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JIA Management
JIA Management
JIA Management
Education Gap
The management of juvenile idiopathic arthritis (JIA) has changed
radically over the last few decades. This article provides an update on
identification of JIA, complications of the condition, and common
management strategies to help practitioners treat affected children in
conjunction with other specialists as part of a multidisciplinary team.
AUTHOR DISCLOSURE Dr Shenoi has Objectives After completing this article, readers should be able to:
disclosed that she has been a speaker for
Novartis. This commentary does contain a 1. Recognize the clinical findings associated with the various categories of
discussion of an unapproved/investigative
use of a commercial product/device.
juvenile idiopathic arthritis (JIA).
2. Recognize the laboratory findings associated with the different
ABBREVIATIONS
ALT alanine aminotransferase categories of JIA and its complications.
ANA antinuclear antibody
3. Formulate a differential diagnosis for children with joint pain.
AST aspartate aminotransferase
CARRA Childhood Arthritis and 4. Recognize the long-term complications associated with JIA.
Rheumatology Research Alliance
CBC complete blood cell 5. Plan the appropriate management of JIA while recognizing adverse
CRP C-reactive protein effects of some therapies.
DMARD disease-modifying antirheumatic
drug
ERA enthesitis-related arthritis
ESR erythrocyte sedimentation rate
FDA Food and Drug Administration INTRODUCTION
HLA human leukocyte antigen
IAS intraarticular corticosteroid
Arthritis is a common cause of disability in childhood. In children, the condi-
injection tion previously was known as juvenile chronic arthritis or juvenile rheumatoid
IL interleukin arthritis. Currently, the preferred name for childhood arthritis is juvenile idio-
ILAR International League of pathic arthritis (JIA) because this term denotes the idiopathic or unknown cause
Associations for Rheumatology
of the condition. The exact incidence and prevalence of JIA is unknown and
IV intravenous
likely varies across the world. The estimated incidence and prevalence of JIA
JIA juvenile idiopathic arthritis
MAS macrophage activation syndrome in the United States is approximately 14 per 100,000 children (95% confidence
NSAID nonsteroidal anti-inflammatory interval: 10–18) and 113 per 100,000 (95% confidence interval: 55–155), respec-
drug tively. (1) JIA is believed to have a multifactorial etiology, with both genetic and
PVNS pigmented villonodular synovitis nongenetic (ie, environmental) contributing causes. Due to the paucity of practicing
RF rheumatoid factor
pediatric rheumatologists, pediatricians or family practice physicians often are
SJIA systemic juvenile idiopathic
arthritis
“on the front line” for initial identification and treatment of JIA. This article
TMJ temporomandibular joint focuses on key points for diagnosis and initial evaluation of JIA and provides an
TNF tumor necrosis factor overview of treatment.
Systemic-onset Systemic-onset juvenile Arthritis and fever (‡2 weeks, documented 1, 2, 3, 4 Adult Still disease
JIA rheumatoid arthritis quotidian 3þ days)
Plus 1 or more:
• Evanescent erythematous rash
• Generalized lymphadenopathy
• Hepatosplenomegaly
• Serositis
ERA¼enthesitis-related arthritis, ILAR¼International League of Associations for Rheumatology, HLA¼human leukocyte antigen, JIA¼juvenile idiopathic
arthritis, OJIA¼oligoarticular juvenile idiopathic arthritis, RF¼rheumatoid factor.
*Exclusion definitions: 1. Psoriasis in patient or first-degree relative; 2. HLA-B27þ male older than age 6 years; 3. Ankylosing spondylitis, ERA, sacroiliitis with
inflammatory bowel disease, Reiter syndrome, or acute anterior uveitis in a first-degree relative; 4. RF-positive in 2 assessments 3 months apart; 5. Systemic-
onset JIA in patient.
Reproduced with permission from inPractice.com, Essentials of Juvenile Idiopathic Arthritis for the Adult Rheumatologist/Internist.
ANA¼antinuclear antibody, ERA¼enthesitis-related arthritis, OJIA¼oligoarticular juvenile idiopathic arthritis, PJIA¼polyarticular juvenile idiopathic
arthritis, SJIA¼systemic juvenile idiopathic arthritis.
