Juvenile idiopathic arthritis and paediatric rheumatology

• Juvenile idiopathic arthritis (JIA) is chronic arthritis that starts before 16 years of age, lasts at least 6 weeks, and remains unexplained after other causes of joint inflammation have been excluded.
• It is the commonest childhood-onset inflammatory rheumatic disease in most series, with seven International League of Associations for Rheumatology (ILAR) categories that must not be mixed up with the adult rheumatoid arthritis labels they resemble.
• The disease is controlled, not cured: paediatric rheumatologists now use NSAIDs, intra-articular and short bridging glucocorticoids, methotrexate, and biologic cytokine inhibitors to reach low or inactive disease activity.
• The stakes are high even when the arthritis looks mild: silent chronic anterior uveitis can damage the eye in 25 to 50% of affected children, and systemic JIA can be complicated by macrophage activation syndrome (MAS), a cytokine storm that can be fatal within days.
• Treat-to-target follow-up, especially ophthalmology screening, is as important as drug choice.

By the end of this page you should be able to:

1. Define JIA and list the seven ILAR categories, giving the one clinical feature that separates each.
2. Stratify a child with JIA for uveitis risk and state the recommended ophthalmology screening interval.
3. Recognise systemic JIA and macrophage activation syndrome, and explain why they are emergencies.
4. Outline the initial and next-step treatment of oligoarthritis, polyarthritis, sacroiliitis or enthesitis, systemic JIA, and JIA-associated uveitis, including the drugs that are preferred and avoided.
5. Interpret the juvenile disease activity score used in the guidelines and explain why intra-articular triamcinolone hexacetonide, subcutaneous methotrexate, and cytokine inhibitors are favoured.
6. Avoid the common errors: NSAIDs or conventional DMARDs as sole treatment for systemic JIA, chronic oral glucocorticoids, and assuming that joint and eye inflammation track together.

The definition is deliberately broad: “idiopathic” means no single cause has been identified, not that the disease is trivial. The label reminds you that JIA in a 4-year-old with an antinuclear antibody (ANA) and quiet oligoarthritis behaves very differently from RF-positive polyarthritis in an adolescent, even though both are called JIA.

The International League of Associations for Rheumatology (ILAR) classifies JIA into seven mutually exclusive categories based on the number of joints involved, extra-articular features, and laboratory markers such as rheumatoid factor (RF) and HLA-B27. ^[1] The terms matter because guidelines and drug licensing group patients by clinical phenotype rather than by every word of the classification, and because a child rarely sits neatly in one box forever.

Two practical cautions follow from the classification. First, RF-positive polyarthritis is the category that most resembles adult rheumatoid arthritis and may persist; RF-negative polyarthritis is commoner and often has a milder course. Second, systemic arthritis is not simply “polyarthritis with fever”: its pathogenesis is closer to an autoinflammatory disease, driven by interleukin-1 (IL-1) and interleukin-6 (IL-6), and it carries the risk of macrophage activation syndrome. ^[3]

Prevalence estimates depend on region and case definition. One guideline source cites an estimated prevalence of 1 per 1,000 children, ^[1] and the British Society for Rheumatology (BSR) scope reports an age-standardised prevalence of 43.5 to 70.2 per 100,000. ^[4] Both sources agree on the more important message: this is the commonest childhood-onset inflammatory rheumatic disease. ^[4]

• Age. Disease onset is before 16 years of age, and JIA can present in the first year of life. ^{[4] [1]}
• Sex. Girls are affected more often overall, but systemic JIA and enthesitis-related arthritis are notable exceptions or have a different sex pattern in late childhood. ^[4]
• Course. Many children continue to need specialist rheumatology or ophthalmology care into adulthood; in a UK study, more than 60% of people diagnosed with JIA in childhood continued under such care beyond 18 years. ^[4]
• Persisting risk. All categories can persist or damage joints, eyes, and growth; earlier recognition and effective treatment have made inactive disease achievable for many, but not all, children. ^[1]

