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Introduction:
JRA is not simply rheumatoid
arthritis (RA) in children. It is also not a single disease.
It is a group of arthritis conditions with a wide variety of
manifestations occurring in about 1 in 1,000 children.
Although less common than the adult form of RA, JRA is as
common in this age group as juvenile diabetes and more common
than cystic fibrosis.
There are 3
major forms of JRA: pauciarticular (meaning �few
joints�) onset, polyarticular (meaning �many
joints�) onset, and systemic onset. These
subsets of JRA will be further described below, but each
displays a distinctly different pattern. This variability and
lack of similarity between most forms of JRA and adult RA have
led some to prefer the term �juvenile chronic arthritis.�
While the
long-term outlook of JRA varies with different forms of the
disease, over 1/3 of children in general will have active
disease that persists into their adult lives, while the
remainder experience a remission by the time they reach
adulthood. Moreover, 30-50% of patients experience
significant limitations in daily functioning 10 years after
the onset of their disease. For these reasons, prompt
recognition of and proper therapy for JRA are crucial and can
have a lasting impact on the quality of the child�s life.
Features of JRA: Before
discussing the different forms of JRA, it is important to
remember a few issues important when dealing with arthritis in
children. First of all, JRA is often diagnosed late due to
the fact that children may communicate symptoms differently or
that symptoms may be misinterpreted as �growing pains.� In
younger children, the only sign that joint disease is present
may be a limp or a reduction in playtime activities without
any complaints on the part of the child.
Secondly, JRA, as well as some of the therapies, affect
growth. This may be manifest as general growth impairment or
as unequal growth of a limb. Depending on the stage of
growth, inflammation of a joint may either speed up or shut
down the rate of growth, leaving the child with one leg or arm
that is longer than the other.
Pauciarticular onset (PaO) is the most common form of JRA and
is also the form with the best long-term outcomes. Children
with this type of JRA typically experience pain and/or
swelling of one or a few joints in the lower limbs, such as
the hip, knee, or ankle. Even within this group of patients,
there are 2 subsets, one with an average onset around the age
of 2 where girls predominate, and one with an average onset
around the age of 10 that is seen more commonly in boys. In
the latter group of patients, lower back and heel pain are
more common, and some of these children evolve into a
condition known as ankylosing spondylitis (AS)
when they become adults (see related section).
Polyarticular
onset (PoO) JRA most closely resembles adult RA. These
children experience pain and swelling in small and large
joints, typically in a symmetrical pattern. The hands,
wrists, elbows, knees, ankles, and feet are the most common
joints involved. Like PaO disease, patients with PoO JRA can
be divided into two groups, one beginning at an average age of
3 and one beginning at an average age of 12. Girls outnumber
boys in both of these subsets of patients. Deforming changes
and joint damage are more common in PoO disease than in any
other form of JRA.
Systemic onset
(SO) disease is characterized by fever, often occurring once
per day, elevated white blood cell count, a transient rash,
and less commonly inflammation of the lining of the heart or
lungs or enlargement of the lymph nodes, liver, or spleen.
Joint disease in SO JRA may either resemble the PaO or PoO
forms of the disease, but in some children the joint disease
may be minimal or absent (somewhat of a misnomer in a disease
classified as �arthritis�). The average age of onset is 5
years, and boys and girls are equally affected. While it is
the least common form of JRA, both growth impairment and
life-threatening complications occur more commonly in SO JRA
than in the other two forms.
To some extent
or another, iritis or uveitis (inflammation of
the eyes) may occur in all forms of JRA. This complication
occurs more commonly in patients with PaO JRA than in other
forms, affecting up to 25-30% of these children, versus 5% or
less of those with PoO or SO disease. While the eye may
become red, painful, or blurry when iritis is present, this
process is often silent and slowly progressive. For this
reason, screening for eye disease through an ophthalmologist
is recommended routinely, anywhere between one to four times
per year depending on the child�s age and type of JRA. Your
doctors will make individual recommendations to patients and
families depending on these factors.
Diagnosis: To diagnose any form of JRA, one or
more swollen joints must be observed for at least 6 weeks, and
other causes of bone or joint disease (tumors, infections,
injuries, etc.) must be excluded. To classify a patient as
�juvenile,� symptoms should be present before the age of 16.
The most important factors in making a diagnosis of JRA are
the history of the symptoms and the findings on examination of
the joints.
Classifying the
form of JRA present depends on the number of swollen joints
present during the first 6 months of the disease. If 4 or
fewer joints are involved, the child has PaO disease; if there
are 5 or more joints involved, the child has PoO disease. SO
JRA can be diagnosed if a daily intermittent fever is present
along with the arthritis or the skin and internal organ
involvement. When arthritis is absent, the diagnosis is more
difficult to confirm.
Laboratory
testing is less helpful in JRA than in adult RA or lupus.
