Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease of childhood. It is not one disease but a group of diseases that share a defining feature — chronic inflammation of joints — and differ in which joints are involved, in their associated antibodies, in the eyes and other organs they affect, and in how aggressively they must be treated.
The word idiopathic is doing real work here: JIA is defined by the absence of an identifiable cause, so the diagnosis is made by recognising a pattern and excluding the alternatives, including infection and malignancy.
Definition
JIA is defined by three inclusion criteria:
- Arthritis beginning before the 16th birthday.
- Persisting for more than 6 weeks.
- Of unknown cause.
The six-week requirement separates JIA from the transient arthritides of childhood, most of which are post-infectious and settle on their own.
Classification: the seven ILAR categories
The (ILAR) classification divides JIA by the pattern of joint involvement and by associated features. The categories are the vocabulary of the disease, because prognosis and treatment follow the category rather than the diagnosis of JIA as a whole. Two of the features used are antibodies: rheumatoid factor (RF), the autoantibody of adult rheumatoid arthritis, and antinuclear antibodies (ANA), autoantibodies against components of the cell nucleus.
| Category | Defining feature |
|---|---|
| Systemic arthritis | Arthritis plus fever for at least 2 weeks, with at least one of rash, serositis (inflammation of the lining of the heart, lungs or abdomen), lymphadenopathy, hepatosplenomegaly |
| Oligoarthritis | Up to 4 joints affected in the first 6 months |
| Polyarthritis, rheumatoid-factor negative | 5 or more joints in the first 6 months, without rheumatoid factor |
| Polyarthritis, rheumatoid-factor positive | 5 or more joints in the first 6 months, with rheumatoid factor on two occasions at least 3 months apart |
| Enthesitis-related arthritis | Arthritis plus inflammation at tendon insertions, typically in older boys |
| Psoriatic arthritis | Arthritis with psoriasis, or with two of dactylitis (a swollen whole finger or toe), nail pitting and a family history of psoriasis |
| Undifferentiated arthritis | Fits no single category, or fits more than one |
In European and North American cohorts, oligoarthritis is the commonest category, accounting for roughly half of all cases; accounts for about 1 in 10 in these populations, and the proportions differ elsewhere.
Most of the categories are told apart by the number of joints involved, the age at which the arthritis begins and the antibodies that accompany it. Systemic arthritis is the exception: there the fever and the inflammation outside the joints dominate the picture, and the danger lies in the systemic illness rather than in the joint count.
Oligoarthritis
Oligoarthritis means inflammation of up to 4 joints. It is divided by what happens afterwards:
| Subtype | Definition |
|---|---|
| Persistent oligoarthritis | 4 or fewer joints throughout the course |
| Extended oligoarthritis | 4 or fewer joints in the first 6 months, then more than 4 |
The typical child is young — onset peaks around 1-2 years of age, younger than the polyarticular categories — and girls are affected more often than boys. Commonly affected joints are the knee, ankle and elbow; the child may present with a limp, or with a leg that looks longer because the inflamed knee is held in flexion.
Rheumatoid factor is negative, and inflammatory markers may be normal, but ANA are positive in roughly three-quarters of children with oligoarticular JIA. ANA positivity is not diagnostic of JIA — it occurs in healthy children too — but in this context it marks a higher risk of eye disease.
That eye disease is , inflammation of the iris and ciliary body at the front of the eye, and it is the complication that justifies the most attention. It produces no symptoms in most children in its early stages, so it is found by screening rather than by anything the child or the family reports, and it can be active while the joints are quiet.
Polyarthritis
Polyarthritis means 5 or more joints affected within the first 6 months. It is divided by rheumatoid factor status, and the two halves behave very differently.
Rheumatoid-factor-positive polyarthritis behaves like adult seropositive (rheumatoid-factor-positive) rheumatoid arthritis:
- Predominantly adolescent girls.
- Symmetric involvement of the small joints of the hands and feet, with morning stiffness.
- Early erosive disease — radiographic damage can develop quickly if treatment is delayed.
- ILAR requires rheumatoid factor to be positive on two occasions at least 3 months apart to make the diagnosis.
- This category has the worst articular prognosis of the JIA subtypes.
Rheumatoid-factor-negative polyarthritis is the most heterogeneous category, and at least three patterns are described within it:
- an early-onset asymmetric form with ANA positivity and a raised risk of uveitis;
- a school-age form resembling adult seronegative rheumatoid arthritis, with symmetric large- and small-joint synovitis and raised inflammatory markers;
- a form with relatively little visible swelling but marked stiffness, flexion contractures and a poor response to treatment.
Enthesitis-related arthritis and psoriatic arthritis
These two categories are defined less by how many joints are inflamed than by what accompanies the arthritis — inflammation at tendon insertions in one, psoriasis or its markers in the other — and both have links to the adult spondyloarthropathies, the inflammatory arthritides of the spine and sacroiliac joints that include ankylosing spondylitis.
affects mainly boys over 6 years of age and combines arthritis with enthesitis — inflammation at the point where tendon or ligament inserts into bone, most often the calcaneus (Achilles tendon and plantar fascia) and the tarsal bones. It is associated with HLA-B27, an inherited tissue-type marker, affects the lower limbs, and may progress to involve the sacroiliac joints and spine, producing a picture similar to ankylosing spondylitis.
Psoriatic arthritis is defined as arthritis with psoriasis, or, when there is no rash, arthritis with two of: a first-degree relative with psoriasis, dactylitis (a swollen “sausage” finger or toe extending beyond the joint), and nail pitting. Most children in this category have an early-onset asymmetric oligoarthritis with ANA positivity and a risk of uveitis; a smaller group resembles the adult spondyloarthropathies.
Prognosis
JIA is a chronic disease, and the aim of modern treatment is to prevent the damage that chronicity used to cause. In cohorts assembled before biologic therapy — drugs that block a specific immune signal — roughly half of children still had active disease 10 years after onset, and long-term functional disability was reported in a few percent to about 10% of patients.
Persistent activity, symmetric disease, early involvement of the wrist or hip, rheumatoid factor positivity, and early radiographic change all predict a worse articular outcome.
Systemic JIA follows a bimodal course: in roughly half of children the disease is monocyclic or intermittent and remits with treatment; in the other half it is unremitting and can cause substantial joint destruction. , an uncontrolled activation of the immune system, can occur at any time.
Beyond the joints, uveitis, growth disturbance, and the consequences of long-term corticosteroid exposure are the other threats to be monitored. Growth deserves specific attention. Both the disease and systemic corticosteroids impair growth, and the window of opportunity for catching up is limited, which is one reason that systemic steroids are used sparingly in children.
Of those threats, the eye is the one that gives no warning at all: it can be inflamed while the joints are quiet and the child feels well, and which children develop it depends on the category and the antibodies rather than on how the joints behave.