Juvenile idiopathic arthritis (JIA) is a chronic disease characterized
by persistent joint inflammation; the typical signs of joint inflammation
are pain, swelling and limitation of movement. “Idiopathic”
means that we don’t know the cause of the disease and “juvenile”,
in this case, means that symptoms appear before 16 years of age.
does chronic disease mean?
A disease is said to be chronic when the appropriate treatment
does not lead to an immediate recovery, but only to an improvement
of symptoms and laboratory test results. This also means that
when the diagnosis is made, it is impossible to say for how long
the child is going to be sick.
frequent is it?
JIA is a rare disease that affects about 80-90 per 100,000 children.
are the causes of the disease?
Our immune system protects us from infections (virus and bacteria).
In doing so, it is able to distinguish what is harmless and part
of our body and what is foreign and potentially dangerous, which
It is believed that chronic arthritis is a consequence of an abnormal
response of our immune system, which, due to unknown causes, loses
part of its capacity to distinguish between dangerous and normal
cells and attacks its own joint components.
For this reason, diseases such as JIA are called autoimmune, meaning
that the immune system reacts against the organs of its own body.
However, the precise mechanisms that cause JIA, as with as most
human chronic inflammatory diseases, are unknown.
it a hereditary disease?
JIA is not a hereditary disease, since it cannot be transmitted
directly from parents to their children. Nevertheless, there are
some genetic factors, largely still to be discovered, that increase
the chance of developing the disease. The agreement in the scientific
community is that this disease is multifactorial, which means
it is the result of a combination of genetic factors and exposure
to environmental factors (probably infections). Even when there
may be a genetic predisposition, it is very rare to have two children
affected in the same family.
is it diagnosed?
Doctors diagnose someone as having JIA when the onset of the disease
is before the age of 16, arthritis lasts for more than six weeks
and the causes are unknown (which means that all other diseases
responsible for arthritis have been ruled out). The arthritis
must be present for more than six weeks in order to exclude forms
of temporary arthritis that may follow viral infections.
The diagnosis of JIA is, therefore, based on the presence and
persistence of arthritis and the careful exclusion of any other
disease by medical history, physical examination and laboratory
happens to the joints?
The synovial membrane is the cellular lining surrounding the joint
and is usually very thin. In JIA it becomes much thicker and filled
with inflammatory cells, while the amount of the synovial fluid
inside it increases. This causes swelling, pain and limitation
of movement. A characteristic feature of joint inflammation is
joint stiffness, which occurs after prolonged rest. It is, therefore,
particularly pronounced in the morning (and referred to as morning
Often the child attempts to reduce pain by keeping the joint in
a position half-way between flexion (fully bent) and extension
(straight), this position is called antalgic indicating the fact
that it is maintained to reduce pain.
If not properly treated, joint inflammation may produce damage
by two main mechanisms:
a) The synovial membrane may get very thick and form what is called
the synovial pannus, which, through the release of various substances,
provokes the erosion of articular cartilage and bone.
b) Keeping the joint in the antalgic position for a long time
causes muscle atrophy, which is the wasting away of muscles and
soft tissues, leading to flexion deformity.
there different types of the disease?
There are several different forms of JIA. They are mainly distinguished
on the presence or absence of systemic symptoms. Systemic symptoms
are symptoms that affect many organs, such as fever or rash and
on the number of joints involved. By convention, the different
forms of JIA are defined according to the symptoms presented during
the first six months of the disease. For this reason, they are
often referred as onset forms.
JIA. This form is diagnosed because of the presence of
systemic features, besides arthritis. The main systemic symptom
is represented by high spiking fever, often accompanied by a salmon
coloured rash that appears during fever spikes. Other symptoms
may include muscle pain, enlargement of the liver, spleen or lymph
nodes (groups of cells that filter out bacteria etc., as a critical
part of the immune system), and inflammation of membranes around
the heart (pericarditis) and lungs (pleuritis). Arthritis may
be present at disease onset, or appear later on. The disease may
affect children at any age.
About half of all patients are diagnosed with systemic features.
These patients tend to have the best long-term prognosis (predicted
outcome). In the other half of patients, systemic symptoms often
tend to subside with time and joint involvement becomes more important.
In a minority of these patients, systemic symptoms persist together
with joint involvement.
Systemic JIA accounts for less then 10% of all JIA cases, but
is seldom observed in adults.
