Juvenile Idiopathic Arthritis (JIA)
The term juvenile idiopathic arthritis (JIA) has been proposed as a replacement for both Juvenile Rheumatoid Arthritis (JRA) and Juvenile Chronic Arthritis (JCA).
Juvenile Idiopathic Arthritis (JIA) is the name applied to a group of disorders characterized by chronic arthritis of one or more joints of unknown cause with a duration of at least 6 weeks and age at onset <16 years.
The International League of Associations of Rheumatologists (ILAR) has proposed and revised criteria for the diagnosis and classification of juvenile arthritis. The ILAR classification of JIA includes Systemic JIA, Oligoarthritis (Persistent or extended), Polyarthritis – RF negative, Polyarthritis – RF positive, Psoriatic arthritis, Enthesitis related arthritis, and undifferentiated arthritis.
Systemic JIA – Arthritis in ≥1 joint with, or preceded by, fever of at least 2 weeks in duration that is documented to be daily (quotidian ) for at least 3 days and accompanied by ≥1 of the following:
Evanescent (non-fixed) erythematous rash
Generalized lymph node enlargement
Hepatomegaly or splenomegaly or both
Oligoarthritis – Arthritis affecting 1-4 joints during 1st 6 months of disease; two subcategories are recognized:
Persistent oligoarthritis—affecting ≤4 joints throughout the disease course
Extended oligoarthritis—affecting >4 joints after 1st 6 months of disease
Polyarthritis – RF negative – Arthritis affecting ≥5 joints during 1st 6 months of disease; a test for RF is negative
Polyarthritis – RF positive – Arthritis affecting ≥5 joints during 1st 6 months of disease; ≥2 tests for RF at least 3 months apart during 1st 6 months of the disease are positive
Psoriatic arthritis – Arthritis and psoriasis, or arthritis and at least 2 of the following:
Nail pitting and onycholysis
Psoriasis in the first-degree relative
Enthesitis related arthritis – Arthritis and enthesitis, or arthritis or enthesitis with at least 2 of the following:
Presence of or history of sacroiliac joint tenderness or inflammatory lumbosacral pain, or both
Presence of HLA-B27 antigen
The onset of arthritis in a male >6 years old
Acute (symptomatic) anterior uveitis
History of ankylosing spondylitis, enthesitis-related arthritis, sacroiliitis with IBD, Reiter syndrome, or acute anterior uveitis in the first-degree relative
Undifferentiated arthritis – Arthritis that fulfills criteria in no category or ≥2 of the above categories
The cause(s) of juvenile arthritis is not known, but several factors relating to etiology have been reported.
The etiology and pathogenesis of JIA are not completely understood, although both immunogenetic susceptibility and an external trigger are considered necessary.
Genetic factors – Major histocompatibility complex class I and class II region, and Non-HLA candidate loci, including polymorphisms in the genes encoding protein tyrosine phosphatase non-receptor 22 (PTPN22), tumor necrosis factor (TNF)-α, macrophage inhibitory factor, interleukin (IL)-6 and its receptor, and IL-1α.
Nongenetic triggers – Bacterial and viral infections, enhanced immune responses to bacterial or mycobacterial heat shock proteins, abnormal reproductive hormone levels, and joint trauma.
Arthritis must be present for ≥6 weeks to make a diagnosis of any JIA subtype.
Initial symptoms may be subtle or acute and often include morning stiffness with a limp or gelling after inactivity.
Easy fatigability and poor sleep quality may be present.
Involved joints are often swollen, warm to touch, and uncomfortable on movement or palpation with reduced ROM, but usually are not erythematous.
Arthritis in large joints, especially knees, initially accelerates linear growth and causes the affected limb to be longer, resulting in a discrepancy in limb lengths.
Continued inflammation stimulates rapid and premature closure of the growth plate, resulting in shortened bones.
The peak age at the onset – 1-5 years
Female to Male ratio – 1:1
Percentage of all JIA cases – 5 -15%
Arthritis pattern – Polyarticular, often affecting knees, wrists, and ankle; also fingers, neck, and hips
Extra-articular features – Daily fever; evanescent rash; pericarditis; Pleuritis
The peak age at the onset – 2-4 years
Female to Male ratio – 3:1
Percentage of all JIA cases – 40-50%
Arthritis pattern – Knee ++, Ankle, finger +
Extra-articular features – Uveitis in 30%of cases
Poly arthritis – RF negative:
The peak age at the onset – 2-4 and 10-14 years
Female to Male ratio – 3:1 and 1:1
Percentage of all JIA cases – 20-35%
Arthritis pattern – Symmetric or asymmetric; small and large joint; cervical spine; temporomandibular joint
Extra-articular features – Uveitis in 10%
Poly arthritis – RF positive:
The peak age at the onset – 9-12 years
Female to Male ratio – 9:1
Percentage of all JIA cases – <10%
Arthritis pattern – Aggressive symmetric polyarthritis
Extra-articular features – rheumatoid nodules in 10%; low-grade fever
The peak age at the onset – 2-4 and 9-11 years
Female to Male ratio – 2:1
Percentage of all JIA cases – 5-10%
Arthritis pattern – Asymmetric arthritis of small or medium-sized joints
Extra-articular features – Uveitis in 10%, psoriasis in 50%
Enthesitis related arthritis:
The peak age at the onset – 9-12 years
Female to Male ratio – 1:7
Percentage of all JIA cases – 5-10%
Arthritis pattern – Predominantly lower limb joints affected; sometimes axial skeleton (but less than in adult, ankylosing spondylitis)
Extra-articular features –Acute anterior uveitis; association with reactive arthritis and inflammatory bowel disease
JIA is a clinical diagnosis without any diagnostic laboratory tests.