*Once uveitis is detected, the treating ophthalmologist determines the frequency of screening to ensure the inflammation is responding appropriately to
the therapy. Patients with JIA onset of age <7 years who reach age 7 years or those with JIA onset of age ‡7 years who are 4 years into their diagnosis are
considered to be at lower risk for uveitis and can transition to annual ophthalmologic examinations going forward.
Reproduced with permission from inPractice.com, Essentials of Juvenile Idiopathic Arthritis for the Adult Rheumatologist/Internist.
frequently (every 3 months) for uveitis. The long-term prog- before being diagnosed with SJIA. Occult MAS can occur in
nosis is usually good if they do not develop extended disease. up to one-third of children and must be recognized and
treated promptly. Clinicians should not be reassured by a
Polyarticular JIA decreasing ESR in an ill-looking patient because this may
By ILAR definition, children who have polyarticular JIA have signify MAS. MAS is considered a secondary form of he-
more than 4 joints involved in the first 6 months of disease mophagocytic lymphohistiocytosis and is a life-threatening
onset. Depending on the presence or absence of rheumatoid condition that involves rapid expansion of macrophages
factor (RF), the disease is classified further as RF-positive or and T cells, leading to massive overproduction of cytokines.
-negative. Because RF is transiently positive in other con- Among the JIA categories, this complication appears to be
ditions such as infections, its positivity should be confir- unique to SJIA. Features of MAS include persistent fevers,
med by repeating RF evaluation 3 months later. There are bleeding diathesis, central nervous system involvement with
typically 2 peaks of presentation: ages 1 to 3 years and dur- drowsiness or seizures, fixed rashes, decreasing white blood
ing adolescence. Fig 2 shows a teenage girl with polyarti- cell and platelet counts, decreasing fibrinogen, elevated
cular JIA and arthritis of several proximal interphalangeal D-dimer, elevated triglycerides, and abnormal liver function
joints bilaterally and flexion contractures with boutonniere tests (aspartate aminotransferase [AST], alanine aminotransfer-
deformity (proximal interphalangeal joint flexion and distal ase [ALT]). Hyperferritinemia (ferritin levels are often >5,000
interphalangeal joint hyperextension) of bilateral fifth fingers. ng/mL [11,235 pmol/Lng/mL]) and hemophagocytosis
(often seen in bone marrow or other tissues such as lymph
Systemic JIA node or spleen) are hallmarks of MAS.
Children who have SJIA must undergo complete infec-
tious and malignancy evaluation for their fevers, including Psoriatic JIA
cultures, serology, imaging, and/or bone marrow examination Children may present with classic psoriasis, nail changes
suggestive of psoriasis, or family history of psoriasis in a
first-degree relative in addition to arthritis. Affected chil-
dren often present with “sausage digits” or dactylitis.
Enthesitis-related Arthritis
Enthesitis-related arthritis (ERA) is more common in boys
and usually presents with enthesitis and arthritis. Axial
involvement of the spine or sacroiliac joints with back pain
is common. This is the only category of JIA that can present
with an “acute painful red eye” rather than asymptomatic
Figure 2. Arthritis of several proximal interphalangeal joints bilaterally
and flexion contractures with boutonniere deformity of bilateral fifth
uveitis. Some children may have the acute iritis months to
fingers in a child who has polyarticular juvenile idiopathic arthritis. years before joint symptoms develop.
Eyes
Complications of uveitis include posterior synechiae pre-
senting as fixed irregular pupillary margin (due to adhesions
between the iris and lens), glaucoma (related to topical cor-
ticosteroid medication or due to inadequate drainage from
circumferential synechiae), band keratopathy, cataracts (due
to inflammation or topical corticosteroids), and eventual
blindness. Thus, it is important to ensure slit lamp oph-
thalmologic evaluations at diagnosis and regular intervals
thereafter. (3)
MANAGEMENT OF JIA
Over the last few decades, there has been a major paradigm
shift in treatment strategies for JIA. Rather than the previously
recommended step-up approach, current recommenda-
tions suggest rapid and aggressive therapy to control in-
flammation, followed by a gradual taper of medications
once complete remission has been established. The avail-
ability of biologic and targeted therapies for JIA has re-
volutionized its treatment. Goals of therapy include pain relief,
maintenance of function and range of motion of joints,
achievement of remission (either on or off medications),
and minimization of adverse effects of medications. The Child-
hood Arthritis and Rheumatology Research Alliance
(CARRA) has published consensus treatment plans for
polyarticular JIA and SJIA. These are not meant to be guide-
Figure 3. Radiograph of foot showing first metatarsal head erosion in a lines but rather outline the most common treatment strate-
boy with enthesitis-related arthritis.