JIA. This is diagnosed because of the involvement of
five or more joints during the first six months of disease and
in the absence of the above mentioned systemic symptoms. The presence
or absence of an autoantibody in the blood called rheumatoid factor
(RF) allows for polyarticular JIA to be distinguished into two
subforms: RF negative and RF positive.
1) RF positive polyarticular JIA. This is rare in children (<5%
of all JIA patients). It is considered the equivalent of adult
RF positive rheumatoid arthritis (the major type of chronic arthritis
in adults). It often causes symmetric arthritis affecting mainly
the small joints of hands and feet, initially, extending to the
other joints as disease progresses. It is much more common in
females than in males and usually has its onset after 10 years
of age. It is often a severe form of arthritis.
2) RF negative polyarticular JIA. This accounts for 15-20% of
all JIA cases and can occur at any age. It is a complex form,
which probably includes different diseases. The variable course
and eventual outcome of the disease in different patients reflect
JIA. This is diagnosed when less then five joints are
involved in the first six months of disease and there are no systemic
symptoms. It affects large joints (such as knees and ankles) in
an asymmetrical way. Sometimes, only one joint is affected (called
the monoarticular form). In some patients the number of joints
affected increases after the first six months of disease to five
or more, this is called extended oligoarthritis.
Oligoarthritis usually has its onset before the age of six and
is mainly observed in females. With appropriate treatment, there
is a good chance of maintaining full joint use where the disease
remains limited to a few joints. It is harder to predict the long
term outcome for those patients who develop an extension of articular
A consistent proportion of patients can develop problems with
their sight (anterior uveitis), the inflammation of the sheet
enveloping the eye and containing its vascular supply (the vessels
that provide blood). Since the iris and the ciliary body form
this part of the eye, the complication is called chronic anterior
uveitis, or chronic iridocyclitis.
If unrecognized and left untreated, anterior uveitis progresses
and can cause very serious damage to the eye. Early recognition
of this complication is, therefore, of utmost importance. Since
anterior uveitis may not be noticed by parents or clinicians,
as there are no obvious symptoms, it is imperative for children
at high risk to have periodic eye check ups with an ophthalmologist
every three months, using a particular instrument called a slit
Oligoarthritis is the most frequent form of JIA, accounting for
50% of cases. The ANA positive type (see Laboratory exams), combined
with uveitis, is a disease typical of childhood, but is not observed
arthritis. This is diagnosed by the presence of arthritis,
associated with psoriasis or psoriatic features. Psoriasis is
a skin disease with patches of scaling skin, mainly located over
the elbows and the knees. The skin disease may precede or follow
the onset of arthritis.
This form is complex in clinical manifestations and prognosis.
associated with enthesitis. The most common manifestation
is an oligoarthritis, mainly affecting the large joints of the
lower limbs and associated with enthesitis. Enthesitis is the
inflammation of the enthesis, the point of insertion of tendons
over bones. The most common site of pain in this form of arthritis
is localized in the foot, behind or below the heel. Sometimes
these patients may present with an acute anterior uveitis. Unlike
the oligoarticular form, anterior uveitis associated with enthesitis
may cause red eye, lachrymation (excessive watering of the eyes),
or increased sensitivity to light. Most patients are positive
for a laboratory test called HLA-B27. The disease affects predominantly
males and usually begins after seven or eight years of age. The
course of disease in this form is variable. In some patients the
disease remits, while in others it extends to affect the spinal
region. Initially, with the involvement of the sacroiliac joints
(around the lower back). Indeed, this form belongs to a group
of diseases that are more frequent in adults and are called spondyloarthropathies,
since they can affect the spine.
causes chronic iridocyclitis? Is there a relationship with arthritis?
As with arthritis, eye inflammation is caused by an abnormal immune
response against the eye (an autoimmune response). The precise
biological mechanisms involved are unknown.
This complication is mainly observed in patients with the oligoarticular
type of arthritis. These patients tend to be of a younger age,
with a positive laboratory test called antinuclear antibodies
It is not known why iridocyclitis is linked with articular disease.
It is important to remember that arthritis and iridocyclitis may
follow independent courses, so periodic slit lamp examinations
have to be continued even if arthritis goes into remission. Periodic
flares, independent of the arthritis flares, characterize the
course of iridocyclitis.
Iridocyclitis usually follows the onset of arthritis, or may be
detected at the same time. It can precede arthritis, but this
is rare. These are usually the most unfortunate cases, since the
disease is asymptomatic, iridocyclitis is not discovered until
it has already caused some symptomatic complications like visual
the disease in children different from the disease in adults?