No cause has been established for most JIA. Genetic susceptibility, environmental exposures, and immune dysregulation all contribute, and systemic JIA in particular behaves like an autoinflammatory disorder rather than classic autoimmunity. ^[3] RF-positive polyarthritis, enthesitis-related arthritis, and psoriatic arthritis carry adult counterparts (rheumatoid arthritis, axial spondyloarthritis, psoriatic arthritis), whereas ANA-positive oligoarthritis and RF-negative polyarthritis with uveitis have no direct adult equivalent. ^[4]

Risk factors for poor outcome and for blindness, rather than for developing JIA itself, are well defined:

• Uveitis risk factors: female sex, arthritis onset before 7 years of age, oligoarticular pattern, and positive ANA. ^{[4] [2]}
• Polyarthritis risk factors for refractory disease: positive RF, positive anti-cyclic citrullinated peptide (anti-CCP) antibodies, or joint damage. ^[1]
• Poor-prognosis joint features: involvement of ankle, wrist, hip, sacroiliac joint, or temporomandibular joint (TMJ), erosive disease, enthesitis, delay in diagnosis, raised inflammatory markers, and symmetric disease. ^[3]

These markers matter because guidelines ask clinicians to escalate treatment faster for children with them, rather than waiting for the “next routine visit”.

The mechanism is inflammation of the synovial membrane that lines the joint. Inflammatory cells and cytokines thicken the synovium, produce excess fluid, erode cartilage and bone in poorly controlled disease, and cause pain, swelling, stiffness, and loss of function. The child may describe stiffness after rest or on waking, and a parent may notice a limp or reluctance to use a hand before any swelling is obvious.

In systemic JIA, fever, rash, and visceral involvement are driven by IL-1 and IL-6 rather than by autoantibodies alone. ^[3] This explains two otherwise puzzling features: the dramatic fevers and rash before arthritis becomes obvious, and the unusual susceptibility to macrophage activation syndrome, a secondary haemophagocytic syndrome. In enthesitis-related arthritis, inflammation at tendon insertion sites and the sacroiliac joints mirrors adult axial spondyloarthritis. ^[4]

• Arthritis: swelling, warmth, pain, morning stiffness, limp, refusal to bear weight, reduced use of a limb, difficulty writing or holding a cup.
• Duration: at least 6 weeks; symptoms that come and go over days suggest other causes.
• Systemic JIA: daily high spiking fevers, often in the evening, with an evanescent salmon-pink rash that comes with the fever, myalgia, arthralgia, and sometimes sore throat or abdominal pain before joints swell. ^[3]
• Uveitis: usually none. Chronic anterior uveitis is silent, which is why screening replaces symptom-based detection. ^[2]
• Acute anterior uveitis in enthesitis-related arthritis: red, painful, photophobic eye, usually unilateral and episodic. ^[2]
• Functional impact: school attendance, sport, fine motor tasks, sleep, and family life.

• Active joint: swelling not due to chronic inactive thickening or bony enlargement, with pain, tenderness, or limited movement. ^[1]
• Joint count and distribution: small joints of hands and feet, knees, ankles, wrists, elbows, hips, sacroiliac joints, and temporomandibular joints.
• Enthesitis: tenderness and swelling where tendons insert into bone. ^[1]
• Systemic signs: fever pattern, rash, lymphadenopathy, hepatosplenomegaly, chest findings if serositis occurs.
• Growth and puberty: short stature, limb-length discrepancy, and muscle wasting in chronic disease.
• Ocular inflammation: only seen on slit-lamp examination by an ophthalmologist; the bedside eye looks normal in chronic anterior uveitis. ^[2]

JIA is a diagnosis of exclusion. The table is not exhaustive, but these are the mimics most likely to be confused with it in practice.

Kawasaki disease and IgA vasculitis are deliberately placed here because they are common paediatric differentials for a febrile child with joint or limb pain. They are not forms of JIA, and management should follow paediatric vasculitis or infectious-disease guidance rather than the JIA ladder.

There is no single blood test that diagnoses JIA. Investigations are used to exclude mimics, classify the subtype, quantify inflammation, and guide monitoring.