gies currently used by pediatric rheumatologists. The goal of
establishing these treatment plans is to collect data to enable
Mediterranean fever, PFAPA [periodic fever, aphthous comparative effectiveness studies and identify superior treat-
ulcers, pharyngitis, adenitis], TRAPS [tumor necrosis factor ment strategies through evidence. The American College
[TNF]-associated periodic syndrome], cryopyrinopathies of Rheumatology has published evidence-based recommen-
(familial cold autoinflammatory syndrome, Muckle-Wells dations for JIA treatment.
syndrome), or hyperimmunoglobulin D syndrome.
Oligoarticular JIA
Initial treatment of oligoarticular disease may include anti-
LONG-TERM COMPLICATIONS OF JIA
inflammatory doses of nonsteroidal anti-inflammatory drugs
Joints (NSAIDs) such as ibuprofen 10 mg/kg per dose 3 times a day
Untreated inflammatory arthritis can lead to early (months) to a maximum of 3,200 mg/day or naproxen 10 mg/kg per
or longer-term destruction of the joint, including cartilage dose twice a day to a maximum of 1,000 mg/day or intra-
loss (manifesting as joint space narrowing) and bony erosions. articular corticosteroid injection (IAS) (triamcinolone hex-
Among the other complications are osteopenia/osteoporosis, acetonide is superior to triamcinolone acetonide because of
Rituximab IV infusion Adults with moderately to severely Refractory PJIA Chimeric cytolytic
Rituxan Refractory PJIA: 375 mg/m2 IV active RA who have inadequate SJIA monoclonal antibody to
Genentech USA, weekly 4 weeks, repeated response to 1 or more TNF Uveitis CD20 (on pre-B and
Inc, South course every 6 months or 750 inhibitors (use in combination mature B cells)
San Francisco, CA mg/ m2 IV on days 1 and 14 with methotrexate)
SJIA uveitis: 375-500 mg/m2 IV
weeks 0 and 2 (with
methotrexate)
Subsequent courses can be
administered every 24 weeks
(based on clinical
examination findings)
Anakinra SC Moderately to severely active SJIA Fully human recombinant
Kineret 1-4 mg/kg SC daily (maximum: DMARD-refractory RA SJIA with MAS IL-1RA (receptor antagonist)
Sobi, Inc, 100 mg/day); best studied at NOMID Competes with IL-1 for
Waltham, MA 1 mg/kg per day (Note: can binding of the receptor
be used as IV or IV continuous so that it is unavailable to
infusion off-label; 1-10 mg/kg bind with IL-1
over 4 hours has been used in
severe MAS with SJIA)
Canakinumab Active SJIA: Age ‡2 years: 4 mg/kg Cryopyrin-associated periodic Fully human anti-IL-1b
Ilaris per dose (maximum dose: 300 syndromes (including familial monoclonal antibody
Novartis mg) for patients with weight cold autoinflammatory
Pharmaceuticals ‡7.5 kg; repeat dose for disease syndrome, Muckle-Wells
Corp, East relapse approximately every syndrome) for patients age
Hanover, NJ 4 weeks ‡4 years
Cryopyrin-associated periodic Tumor Necrosis Factor Receptor-
syndromes: Weight 15-40 kg: Associated Periodic Syndrome
2 mg/kg per dose (can (TRAPS)
increase to 3 mg/kg if Hyperimmunoglobulin D
unresponsive) Syndrome (HIDS)/Mevalonate
Weight >40 kg: 150 mg/dose; Kinase Deficiency (MKD)
SC dose every 8 weeks Familial Mediterranean Fever
(FMF)
SJIA ‡2 years
Rilonacept SC Cryoprin-associated periodic SJIA IL-1 trap agent acts as a
Arcalyst Loading dose 4.4 mg/kg syndromes for patients age Age ‡4 years: soluble decoy receptor
Regeneron, (maximum: 320 mg) in 1-2 SC ‡12 years 4.4 mg/kg and consequently blocks
Tarrytown, NY injections (same day, different per week IL-1 signaling
sites), maximum volume
2 mL/injection; maintenance
dosing 2.2 mg/kg per dose
(maximum: 160 mg) weekly
AS¼ankylosing spondylitis, DMARD¼disease-modifying antirheumatic drug, FDA¼US Food and Drug Administration, IL¼interleukin, IV¼intravenous,
MAS¼macrophage activation syndrome, NOMID¼neonatal-onset multisystem inflammatory disease, PJIA¼polyarticular juvenile idiopathic arthritis,
PsA¼psoriatic arthritis, RA¼rheumatoid arthritis, SC¼subcutaneous, SJIA¼systemic juvenile idiopathic arthritis, TNF¼tumor necrosis factor. Reproduced
with permission from inPractice.com, Essentials of Juvenile Idiopathic Arthritis for the Adult Rheumatologist/Internist.