Mostly, yes. The polyarticular RF positive form, which is responsible
for about 70% of adult rheumatoid arthritis cases, accounts for
less than 5% of cases of JIA. The oligoarticular form with early
onset represents about 50 % of JIA cases and is not observed in
adults at all. Systemic arthritis is characteristic of children
and is seldom observed in adults.
laboratory exams are needed?
At the time of diagnosis, some laboratory examinations help to
better define the type of JIA a patient is suffering from. They
can also help to identify patients at risk of developing some
complications, such as chronic iridocyclitis.
Rheumatoid factor (RF) is an autoantibody that is positive and
in high concentration only in the polyarticular form of JIA, which
is the childhood equivalent of RF positive adult rheumatoid arthritis.
Antinuclear antibodies (ANA) are frequently positive in patients
with oligoarticular early-onset JIA. This identifies JIA patients
at high risk of developing chronic iridocyclitis and who have
to have an ocular examination with a slit lamp every three months.
HLA-B27 is a cellular marker that is positive in up to 80% of
patients with enthesitis associated arthritis. Its frequency in
the general, healthy population is much lower (5-8%).
Other exams, such as erythrocyte sedimentation rate (ESR), or
C-reactive protein (CRP), measure the extent of general inflammation
and are useful in disease management, along with clinical examinations.
Periodic X-ray examinations are useful to assess potential disease
progression and, therefore, to ensure the therapeutic regimen
Depending on the drug regimen, patients may need periodic laboratory
examinations to assess potential drug toxicity.
can we treat it?
There is no specific therapy to cure JIA. The aim of treatment
is to allow children to conduct a normal life and prevent joint
and organ damage, while waiting for spontaneous disease remission.
Treatment is based mainly on the use of drugs that inhibit inflammation
and on rehabilitation procedures that preserve joint function
and help to prevent deformities.
Therapy is complex and needs the cooperation of different specialists
(e.g. paediatric rheumatologists, orthopaedic surgeons, physical
and occupational therapists, ophthalmologists).
1) Non-steroidal anti-inflammatory drugs (NSAIDs). They are symptomatic
anti-inflammatory and antipyretic (controls fever) medications.
Symptomatic means that they cannot induce disease remission, but
serve to controls symptoms due to inflammation. The most widely
used are naproxen and ibuprofen. Aspirin, although effective and
cheap, is much less used nowadays, because of its risk of toxicity.
NSAIDs are usually well tolerated and gastric discomfort, the
most common side effect in adults, is uncommon in children. NSAIDs
are not prescribed in association with one another, but one NSAID
may be effective where another has failed. The optimal effect
on joint inflammation occurs after several weeks of therapy.
2) Joint injections. These are used when few joints are involved
and there is a risk of long term damage. The drug injected is
a long-acting steroid preparation. Triamcinolone hexacetonide
is preferred for its prolonged effect (frequently many months).
3) Second level drugs. These are prescribed for children that
have a progressive polyarthritis, despite adequate therapy with
NSAIDs and steroid injections. Second level drugs are added to
previous NSAID therapy, which therefore, has to be continued.
The effect of most second level drugs only becomes fully evident
after several weeks or months of treatment.
The drug of first choice is low-dose weekly methotrexate, as it
is effective in the majority of patients. It has an anti-inflammatory
activity, but is also able, in some patients, to induce disease
remission, although it is not yet understood how this happens.
It is usually well tolerated, with gastric intolerance and an
increase in transaminase levels (a type of enzyme), representing
the most common side effects. Potential toxicity needs monitoring
during treatment with periodic laboratory tests, as discussed
above. Folic acid, a vitamin, diminishes the risk of side effects.
Salazopyrine has also been showed to be effective in JIA, but
is usually not as well tolerated as methotrexate. The experience
with salazopyrine is much more limited than with methotrexate.
So far, no proper studies have been conducted in JIA to assess
the efficacy of other potentially useful drugs, such as cyclosporin
or leflunomide. Cyclosporin is a valuable drug for the treatment
of steroid-resistant macrophage activation syndrome (a serious
complication in many childhood inflammatory disorders). This is
a severe and potentially life-threatening complication of systemic
JIA, which is secondary to a massive general activation of the
inflammatory process. Very little information about the use of
leflunomide on children is available.
In the last few years anti-TNF drugs have been introduced. Anti-TNF
drugs selectively block tumor necrosis factor (TNF), an essential
mediator of the inflammatory process. They are used alone, or
in association with methotrexate, and are effective in most patients.
