BACKGROUND

0 Chronic Arthritis in Childhood characterized as Juvenile

Rheumatoid Arthritis JRA
0 Age of onset < 16 years of age.
 BACKGROUND
Epidemiology
Overall prevalence of juvenile rheumatoid
arthritis is estimated to be from 30 - 150 per
100,000 children.

In the United States and Canada there are an

estimated 30,000 to 60,000 children and
adolescents with juvenile rheumatoid arthritis.

- Females predominate 2:1

 JUVENILE RHEUMATOID
ARTHRITIS
Epidemiology

described in all races and geographic areas

incidence: 6 19.6 cases/100,000 children
prevalence: 16-150/100,000
 BACKGROUND
Pathogenesis and Etiology of JRA: Multi-factorial
Genetic, Hormonal, Immunologic
Pathogenesis
Characterized by chronic inflammation of the synovium;
Presence of articular cartilage damage;
Accompanied by extra-articular systemic
manifestations.
Heterogeneity of JRA
At least 3 primary types of onset of JRA:
Pauciarticular (Oligoarticular) < 5 joints
Polyarticular and
Systemic
 BACKGROUND
Pathogenesis (Continued)
Genetic
Basis of immune distinction between self and non-
self is the major histocompatibility complex (MHC)
that in humans is called the human leukocyte
antigen (HLA).
HLA system comprises a family of polymorphic
genes located on the short arm of chromosome 6.
Polymorphisms of JRA suggest a non-mendelian
inheritance.

Hormonal Factors
Differences in the sex ratio of JRA subtype onset
Pre-adolescent or post-adolescent peaks
 BACKGROUND
Immune Mechanisms
Disease process involves loss of tolerance towards
auto-antigens chronic synovitis;
Production of auto-antibodies:
Anti-nuclear antibodies (ANA): associated with
increased risk of iridocyclitis (eye inflammation);
Rheumatoid factors (RF): auto-antibodies directed
against the Fc fragment of IgG (associated with
~10% of polyarticular JRA);
Complement activation by circulating immune
complexes may also contribute to the disease
process.
 BACKGROUND
Immune Mechanisms (Continued)
Cytokines: act on the immune system and other
cells to initiate and sustain inflammation:
Intercellular mediators: Interleukin-1 (IL-1),
IL-6, and tumor necrosis factor-alpha (TNF-);
Immunomodulatory cytokines produced by T-
cells Interferon gamma (IFN-), IL-4, IL-2.
 CLASSIFICATION OF
JUVENILE RHEUMATOID ARTHRITIS

American College of Rheumatology (ACR)

pediatric criterion for juvenile rheumatoid
arthritis was established in 1977.
 CLASSIFICATION OF JRA
ACR Criteria
Age at onset: < 16 years of age;
Arthritis - swelling or effusion or the presence of 2 or
more of the following signs:
Limitation of range of motion,
Tenderness or pain on motion and
Increased heat in one or more joints;
Duration of disease > 6 weeks;
Onset type is defined by the type of disease in the first 6
months:
Oligoarticular (Pauciarticular) 4 inflamed joints;
Polyarticular: > 4 inflamed joints;
Systemic onset: arthritis with characteristic fever.
Exclusion of other forms of childhood arthritis.
CLINICAL MANIFESTATIONS of JRA
 JRA by the Type-of-Onset
Characteristic Pauciarticular Polyarticular Systemic

% Cases (F:M) 60 (5:1) 30 (3:1) 10 (1:1)

# Joints <4 >5 Variable

Thru
Age at onset Early childhood, peak Thru childhood, childhood,
1-2 yr peak 1-3 yr no peak

None; Mild; unremitting Systemic self-

Systemic involvement uveitis (++) articular limited; chronic
involvement destructive
arthritis ~50%
Chronic Uveitis 5-15% 5% Rare

RF/ANA Rare/75-85% 10%/40-50% Rare/10%

Prognosis Excellent except for Guarded to Moderate to poor

eyesight moderately good

JT Cassidy, RE Petty, RM Laxer, CB Lindsley. Textbook of Pediatric Rheumatology, 2005

 Extra-Articular Manifestations of JRA

Pauciarticular Polyarticular Systemic

Fever 0% 30% 100%

Rheumatoid rash 0 2 95
Rheumatoid nodules 0 10 5
Hepatosplenomegaly 0 10 85
Lymphadenopathy 0 5 70
Chronic uveitis 20 5 1
Pericarditis 0 5 35
Pleuritis 0 1 20
Abdominal pain 0 1 10
 PROGNOSIS OF JRA
Pauciarticular JRA
Boys may be affected in older childhood or
adolescence; this may represent an early manifestation
of a spondyloarthropathy.
Leg length discrepancy from asymmetric knee synovitis
and bone growth may cause flexion contractures, gait
abnormalities and long-term growth abnormalities.
Eye involvement as anterior uveitis, may lead to
scarring or blindness in ~ 15-20% of children.
Active arthritis into adulthood in 40% to 50% of
patients.
Radiographic joint damage within 5 years.
 PROGNOSIS OF JRA

Polyarticular JRA and Systemic JRA

Active arthritis into adulthood: 50% to 70% of polyarticular
or systemic onset JRA;

Long-term disabilities: 30% to 40% of children

Unemployment: 25% to 50% of adult JRA patients;
May need major surgery (joint replacement).

Radiographic joint damage within 2 years;

Mortality rate: 0.4% to 2% (greater risk with systemic JRA

than with polyarticular JRA).
Medications in the Treatment of JRA
NSAID

intra-articular steroids
sulfasalazine
hydroxychloroquine
(auranofin)

methotrexate
(IM gold)
(D-penicillamine)

etanercept
azathioprine
cyclophosphamide
cyclosporin
 JUVENILE RHEUMATOID
ARTHRITIS
Treatment: physical measures
heat: analgesia
muscle relaxation
splinting: provide joint rest
maintain functional position
correct deformities
exercise: passive, active assisted and
active range of motion
general conditioning
rest
JUVENILE RHEUMATOID ARTHRITIS
Treatment: physical measures

understand disease process, treatment

and prognosis
understand roles in care
as normal possible:
discipline/family life
school
peer relationships
counseling
JUVENILE RHEUMATOID ARTHRITIS
Poor Prognostic Signs
pauciarticular
long duration of active disease
conversion to polyarticular disease (30%)
chronic uveitis
polyarticular
long duration of active disease
articular erosions
RF positivity/rheumatoid nodules
systemic
conversion to polyarticular disease (25-50%)