CHAPTER II

REVIEW OF RELATED LITERATURE

This chapter aims to provide information from books, periodicals, journals, and studies that
will support the diagnoses of the study. Thus, this helps the reader to have a better understanding
with regards to the focused client’s case.

JUVENILE ARTHRITIS
According to WebMD (2019), juvenile arthritis is a disease in which there
is inflammation (swelling) of the synovium in children aged 16 or younger. The synovium is the
tissue that lines the inside of joints.
Juvenile arthritis is an autoimmune disease. That means the immune system, which
normally protects the body from foreign substances, attacks the body instead. The disease is also
idiopathic, which means that no exact cause is known. Researchers believe juvenile arthritis may
be related to genetics, certain infections, and environmental triggers (WebMD, 2019).

JUVENILE IDIOPATHIC ARTHRITIS

According to Mayo Clinic (2017), juvenile idiopathic arthritis, formerly known as juvenile
rheumatoid arthritis, is the most common type of arthritis in children under the age of 16.

Juvenile idiopathic arthritis can cause persistent joint pain, swelling and stiffness. Some
children may exp9erience symptoms for only a few months, while others have symptoms for the
rest of their lives (MC, 2017).

Some types of juvenile idiopathic arthritis can cause serious complications, such as growth
problems, joint damage and eye inflammation. Treatment focuses on controlling pain and
inflammation, improving function, and preventing joint damage (MC, 2017).

The most common signs and symptoms of juvenile idiopathic arthritis are:

Pain. While your child might not complain of joint pain, you may notice that he or she
limps — especially first thing in the morning or after a nap.
 Swelling. Joint swelling is common but is often first noticed in larger joints such as the
knee.

Stiffness. You might notice that your child appears clumsier than usual, particularly in the
morning or after naps.

Fever, swollen lymph nodes and rash. In some cases, high fever, swollen lymph nodes
or a rash on the trunk may occur — which is usually worse in the evenings.

Juvenile idiopathic arthritis can affect one joint or many. There are several different
subtypes of juvenile idiopathic arthritis, but the main ones are systemic, oligoarticular and
polyarticular. Which type your child has depends on symptoms, the number of joints affected, and
if a fever and rashes are prominent features (MC, 2017).

Like other forms of arthritis, juvenile idiopathic arthritis is characterized by times when
symptoms flare up and times when symptoms disappear.

JUVENILE IDIOPATHIC ARTHRITIS SYMPTOMS

These are some of the most common early signs and symptoms of arthritis in children. A
child may not have all of these symptoms.

Joints that are warm to the touch

Swelling and tenderness at joints

Fever

Rash

Favoring one limb over another or limping

Pain (often worse following sleep or inactivity)

Stiffness, especially upon waking in the morning

 Inability to bend or straighten joints completely

Decreased physical activity

Fatigue

Sleep problems

Swollen lymph nodes

Reduced appetite and/or weight loss

Not all children with JIA will have the same symptoms, and some symptoms are specific
to a subtype of JIA. Symptoms can change from day to day or throughout a single day.

It’s important to talk to a child’s doctor to ensure that these symptoms mean that a child
has JIA instead of an injury or a different illness. Then parents and the doctor can begin the process
of monitoring symptoms to establish a pattern. Arthritis affects every child differently, so it’s
important to recognize the signs so that a timely and accurate diagnosis can be made to ensure the
best possible outcome for a child’s health and well-being (Arthritis Org, 2019).

SYSTEMIC ONSET JUVENILE IDIOPATHIC ARTHRITIS

According to the Genetic and Rare Dieseases Information Center (2019), Systemic-onset
juvenile idiopathic arthritis is marked by the severity of the extra-articular manifestations (fever,
cutaneous eruptions) and by an equal sex ratio.

It represents 10-11% of cases of juvenile idiopathic arthritis (JIA). The prevalence has been
estimated at 1-10 in 30,000 children with an annual incidence of 1-20 in 900,000 children.