While many abnormalities may be present in certain children
and may help classify their disease, it is not unusual for
children with active arthritis to have entirely normal
laboratory studies. Markers of inflammation, while often
elevated, are unreliable at measuring disease activity is most
JRA patients. A positive rheumatoid factor, found in
most patients with adult RA, is infrequently seen other than
in older children with PoO disease. The antinuclear
antibody, seen in almost all patients with lupus, may be
positive in up to 1/2 of patients with PaO or PoO JRA, at
times causing physicians to mislabel a JRA patient as having
lupus. The gene HLA-B27, seen in most patients with
AS, is positive in about 1/2 of older children with PaO
disease.
X-ray studies of
involved joints are most useful to assess for joint damage,
evaluate the growth status of a limb, and exclude other
diagnoses. Because of concerns regarding radiation exposure
in children, these studies are ordered less frequently than in
adult patients. Magnetic resonance imaging (MRI) may be used
if evaluating for a bone or soft tissue tumor but is not
routinely needed diagnose JRA.
Therapy:
The goals of therapy for JRA are to reduce symptoms but
more importantly prevent or at least minimize the long-term
complications of the disease, namely joint damage and loss of
function. Just as JRA has many forms, the treatment required
to achieve these goals also consists of many different
strategies.
Non-steroidal
anti-inflammatory drugs (NSAIDs), such as ibuprofen
(Motrin) and naproxen (Naprosyn) are often sufficient to treat
milder JRA. In fact, over 1/2 of patients will respond to
such therapies, and an additional 1/2 that fail will respond
to treatment with a different NSAID. Responses are generally
seen within 1 to 3 months, after which time other therapies
must be considered. Depending on the age of the child, oral
suspensions or syrups may be preferred over pills.
Corticosteroids such as prednisone are effective in JRA
but must be used with caution. While these medications
rapidly reduce swelling and pain in involved joints and reduce
signs of SO JRA, there is a risk of infection, weight gain,
weakening of the bones, as is the case with adults taking
these medications long-term. An additional consideration in
children is that steroids slow down growth when given for
prolonged periods of time. For these reasons, corticosteroids
are often best used for temporary treatment of disease
flares. An additional role of steroids is to administer by
joint injection in patients with PaO disease where one or two
joints are swollen. The procedure is best performed under
general anesthesia in younger children. This approach may
reduce contractures of the limb or limit problems with growth
of a limb.
Disease
modifying anti-rheumatic drugs (DMARDs) should be
started in a child with JRA failing to respond to NSAIDs after
2 to 3 months of therapy. Methotrexate (MTX),
given as a once weekly dose, is the drug many physicians
prefer due to the evidence that this agent improves function
and limits joint damage in JRA. Children with PoO or SO JRA
are given this medication more frequently than those with PaO
JRA. Reduction in blood counts, elevation of liver enzymes,
and susceptibility to infection are potential side effect to
monitor but generally are less frequent in children than in
adults.
Other DMARDs
that are often effective in JRA include sulfasalazine (Azulfadine),
hydroxychloroquine (Plaquenil), cyclosporine (Neoral),
azathioprine (Imuran), and leflunomide (Arava).
In general, less evidence is present to support the
effectiveness of these therapies in JRA, but for PaO JRA,
sulfasalazine appears to be particularly effective in certain
patients.
Tumor
necrosis factor (TNF) antagonists such as
etanercept (Enbrel), infliximab (Remicade), and
adalimumab (Humira) have recently been shown to be quite
effective in treating JRA. While only Enbrel is approved by
the FDA for treating JRA, the other agents in this class also
appear to be equally effective. As in adults, a risk for
infection does seem to be increased in patients using these
medications. Because of the cost of these therapies and the
need for either injection or intravenous infusion, TNF
antagonists are generally used in patients resistant to
standard therapies, particularly for children with PoO
disease.
A recent
preliminary observation is that anakinra (Kineret), a
medication that blocks the effects of a chemical known as
IL-1, seems to be quite effective in treating SO JRA. This
medication must be given by daily injection, is expensive, and
does somewhat increase the risk of infection. Nonetheless,
the promising early results suggest that Kineret may play a
prominent role in treating SO JRA resistant to other
medications.
Occasionally,
iritis or a manifestation of SO JRA involving another part of
the body may guide therapy more so than the joint disease. In
this event, preventing vision loss or damage to different
organs must also be factored in as a goal of therapy.
Fortunately, the above medications generally treat these
features of the disease as well, but a more aggressive
approach may be needed in children with some of these
complications of JRA.
Physical
therapy is another important addition to the treatment of
JRA in many children. Maximizing strength and function in
diseased joints and splinting or stretching to minimize
contractures or deformities are reasonable approaches to
treating this disease and allow the child to actively
participate in his or her recovery.
Finally, because
many children with JRA feel isolated from their peers due to
their limitations, activities in the community sponsored by
the Arthritis Foundation or other such organizations can play
a valuable role by providing support. Information for the
child�s teachers and classmates provided by the Foundation can
also assist in their understanding of the disease. Arthritis
camps, support groups for families, and other programs help
the child and the family realize that they are not alone with
JRA.
Much can be done
for JRA, but it must first be recognized and appropriately
treated. As education of the community and medical
professionals improves and therapies continue to be developed,
hopefully so will the care provided to children suffering from
various forms of JRA improve. |
