REFERAT

JUVENILE IDIOPATIC ARTHRITIS

R. Gantira W. Danasasmita

Residency Program, Internal Medicine Departement

Medical Faculty, University of Indonesia
Cipto Mangunkusumo Hospital, Jakarta
OUTLINE
• Introduction
• Epidemiology
• Definition
• Pathogenesis
• Clinical Criteria
• Imaging and Laboratory
• Management
INTRODUCTION
• Juvenile idiopathic arthritis (JIA) is defined by the International
League of Associations for Rheumatology (ILAR) as arthritis of
unknown etiology that begins before the sixteenth birthday and
persists for at least 6 weeks with other known conditions excluded
• more common chronic diseases of childhood, with a prevalence of
approximately 1 per 1,000

Beukelman T, Patkar NM, Saag KG. 2011 American College of Rheumatology Recommendations for the
Treatment of Juvenile Idiopathic Arthritis: Initiation and Safety Monitoring of Theurapeutic Agents for the
Treatment of Arthritis and Systemic Features. Arthritis Care & Research Vol. 63, No. 4, April 2011, pp 465–482
EPIDEMIOLOGY
 Juvenile idiopathic arthritis
 most common cause of
chronic arthritis in
childhood
 epidemiological studies 
0.07-4.01 per 1000 children
worldwide

Source: Public Health Agency of Canada using Canadian

Community Health Survey, 2007-2008, Statistics Canada
EPIDEMIOLOGI
The prevalence of JIA is about 6 in 10,000 children. The annual incidence of JIA is
about 1 per 10,000 children.

PJ Manners, C Bower. Worldwide prevalence of juvenile arthritis - why does it vary so much?
Journal of Rheumatology 2002 29: 1520-1530.
CRITERIA DIAGNOSIS
 Pathophysiology

• The increased frequency of autoimmune diseases among JIA patients

suggests the genetic basis of the disease
• Human leukocyte antigen (HLA) B27 and the other HLA tissue types
are the most commonly mentioned genetic factors
• Various infections are considered to be responsible for induce JIA
pathogenesis: enteric infections, parvovirus B19, rubella, mumps,
hepatitis B, Epstein-Barr virus, mycoplasma and chlamydia infections

Barut K, et al. Juvenile idiopathic arthritis. Balkan Med J 2017;34:9

 Defect
PATHOGENESIS immune
HLA
(genetic enviroment
susceptibility)

Imbalance
immune
response

Barut K, et al. Juvenile idiopathic arthritis. Balkan Med J 2017;34:9

 Pathogenesis

Prakken B, Albani S, Martini A. Juvenile Idiopathic Arthritis. Lancet 2011;377: 2138-49.

 DIAGNOSTIC ARTRITIS IN
CHILDHOOD - HISTORY
• joint pain and swelling (incl. previous episodes)
• morning stiffness (>15 minutes, improves during the
day)
• noticing problems with (eg: walking, running,
climbing stairs, standing up, writing, or sleeping.)
• autoimmune disease in relatives
• in suspected psoriatic arthritis and enthesitis related
arthritis  ask about specific family history
• systemic features such as rash or intermittent
pyrexia
 CLINICAL FEATURES
strongly depend on :
• subtype
• age at onset of disease
• number and location of joints
involved
• disease course
• presence of antinuclear
antibodies or rheumatoid
factor
• presence of chronic or acute
uveitis
• presence of systemic features
• HLA allelic associations
CRITERIA DIAGNOSIS
SYMPTOMS
DIAGNOSTIC - LABORATORY
 JUVENILE IDIOPATHIC ARTHRITIS, SYSTEMIC CATEGORY
• Approximately 2% to 17% of children with JIA have systemic juvenile
idiopathic arthritis (sJIA)
• Daily fever of at least 2 weeks duration that for at least three of
those days is documented to be quotidian (defined as a daily
recurrent fever that rises to ≥39°C once a day and returns to 37°C or
below between fever spikes) and at least one of the following:
• (a) an evanescent, nonfixed, erythematous rash;
• (b) generalized lymph node enlargement;
• (c) hepatomegaly and/or splenomegaly;
• (d) serositis (pericardial, pleural or peritoneal).
 Systemic JIA is excluded if criteria a, b, c, or d from the list of exclusion
criteria are present
Lovell DJ. Juvenile Idiopathic Arthritis A. Clinical Features. In : Primer on Rheumatic Disease 13 th ed.
JUVENILE IDIOPATHIC ARTHRITIS, SYSTEMIC CATEGORY
• Rash : pale pink, blanching, transient (lasting minutes to a few hours),nonpuritic in 95% of cases, and
characterized by small macules or maculopapules.
• Growth delay, osteopenia, diffuse lymphadenopathy, hepatosplenomegaly, serosistis, anemia,
leukocytosis, thrombocytosis, and elevated acute-phase reactants.
• The extra-articular features are usually mild to moderate in severity and almost always self-limited.
• Most systemic features will resolve when the fevers resolve
• sJIA patients can develop pericardial tamponade, severe vasculitis with secondary consumptive
coagulopathy, and macrophage activation syndrome, all of which require intense steroid therapy

