Juvenile idiopathic arthritis (JIA) is arthritis that begins before the 16th birthday, persists for more than 6 weeks and has no identifiable cause. It is a group of categories rather than a single disease: some affect up to 4 joints (oligoarthritis), some 5 or more (polyarthritis), and in fever and inflammation outside the joints dominate.
Treatment is built on a single organising idea: joint damage that is allowed to accumulate cannot be undone, so the aim is to suppress the inflammation completely and to do it early. What the treatment looks like in an individual child then depends on which category of JIA they have and on how much of the joint disease is active, because a single inflamed knee in a toddler positive for antinuclear antibodies (ANA) and a fever-driven systemic illness are managed with different drugs.
Treat-to-target
The approach to treatment changed fundamentally with the arrival of biologic drugs — engineered proteins that block a single immune signal. The older pyramid approach — non-steroidal anti-inflammatory drugs (NSAIDs) first, then immunosuppressants, with biologics reserved for refractory disease — allowed damage to accumulate while treatment escalated slowly, and it failed many patients. The current strategy is the reverse:
- Start effective treatment early, before erosions (bone damage at the joint margins) develop.
- Set a target of inactive disease and minimal long-term damage.
- Withdraw medication sequentially once the target is reached, rather than continuing indefinitely.
- Review the target at fixed intervals and escalate if it has not been met.
The building blocks
The strategy uses five kinds of treatment. They differ in whether they only relieve symptoms or change the course of the disease: a (DMARD) suppresses the underlying inflammation rather than just its symptoms.
| Modality | Role |
|---|---|
| NSAIDs | Symptomatic control; they do not modify the disease in JIA |
| Intra-articular corticosteroids (triamcinolone hexacetonide) | First-line for oligoarticular disease, and a bridge in polyarticular disease while a DMARD takes effect |
| Methotrexate | The first conventional DMARD, given weekly by mouth or by injection |
| Biologic agents | Tumour necrosis factor (TNF) inhibitors (etanercept, adalimumab, infliximab), the interleukin-1 (IL-1) inhibitor anakinra, the interleukin-6 (IL-6) inhibitor tocilizumab, and the T-cell costimulation blocker abatacept |
| Systemic corticosteroids | Reserved largely for systemic JIA with uncontrolled systemic features, where they are used at the lowest effective dose and for the shortest possible time |
The choice of intra-articular rather than systemic steroid in non-systemic JIA is deliberate: a joint injection controls local inflammation in the joint that is driving contracture and leg-length discrepancy, without exposing the child to growth suppression and the other systemic effects of corticosteroids.
Local adverse effects of intra-articular injection are uncommon; subcutaneous atrophy is the most frequent, and rare complications include periarticular calcification, crystal-induced synovitis, avascular necrosis of the bone, transient cushingoid features (the appearance produced by excess corticosteroid), septic arthritis and anaphylaxis. In the joints that matter for growth and gait, the balance is usually in favour of injecting.
Methotrexate
Methotrexate is the workhorse of JIA treatment, and using it well depends on a few practical points:
- A folate analogue (a drug that resembles folic acid and interferes with its use), given once weekly, orally or parenterally, with folic or folinic acid about 24 hours later to reduce adverse effects.
- Nausea and vomiting are the commonest adverse effects and a frequent reason for stopping treatment; they can often be reduced by switching to the subcutaneous route or by antiemetic strategies.
- Raised liver enzymes occur and are usually mild and reversible; monitoring is by periodic blood tests, and the drug is usually withheld during an acute bacterial infection until antibiotics have finished.
- Immunisation should be kept up to date, including influenza and pneumococcal vaccines; live vaccines are generally avoided while on higher-dose immunosuppression, though the evidence on live boosters during methotrexate use suggests they are safe.
A sequential approach
The building blocks are combined in a sequence that depends on the same features that define the categories: how many joints are involved, and whether systemic features are active. The exact agents and thresholds differ between guidelines, but the shape of a common European algorithm is as follows.
Arthritis in 4 or fewer joints
- Low disease activity: NSAID alone.
- Moderate or high disease activity: intra-articular corticosteroid injection, with or without methotrexate.
- Disease still active after about 3 months of methotrexate, or poor prognostic features: a TNF inhibitor.
Arthritis in 5 or more joints
- Methotrexate, usually with a bridge of NSAID or intra-articular injection.
- Disease still active after about 3 months of methotrexate: a TNF inhibitor.
- Disease still active after about 4 months of a TNF inhibitor: a second TNF inhibitor or abatacept.
Systemic JIA with active systemic features
- Low fever activity: NSAID.
- Higher activity, or fever persisting after 2 weeks of an NSAID: systemic corticosteroid, with or without an NSAID.
- Fever persisting despite corticosteroid: anakinra (an IL-1 inhibitor), with or without corticosteroid.
Systemic JIA with active arthritis but no systemic features
- NSAID with intra-articular injection as needed, reviewed at about 1 month.
- Persistent disease: methotrexate.
- Persistent disease after about 3 months of methotrexate: a TNF inhibitor or anakinra.
- Persistent disease after about 4 months of a TNF inhibitor: abatacept.
The American College of Rheumatology (ACR)/Arthritis Foundation guidelines agree on the general sequence — methotrexate is preferred over other conventional DMARDs when NSAIDs and injections are insufficient, a TNF inhibitor is the usual next step in non-systemic disease, and IL-1 or IL-6 blockade is favoured in systemic JIA — while differing in some details and in the recommended timing.
Measuring the target
Most steps in that sequence are triggered by disease that is still active, so treat-to-target only works if the target is measured. Children on these drugs need regular assessment of joint counts and inflammatory markers, blood tests for drug toxicity, growth and blood pressure checks, and ophthalmological screening. A child whose joints are quiet but whose eye is inflamed, or whose growth is falling away from the curve, is not at target even when the joint count looks reassuring.
Every one of these decisions begins with knowing which disease, and which category of it, is in front of you. The three diseases in this family are hardest to tell apart precisely when the child is febrile and the presentation is at its least specific.