This document discusses juvenile idiopathic arthritis (JIA), including its definition, signs and symptoms, patterns of onset, and treatment approaches. JIA is the most common rheumatic disease of childhood and can be divided into subtypes based on characteristics. Treatment involves NSAIDs initially and may progress to DMARDs like methotrexate or biological agents if needed. Management of uveitis associated with JIA relies on regular screening by an ophthalmologist and corticosteroid therapy if detected. The goal of JIA treatment is to minimize inflammation, control pain, preserve movement, and promote development.

1. Week
4
Juvenile Idiopathic
Arthritis
Anas Bahnassi PhD CDM CDE

2. Definition:
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JIA usually begins before the age of 16 and must
present with objective signs of joint inflammation
(e.g., swelling, pain, limited ROM, warmth,
erythema) for at least 6 weeks in at least one joint
or at least two of the following: tenderness, pain
with movement, joint warmth, or limited motion.
Other conditions causing arthritis such as
infectious arthritis and malignancy must be
excluded.
The onset of disease is rare before 6 months of
age, and the peak age of onset ranges from 1 to 3
years. However, new cases are seen throughout
childhood.

3. Signs and Symptoms:
1. JIA begins with synovial inflammation.
2. Morning stiffness and joint pain probably occur in JIA as frequently as in RA;
however, children should be observed carefully for symptoms because they often
cannot articulate complaints.
3. Morning stiffness and joint pain may manifest as increased irritability, guarding of
involved joints, or refusal to walk.
4. Fatigue and low-grade fever, anorexia, weight loss, and failure to
grow are other manifestations.
5. JIA can be divided into several subsets based on characteristic signs
and symptoms during the first 4 to 6 months of disease:
a)
b)
c)
d)
e)
f)
Polyarticular
pauciarticular or oligoarthritic,
systemic arthritis,
enthesitis related,
psoriatic,
other

4. JIA Patterns of Onset:
Seropositive
( RF positive 510% of all JIA
patients)
Both
common in
girls more
than boys
Polyarticular
More
common in
children
over 8
More
common in
children
under 5
Seronegative
( RF negative
20%–25% of all
JIA patients)

5. JIA Patterns of Onset:
Onset can be
acute but
mostly insidious
Temporomandibular
joint injury is
common leading to
limited bite &
micrognathia
Polyarticular
Systemic
manifestations rare: fever,
slight hepatosplenomegaly,
lymphadenopathy,
pericarditis, and chronic
uveitis
Large fast
growing joints
are mostly
affected

6. JIA Patterns of Onset:
Early childhood
onset
More common
Oligoarthritic
or
Pauciarticular
40-60%
Mostly girls
between
1-5 years
old
Mostly boys
over 8 years
of age
Late childhood
onset

7. JIA Patterns of Onset:
1. 20%-30% develop
iridocyclitis
(uvititis)
2. Test positive for
ANA
1. Test negative for
ANA
2. No extra articular
manifestation
Children
with late
onset
3. Hip involvement.
Oligoarthritic
or
Pauciarticular
Children
with early
onset
3. Joints commonly
affected: knees,
ankles, hands,
feet, and wrists.
4. No hip involved

8. Onset of
polyarthritis
/oligoarthritis
in a boy >8
years of age
HLA B27
positivity
Acute
anterior
uveitis
JIA Patterns of Onset:
Inflammatory
spinal pain
Enthesitis-related JIA
should have two of these
six reds:
Sacroiliac
joint
tenderness
Family
history of
enthesitisrelated JIA

9. JIA Patterns of Onset:
Dactylitis:
Finger or toe
inflammation
All are
HLA B27
positive
Psoriatic JIA
should have two of the
three reds:
Family
history of
psoriasis
Onycholysis:
Nail pitting

10. •
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J.R., a 4-year-old girl, is hospitalized for high fever and arthritis.
Several weeks before admission, J.R. developed a daily fever ranging from 103°F to 106°F.
One week before admission, her knees became painful and swollen.
J.R. is listless and irritable during her physical examination.
The rectal temperature is 102.4°F. She refuses to walk.
The right hip is tender and the right wrist and both knees
are warm, red, and swollen.
Minimal generalized lymphadenopathy and splenomegaly
are present.
The Westergren ESR is 82 mm/hour, the WBC count 37,000
cells/mm3 with a mild left shift, and Hct 33%.
Cultures of the throat, urine, stool, and blood are negative.
An intermediate-strength purified protein derivative,
antistreptolysin-O titer, ANA titer, and RF titer all are
normal.
Radiographs of the chest and involved joints all are normal.
An electrocardiogram reveals only tachycardia.
After hospitalization and withholding aspirin, an evanescent
rash becomes apparent in conjunction with fever spikes.