Typical rash in children

with sJIA

Lovell DJ. Juvenile Idiopathic Arthritis A. Clinical Features. In : Primer on Rheumatic Disease 13 th ed.
JUVENILE IDIOPATHIC ARTHRITIS, SYSTEMIC
CATEGORY
• The long-term prognosis for sJIA is determined by the severity of the arthritis,
• In some patients does not develop for weeks or months after the onset of the
fever.
• sJIA may develop at any age <16 years, but the peak age of onset is 1 to 6 years
old.
• Boys and girls are equally affected

Lovell DJ. Juvenile Idiopathic Arthritis A. Clinical Features. In : Primer on Rheumatic Disease 13 th ed.
JUVENILE IDIOPATHIC ARTHRITIS, SYSTEMIC
MACROPHAGE ACTIVATION SYNDROME
• 50% cases  complication macrophage
activation syndrome (MAS)
• Increase proinflammatory cytokine 
Haemophagocytosis  pancytopenia,
coagulopathy, liver disfunction,
neurological deficit
• Laboratory : increase acute phase protein ferritin
• Gold standard : haemophagocytosis in bone
marrow biopsy
 JUVENILE IDIOPATHIC ARTHRITIS, POLYARTHRITIS RHEUMATOID
FACTOR POSITIVE AND RHEUMATOID FACTOR NEGATIVE CATEGORIES

• Arthritis in 5 or more joints during the first 6 months of the disease.

• To be considered RF+, the patient must have at least two positive results for RF
at least 3 months apart during the first 6 months of disease.
• Clinical manifestations and outcome of both poJIA categories are highly
variable, and include fatigue, anorexia, protein–caloric malnutrition, anemia,
growth retardation, delay in sexual maturation, and osteopenia.
• poJIA may develop at any age less than 16 years
• Girls : boys  3 to 1

Lovell DJ. Juvenile Idiopathic Arthritis A. Clinical Features. In : Primer on Rheumatic Disease 13 th ed.
 JUVENILE IDIOPATHIC ARTHRITIS, OLIGOARTHRITIS
• Arthritis in 4 or less joints during the first 6 months of the disease.
• Two subcategories: persistent and extended.
• Persistent oJIA patients never have a cumulative total of more than 4 joints with
arthritis during the course of the disease
• Extended oJIA patients demonstrate a cumulative total during the course of the
disease of arthritis in 5 or more joints after the first 6 months of the disease.

Lovell DJ. Juvenile Idiopathic Arthritis A. Clinical Features. In : Primer on Rheumatic Disease 13th ed.
 JUVENILE IDIOPATHIC ARTHRITIS,
OLIGOARTHRITIS
• oJIA is the most frequent of the JIA categories (24%–58% of all JIA patients)
• The severity of joint symptoms is usually very mild
• Up to 50% of oJIA cases will evolve to the extended subcategory and 30% will do
so in the 2 years after disease onset.
• Patients with oJIA : commonly younger (1–5 years old at onset), are more likely to
be girls (girls outnumber boys 4 to 1), are often ANA positive, and have the
greatest risk for developing chronic eye inflammation

Lovell DJ. Juvenile Idiopathic Arthritis A. Clinical Features. In : Primer on Rheumatic Disease 13th ed.
JUVENILE IDIOPATHIC ARTHRITIS, PSORIATIC ARTHRITIS
• Onset at or before the age of 16
• The classic psoriatic rash may not appear for many years after the onset of the
arthritis
• Arthritis and at least 2 of the following 3 criteria: dactylitis, nail pitting or
onycholysis, and psoriasis in a first-degree relative.
• In the vast majority of cases : the arthritis is peripheral, asymmetric, and often
involves the knees, ankles, and small joints of the hands and feet.
• The dactylitis (“sausage digit”) involves inflammation of not only the small joints
of the toes or fingers but also the tendon sheath  often asymptomatic despite
obvious swelling and loss of motion in the digit.
• At onset, about 70% of the pJIA patients have arthritis in 4 or more joints.
Lovell DJ. Juvenile Idiopathic Arthritis A. Clinical Features. In : Primer on Rheumatic Disease 13th ed.
JUVENILE IDIOPATHIC ARTHRITIS, ENTHESITIS RELATED
• Both arthritis and enthesitis or have either arthritis or enthesitis with any 2 of the 5 following
manifestations:
• (1) sacroiliac tenderness and/or inflammatory lumbosacral pain;
• (2) positive HLA-B27;
• (3) onset of arthritis in a male ≥6 years old;
• (4) acute (symptomatic) anterior uveitis;
• (5) presence in a first-degree relative of ankylosing spondylitis, enthesitis-related arthritis,
inflammatory bowel disease with sacroiliitis, reactive arthritis or acute anterior uveitis
• Enthesitis  inflammation at the insertion of the tendon, ligament, joint capsule, or fascia into the bone
 pain, tenderness, swelling
• The most common sites : the superior curve of the patella, infrapatellar at the tibial tuberosity,
attachment of the Achilles tendon, back of the foot (attachment of plantar fascia to the calcaneous),
and sole of the foot at the metatarsal heads