• Full blood count may show anaemia of chronic disease, leukocytosis in systemic JIA, or cytopenias that raise concern for leukaemia or MAS.
• ESR and CRP usually rise with active inflammation, but can be normal in oligoarticular disease.
• ANA is measured because it is a risk factor for uveitis, not because every positive result means lupus. ^[4]
• RF and anti-CCP antibodies identify the RF-positive polyarthritis category and poor-prognosis risk. ^[1]
• HLA-B27 supports enthesitis-related arthritis when the clinical picture fits. ^[1]
• Radiographs and MRI assess damage, sacroiliitis, and temporomandibular joint disease, and ultrasound can guide intra-articular injection.
• Synovial fluid analysis is useful when infection is possible; in JIA it is inflammatory but cultures are negative.
• Ophthalmology slit-lamp examination detects chronic anterior uveitis before symptoms occur. ^[2]

The diagnosis itself is clinical: arthritis in one or more joints for at least 6 weeks before 16 years of age, after exclusion of other disease, classified by ILAR criteria. ^[1] No ILAR category alone dictates drug choice; clinicians then define the broader clinical phenotype.

Disease activity is measured so that treatment can be escalated to a target rather than adjusted on impression alone. The 2019 ACR polyarthritis guideline used the clinical Juvenile Arthritis Disease Activity Score based on 10 joints (cJADAS-10), calculated as the sum of active joint count (to a maximum of 10), physician global assessment of disease activity (0 to 10), and parent or patient global assessment of well-being (0 to 10). ^[1] In that guideline, cJADAS-10 at or under 2.5 (with at least one active joint) represented low disease activity and above 2.5 moderate or high disease activity. ^[1] The score is a guide to shared decision-making, not a substitute for examining the child; global scores are not fully standardised. ^[1]

The aim is complete remission of arthritis, uveitis, enthesitis, systemic features, and MAS; avoidance of joint, ocular, and organ damage; full physical function; good quality of life; and minimal drug toxicity. ^[4]

• NSAIDs are useful as adjuncts for symptom control, but should not be sole long-term treatment for chronic synovitis. ^[1]
• Intra-articular glucocorticoids, preferably triamcinolone hexacetonide, are strongly recommended over triamcinolone acetonide because responses are more complete and durable. ^[1]
• Oral glucocorticoids are avoided whenever possible in children because of growth suppression, weight gain, osteopenia, and cataracts; if used, they should be the lowest dose for the shortest time. ^[1]
• Methotrexate is the conventional DMARD of choice, given subcutaneously when uveitis is present or when oral bioavailability is a concern. ^[1] A 3-month trial is conventional, but therapy can be changed if little or no response is seen after 6 to 8 weeks. ^[1]
• Biologics are IL-1 and IL-6 inhibitors for systemic JIA, and TNF inhibitors or other biologics for polyarthritis and uveitis, with no single preferred first biologic in many categories because head-to-head trials are lacking. ^[3]

For non-systemic polyarthritis, the 2019 ACR guideline recommends: ^[1]

• Start with a DMARD, strongly preferred over NSAID monotherapy. ^[1]
• Use methotrexate rather than leflunomide or sulfasalazine, and subcutaneous rather than oral methotrexate when the child has uveitis or poor response.
• Use intra-articular glucocorticoids as adjunct therapy; triamcinolone hexacetonide is strongly preferred for injection. ^[3]
• Consider a short bridging course of oral glucocorticoids, under 3 months, only in moderate or high disease activity; do not use in low disease activity. ^[1]
• Never add chronic daily oral glucocorticoids.
• Consider NSAIDs and physical or occupational therapy for function.