11. What signs and symptoms of JIA does J.R. manifest?
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The signs and symptoms (i.e., the spiking fever
episodes, evanescent rash, arthritis, lymphadenopathy,
splenomegaly) that J.R. experienced are characteristic of
systemic-onset JIA.
These children also may have a normocytic,
hypochromic anemia, elevated ESR, thrombocytosis,
and leukocytosis.
Leukocytosis is common and a WBC count of 30,000 to
50,000 cells/mm3 is seen occasionally.
A positive RF titer is uncommon in JIA and is present in
only 5% to 10% of all cases.
The ANA titer more often is positive and is most
prevalent in young girls and children with early-onset
pauciarticular arthritis and uveitis.

12. What is the goal of therapy for J.R?
The goal of JIA treatment is to:
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Minimize the destructive effects of
inflammation.
Control pain
Preserve or restore movement.
Promote development and growth, to
facilitate an acceptable quality of life.

13. What is the initial drug therapy for JIA?
• NSAID therapy is the treatment of choice.
• At least two different NSAIDs should be tried before ruling
out this group.
• Failure to respond to an NSAID in a particular chemical class
does not rule out the efficacy of others in the same class.
• Naproxen is the most prescribed dosed at 10 to 15 mg/kg/day
(maximum, 750 mg) in two daily divided doses.
• Oxaprozin can be administered once daily as a 600-mg dose if
weight is between 22 and 31 kg, 900 mg if weight is between 32
and 54 kg, and 1,200 mg if weight is >55 kg.
• Nabumetone is also frequently used for JIA because of
convenient once daily dosing.
• Ibuprofen doses should not exceed 40 to 50 mg/kg/day.
• Tolmetin usually is dosed at 20 mg/kg/day in three to four
divided doses.

14. Should aspirin be discontinued in a JIA patient who experiences
chickenpox because of the potential for causing Reye syndrome?
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Reye syndrome occurs in association with the use of aspirin as an
antipyretic in children during the prodromal phase of viral
illnesses such as influenza and chickenpox.
Reye syndrome is characterized by fatty vacuolization of the liver
producing hepatic injury, vomiting, hypoglycemia, and progressive
encephalopathy.
Aspirin should not be given to febrile children who are at risk for
Reye syndrome by virtue of possible infection with either
influenza virus or chickenpox.
Patients with JIA should avoid salicylate ingestion during febrile
illnesses that represent possible infection with either influenza or
chickenpox.

15. When should DMARDs be used in JIA?
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Most children with JIA improve significantly with NSAID treatment, especially pauciarticular disease.
Patients with polyarticular, RF-positive disease and patients with earlyonset polyarthritis in association with systemic-onset disease both
have poor prognosis in terms of ultimate joint function and should
receive early consideration for DMARD therapy.
Children with polyarticular-onset, RF-negative disease generally have a
better prognosis than patients with polyarticular involvement and may
wait considerably longer before introducing a DMARD for these
patients.
Most DMARDs used for adult RA are not effective for JIA.
MTX is clearly the DMARD of choice for polyarthritic JIA.
The recommended dose of MTX for JIA treatment is 5 to 15 mg/m2
(0.15–0.5 mg/kg) orally or subcutaneously each week.
Pediatric patients are often prescribed the injectable form of MTX for
oral consumption via a suspension.
Food reduces the bioavailability of MTX, so MTX should be
administered on an empty stomach or parentrally if bioavailability is
an issue parenteral preparations should be used.

16. When should DMARDs be used in JIA?
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Children tolerate MTX therapy well and generally experience few serious or
troublesome adverse effects (e.g., transient liver enzyme elevations, nausea,
vomiting, oral ulcerations).
These adverse effects are reduced with daily folic acid therapy(1 mg)
or weekly folinic acid (the day after MTX dosing).
The combination of MTX and other DMARDs has not been fully
evaluated.
If MTX is not tolerated or is ineffective, SSZ is often the next DMARD
selected.
SSZ (30–50 mg/kg/per day in two divided doses with a maximum of 2
g/day) is effective for pauciarticular and polyarticular JIA, but
numerous adverse effects (e.g., liver enzyme elevations, leukopenia,
hypoimmunoglobulinemia, hematomas, diarrhea, anorexia) lead to
discontinuation of therapy in about 30% of patients.
HCQ may be considered if SSZ fails, but efficacy data from welldesigned randomized controlled trials are not available.