Onset usually occurs between 3 and 5 years of age. The clinical signs include fever with
oscillating temperatures over a 24-hour period and peaks of over 39°C or more. These fever peaks
are associated with transient cutaneous eruptions and diffuse erythematosis or urticarial-like
lesions. The presence of arthritis is essential for diagnosis but may appear later in the disease
course. The number of sites affected is variable (mono-, oligo- or polyarthritis) affecting both the
small and large joints in a nearly symmetrical manner. This characteristic diagnostic triad may also
be associated with an adenopathy and hepatosplenomegaly. Visceral complications (pericarditis,
pleural effusion or serous peritonitis with abdominal pain) may be present. There are no specific
biological signs but the inflammatory disease is severe with a large increase on the level of ferritin
and a decrease in the percentage of glycosylated ferritin (GARD, 2019).

OLIGOARTICULAR JUVENILE IDIOPATHIC ARTHRITIS

According to Weiss, P.F., MD (2019), oligoarticular juvenile idiopathic arthritis (formerly

called pauciarthritis or pauciarticular-onset juvenile rheumatoid arthritis) is defined as juvenile
idiopathic arthritis (JIA) involving fewer than five joints. It is the most common subgroup,
constituting approximately 50 percent of cases of JIA. This subgroup of JIA is further divided into
persistent oligoarthritis, in which there is no additional joint involvement after the first six months
of illness, and extended oligoarthritis, in which there is involvement of additional joints after the
first six months such that more than four joints are ultimately affected. Approximately 50 percent
of children with oligoarticular disease go on to have extended oligoarticular disease.

Oligoarticular juvenile idiopathic arthritis (JIA) affects females more often than males, as
does polyarticular disease. The peak incidence of oligoarticular JIA is in the second and third years
of life. It is less common over five years of age and rarely begins after age 10 years (Weiss, P.F.,
MD, 2019).

The typical child with oligoarticular JIA is a toddler girl who is noticed to be limping
without complaint. Often, the family notices that the child "walks funny" in the morning, but after
a little while seems fine. In many cases, the child has never complained of pain; the family seeks
medical advice only because the knee is swollen. It is unusual for the family to be able to specify
exactly when the illness started (Weiss, P.F., MD, 2019).

Oligoarticular JIA affects the large joints (typically knees and ankles, sometimes also
wrists and elbows, but rarely the hips). Systemic manifestations (other than uveitis) are
characteristically absent. Thus, fever, rash, or other constitutional symptoms suggest a different
diagnosis (Weiss, P.F., MD, 2019).
POLYARTICULAR JUVENILE IDIOPATHIC ARTHRITIS

Juvenile idiopathic arthritis (JIA) is a group of disorders characterized by arthritis

persisting for at least 6 weeks with onset before the age of 16 years. Within this cluster of
conditions, the polyarticular form (involving more than four joints within the first 6 months) is
further divided based on the presence of rheumatoid factor. Children with polyarticular JIA pose
unique diagnostic and therapeutic challenges compared to children with involvement of fewer
joints. Polyarticular JIA patients tend to have a more refractory course and therefore are at
increased risk for joint damage, resulting in poorer functional outcomes and decreased quality of
life. Although the ability to treat this disorder continues to improve, especially with the advent of
biologic agents, there is still much about the epidemiology and pathogenesis of polyarticular JIA
that is unknown. The epidemiology of polyarticular JIA varies worldwide with a vast difference
in reported cases between different global regions as well as within individual countries. Several
genetic risk loci have been identified conferring increased susceptibility to JIA, many within the
human leukocyte antigen region. Beyond the genome, environmental factors also seem to
contribute to the etiology of polyarticular JIA. This review article will focus on the epidemiology
and current treatments of polyarticular JIA and briefly discuss genetic and environmental
influences on the pathogenesis of JIA as well as new and emerging therapies (C.E., 2014).