Treatment is then escalated by activity. For low disease activity, escalating therapy is conditionally recommended over standing still, using joint injections, optimisation of methotrexate dose, a trial of methotrexate if it has not been used, and adding or changing biologics. For moderate or high disease activity in a child on DMARD monotherapy, adding a biologic is recommended over switching to another conventional DMARD or triple therapy. If the first TNF inhibitor fails, changing to a non-TNF inhibitor biologic such as tocilizumab or abatacept is preferred over a second TNF inhibitor, although a second TNF inhibitor may suit secondary failure. ^[1]

Risk factors matter early: in children with risk factors and involvement of high-risk joints such as the cervical spine, wrist, or hip, or very high activity, initial therapy that includes a biologic may be reasonable despite the general recommendation to start with a DMARD. ^[1]

The 2021 ACR guideline complements the 2019 document for oligoarthritis: ^[3]

• A short trial of scheduled NSAIDs is conditionally recommended, followed by rapid escalation rather than prolonged waiting.
• Strongly recommend intra-articular glucocorticoids as part of initial therapy, again favouring triamcinolone hexacetonide; oral glucocorticoids are conditionally recommended against initially. ^[1][3]
• Strongly recommend conventional DMARDs, usually methotrexate first, if NSAIDs or injections are insufficient.
• Strongly recommend biologics if there is inadequate response to or intolerance of NSAIDs or injections and at least one conventional DMARD, with no single preferred agent.
• TMJ arthritis deserves particular attention because it can be destructive and under-recognised; treatment should not be withheld when there are no symptoms.

Systemic JIA is a distinct autoinflammatory illness. The 2021 ACR guideline recommends: ^[3]

• NSAIDs are conditionally recommended as initial monotherapy, but many clinicians avoid them because the response can be incomplete.
• Oral glucocorticoids are conditionally recommended against as initial monotherapy.
• Conventional DMARDs are strongly recommended against as initial monotherapy, because they do not reliably control systemic features and leave children steroid-dependent. ^[3]
• IL-1 and IL-6 inhibitors are conditionally recommended as initial monotherapy, with no preferred agent; they are strongly preferred over conventional DMARDs for inadequate response to NSAIDs or glucocorticoids. ^[3]
• For residual arthritis or incomplete response to IL-1 or IL-6 inhibitors, biologic or conventional DMARDs are strongly recommended over long-term glucocorticoids. ^[3]
• Glucocorticoids and biologics should be tapered after inactive disease is attained; stopping glucocorticoids is strongly recommended and stopping biologics conditionally recommended. ^[3]

This recommendation ladder has had major impact: IL-1 and IL-6 inhibitors have allowed large reductions in glucocorticoid use, with the caveat that children, especially younger children with MAS or a history of reactions to tocilizumab, can develop severe systemic JIA-associated lung disease. ^[3] That rare complication should be remembered, but it does not override the effectiveness of cytokine inhibitors in refractory disease.

MAS is a secondary haemophagocytic syndrome: a cytokine storm producing hyperinflammation that can progress to multiorgan failure and death within days. ^[5] It complicates systemic JIA in up to 40% of cases and can occur at presentation or later. ^[3]

Warning signs are fevers with high ferritin, cytopenias, elevated liver enzymes, high triglycerides, and low fibrinogen, together with mental status, liver, spleen, or bleeding changes. ^[3] MAS also occurs with Kawasaki disease, other rheumatic diseases, and infections, so the trigger and host both matter. ^[5]

The 2016 EULAR, ACR, and PRINTO classification criteria exist specifically for MAS in systemic JIA and were developed against expert consensus with 91.4% agreement; in validation they had sensitivity of 0.73 and specificity of 0.99. ^[6] They rely on ferritin and on platelets, liver transaminases, triglycerides, and fibrinogen as central measures. ^[6] In practice the validated MS score and HScore are also used, but MAS is recognised clinically before a score is complete.

Management is an emergency:

• Hospitalise, investigate and treat triggers such as infection where possible.
• Treat MAS early and aggressively with glucocorticoids. ^[5]
• Add ciclosporin or an IL-1 inhibitor such as anakinra when response is incomplete; ^{[3] [5]}
• For biologic-resistant disease, other agents such as emapalumab or JAK inhibitors have been used, but the evidence base remains small and is not universally available. ^[5]

The 2021 ACR guideline also notes that, for systemic JIA with MAS, IL-1 and IL-6 inhibitors are conditionally recommended over calcineurin inhibitors alone, with glucocorticoids as part of initial treatment. ^[3]

Uveitis is the most common extra-articular manifestation of JIA and affects 20 to 25% of people with JIA in UK data, ^[4] while chronic anterior uveitis develops in 10 to 20% of children with JIA. ^[2] The two figures reflect different populations and definitions and should not be averaged.

