What is juvenile idiopathic arthritis?
Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease of childhood. Its shared defining feature is chronic inflammation of joints, and no identifiable cause is found for it.
The tissue that stays inflamed is the synovium. In rheumatoid arthritis, when the lining stays inflamed, it thickens and can grow across the cartilage and bone at the edges of the joint, eroding them. The erosion does not heal back. If untreated, JIA may cause irreversible joint damage.
Three things define the disease:
- the arthritis begins before the 16th birthday;
- it persists for more than 6 weeks;
- its cause is unknown.
A child’s joint can swell for many reasons, so how is this one told apart?
How is it told apart from arthritis that clears?
The diagnosis is made by recognising a pattern and excluding the alternatives, including infection and malignancy. The 6-week requirement does the first sorting. Most transient arthritides of childhood are post-infectious and settle on their own. Arthritis of that kind is often set off by a viral infection. Arthritis still present after 6 weeks is no longer behaving like the transient kind, and that separates JIA from it.
Once the arthritis has lasted past 6 weeks, the next question is which kind of JIA it is.
Why are there several kinds, and how are they sorted?
JIA is a group of diseases, not one disease. The categories differ in the joints involved, the associated antibodies, the eyes and other organs affected, and how aggressive the treatment needs to be.
The ILAR classification divides JIA by pattern of joint involvement and associated features. It has seven categories, and they 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) and antinuclear antibodies (ANA).
The seven categories are:
- oligoarthritis, either persistent or extended;
- polyarthritis, RF negative;
- polyarthritis, RF positive;
- enthesitis-related arthritis;
- psoriatic arthritis;
- systemic arthritis;
- undifferentiated arthritis, for a child who fits no single category or fits more than one.
Most categories are told apart by the number of joints involved, the age at onset and the accompanying antibodies. The kind with the fewest joints comes first.
What is the few-joint kind?
Oligoarthritis means inflammation of up to 4 joints in the first 6 months. In European and North American cohorts it is the commonest category, roughly half of all cases. It is divided by what happens afterwards. In persistent oligoarthritis, 4 or fewer joints are affected throughout the course. In extended oligoarthritis, 4 or fewer joints are affected in the first 6 months and more than 4 afterwards.
The typical child is young, with onset peaking around 1-2 years of age. That is younger than the polyarticular categories. Girls are affected more often than boys. The commonly affected joints are the knee, ankle and elbow.
The child may present with a limp. Or the child may present with a leg that looks longer, because the inflamed knee is held in flexion.
Rheumatoid factor is negative, and inflammatory markers may be normal. ANA are positive in roughly three-quarters of children with oligoarticular JIA. This does not diagnose JIA, because ANA positivity occurs in healthy children too. What it does is mark a higher risk of eye disease. ANA positivity travels with that risk; it is an association, and it does not show that the antibody causes the eye inflammation. The eye disease is chronic anterior uveitis, and we return to it at the end.
When more joints are involved, the categories are split by RF.
Many joints: RF negative and RF positive
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. The RF-negative half is the messy one. The RF-positive half looks like adult rheumatoid arthritis.
RF-negative polyarthritis has 5 or more joints in the first 6 months, without rheumatoid factor. It is the most heterogeneous category. At least three patterns are described:
- 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. A child avoids moving a painful joint, and the avoidance tightens the tendons and can leave the joint held bent.
RF-positive polyarthritis has 5 or more joints in the first 6 months, with rheumatoid factor on two occasions at least 3 months apart. ILAR requires both positive results to make the diagnosis. RF is the autoantibody of adult rheumatoid arthritis, and this category behaves like adult seropositive rheumatoid arthritis. RF-positive JIA is thought to be genetically closer to the adult disease than the other categories are. The children are predominantly adolescent girls. Involvement is symmetric in the small joints of the hands and feet, with morning stiffness. The disease is erosive early, and radiographic damage can develop quickly if treatment is delayed. This category has the worst articular prognosis of the JIA subtypes.
Some children are named not by how many joints are inflamed but by what comes with the joints.
Arthritis defined by what comes with it
Enthesitis-related arthritis and psoriatic arthritis are defined less by the number of joints inflamed than by what accompanies the arthritis. Enthesitis-related arthritis is defined by inflammation at tendon insertions; psoriatic arthritis by psoriasis or its markers. Both have links to adult spondyloarthropathies.
Enthesitis-related arthritis affects mainly boys over 6 years of age, and it combines arthritis with enthesitis. The enthesitis is most often at the calcaneus, in the Achilles tendon and plantar fascia, and at the tarsal bones. The arthritis affects the lower limbs. The category is associated with HLA-B27. It may progress to involve the sacroiliac joints and spine, producing a picture similar to ankylosing spondylitis.
Psoriatic arthritis is defined as arthritis with psoriasis. Without the rash, it is arthritis with two of these: a first-degree relative with psoriasis, dactylitis, and nail pitting. Dactylitis shows as a swollen “sausage” finger or toe, with the swelling extending beyond the joint. Most children with psoriatic arthritis have an early-onset asymmetric oligoarthritis with ANA positivity and a risk of uveitis. A smaller group resembles adult spondyloarthropathies.
In one category the joints are not the main picture.
When the whole body is involved
Systemic arthritis is arthritis plus fever for at least 2 weeks, together with at least one of rash, serositis, lymphadenopathy and hepatosplenomegaly. In European and North American cohorts systemic JIA accounts for about 1 in 10 cases. The proportions differ elsewhere.
Systemic arthritis is the exception to the rule that categories are told apart by joint count, age and antibodies. Fever and inflammation outside the joints dominate the picture. The danger lies in the systemic illness rather than in the joint count.
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. Macrophage activation syndrome can occur at any time in systemic JIA.
The systemic kind shows that the joints are not the whole story, which raises the question of what a chronic disease costs.
What does a chronic disease cost?
JIA is chronic, and the aim of modern treatment is to prevent the damage that chronicity used to cause. In cohorts assembled before biologic therapy, roughly half of children still had active disease 10 years after onset. Long-term functional disability is reported in a few percent to about 10% of patients.
Some features predict a worse articular outcome:
- persistent activity;
- symmetric disease;
- early involvement of the wrist or hip;
- rheumatoid factor positivity;
- early radiographic change.
But the damage is not only in the joints.
What else is at risk beyond the joints?
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. Chronic inflammation and long-term corticosteroid use each add to growth disorders. The window of opportunity for catching up is limited. This is one reason systemic steroids are used sparingly in children.
Of these threats, the eye is the one that gives no warning.
The eye that gives no warning
The eye disease is chronic anterior uveitis. It is the complication that justifies the most attention. In most children it produces no symptoms in its early stages. The front of the eye can be inflamed without pain, so the child and family have nothing to report. It is found by screening rather than by anything they notice. The uveitis can be active while the joints are quiet, and the child feels well.
Which children develop uveitis depends on the category and the antibodies rather than on how the joints behave. So which children need their eyes looked at most often, and how is the inflammation found?