JIA

• Juvenile idiopathic arthritis (JIA), a heterogeneous group of chronic

arthritis, is the most common chronic rheumatological condition in
children. There are 7 different JIA subtypes with distinct phenotypes,
genetic predispositions, pathophysiology, laboratory findings, disease
course, and prognosis.
• Juvenile idiopathic arthritis (JIA) is a heterogeneous group of
idiopathic inflammatory arthritis affecting children younger than 16
and lasting 6 weeks or longer.
 there are 7 JIA categories:
• a) oligoarthritis-- 50% to 60%
• b) rheumatoid factor (RF) positive polyarthritis-- 2% to 7%
• c) RF negative polyarthritis-- 11% to 28%
• d) systemic arthritis-- 10% to 20%
• e) psoriatic arthritis-- 2% to 15%
• f) enthesitis-related arthritis-- 1% to 7%
• g) undifferentiated arthritis
• These subtypes have distinct phenotypes, genetic predispositions,
pathophysiology, laboratory findings, disease course, and prognosis.
Although chronic arthritis is mandatory for all subtypes, the
extraarticular and the systemic manifestations characterized every
specific subtype.
• Etiology
• The cause and trigger of chronic arthritis in JIA remain unclear.
Abnormal immune responses triggered by the interactions between
environmental factors in a genetically susceptible individual are
speculative. Some environmental factors such as antibiotic exposure
and C-section deliveries are potential risks; however, breastfeeding and
household siblings are possible protectives.
• Based on familial aggregation studies and the concordance rate of
25% to 40% in monozygotic twins, genetic factors play a significant
role. Specific HLA alleles and non-HLA genes may be vulnerable to
particular JIA subtypes and uveitis.
• The JIA has the general pattern of inflammatory joint disease
(synovitis, joint effusion, soft tissue swelling, osteopenia, bone
edema, and erosions) with some additional elements related to
developmental age, such as epiphyseal growth disturbances,
premature physeal fusion, and limb length inequality.
Ix
• A diagnosis of JIA is considered in any children younger than 16 years
with arthritis for at least six weeks and exclusion of other causes of
chronic arthritis.
• There is no specific test for diagnosis and predicting disease activity in JIA.
• Laboratory
• Initial laboratory tests should include complete blood count, erythrocyte
sendimentation rate, C-reactive protein, antinuclear antibody, rheumatoid
factor (RF), anti-cyclic citrullinated peptide antibodies (anti-CCP), and HLA-
B27. The typical inflammatory markers are common, especially
in oligoarthritis. A positive RF or anti-CCP provides little value for the
diagnosis but may indicate a poorer disease course and outcome. Ferritin,
fibrinogen, AST, triglyceride are recommended when there is a concern of
macrophage activation syndrome (MAS). Other tests for excluding other
diseases may be considerations depending on the differential diagnosis.
Imaging
• Radiography remains initial imaging used for symptomatic joints;
however, the radiographic changes are undetectable in an early stage
of JIA. The indirect signs of arthritis in radiography are soft tissue
swelling, increased density of soft tissue as well as dislocation of fat
folds.
• Other features are periarticular osteoporosis, joint space narrowing,
bone erosion and deformity, and joint subluxation or ankyloses in an
advanced stage.
• Ultrasound (US) - allows the comparison with the contralateral side
and the dynamic evaluation of joints. The US is capable of assessing
synovial thickening, joint effusion, tenosynovitis, enthesitis, and
bone erosions. US evaluation of the synovial thickening and the
synovitis is particularly important for the diagnosis. They appear as
abnormally hypoechoic tissue associated with joint lines or
surrounding tendons. In addition to detecting synovitis, the US
accurately guides for intra-articular corticosteroid injections.
Ultrasound allows evaluation without sedating the patient.
• Magnetic resonance imaging (MRI) is the modality gold standard for
the study of JIA. All joints affected by pathological inflammatory
phenomena can be easily examined in all possible plans and with an
excellent contrast resolution of bone and soft tissues. It is the most
sensitive imaging technique detecting synovitis. The standard MR
imaging protocol needs to include: T1 spin-echo (SE) sequence, fat-
suppressed sequence (classic T2 fat-sat; short tau inversion recovery,
STIR; DIXON fat-suppression sequence); T1 fat-suppressed sequence
precontrast and postcontrast. MRI is the only modality able to
objective bone marrow edema and the most sensitive to detect bone
erosions.