PSORIATIC JUVENILE IDIOPATHIC ARTHRITIS

Psoriatic juvenile idiopathic arthritis is a subtype of juvenile idiopathic arthritis that is

characterized by both arthritis and psoriasis. Other signs and symptoms may include dactylitis
(inflammation and swelling of an entire finger or toe); nail pitting or splitting; and eye problems.
Although the underlying cause of psoriatic juvenile idiopathic arthritis is currently unknown
(idiopathic), it is thought to occur due to a combination of genetic and environmental factors. It is
very rare for more than one member of a family to have juvenile arthritis; however, research
suggests that having a family member with juvenile arthritis or any autoimmune disease may
increase the risk of having juvenile arthritis, in general. Treatment usually involves different types
of medications to help manage symptoms and/or physical therapy (GARDIC, 2019).
COMPLICATIONS OF JUVENILE IDIOPATHIC ARTHRITIS
There are several complications of JIA which may or may not affect your child, depending
on the type of JIA they have, how severe it is, and how well it is managed. Complications can
affect various parts of the body from bones and joints to the muscles and eyes.
Unpredictable flares in JIA. Sometimes, young people with JIA can go for months or
even years without their disease bothering them, but then it comes back. This is called a flare-up
or flare. Most young people have ups and downs in their symptoms for many years, depending on
what type of JIA they have. It is important to remember that flare-ups just happen and can’t be
prevented. Usually, the cause of the flare is unknown. It can be upsetting to see such changes when
it seemed like the JIA had improved or disappeared. Do not give up hope. There are many excellent
treatments available to help get the inflammation back under control.
Growth problems in JIA. Young people who are still growing have growth plates at the
end of their bones. These growth plates fuse or close when they have reached their adult height.
The inflammation of JIA can affect how the body grows. Inflammation causes an increase in blood
flow to the growth plates, which leads to more rapid growth of the bones in the affected joints.
Therefore, the side affected by arthritis may be larger or longer than the unaffected side.
However, in some cases, the inflammation can cause the growth plate to fuse or close
earlier than it was supposed to. This can cause the affected side to be smaller or shorter than the
unaffected side. Jaw inflammation can result in a smaller or misshaped chin. Knee inflammation
can lead to one leg being longer than the other. Occasionally, if the JIA is severe, overall growth
(height) might be slow. Your child's growth will usually improve once the inflammation settles.
Some of the medications your child takes to manage JIA, such as corticosteroids, may also
slow their growth. Keeping JIA in good control with medications is the best way to avoid these
types of growth problems. The health-care team will pay careful attention to your child's growth.
Joint contractures in JIA. Inflammation causes pressure and sometimes pain in and
around the joint. Sometimes, children and teens with JIA will keep the inflamed joint in the most
comfortable position, which is usually bent. If a joint stays bent for too long, both the muscles and
the structures that attach muscles to bones, called tendons, will shorten and not grow properly. As
a result, the joint becomes stuck in a bent position. This is called a joint contracture.
In children and teens, unlike adults, cartilage and bone can still grow. This allows for healing and
repair of joint damage. Joint tightness can be reduced with regular stretching exercises and
splinting. A splint is a brace that helps to keep a joint (like your knee or your wrist) in one position.
Sometimes an injection of medicine into the joint is very helpful. It can rapidly decrease the
inflammation in the joint so that your child can do the stretching exercises more effectively.
Muscle weakness and muscle loss in JIA. Muscle weakness and muscle loss around an
inflamed joint are common in people with JIA. When a joint is swollen, stiff, and painful to move,
it is natural for your child to want to reduce their activities. However, doing this can make their
muscles weaker. When muscles are not used regularly, they will become smaller.
Exercising helps prevent muscle weakness or even muscle loss. Using a brace or splint might not
help, because they prevent the muscles from working properly. Talk to your child's doctor or
physiotherapist about how to improve muscle strength safely.
Osteoporosis in JIA. Osteoporosis is when the bones become thin and weak. Bones with
osteoporosis are easy to fracture. Osteoporosis can develop in young people with JIA for many
reasons. These include not staying active and not getting enough calcium, both of which are needed
to help make bones strong and healthy. Taking certain medications like corticosteroids for a long
time may also lead to osteoporosis. Prolonged joint inflammation or arthritis can also lead to
osteoporosis.
You can help prevent osteoporosis by staying active. Your medical team may also ask you
to take calcium and vitamin D supplements. You might need special bone density tests once in a
while to check for osteoporosis. You will learn more about this in the Diagnosis section.
Eye problems and JIA. In addition to joint problems, JIA may cause problems with your eyes
including uveitis, glaucoma, or cataracts. All young people with JIA should get their eyes checked
regularly by an ophthalmologist or optometrist. An ophthalmologist is a medical doctor with
special training in eye care and treatment. An optometrist is a health care professional who can
diagnose eye problems. Your rheumatology team will let you know how often you need to see
your eye doctor.

