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Fifteen-minute guide to managing oligoarticular juvenile idiopathic arthritis
  1. Dearbhla McKenna1,
  2. Diarmuid McLaughlin2,
  3. Cathy Campbell1,
  4. Melissa Mulholland3,
  5. Andrew Thompson3,
  6. Clare Loughran3,
  7. Paul Jackson1,
  8. Madeleine Rooney4
  1. 1 Paediatric Rheumatology, Musgrave Park Hospital, Belfast, UK
  2. 2 Neonatology, Royal Jubilee Maternity Service, Belfast, UK
  3. 3 General Paediatrics, Royal Belfast Hospital for Sick Children, Belfast, UK
  4. 4 Centre for Infection and Immunity, QUB, Belfast, UK
  1. Correspondence to Dr Cathy Campbell, Musgrave Park Hospital, Belfast, Antrim BT9 7JB, UK; ccampbell44{at}qub.ac.uk

Abstract

Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease affecting children and young people today. However, it is not a single disease entity, but an umbrella term that gathers together a heterogeneous collection of complex, chronic inflammatory conditions with oligoarticular JIA the most common form in both Europe and North America. Due to its relative rarity in daily practice and potential to mimic other conditions, oligoarticular JIA can present a diagnostic and management challenge to healthcare professionals in both primary care and general paediatrics. The aim of this article is to provide a summary of the key aspects of diagnosis, investigation and management of this condition, with the hopes of building clinicians’ confidence when facing a possible case of oligoarticular JIA.

  • rheumatology
  • therapeutics

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Introduction

Juvenile idiopathic arthritis (JIA) is not a single disease entity, rather it is an umbrella term that gathers together a heterogeneous collection of complex, chronic inflammatory conditions characterised by:

  • An arthritis of unknown origin.

  • Affecting individuals under the age of 16 years old.

  • Symptoms persisting for longer than 6 weeks.

As suggested by its name, the exact aetiology of JIA remains unclear. What is evident, however, is that it is a family of complex autoimmune diseases in which genetic susceptibility, in combination with environmental factors, produces a pro-inflammatory immune response leading to clinical disease.

It has an estimated UK incidence of 8–9/100 000 with an overall female predominance.1 Reports of JIA prevalence worldwide vary between 0.07 and 4.01 per 1000 children.2 It is the most common chronic rheumatological disease affecting children and young people today. However, it remains a relatively rare disease and one that is not frequently encountered by paediatricians and general practitioners which can lead to diagnostic error and delayed care provision.3

The current classification criteria for JIA, as defined by the International League Against Rheumatism (ILAR), is based on the signs and symptoms present during the first 6 months of the disease, with each category being mutually exclusive (table 1).2

Table 1

ILAR Classicfication Criteria for juvenile idiopathic arthritis

Oligoarthritis is the most common form of JIA in Europe and North America accounting for up to 60% of cases and most commonly occurs in children under the age of 6 years.4 As it is the most common form of JIA encountered in our population, we aim through this article to consider its diagnosis, investigation and management with the hopes of building clinicians’ confidence when facing a possible case of oligoarticular JIA.

Diagnosis

As with all forms of JIA, there is no single test to confirm diagnosis. As such a detailed and through history and examination are the keys to a timely and accurate diagnosis.

What to ask in the history?

Patient demographics

Oligoarticular JIA typically presents in children between the ages of 2 and 6 years. New onset is rare in children over 10 years of age. There is a strong female predominance, with a female to male ratio of approximately 3:1.5 6

Onset of symptoms and musculoskeletal history

Pain is not a useful predictor of arthritis, as the arthritis can be painless. Erythema, swelling and stiffness are more specific. The typical presentation is of a toddler who presents with a limp or who has an obviously swollen joint. The altered gait is usually more noticeable in the morning. Symptoms are often insidious, and families find it difficult to pinpoint exactly when the illness started.

Systemic enquiry

Fatigue is often reported with the absence of other systemic features such as fever, rash, lymphadenopathy, anaemia and weight loss. These other features are suggestive of an alternative diagnosis (table 2).

Table 2

Differiential diagnosis for juvenile idiopathic arthritis

Trauma

Establishing a positive or negative history of trauma (including non-accidental injury) is important when faced with an acutely swollen joint or newly altered gait. Even in the absence of a witnessed event, a post-traumatic aetiology is often assumed.

Family history

The majority of cases of JIA are sporadic. A positive family history is still important however there are well-documented genetic associations. Most notably, oligoarticular JIA is positively associated with human leucocyte antigen (HLA)-A2, HLA-DRB1*11 and HLA-DRB1*08, while DRB1*04 and HLA-DRB1*07 are reduced.7 Overall, a sibling of a person with oligoarticular JIA has a 22 times higher risk than the general population of developing the condition.8 In addition, it is essential to specifically ask about a history of psoriasis in the patient and any first-degree relatives as this is an exclusion criterion for oligoarticular JIA (table 1).

