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Juvenile rheumatoid arthritis

A disease of many faces

Learning Objectives

to describe the number of distinct presentations, types and courses of JRA

to describe the value of different kinds of laboratory testing for JRA
to describe the therapies available for patients with JRA (medication, family,
occupational and physical)

CASE:
A mother of a 2-year-old girl brings
her daughter to a pediatrician for a
third opinion. For the past five
weeks, the girl has been feeling not
quite herself in the morning. She
has been irritable and slow to get
out of bed, sometimes refusing to
get up altogether, and walks more
stiffly than usual. She gets better as
the day goes on but worsens again
after her afternoon nap, and seems
especially uncomfortable when her
diaper is being changed. Two weeks
after the onset of symptoms, the
mother consulted with the childs
family doctor, who surmised the
cause to be either normal growing
pains or a bad fall on the knee. He
referred the girl to an orthopedic
surgeon, who failed to detect any
evidence of a fall and referred the
child to the pediatrician in question.

EPIDEMIOLOGY AND
CLINICAL PRESENTATION
Juvenile arthritis (JA), encompasses the spondyloarthropathies and
reactive arthritis. Juvenile rheumatoid arthritis (JRA), also known as
juvenile idiopathic arthritis (JIA),
comprises three distinct presentations, the most common of which is
early-onset pauciarticular disease
seen most frequently in girls, as in
the above case. By definition, one of
the criteria for JRA requires the
exclusion of other forms of JA.
Estimates for the overall prevalence
of JRA in children under 16 cluster
around the 0.01% mark.
JRA is subdivided into three
types with distinct presentations
and courses:
Pauciarticular JRA (paJRA,
four or fewer joints involved)
accounts for 50% of JRA cases.

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JUVENILE RHEUMATOID ARTHRITIS

paJRA patients are typically

very young (one to four years)
girls or older boys, although both
young boys and older girls may be
affected. Chronic uveitis involving
the anterior chamber of the eye,
a fairly frequent manifestation of
paJRA, may cause permanent
damage to the eye but more
commonly produces only minimal symptoms. Uveitis eventually
affects up to 20% of children with
paJRA, and is usually asymptomatic.
Polyarticular onset JRA (poJRA,
five or more joints involved)
occurs in 40% of the JRA population. Clinical manifestations
include irritability, fatigue,
anorexia, anemia and growth
retardation along with joint symptoms. poJRA may develop at any
age and affects girls more often
than boys, particularly the subtype with later onset and
rheumatoid factor (RF) positivity.
Systemic onset JRA (sJRA)
accounts for about 10% of cases
and is initially characterized by
daily or twice-daily fever spikes
and a characteristic pale pink
rash, most commonly on the
trunk and proximal extremities.
Fever, which may be subnormal
in the morning, must be present
for a minimum of two weeks. In

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addition to the rash and fever,

children often have other visceral
disease, including hepatosplenomegaly, lymphadenopathy,
plevitis and pericarditis. sJRA
affects boys and girls equally and
may strike at any time, though
the peak age of onset is one to six
years. There is no increased frequency of occurrence at any age.
The most telling clinical symptom of JRA (as reported by
either children or parents) is
morning stiffness and hesitancy
of movement in the affected
areas. A recent history of fever
spikes and rash on the torso raise
the spectre of sJRA, while fatigue
and poor appetite suggest poJRA.
Constitutional symptoms such as
fatigue, poor appetite and weight
loss suggest sJRA and poJRA. A
physical examination often
reveals swelling (but not redness)
in the affected joints.
DIFFERENTIAL DIAGNOSIS
The above case represents a fairly
common sequence of doctor visits.
Because joint injuries (falls,
sprains, etc.) are especially common in children, family doctors are
often inclined to attribute joint discomfort to an injury rather than to
JRA, which is much rarer. In this
regard, it is helpful to remember that

JUVENILE RHEUMATOID ARTHRITIS

joint pain alone (i.e. in the absence

of any swelling, stiffness, tenderness, etc.) is never sufficient to
establish a diagnosis of JRA. To
rule out arthropathy caused by a
viral infection, a JRA diagnosis also
requires that symptoms be present
for at least six consecutive weeks.
Other forms of juvenile arthritis
must be excluded, including arthritis
associated with IBD, psoriasis, ankylosing spondylitis and reactive
arthritis, along with other connective tissue diseases such as
dermatomyositis. Other conditions
that can initially present in the
bones and joints, as well as cause
fever and general malaise, include
septic arthritis, osteomyelitis, IBD,
other connective tissue diseases,
leukemia and neuroblastoma.
However, a child with septic arthri-

JRA DIAGNOSIS AT A GLANCE

Symptoms: Morning stiffness,

restricted or awkward movements, pain on motion, tenderness
Physical findings:
Swelling, joint warmth
Laboratory findings: Rheumatoid
factor, ANA positivity, erosions,
joint space narrowing
Radiograph changes: Soft tissue
swelling, erosions, localized
growth disturbances, with
advanced maturation of epiphyseal ossification centres
Differentiate from: Sprains,
strains, fractures, growing
pains, viral infection, septic
arthritis, osteomyelitis, leukemia,
neuroblastoma, etc.