Their effect is quite rapid and their safety has been shown to
be good, so far, but follow-up studies are needed to establish
potential long-term side effects. As with all second level drugs,
they must be administered under strict medical control. Anti-TNF
drugs are very expensive.
4) Corticosteroids. These are the most effective available anti-inflammatory
drugs, but their use is limited because their long-term use is
associated with several important side effects, including osteoporosis
and stunted growth. They are, however, valuable for the treatment
of systemic symptoms that are resistant to other therapies, for
life threatening systemic complications and as a bridge drug to
control acute disease while waiting for second level drugs to
Topical steroids (eye drops) are used in the treatment of iridocyclitis.
In more severe cases, steroid injections around the eye, or systemic
steroid administration, may be required.
5) Orthopedic surgery. The main procedures are prosthetic joint
replacement in the case of articular destruction and surgical
releasing of soft tissues in the case of permanent contractures.
6) Rehabilitation. This is an essential component of treatment.
It includes appropriate exercises and, where necessary, wearing
splints to correct posture. It must be started early and should
be performed routinely to keep the range of movement, muscle trophism
and strength and to prevent, limit or correct deformities.
are the main side effects of therapy?
The drugs used in the treatment of JIA are usually well tolerated.
Gastric intolerance, the most frequent side effect of NSAIDs (which
should, therefore, be taken with food), is less common in children
than in adults. NSAIDs can cause increases in some liver enzymes
in the blood, but this is a rare event with drugs other than aspirin.
Methotrexate is also well tolerated, but gastroenteric side effects,
such as nausea and vomiting, are not uncommon. To monitor potential
toxicity, it is important to perform periodic laboratory tests.
The most frequent laboratory anomaly is an increase in liver enzymes,
which normalizes with drug withdrawal or dose reduction. The administration
of folinic or folic acid is effective in reducing the frequency
of hepatic toxicity. Hypersensitivity reactions to methotrexate
can occur, but are rare.
Salazopyrine is reasonably well tolerated. The most frequent side
effects are cutaneous rash, gastrointestinal problems, hypertransaminasemia
(liver toxicity) and leukopenia (lowering of white blood cells
leading to risk for infections). For these reasons, as with methotrexate,
periodic laboratory examinations are needed.
Anti-TN agents are usually well tolerated, but patients should
be carefully monitored for severe infections.
The long-term use of steroids in significant dosage is associated
with several side effects. These include stunting growth and osteoporosis.
Steroids, at high doses, cause a marked increase in appetite,
which leads to obesity. It is, therefore, important to instruct
children to eat foods that can satisfy the appetite without increasing
long should treatment last for?
Treatment should last as long as the disease persists. Disease
duration is unpredictable, but, in the majority of cases, JIA
goes into spontaneous remission. The course of JIA often includes
periods of remission and exacerbation, which require very different
treatments. Treatment is only withdrawn completely after prolonged
and complete disease remission.
examination (Slit lamp examination). How often is it necessary
and for how long?
For patients at risk (those with an ANA positive laboratory test
result), slit lamp examination has to be performed at least every
three months. Those who have developed iridocyclitis should be
submitted to more control tests, the frequency of which depends
on the severity of eye involvement.
The risk of developing iridocyclitis decreases with time, but
iridocyclitis can still develop many years after arthritis onset.
It is, therefore, prudent to check the eyes for many years, even
if arthritis is in remission.
Acute uveitis in patients with arthritis and enthesitis is symptomatic
(red eye, pain and photophobia) and, therefore, there is no need
of periodic slit lamp examinations for early diagnosis.
is the long-term prognosis (predicted course of disease) of arthritis?
The prognosis of arthritis depends on its severity, the clinical
form of JIA, how early treatment begins and how adequate the course
of treatment followed is. The prognosis for JIA has been considerably
improved by the progresses in therapy that have occurred over
the last ten years.
Systemic JIA has a variable prognosis. About half of patients
have few signs of arthritis and the disease is mainly characterized
by periodic disease flares. The ultimate prognosis is often good,
as the disease frequently goes into spontaneous remission. In
the other half of patients, the disease is characterized by persistent
arthritis, while systemic symptoms tend to fade. Severe articular
destruction can also develop in this subset of patients. In a
tiny minority of this second group of patients, systemic symptoms
persist together with articular involvement. These patients have
the worst prognosis and may develop amyloidosis, a severe complication
requiring aggressive therapy.
RF positive polyarticular JIA usually has a progressive, articular
course that can lead to severe joint destruction.
