/symptoms of pericarditis
PROGNOSIS
• 50-60% ultimately remit, but functional ability depends on adequacy of long-term therapy (disease control, maintaining muscle and joint function).
• Poorest prognosis in patients who have polyarticular juvenile arthritis with positive rheumatoid factor, or patients with systemic JRA
COMPLICATIONS
• Blindness
• Band keratopathy
• Glaucoma
• Short stature
• Debilitating joint disease
• DIC, hemolytic anemia
• Patient on NSAIDs
- Peptic ulcer
- Gastrointestinal hemorrhage
- CNS reactions
- Renal disease
- Leukopenia
• Patient on disease-modifying antirheumatic drug
- Bone-marrow suppression
- Hepatitis
- Renal disease
- Dermatitis
- Mouth ulcers
- Retinal toxicity (antimalarials); rare
• Osteoporosis
• Macrophage activation syndrome
- Decreased blood cell precursors secondary to histiocyte degradation of marrow
PATIENT MONITORING
Determined by medication
• NSAIDs: Periodic CBC, urinalysis
• Aspirin and/or other salicylates: Transaminase and salicylate levels, weekly for 1st month, then every 3-4 months
• Methotrexate: Monthly LFTs, CBC
• Antimalarials: Ophthalmologic monitoring
REFERENCES
1. Stagi S, et al. Thyroid function, autoimmune thyroiditis and coeliac disease in juvenile idiopathic arthritis. Rheumatology (Oxford). 2005;44(4):517-520.
2. Ruperto N, et al. A randomized trial of parenteral methotrexate comparing an intermediate dose with a higher dose in children with juvenile idiopathic arthritis who failed to respond to standard doses of methotrexate. Arthritis Rheum. 2004;50(7):2191-201.
3. Hashkes PJ, Laxer RM. Medical treatment of juvenile idiopathic arthritis. JAMA. 2005;294(13):1671-1684 .