CHILDREN WITH LIMITED ARTHRITIS

Complications of oligoarticular JIA and psoriatic arthritis include joint contractures,
uveitis, and leg-length discrepancy. Uveitis is almost always asymptomatic and more frequent in
young girls who have positive levels of antinuclear antibody. Evaluation with a slit-lamp every 4
months by a pediatric ophthalmologist can detect early disease to prevent permanent eye damage
and even blindness.
Leg-length discrepancy may complicate unilateral knee involvement. In young children, it
may result from neovascularization of growth plates, so the involved limb is longer. In early
puberty, unilateral arthritis can lead to premature fusion of the epiphysis, in which case the short
limb is on the affected side. The problem may not be detected in patients with a knee flexion
contracture until the contracture is corrected. Both flexion contractures and leg-length
discrepancies are much less frequent with early intervention.

CHILDREN WITH WIDESPREAD ARTHRITIS

Complications of polyarticular JIA include skeletal abnormalities such as increased size of
epiphyses, accelerated bone age, narrowed joint spaces, swan-neck and/or boutonniere
deformities, joint subluxation, and cervical spine involvement.
Difficulty extending the spine may create a problem for intubation prior to surgery, so
anesthesiologists need to be informed of the patient's diagnosis. Cervical spine radiography (in
flexion and extension) may help to screen for potential difficulties during induction of anesthesia.
High-level subluxation is a potential complication.

INFLAMMATORY MARKERS AND DISEASE ACTIVITY IN JUVENILE IDIOPATHIC

ARTHRITIS

Inflammatory markers and disease activity decreased in all subtypes of JIA with treatment
without biologics. Acute phase markers often remain elevated in inactive disease state. Similarly,
normal level of an inflammatory marker does not necessarily indicate absence of active disease
(IJP, 2017).

JIA is the most common chronic childhood arthritis; it is a diagnosis of exclusion.

Unfortunately, no diagnostic tool is available, but the comprehensive history, including family
history, and complete physical examination are the most helpful tools in differentiating the various
causes of articular disorders in children. Genetic musculoskeletal disorders that mimic chronic
polyarthritis should be considered in the differential diagnostics of JIA. Normal inflammatory
markers and characteristic radiological features are able to distinguish these disorders from JIA.
However, molecular genetic findings are the confirmatory test. Timely diagnosis of these disorders
is crucial to offer the family proper genetic counseling and avoid inappropriate therapy (Al-
Mayouf, S.M., 2018).

DIAGNOSIS OF JUVENILE IDIOPATHIC ARTHRITIS

Diagnosis of juvenile idiopathic arthritis can be difficult because joint pain can be caused
by many different types of problems. No single test can confirm a diagnosis, but tests can help rule
out some other conditions that produce similar signs and symptoms (M.C., 2017).

Blood tests

Some of the most common blood tests for suspected cases include:

Erythrocyte sedimentation rate (ESR). The sedimentation rate is the speed at which your
red blood cells settle to the bottom of a tube of blood. An elevated rate can indicate inflammation.
Measuring the ESR is primarily used to determine the degree of inflammation.