RF negative Polyarticular JIA is complex, both in clinical manifestations
and prognosis. The overall prognosis, however, is much better
than that of RF positive polyarticular JIA, only about one quarter
of patients develop articular damage.
Oligoarticular JIA has a good articular prognosis when the disease
remains limited to a few joints. Patients in which the articular
disease extends to involve several joints have a prognosis similar
to that of patients with polyarticular RF negative JIA.
Most patients with psoriatic JIA have a disease similar to oligoarticular
JIA, but have a somewhat higher tendency to become polyarticular
JIA associated with enthesopathy also has a variable prognosis.
In some patients the disease remits, while in others it progresses
and may involve sacroiliac joints.
So far, no reliable clinical or laboratory features to predict
which patient will have the worst prognosis are available during
the early stages of disease. Such predictors would be of considerable
clinical use, since they could allow the identification of patients
who should be prescribed a more aggressive treatment from the
beginning of the disease.
is the long-term prognosis of iridocyclitis?
Iridocyclitis, if left untreated, may have very serious consequences,
including problems such as cloudiness of the lens of the eyes
(cataract) and blindness. However, if treated in its early stages,
it usually responds very well to therapy. Early diagnosis is,
therefore, the major determinant of prognosis.
If a patient is being treated with an immunosuppressive therapy
(steroids, methotrexate, anti-TNF etc.) vaccinations with live,
micro-organisms (such as anti-rubella, anti-measles, anti-parotitis,
anti-polio Sabin and BCG) have to be postponed, because of the
potential risk of infections spreading, due to the reduced immune
defences. Vaccines that do not contain living micro-organisms,
but only infectious proteins (anti-tetanus, anti-diphtheria, anti-polio
Salk, anti-hepatitis B, anti-pertussis, pneumococcus, haemophilus,
meningococcus) can be performed, the only theoretical risk is
vaccination failure, due to the immunosuppressive treatment.
diet influence the course of the disease?
There is no evidence that diet can influence the disease. In general
the child has to take a balanced, normal diet. Overeating has
to be avoided in patients taking steroids, since steroids increase
climate influence the course of the disease?
There is no evidence that climate can affect the disease.
Playing sports is an essential aspect of the everyday life of
a normal child. One of the main aims of JIA therapy is to allow
children to conduct a normal life and not to consider themselves
different from their peers. Therefore, the general tendency is
to leave patients to play the sports they want and to trust that
they will stop if a joint hurts. Although mechanical stress is
not beneficial in an inflamed joint, it is assumed that the little
damage that could ensue, is much smaller that the psychological
damage of being prevented from playing sports with friends because
of the disease. This choice is part of a more general attitude
that tends to encourage the child to be autonomous and able to
cope with the limits imposed by the disease.
As part of these considerations, it is better to favour sports
in which mechanical stress to the joints is absent or minimal,
such as swimming and riding a bike.
the child attend school regularly?
It is extremely important that the child attends school regularly.
There are a few factors that may cause problems with school attendance
though, such as difficulty in walking, minor resistance to fatigue,
pain or stiffness. It is, therefore, important to explain to the
teachers the child’s possible needs, which are likely to
include proper tables, regular movements during school hours to
avoid articular stiffness and difficulty in writing. Patients
should take part in gym lessons wherever possible, but in this
case the considerations discussed above in the issue of sports
have to be taken into account.
School, for a child, is a place where he learns how to become
an autonomous person, productive and independent. Parents and
teachers have to do whatever they can to make the sick children
participate in school activities in a normal way in order to have
academic success. In addition to this, it is at school that the
child develops the ability to communication effectively with peers
and adults and to be accepted and appreciated by his friends.
the child have a normal adult life?
This is one of the main goals of therapy and it can be reached
in the majority of cases. Therapy for JIA has improved dramatically
in the last ten years and it is conceivable that several new drugs
will be available in the near future. The combined use of pharmacological
treatment and rehabilitation prevents joint damage in the majority
Major attention should also be paid to the psychological impact
of the disease on the child and his family. A chronic disease
like JIA is a difficult challenge for the whole family and, of
course, the more serious the disease, the harder it is to cope
with it. It will be difficult for the child to cope properly with
his disease if the parents don’t. The parents may develop
a strong attachment towards their sick child and, in order to
prevent him from any possible problem, can become-overprotective.
A positive attitude from parents who support and encourage the
child to be as independent as possible, despite the disease, is
extremely valuable in helping the child to overcome difficulties,
to successfully cope with his peers and to develop an independent,
The paediatric rheumatology team should offer psychosocial support