1. A 3-year-old child is evaluated for 7 weeks of morning stiffness and pain in her knees REQUIREMENTS: Learners
that improves as the day progresses. The joint stiffness seems to worsen again if the can take Pediatrics in Review
child tries to rest for prolonged periods. The parents have also noted swelling in quizzes and claim credit
both knees. There has been no fever or rash. On physical examination, the child clearly online only at: http://
has decreased range of motion in the knees bilaterally as well as swelling and pedsinreview.org.
warmth of both joints. Laboratory studies are ordered. Which of the following is the
To successfully complete
single most helpful finding in establishing the diagnosis of juvenile idiopathic arthritis
2017 Pediatrics in Review
(JIA) in this child?
articles for AMA PRA
A. Cartilage biopsy. Category 1 CreditTM, learners
B. Characteristic clinical findings. must demonstrate a minimum
C. Elevated antinuclear antibody. performance level of 60% or
D. Elevated erythrocyte sedimentation rate. higher on this assessment,
E. Elevated rheumatoid factor. which measures achievement
2. A 3-year-old child has been diagnosed with oligoarticular JIA. During the discussion about of the educational purpose
long-term care and follow-up, the family is told that frequent visits to an ophthalmologist and/or objectives of this
are particularly important. Which of the following is the most appropriate rationale for the activity. If you score less than
importance of the frequent visits to the ophthalmologist? 60% on the assessment, you
A. Children frequently complain of eye pain. will be given additional
B. Children with JIA need frequent changes in their corrective lenses. opportunities to answer
C. Eye exercises can substantially decrease the rate of complications. questions until an overall 60%
D. Ocular inflammation in JIA is often asymptomatic. or greater score is achieved.
E. Children with JIA require vision correction early in their lives. This journal-based CME
3. A 14-year-old girl with systemic JIA who is taking methotrexate presents to the emergency activity is available through
department with the acute onset of fever, bleeding from the gums, seizures, decreased Dec. 31, 2019, however, credit
white blood cell and platelet counts, elevated D-dimer, and elevated aspartate will be recorded in the year in
aminotransferase and alanine aminotransferase. Her erythrocyte sedimentation rate today which the learner completes
is lower than it was 2 weeks ago during a regular follow-up visit. Which of the following is the quiz.
the most likely diagnosis in this patient?
A. Autoimmune hemolysis.
B. Macrophage activation syndrome.
C. Methotrexate overdose.
D. Overwhelming sepsis.
E. Secondary leukemia. 2017 Pediatrics in Review now
is approved for a total of 30
4. A 3-year-old girl with oligoarticular JIA presents to the clinic with a limp on the
Maintenance of Certification
right side associated with spiking fevers. Her right knee and ankle appear
(MOC) Part 2 credits by the
normal on physical examination, with no redness, warmth, or swelling. You
American Board of Pediatrics
order point-of-care right hip ultrasonography. Which of the following is the
through the AAP MOC
most important information that this imaging study will provide you in this
Portfolio Program. Complete
patient?
the first 10 issues or a total of
A. Confirm the presence of late ischemic changes of the joint. 30 quizzes of journal CME
B. Diagnose malignant bone tumors in deep-seated joint spaces. credits, achieve a 60% passing
C. Distinguish between inflammatory and infectious arthritis. score on each, and start
D. Evaluate the integrity of the lymphatic drainage of the affected limb. claiming MOC credits as early
E. Identify active synovitis of the hip joint. as October 2017.
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