17. What biological agents are effective in JIA?
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Etanercept (Enbrel), the only FDA-approved biological agent for the
treatment of JIA, is indicated for patients 4 years of age and older
whose conditions have failed to respond to one or more DMARDs.
The recommended dose is 0.4 mg/kg (maximum, 25 mg)
subcutaneously twice weekly.
Etanercept monotherapy at this dose would be expected to yield
about a 76% response rate.
Safety of etanercept in children is comparable to adults with the
exception of significantly more abdominal pain vomiting.
JIA patients should be current on immunizations before initiation of
etanercept therapy because the effect of etanercept on vaccine
response is unknown.
Safety and efficacy data reflecting up to 8 years of treatment support
the long-term use of etanercept for JIA.

18. What is the evidence supporting the use of intra-articular corticosteroid
therapy in JIA?
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Intra-articular corticosteroid therapy seems to be highly efficacious
in JIA.
Full disease remission of injected joints lasting longer than 6 months
can be expected in 84% of patients with JIA, and 60% of patients
could be expected to be able to discontinue all oral medications, with
even greater success in patients with pauciarticular JIA.
Long-term negative effects of corticosteroid therapy (e.g., joint
stability, osteonecrosis, soft tissue atrophy) are not usually
encountered.
Intra-articular corticosteroid therapy seems to be a safe and effective
option for JIA, particularly in pauciarticular disease limited to a few
troublesome joints.

19. J.R. is scheduled to be seen by an ophthalmologist every 6 months to
screen for uveitis. How should her uveitis be managed?
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Uveitis associated with JIA (Iridocyclitis) is a nongranulomatous
inflammation involving the iris and ciliary body.
The posterior uveal tract, or choroid, rarely is affected.
Chronic uveitis can progress, leading to cataracts, glaucoma, and
blindness.
Careful screening and early detection are effective at preventing
these conditions.
Uveitis is most common in ANA-positive oligoarthritis JIA and usually
occurs within 4 to 7 years of JIA diagnosis.
Fewer than 1% of patients with systemic JIA develop uveitis.
Uveitis rarely presents with symptoms, and even if symptoms occur,
children may have difficulty recognizing them (e.g., ocular pain,
decreased vision, headaches, red eye, unequal pupils).

20. J.R. is scheduled to be seen by an ophthalmologist every 6 months to
screen for uveitis. How should her uveitis be managed?
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Prevention of uveitis relies on compliance with regularly scheduled
slit-lamp examinations performed by an ophthalmologist.
Direct ophthalmoscopy cannot detect uveitis.
All JIA patients must have a baseline slit-lamp examination within 1
month of diagnosis.
The highest-risk JIA patients for uveitis (e.g., ANA-positive
oligoarthritis or polyarthritis, ≤6 years of age at JIA onset and ≤4
years JIA duration) require slit-lamp examination every 3 months.
At the opposite extreme, low-risk oligoarthritis or polyarthritis
patients (i.e., >7 years JIA duration, >6 years of age at JIA onset and
>4 years JID duration, ≤6 years of age at JIA onset and >4 years JIA
duration who are ANA negative, >6 years of age at JIA onset and ANA
negative) and systemic JIA patients require slit-lamp examination
once a year.
If detected early, the prognosis for uveitis is very good.

21. J.R. is scheduled to be seen by an ophthalmologist every 6 months to
screen for uveitis. How should her uveitis be managed?
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The initial drug of choice is a topical corticosteroid (e.g.,
dexamethasone, prednisolone), which usually reduces ocular
inflammation rapidly.
More severe and chronic uveitis may require a 1- to 3-day course of
intravenous methylprednisolone (30 mg/kg once daily, maximum 1
g/dose).
Uveitis that responds poorly to corticosteroids should be treated
with systemic NSAIDs, followed by serial trials of by MTX and antiTNF agents if responses are inadequate

22. Pharmacottherapy
Anas Bahnassi PhD CDM CDE
abahnassi@gmail.com
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