The meticulous clinical exclusion of other diseases and many mimics is therefore essential.
Laboratory studies, including tests for ANA and RF, are only supportive or prognostic, and their results may be normal in patients with JIA.
Hematologic abnormalities often reflect the degree of systemic or articular inflammation, with elevated white blood cell (WBC), platelet counts, and microcytic anemia. Inflammation may also cause elevations in ESR and C-reactive protein, although it is not unusual for both to be normal.
Elevated ANA titers are present in 40–85% of children with oligoarticular or polyarticular JIA, but are rare with sJIA. ANA seropositivity is associated with an increased risk of chronic uveitis in JIA. Approximately 5–15% of patients with polyarticular JIA are seropositive for RF. Anti–cyclic citrullinated peptide antibody, as with RF, is a marker of more aggressive disease.
Early radiographic changes of arthritis include soft tissue swelling, periarticular osteopenia, and periosteal new-bone apposition around affected joints. Continued active disease may lead to subchondral erosions, loss of cartilage, with varying degrees of bony destruction, and fusion.
Characteristic radiographic changes in the cervical spine, most frequently in the neural arch joints at C2-C3, may progress to atlantoaxial subluxation. MRI is more sensitive than radiography to detect early changes.
The goals of treatment are to achieve disease remission, prevent or halt joint damage, and foster normal growth and development.
All children with JIA need individualized treatment plans, and management is tailored according to disease subtype and severity, presence of poor prognostic indicators, and response to medications.
Non-steroidal anti-inflammatory drugs – Naproxen (15mg/kg/day), Ibuprofen (40mg/kg/day) – Polyarthritis, systemic and Oligoarthritis
Disease-modifying antirheumatic drugs – Methotrexate (0.5-1 mg/kg/week) – Polyarthritis, systemic, persistent or extended oligoarthritis; Sulfasalazine (12.5mg/kg/day to 40-50mg/kg/day) and Leflunomide (10-20 mg/day) – Polyarthritis
Biologic agents – Anti-tumor necrosis factor-alpha (Etanercept, infliximab, adalimumab), Anti Cytotoxic T-lymphocyte-associated antigen-4 immunoglobulin (Abatacept), Anti CD 20 (Rituximab), Interleukin-1 inhibitors (Anakinra, Canakinumab, Rilonacept), Interleukin-6 receptor antagonist (Tocilizumab) – Polyarthritis and Systemic JIA
The course of JIA in an individual child is unpredictable.
Children with persistent oligoarticular disease farewell, with a majority achieving disease remission. Those with the extended oligoarticular disease have a poorer prognosis.
Children with oligoarthritis, particularly girls who are ANA positive and with the onset of arthritis before 6 years of age are at greatest risk for the development of chronic uveitis. There is no association between the activity or severity of arthritis and uveitis. Persistent, uncontrolled anterior uveitis can cause posterior synechiae, cataracts, glaucoma, and band keratopathy, with resultant blindness.
Predictors of severe and persistent polyarticular JIA include young age at onset, RF seropositivity or rheumatoid nodules, presence of anti-cyclic citrullinated peptide antibodies, and many affected joints. Disease involving the hip and hand/wrist is also associated with a poorer prognosis and may lead to significant functional impairment.
In systemic JIA, the poorer prognosis is related to the polyarticular distribution of arthritis, fever lasting >3 months, and increased inflammatory markers, such as platelet count and ESR, for >6 mo. IL-1 and IL-6 inhibitors have changed the management and improved the outcomes for children with severe and prolonged systemic disease.
Orthopedic complications include leg length discrepancy and flexion contractures, particularly of the knees, hips, and wrists.
Psychosocial adaptation may be affected by JIA. Disability not directly associated with arthritis may continue into young adulthood in as many as 20% of patients, together with continuing chronic pain syndromes at a similar frequency. Psychological complications include problems with school attendance and socialization.