24th February 2025

Juvenile idiopathic arthritis (JIA)

Overview of JIA

JIA describes a collection of inflammatory arthritides that occur in children of any age below 16 years old (but typically less than six years old), with an incidence of approximately 1:1000. There are a number of subsets described including oligo-JIA, poly-JIA and systemic-JIA. The pathophysiology is thought to be similar in mechanism to that of RA.

Historically, the diagnosis of JIA was delayed, in part due to the wide differential list. A high index of suspicion is required for what is a clinical diagnosis, and in suspected cases, treatment should begin prior to being seen by a Paediatric Rheumatologist. Primarily, this is to provide timely pain relief but also to rapidly limit the degree of joint damage, which can lead to subsequent growth restriction and later deformity.

Management typically involves intra-articular or systemic corticosteroid, whilst DMARDs take effect. On occasion, biologic therapies are required. Interestingly, 10-20% of JIA cases are associated with uveitis and so prompt referral to Ophthalmology is prudent. Otherwise, holistic management is best achieved via a multidisciplinary team approach, including psychological support. Approximately 25% of those with JIA experience ongoing inflammatory arthritis in adulthood.

Signs and symptoms of JIA

The typical features are swollen, erythematous, stiff, painful joints and entheses, associated with a reduced range of movement. In order to reach the diagnostic threshold, one or more joints must be involved for more than six weeks. Sometimes, there are systemic features such as fever and rash.

Clearly, there is overlap with other differential diagnoses, including reactive and septic arthritis, psoriatic arthritis, osteomyelitis, Kawasaki disease, Lyme disease, tuberculosis, SLE and even haematological malignancies such as leukaemia, lymphoma or sarcoma, which need appropriate work up. Red flags would include systemic upset, significant weight loss, headaches, unremitting pain of a non-mechanical nature, pain at night, significant gait disturbance, neurological signs or symptoms and overlying skin changes, including petechiae.

Investigation of JIA

JIA is a clinical diagnosis, though laboratory investigations in a suspected case would typically include blood tests for FBC (anaemia of chronic disease, inflammation/ infection), CRP and ESR (though, unlike RA, in children these markers do not tend to correlate with disease activity and grossly raised counts should make you consider malignancy) and auto-antibodies including ANA, RF, anti-CCP and ferritin levels. X-rays and ultrasound can qualify joint inflammation and erosion.

Management of JIA

The recurring theme, regardless of JIA-subtype is early administration of NSAIDs. For oligo-JIA (less than or equal to four joints), intra-articular corticosteroid is given as a bridge for disease-modifying therapy to take effect, which is typically methotrexate. For poly-JIA (more than or equal to five joints), oral corticosteroid is substituted. If methotrexate is poorly tolerated or disease is refractory, then either the DMARD is substituted like in RA, or usually biologic therapy is initiated (similar agents as used in RA). Systemic-JIA (around 5% of cases, previously known as Still’s disease) usually has grossly elevated WCC, CRP and ESR counts on laboratory investigations and is managed similarly to other subtypes of JIA, but with a lower threshold for biologics.

A recognised complication is secondary haemophagocytic lymphohistiocytosis (HLH) or macrophage activation syndrome (MAS), where haemopoietic stem cells in the bone marrow are destroyed by macrophages as part of the ‘cytokine storm’ in response to an infective trigger. This has non-specific features, but the child is invariably unwell with severe systemic upset and often multi-organ failure. It is diagnosed in the setting of cytopenias, falling inflammatory markers, platelets and fibrinogen and elevated ferritin and triglycerides. As well as providing organ support, treatment involves aggressive broad-spectrum antimicrobial therapy to cover for sepsis and specifically pulsed methylprednisolone, IVIG and then biologics (in that order of escalation). The all-cause mortality in secondary HLH is 8-22%. 

Overall, multidisciplinary team involvement is vital for a good outcome in JIA, and indeed, with modern treatments, outcomes are improving. Reassuringly, the incidence of joint replacement in later life is falling as long-term remission of JIA is now more possible. However, vision loss due to uveitis occurs in approximately 25% of cases with minimal symptoms to suggest deteriorating vision, reiterating the importance of screening programmes. The same concern needs to be had for patients with JIA as with all immunocompromised patients, particularly in regards to opportunistic infections. Vaccinations, including live ones, are still recommended even if immunosuppressed, as their benefits far outweigh the risks.

References

• Clunie, G, Wilkinson N, Nikiphorou E, Jadon D. Oxford Handbook of Rheumatology. Fourth Edition. Oxford: Oxford University Press; 2018
• Clinch J & Smallwood N. Juvenile Idiopathic Arthritis [Internet]. BMJ Best Practice. BMJ Publishing Group; 2023 [Cited 2023 August 17]. Available from: https://bestpractice.bmj.com/topics/en-gb/806