Uncontrolled chronic anterior uveitis leads to sight-threatening complications such as synechiae, cataracts, and glaucoma in 25 to 50% of children and vision loss in 10 to 20%. ^[2] Early detection by scheduled ophthalmology screening, then timely topical and systemic treatment, are what prevent blindness. ^[2]

The 2019 ACR uveitis guideline makes these risk-based recommendations: ^[2]

• High-risk children (oligoarthritis, polyarthritis with negative RF, psoriatic arthritis, or undifferentiated arthritis; ANA-positive; JIA onset under 7 years; and JIA duration of 4 years or less) should be screened every 3 months. ^[2]
• Lower or moderate-risk children should be screened every 6 to 12 months, depending on their combination of risk factors. ^[2]
• Systemic and RF-positive polyarthritis, systemic JIA, and enthesitis-related arthritis carry lower risk of chronic anterior uveitis, but children with HLA-B27 are also at risk of acute anterior uveitis and still require screening and education. ^[2]
• Acute anterior uveitis in spondyloarthritis is episodic, usually unilateral, painful, and photophobic and generally does not need systemic therapy. ^[2]

Once uveitis is diagnosed, treat-to-target monitoring is stricter than joint monitoring: ^[2]

• Ophthalmology monitoring within one month after each change of topical glucocorticoids. ^[2]
• No less than every 3 months when disease is controlled on stable therapy. ^[2]
• Within two months of a change in systemic therapy. ^[2]
• In uncontrolled disease, examinations often occur at 2 to 6-week intervals, tailored to medication, inflammation, and complications. ^[2]

Treatment of chronic anterior uveitis follows a step ladder: ^[2]

• Topical prednisolone acetate 1% drops are preferred over difluprednate; frequent drops are used initially, then tapered.
• Topical glucocorticoids should be used as short-term therapy of 3 months or less; the goal is discontinuation because of glaucoma and cataract risk. ^[2]
• If 1 to 2 drops a day are still needed for 3 months, escalate systemic therapy. ^[2]
• Systemic treatment starts with subcutaneous methotrexate; for severe active disease with sight-threatening complications, combine methotrexate with a monoclonal antibody TNF inhibitor from the start. ^[2]
• Use adalimumab or infliximab, not etanercept, for active chronic anterior uveitis.
• If the response is inadequate at standard dose, escalate the dose or frequency (infliximab up to 20 mg per kg every 2 weeks and adalimumab weekly have been reported) before switching to another monoclonal antibody TNF inhibitor. ^[2]
• After two monoclonal antibody TNF inhibitors at above-standard dosing have failed, abatacept or tocilizumab and non-biologic DMARDs are options.
• Taper topical glucocorticoids before systemic therapy; require about 2 years of well-controlled disease before considering systemic taper. ^[2]

• Joint damage and disability: uncontrolled synovitis damages cartilage and bone, limits function, and can distort growth.
• Uveitis complications: synechiae, cataracts, glaucoma, and vision loss in untreated or prolonged active disease. ^[2]
• Systemic inflammation: growth delay, anaemia, serositis, and reduced quality of life.
• Macrophage activation syndrome: a life-threatening complication of systemic JIA. ^[3]
• Medication complications: methotrexate intolerance, biologic infection risk, and the glucocorticoid toxicities of growth suppression, osteopenia, weight gain, and cataracts. ^[1]
• Transition: loss of care at the move from paediatric to adult services. ^[4]