Lovell DJ. Juvenile Idiopathic Arthritis A. Clinical Features. In : Primer on Rheumatic Disease 13th ed.
JUVENILE IDIOPATHIC ARTHRITIS, ENTHESITIS RELATED
• Peripheral arthritis in approximately 80% of eJIA patients
• In about 85% of the patients, the arthritis will involve 4 or more joints.
• In eJIA, tests for ANA and RF are negative, and plain radiographs often do not show the
characteristic changes in the SI or lumbosacral spine for many years.
• Bone scans are seldom helpful because radioisotope uptake is typically increased in the
SI joints and the lumbar spine in all children as a consequence of skeletal growth.
• Computed tomography (CT) and magnetic resonance imaging (MRI) scans can be useful
studies if interpreted by a radiologist familiar with axial imaging of children.
• There are no pathognomonic laboratory tests

Lovell DJ. Juvenile Idiopathic Arthritis A. Clinical Features. In : Primer on Rheumatic Disease 13th ed.
JUVENILE IDIOPATHIC ARTHRITIS, UNDIFFERENTIATED

• The manifestations do not fulfill the inclusion criteria for any category or the patient fulfills
criteria for more than one category.
• In those classified as uJIA, 60% failed to demonstrate characteristics that fulfilled the eligibility
criteria for one of the other JIA categories and 40% demonstrated criteria from more than one
JIA category

Lovell DJ. Juvenile Idiopathic Arthritis A. Clinical Features. In : Primer on Rheumatic Disease 13 th ed.
OCULAR INVOLVEMENT IN JUVENILE IDIOPATHIC ARTHRITIS

• A unique manifestation of JIA is chronic uveitis.

• Risk Factors : articular features, age at onset of the arthritis, duration of disease, and
presence of ANA.
• The identification of effective treatments for JIA-associated uveitis that are able to avoid or
minimize the eye damage associated with chronic steroid treatment and chronic inflammation
of the eyes is an important and unsolved
problem at this time.

Lovell DJ. Juvenile Idiopathic Arthritis A. Clinical Features. In : Primer on Rheumatic Disease 13th ed.
 Assessment Tools
for JIA

Haskes PJ, Laxer RM. Juvenile Idiopathic Arthritis A.

Treatment and Assessment. In : Primer on Rheumatic
Disease 13th ed.
 Measuring disease activity and improvement
The Juvenile Arthritis Disease Activity Score (JADAS-71, -
27 or -10) is used in clinical practice by simply adding the
points scored in four domains:
• Physician global (0–10),
• Patient or parent global (0–10),
• Active joint count (in 71, 27 or 10 joints, respectively)
• Normalized ESR.

Hinze C, et al. Management of juvenile idiopathic arthritis: hitting the target. Nat Rev Rheumatol. 2015
 Biomarkers and imaging
• Biomarkers can be broadly classified as:
• Biochemical (identified in serum, plasma or synovial fluid),
• immunological (such as cytokines),
• molecular (proteomics, transcriptomics or metabolomics) or genetic.
• Biomarkers can be used as markers for diagnosis, relapse or remission, response
to treatment or treatment withdrawal, or as surrogate markers.

Hinze C, et al. Management of juvenile idiopathic arthritis: hitting the target. Nat Rev Rheumatol. 2015
Hinze C, et al. Management of juvenile idiopathic arthritis: hitting the target. Nat Rev Rheumatol. 2015
MANAGEMENT
ALGORITHM THERAPY
 MANAGEMENT
ALGORITHM THERAPY

Beukelman T, Patkar NM, Saag KG, et al. 2011 American College of Rheumatology
Recommendations for the Treatment of Juvenile Idiopathic Arthritis: Initiation and
Safety Monitoring of Therapeutic Agents for the Treatment of Arthritis and Systemic
Features. Arthritis Care & Research Vol. 63, No. 4, April 2011, pp 465– 482
 MANAGEMENT
ALGORITHM THERAPY

Beukelman T, Patkar NM, Saag KG, et al. 2011 American College of Rheumatology
Recommendations for the Treatment of Juvenile Idiopathic Arthritis: Initiation and Safety
Monitoring of Therapeutic Agents for the Treatment of Arthritis and Systemic Features. Arthritis
Care & Research Vol. 63, No. 4, April 2011, pp 465– 482
 MANAGEMENT
ALGORITHM THERAPY

Beukelman T, Patkar NM, Saag KG, et al. 2011 American College of Rheumatology
Recommendations for the Treatment of Juvenile Idiopathic Arthritis: Initiation and Safety
Monitoring of Therapeutic Agents for the Treatment of Arthritis and Systemic Features.
Arthritis Care & Research Vol. 63, No. 4, April 2011, pp 465– 482
 MANAGEMENT
ALGORITHM THERAPY

Beukelman T, Patkar NM, Saag KG, et al. 2011 American College of Rheumatology
Recommendations for the Treatment of Juvenile Idiopathic Arthritis: Initiation and
Safety Monitoring of Therapeutic Agents for the Treatment of Arthritis and Systemic
Features. Arthritis Care & Research Vol. 63, No. 4, April 2011, pp 465– 482