• Clinical-Laboratory Classification
• The clinical manifestations and the test results of RF and HLA-B27 will
be used to categorized JIA subtypes based upon the ILAR
classification.
• Oligoarthritis is defined as chronic arthritis affecting four joints or
less during the first six months of disease. Persistent oligoarthritis is
defined as the affected joints being 4 or less after the first 6 months,
and extended oligoarthritis is defined as more than four affected
joints after the first 6 months.
• RF negative polyarthritis is defined as arthritis affecting 5 joints or
more during the first 6 months of disease with a negative
immunoglobulin (Ig)M RF.
• RF positive polyarthritis is arthritis affecting 5 joints or more during the
first 6 months of disease with a positive IgM RF on at least 2 tests three
months apart.
• Systemic arthritis is arthritis with or preceded by a fever of at least a 2-
week duration and accompanied by at least 1 of the following:
evanescent erythematous rash, generalized lymph node enlargement,
hepatomegaly, and/or splenomegaly, or serositis (pericarditis and/or
pleuritis and/or peritonitis).
• Psoriatic arthritis is defined as chronic arthritis with psoriasis or
chronic arthritis with at least 2 of the following: dactylitis, nail pitting,
onycholysis, or psoriasis in a first-degree relative.
• Enthesitis related arthritis (ERA) is defined as arthritis with enthesitis,
or arthritis or enthesitis with at least 2 of SI joint tenderness and/or
inflammatory lumbosacral pain, a positive HLA-B27, the onset of
arthritis in a boy older than 6, acute anterior uveitis, history of
ankylosing spondylitis, ERA, sacroiliitis with inflammatory bowel
disease, reactive arthritis or acute anterior uveitis in a first-degree
relative. Undifferentiated arthritis is defined as chronic arthritis, which
does not fulfill criteria in any subtype or fulfills two or more subtypes.
• Treatment / Management
• Treatment of JIA requires anti-inflammatory and immunomodulatory drugs
and physical therapy, and eventually, surgery, nutritional support, and
psychosocial support may be needed. The choice of pharmacological
treatment depends on the disease subtypes, disease severity and damage,
associated disease, and family acceptance. Nonsteroidal anti-inflammatory
drugs (NSAIDs) are the mainstay of initial symptomatic treatment for all
subtypes. The NSAID use in JIA has decreased over time with modern
aggressive treatment, including methotrexate and biologics. Physical therapy
emphasizes range of motion with minimal stress on joints. Swimming is
often a good option. Patients should participate in moderate fitness,
flexibility, and strengthening exercises.
Medical management
• Infection surveillance (Table 6) Tuberculosis (TB) TB screening is conditionally
recommended prior to starting biologic disease-modifying antirheumatic drug
(DMARD) therapy and when there is a concern for TB exposure thereafter.
Concern for TB exposure should be interpreted broadly and could include contact
with someone with active TB, travel to locations where TB is endemic, contact
with high-risk individuals (e.g., prisoners, visitors from TB-endemic areas), or living
in communities with a higher frequency of TB . The conditional recommendation
reflects 2 major concerns: In certain urgent clinical situations, the harms of waiting
for results of TB screening may outweigh the benefits of treatment. For example,
in a child with active systemic JIA and macrophage activation syndrome (MAS),
treatment should not be delayed pending TB screening results. Annual screening
for TB can pose problems for children and families. Insurers or institutions may
require a specific method that is potentially problematic (44,45).
• For example, TB screening may be done by questionnaire; however,
this depends on knowledge of exposure. The interferon-γ release
assay is expensive, not valid in young children, and subject to
frequent indeterminate results, particularly during anergy. Tuberculin
skin testing is user dependent and inconvenient because 2 visits are
required. In addition, false-positive results often lead to unnecessary
chest radiography and isoniazid treatment. For children living in areas
with a low prevalence of TB, mandatory annual laboratory-based TB
screening represents a high burden of cost, inconvenience, and pain
that is not supported by the literature reviewed
• Viral infections Voting panelists could not reach consensus on
whether all children with JIA should have antibody titers for specific
infections (e.g., measles, varicella, hepatitis B, hepatitis C) checked
prior to starting immunosuppressive medication, although more
panelists were against this practice than for it. Some panelists
believed the information might be useful for risk management in case
of an outbreak or exposure. Most believed that screening a fully
immunized child was of low benefit and might delay treatment and
incur unnecessary cost. Although
• screening for hepatitis B and C is done in adults prior to treatment
with DMARDs, most children are effectively immunized against
hepatitis B as infants (46), and the number of children below the age
of 19 years with hepatitis C in the US remains exceedingly low (47).