Prognosis is much better than it was a generation ago because of earlier DMARD use, biologics, and treat-to-target care. Many children achieve inactive disease, but a substantial minority have persistent disease into adulthood and require ongoing immunosuppression and eye surveillance. ^{[1] [4]} Poor-prognosis features such as RF positivity, damage at presentation, or certain HLA patterns push treatment towards earlier escalation. ^[3]

Prevention is not vaccination-specific for JIA, but prevention of damage is the central project of paediatric rheumatology:

• Uveitis screening according to risk category, as above. ^[2]
• Early referral and treatment of arthritis to prevent joint damage and steroid dependence. ^[1]
• Vaccination according to current guidance, generally given when the child is clinically stable and planned around immunosuppression; live vaccines are avoided in many immunosuppressed children. EULAR/PReS recommendations on vaccination in paediatric rheumatic disease are the relevant European reference. ^[4]
• Transition planning into adult care, because JIA is often a lifelong condition. ^[4]

• Young children: drug choice is constrained by formulation, weight-based dosing, and the higher risk of uveitis; methotrexate has the longest paediatric experience. ^[1]
• Adolescents: adherence, body image, fertility discussions, and school and sport planning matter as much as inflammation.
• Systemic-onset disease in children with Down syndrome or ILD risk factors: use biologics cautiously and watch for lung disease. ^[3]
• Pregnancy: drugs such as methotrexate and leflunomide are not used; planning should occur before conception with the adult rheumatology team. The BSPAR scope notes that JIA often spans paediatric and adult care. ^[4]
• Low-resource settings: triamcinolone hexacetonide, biologics, MRI, and even slit-lamp screening may be unavailable. Intra-articular steroid injections, methotrexate, careful clinical follow-up, and referral to the nearest specialist centre provide the most achievable benefit; where eye screening is impossible, educate families about uveitis red flags and seek urgent ophthalmology if any concern arises.

• JIA can usually be recognised clinically; do not let lack of advanced imaging delay referral if swelling, morning stiffness, or systemic features are present.
• Intra-articular glucocorticoids and methotrexate remain the most accessible steroid-sparing treatments. ^[1]
• Uveitis screening by risk category is the highest-yield preventive intervention when available, and even a basic slit-lamp examination is better than symptom-based detection. ^[2]
• When biologics are unavailable, optimise methotrexate dose and route, use bridging glucocorticoids for the shortest possible period, and refer early for funding or trial access. ^[1]

• JIA is arthritis before 16 years of age lasting at least 6 weeks, after exclusion of other causes; seven ILAR categories describe different clinical patterns.
• Prevalence is roughly 1 per 1,000 children in some series, and up to 43.5 to 70.2 per 100,000 in UK data; JIA is the commonest childhood-onset inflammatory rheumatic disease. ^{[1] [4]}
• Systemic JIA is driven by IL-1 and IL-6 and can be complicated by macrophage activation syndrome in up to 40% of cases. ^[3]
• Chronic anterior uveitis affects 10 to 20% of children and is usually silent, but can threaten sight in 25 to 50% if uncontrolled. ^[2]
• Ophthalmology screening every 3 months is recommended for high-risk children and every 6 to 12 months for lower-risk children. ^[2]
• DMARD monotherapy, usually methotrexate, is strongly preferred over NSAIDs for chronic polyarthritis or oligoarthritis; chronic daily oral glucocorticoids are strongly avoided. ^[1]
• Intra-articular triamcinolone hexacetonide, subcutaneous methotrexate for uveitis, and IL-1 or IL-6 inhibitors for systemic JIA are preferred strategies. ^{[1] [3]}
• Treatment is guided by treat-to-target disease activity scores such as cJADAS-10, with low activity defined at or under 2.5. ^[1]
• Joints and eyes are tracked separately; inactive arthritis does not exclude active uveitis. ^[2]
• Kawasaki disease and IgA vasculitis are differential diagnoses, not forms of JIA, and should be managed on their own pathways.

Further MedGrasp musculoskeletal topics, including rheumatoid arthritis, axial spondyloarthritis, psoriatic arthritis, and pharmacology topics for methotrexate and biologic agents, will be cross-linked once their own topic files are verified.