Clinical examination

Joint examination

It is important to initially examine all joints, not just those that are symptomatic or obviously swollen. Examine joints symmetrically to form a comparison. Affected joints can be swollen but may not be painful. Feeling for warmth is particularly important, as this is a sensitive sign. In oligoarticular JIA, there is typically an asymmetrical involvement of large joints in the lower limb. The knee is most commonly affected and approximately 80% of cases will present with either single joint or bilateral knee involvement.9 Smaller joints can be involved although this is rare within the first 6 months of onset and would be more in keeping with other forms of arthritis.

Growth assessment

It is essential to obtain and record basic anthropometric measurements such as height and weight. Any child presenting with unexplained growth disturbance should have a full musculoskeletal assessment. Leg length discrepancies can be seen in all subtypes of JIA but occur more frequently in oligoarthritis due to asymmetrical joint involvement. Inflammation triggers accelerated growth of the affected side. There is also an increased risk of short stature. However, this is seen most frequently in children with systemic JIA.10 11 Early diagnosis and quickly achieving clinical remission can help mitigate these complications.

Investigations

Although oligoarticular JIA is largely a clinical diagnosis, targeted investigation can assist with excluding other disorders and aid with confirming the diagnosis.

Blood investigations

The main purpose of blood investigations in suspected oligoarticular JIA is to assist in excluding other diagnoses such as infection or malignancy. Inflammatory markers including erythrocyte sedimentation rate, and C reactive protein can have a mild to moderate rise but can also be normal. White cell counts, platelet and haemoglobin levels are usually normal.2 5

More specialised blood tests, such as antinuclear antibodies (ANAs), rheumatoid factor and HLA B27, are not required for diagnosis but can assist rheumatologists with JIA classification and treatment planning. ANAs are positive in approximately two-thirds of all children diagnosed with oligoarticular JIA. They are positive more frequently in females and those with uveitis. Rheumatoid factor, antibodies to double-stranded DNA, histones and anticyclic citrullinated peptides are usually negative. Elevated levels of complement proteins can be seen in approximately one-third of patients with active oligoarticular JIA.5

Synovial fluid

Synovial fluid analysis does not aid in diagnosing oligoarticular JIA as it will not distinguish between the different subtypes of JIA. It can help however in excluding rarer causes of joint swelling including neoplasia. Fluid analysis in JIA usually shows a moderate inflammatory content with elevated cell counts of 5–20 000 cells/mm3 consisting mainly of polymorphonuclear leucocytes.2 5

Imaging

Modes of imaging used most frequently in JIA include plain radiographs (XR), ultrasound scanning (USS) and MRI.12

XR is mainly useful for excluding other diagnoses, such as fracture, malignancy or infection, and is rarely helpful in diagnosing JIA. Furthermore, XR findings are less frequent and less severe in oligoarticular JIA in comparison with the other subtypes. Bony overgrowth is the most common finding particularly at the knee, which can be correlated clinically with evidence of leg length discrepancy on the affected side. Osteopenia may also be seen. Other less frequent XR findings include joint space narrowing and erosions.13

USS is useful in helping to identify active synovitis and increased intra-articular fluid. It can detect early cartilage thickness changes and also be used for aiding the administration of intra-articular corticosteroid injection (IACI).

MRI can be helpful in excluding other causes in a child with a monarthritis rather than as a primary imaging modality. Findings with a non-contrast MRI in oligoarticular JIA can include the presence of increased intra-articular fluid, synovial thickening and bone marrow oedema. Contrast enhancement is useful for increasing sensitivity of imaging in certain joints, such as the temporomandibular or sacroiliac joints. (figure 1)

Figure 1

Summarises the key history, examination and investigation findings in oligoarticular JIA. ANA, antinuclear antibody; HLA, human leucocyte antigen; JIA, juvenile idiopathic arthritis; RF, rheumatoid factor.

Uveitis screening

A diagnosis of oligoarticular JIA is strongly associated with chronic, non-granulomatous, anterior uveitis, which, if left undiagnosed, can lead to severe visual impairment. The risk of uveitis is increased by the presence of ANAs. It can be completely asymptomatic in its early stages with either unilateral or bilateral eye involvement.

Most cases occur at the time of, or shortly after the diagnosis of JIA, however uveitis can precede the onset of arthritis in a small number of patients. Slit lamp examination of both eyes by an ophthalmologist is thus essential in every child diagnosed or with suspected oligoarticular JIA.

The examination should occur as soon as possible and no later than 6 weeks from referral for asymptomatic patients and within 1 week in symptomatic patients. Screening thereafter should occur at 2 monthly intervals for the first 6 months followed by 3–4 monthly screening for a number of years depending on the age of the child at the time of diagnosis.2 14

Treatment of oligoarticular JIA

JIA is best managed by a multidisciplinary team. Drug therapies include non-steroidal anti-inflammatory drugs (NSAIDs), IACIs, and methotrexate or biological therapies in more severe cases.