• Differential Diagnosis
• The differential diagnosis of chronic arthritis is broad, depending on the
clinical presentation and the JIA subtypes. Since JIA is a diagnosis of
exclusion, any patients with a positive review of the system should be
considered for possible diseases. The following differential diagnosis should
be considered:
• A) Oligoarthritis need to exclude post-streptococcal reactive arthritis, Lyme
arthritis, acute rheumatic fever, reactive arthritis, toxic synovitis, septic
arthritis, pyomyositis, steroid-induced osteonecrosis, sickle cell disease,
hemophilia, scurvy, osteomyelitis, chronic nonbacterial osteomyelitis (CNO),
sports injury, non-accidental injury, pigmented villonodular synovitis,
osteoid osteoma, bone tumors, neuroblastoma, leukemia, and lymphoma.
• B) Polyarthritis need to exclude post-streptococcal reactive arthritis, Lyme
arthritis, acute rheumatic fever, reactive arthritis, scurvy, CNO
or chronic recurrent multifocal osteomyelitis, non-accidental
injury, systemic lupus erythematosus (SLE), Mixed connective
tissue disease, Sjögren syndrome, scleroderma, sarcoidosis,
Blau syndrome, arthritis associated with inflammatory bowel
diseases, Farber disease, benign hypermobility joint syndrome
and amplified musculoskeletal pain syndrome
• C) Systemic arthritis need to exclude infections (mycoplasma, cat scratch disease,
bacterial endocarditis, Lyme disease), acute rheumatic fever, syndrome of periodic
fever, aphthous stomatitis, pharyngitis and cervical adenitis (PFAPA syndrome),
autoinflammatory syndromes, systemic vasculitis (polyarteritis nodosa, Kawasaki
disease), inflammatory bowel disease, malignancy (leukemia, lymphoma,
neuroblastoma), Castleman disease
• D) Enthesitis-related arthritis. Apophysitis (especially Osgood-Schlatter, Sever disease),
inflammatory bowel diseases, chronic recurrent multifocal osteomyelitis, amplified
musculoskeletal pain syndrome.
• Arthralgias are common early in the course of sJIA, but arthritis is not always prominent. Any
number of joints may be involved when arthritis becomes apparent. Disease in the wrists,
knees, and ankles is most typical. Hands, hips, cervical spine, and temporomandibular joints
are also sometimes affected, unlike the oligoarticular and polyarticular subtypes of JIA
Arthralgias are common early in the course of sJIA, but arthritis is not always prominent. Any
number of joints may be involved when arthritis becomes apparent. Disease in the wrists,
knees, and ankles is most typical, but the hands, hips, cervical spine, and temporomandibular
joints are also sometimes affected. Unlike the oligoarticular and polyarticular subtypes of JIA.
Musculoskeletal complaints in children with joint pain are common in general practice and
increase significantly after ten years of age in general practice.[23] The most common
presentation of musculoskeletal complaints is joint pain and soft tissue pain (65%), and the
most common cause of all ages of children is trauma (45%).
• Prognosis
• The prognosis of JIA has changed dramatically in recent years thanks to the
availability of novel drugs, which can inhibit the biological mechanisms responsible
for persistent inflammation selectively. Prompt and accurate diagnosis and
treatment are essential to prevent permanent joint damage and preserve joint
functionality. Some studies support the possibility of the existence of a “window of
opportunity” in early disease, during which prompt treatment induces higher rates
of remission and improves long-term outcomes.
• A recent study on 168 patients showed the remission off medication in 48.8% of
cases, the remission on medication (or minimal disease activity) in 49.9% of cases,
and only 1.3% of subjects were no-responders. No association was found between
the state and duration of remission and age of patients, clinical features, disease
course, or laboratory findings.
• Complications
• The most common complications of JIA are leg-length discrepancy
and joint contracture. An extremely fearsome complication is
macrophage activation syndrome, due to the uncontrolled activation
and proliferation of T lymphocytes and macrophages. The frequency
of this syndrome in patients with JIA is unknown, but some studies
report that it occurs in up to 10% of cases.
• Other important complications are growth retardation, low bone
mineral density for chronologic age, severe hip involvement with the
need oh hip prosthesis, and amyloidosis.