Fig. 2: Juvenile rheumatoid arthritis

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JUVENILE RHEUMATOID ARTHRITIS

tis usually has joint redness as well

as severe limitation of movement;
osteomyelitis reveals itself through a
characteristic bony tenderness; in
the case of leukemia, careful physical examination would reveal
enlargements in the liver, spleen,
and/or lymph nodes (also characteristic findings of systemic JRA); and
neuroblastoma involves generalized
pain and possibly an abdominal
mass. In some cases, what appears
to be a simple case of JRA turns out
to be fibromyalgia (or coexisting JRA
and fibromyalgia). This possibility
should be considered in older children if treatment does not produce
improvement within the expected
range. It may also be very difficult to
distinguish systemic JRA from
leukemia; in these cases, a bone
marrow aspirate is indicated.
LABORATORY TESTING
JRA is a diagnosis of exclusion,
meaning there are no tests that can
specifically rule it in. That said, the
antinuclear antibody (ANA) test can
be of value when clinical findings
strongly suggest JRA, as the test is
positive in 60% to 80% of JRA
patients, particularly those with
pauciarticular disease. ANAs have a
high prevalence (65% to 85%) in
children with pauciJRA and chronic
uveitis. Therefore, it is an important

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test for identifying which children

are at increased risk for developing
chronic anterior uveitis. On the
other hand, the RF test, often used
to corroborate a diagnosis of adult
RA, is positive in only 15% to 20% of
children with JRA. It is more frequently seen in children with later
onset polyarthritis, and is associated
with a more aggressive disease
course.

WHEN TO REFER

JRA diagnosis is uncertain

and needs to be established
or confirmed
JRA diagnosis is established; in
all such cases, patients need to be
under the care of a rheumatologist (ideally one with a
subspecialty in pediatric
rheumatology)

EXPECTED COURSE
& MANAGEMENT
Between 40% and 50% of JRA
patients have disease that persists
into adulthood, and more than 30%
have significant functional limitations after 10 or more years of
follow-up. The outcome for JRAassociated uveitis has improved
significantly over the past few

JUVENILE RHEUMATOID ARTHRITIS

decades, and the majority of JRA

patients with uveitis are able to maintain their visual acuity over time.
Although prognosis for sight is
improving, it is estimated blindness
occurs in as many as 15% to 30% of
cases. Therefore, immediate referral
to an ophthalmologist at disease
onset particularly if the patient is
ANA-positive is critical, as is
annual follow-up.
The therapeutic goals for JRA

patients include relieving symptoms,

maintaining joint motion and muscle strength, minimizing joint
damage and promoting a positive
self-image. Rehabilitation plays a
key role with JRA patients. Regular
monitoring is important to detect
flares and impairments that can
lead to disability. Exercise and
splinting help to maintain and
improve function. Therapist
involvement in the classroom can

DIAGNOSTIC & TREATMENT SUMMARY

Criteria for systemic JRA:
Persistent arthritis in one or more
joints for at least six weeks
Exclusion of other forms of arthritis
Persistent (minimum of two weeks)
intermittent fever (daily temperature
peaks of 101 or higher)
Stills rash (variable)

Criteria for polyarticular JRA:

Persistent arthritis in one or more
joints for at least six weeks
Arthritis in five or more joints over
the first six months of disease
Exclusion of other forms of arthritis
including systemic JRA
Uveitis (uncommon) 5% of patients

Criteria for pauciarticular JRA:

Persistent arthritis in one to four
joints for at least six weeks
Arthritis in no more than four joints
during the first six months of disease
Exclusion of other forms of arthritis
including systemic JRA
Uveitis (variable) 20% of patients

Treatment:
Physical and occupational therapy
Assistance with psychosocial
adjustments (for patient and family)
In milder cases: NSAIDs
In more severe cases: methotrexate
and/or other DMARD as well as
NSAIDs
Oral or injected steroids as needed
(in restricted cases)

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JUVENILE RHEUMATOID ARTHRITIS

facilitate function and accommodation. Parents and families often

benefit from psychosocial support.
Pharmacological management of
JRA encompasses treatment of the
articular, ocular, and other manifestations of the disease. In patients
with milder disease, the articular
manifestations can be treated with
nonsteroidal anti-inflammatory drugs
(NSAIDs), with the caveat that the
dose required for an anti-inflammatory effect is up to twice the dose
needed for pain control. Children
are often inadequately treated with
NSAIDs alone, and require therapy
with methotrexate and/or diseasemodifying anti-rheumatic drugs
(DMARDs). Almost half of children
with JRA require DMARDs. In cases
of severe polyarticular JRA, oral
steroids are sometimes used while
waiting for DMARD therapy to take
effect. In systemic JRA, oral steroids
are often used for control of systemic
features. In all three types of JRA,
intra-articular corticosteroids can be
used. The role of the new biological
agents continues to be determined.
Treatment of uveitis should be
directed by an experienced ophthalmologist. Early detection, topical
corticosteroids, dilating agents and
frequent follow-up are critical and
effective in the majority of cases.

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QUESTIONS
1. In what respects does juvenile
rheumatoid arthritis differ from
adult rheumatoid arthritis?
JRA correlates much more poorly
with a positive RF test than does
adult RA. Several clinical manifestations of JRA, such as uveitis
(mostly with paJRA) and pale
pink rash (with sJRA), are not
seen in adult JRA.
2. What aspects of a young patients
history are most suggestive of
JRA?
Persistent arthritis in affected
joints, pain on motion, limitation
of motion, tenderness, joint
warmth, stiff or awkward movements (often noted by caregivers),
and difficulty or reluctance to get
out of bed.