C-reactive protein. This blood test also measures levels of general inflammation in the body
but on a different scale than the ESR.

Anti-nuclear antibody. Anti-nuclear antibodies are proteins commonly produced by the

immune systems of people with certain autoimmune diseases, including arthritis. They are a
marker for an increased chance of eye inflammation.

Rheumatoid factor. This antibody is occasionally found in the blood of children who have
juvenile idiopathic arthritis.
 Cyclic citrullinated peptide (CCP). Like the rheumatoid factor, the CCP is another
antibody that may be found in the blood of children with juvenile idiopathic arthritis.

JUVENILE IDIOPATHIC ARTHRITIS TESTING

In many children with juvenile idiopathic arthritis, no significant abnormality will be found
in these blood tests (M.C. 2017).

Imaging scans

X-rays or magnetic resonance imaging (MRI) may be taken to exclude other conditions, such as
fractures, tumors, infection or congenital defects.

Imaging may also be used from time to time after the diagnosis to monitor bone development and
to detect joint damage.

Ultrasonography

In the recent years, musculoskeletal ultrasound (MSUS) has been regarded as especially
promising in the assessment of juvenile idiopathic arthritis (JIA), as a reliable method to precisely
document and monitor the synovial inflammation process (Magni-Manzoni, S., 2016).

MSUS is particularly suited for examination of joints in children due to several advantages
over other imaging modalities. Some challenges should be considered for correct interpretation of
MSUS findings in children, due to the peculiar features of the growing skeleton. MSUS in JIA is
considered particularly useful for its ability to detect subclinical synovitis, to improve the
classification of patients in JIA subtypes, for the definition of remission, as guidance to
intraarticular corticosteroid injections and for capturing early articular damage. Current evidence
and applications of MSUS in JIA are documented by several authors. Recent advances and insights
into further investigations on MSUS in healthy children and in JIA patients are presented and
discussed in the present review (Magni-Manzoni, S., 2016).
 MSUS shows great promise in the assessment and management of children with JIA.
Nonetheless, anatomical knowledge of sonographic changes over time, underlying
immunopathophysiology, standardization and validation of MSUS in healthy children and in
patients with JIA are still under investigation. Further research and educational efforts are required
for expanding this imaging modality to more clinicians in their daily practice (Magni-Manzoni, S.,
2016).

MEDICATIONS OF JUVENILE IDIOPATHIC ARTHRITIS

Medications

The medications used to help children with juvenile idiopathic arthritis are chosen to decrease
pain, improve function and minimize potential joint damage.

Typical medications include:

Nonsteroidal anti-inflammatory drugs (NSAIDs). These medications, such as ibuprofen

(Advil, Motrin IB, others) and naproxen sodium (Aleve), reduce pain and swelling. Side effects
include stomach upset and liver problems.

Disease-modifying antirheumatic drugs (DMARDs). Doctors use these medications

when NSAIDs alone fail to relieve symptoms of joint pain and swelling or if there is a high risk of
damage in the future.

DMARDs may be taken in combination with NSAIDs and are used to slow the progress of
juvenile idiopathic arthritis. The most commonly used DMARD for children is methotrexate
(Trexall). Side effects of methotrexate may include nausea and liver problems.

Biologic agents. Also known as biologic response modifiers, this newer class of drugs
includes tumor necrosis factor (TNF) blockers, such as etanercept (Enbrel) and adalimumab
(Humira). These medications can help reduce systemic inflammation and prevent joint damage.
 Other biologic agents work to suppress the immune system, including abatacept (Orencia),
rituximab (Rituxan), anakinra (Kineret) and tocilizumab (Actemra).

Corticosteroids. Medications such as prednisone may be used to control symptoms until

another medication takes effect. They are also used to treat inflammation when it is not in the
joints, such as inflammation of the sac around the heart (pericarditis).

These drugs can interfere with normal growth and increase susceptibility to infection, so
they generally should be used for the shortest possible duration.
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