JIA is a chronic condition best managed by a multidisciplinary team. The main aim of treatment is to rapidly control inflammation, thereby preventing long-term joint damage, and so preserve as normal a function as possible. Retaining and improving functional ability is the main focus of physiotherapy, occupational therapy and podiatry treatment.

Education of the child and their family, tailored to their individual needs, is essential to ensure they are equipped with appropriate self-management strategies and knowledge required to be active participants in all aspects of their care. This is achieved through the key role of the specialist nurse in addition to the medical team. Psychology can play a fundamental role in the management of JIA, as in many chronic paediatric conditions, and it is imperative that patients have access to this resource in order to provide a holistic service.

Drug therapy is usually required in oligoarticular JIA and therapeutic options are discussed below.

Non-steroidal anti-inflammatory drugs

The first-line therapy for the treatment of oligoarticular JIA is NSAID. The mechanism of action is through the blocking of cyclo-oxygenase and therefore prostaglandin.15 NSAIDs work to reduce pain and inflammation. It can take up to 12 weeks for an NSAID to be fully effective in controlling the inflammation. Some children may need to use an NSAID for a prolonged period in order to control their JIA, however persistent use may indicate a need to escalate therapy. They are available in various different preparations—including as a tablet, liquid form and as a melt. There are a number of different types of NSAID that can be used as detailed in table 3.

Table 3

Non steroidal ani-inflammatory medications for use in juvenile idiopathic arthritis20

NSAIDs are generally well tolerated in children and young people. The main side effect, although rare, is gastrointestinal disturbance, usually mild abdominal pain, nausea or diarrhoea. However, more severe abdominal pain and ulceration, accompanied with bleeding, can occur. Clinicians may prescribe a proton pump inhibitor to assist with reducing these symptoms. Other side effects include worsening renal function, clotting dysfunction—particularly in those with preceding clotting abnormalities and bronchospasm, although this is extremely rare, even in those with asthma. There are no specific monitoring requirements for those who use NSAID as their mainstay of treatment.

Intra-articular corticosteroid injections

Indications

IACIs have been used in the adult population for treating inflammatory arthritis since the 1950s and were first used for the treatment of JIA in 1979. Since this time, IACIs have become an accepted management intervention for JIA.16

Glucocorticoids have anti-inflammatory and immunosuppressive effects, but with their systemic use comes systemic side effects. Targeting the treatment to a specific joint allows treatment of this joint, without the systemic side effects. IACIs are effective in reducing synovitis, improving tenosynovitis and preventing the deformities that can occur in oligoarticular JIA, such as leg length discrepancies and contractures. IACI can be used for single or multiple joints.

In previous times, IACIs were reserved for when NSAIDs had not controlled the disease sufficiently. However, many paediatric rheumatologists now use them early in the disease course to control synovitis, provide pain relief and aid rehabilitation. The effects of an IACI tend to last for several months. Patients should be assessed 3–6 months after the joint injection with reinjection offered if needed. Potential adverse effects are documented in box 1. If there is extension of arthritis to >4 joints, more than two injections within 12 months or evidence of severe/erosive disease in any joint, other treatment options beyond IACI need to be considered.17

Box 1

Potential adverse outcomes of intra-articular corticosteroid injections in children

  • Peri-articular calcifications.

  • Subcutaneous atrophy at injection site.

  • Hypopigmentation at injection site.

  • Crystal synovitis.

  • Transient suppression of endogenous cortisol production/exogenous hypercortisolism >10 joints injected.

  • Avascular necrosis of the femoral head.

  • Difficulty maintaining glucose control in children with diabetes.

Sedation

IACI in JIA can be performed under local anaesthetic, conscious sedation or under general anaesthetic. This decision will be made by the clinician, patient and their family.

Procedural technique

There is no specified standard when describing specific IACI technique. It is dependent on the patient, their underlying diagnosis, the administering clinician’s skill, and training and resources available.

We have provided below an overview and images of our team’s technique for use in this patient population (figures 2–4).

Figure 2

Technique for joint injection. USS, ultrasound scanning.

Figure 3

Intra-articular aspiration of knee effusion.

Figure 4

Intra-articular steroid injection of knee effusion.

Use of USS in IACI

USS is the ideal imaging modality in the paediatric population. It is painless and provides real-time findings. The use of USS allows specific guidance of the needle during the intra-articular injection. This can be particularly helpful for small or complicated joints. The use of USS in IACI has been well researched and documented in adult practice, but there is less evidence within the paediatric population. Importantly though, to be safe and accurate, it must be used by an experienced practitioner.18

Disease-modifying antirheumatic drugs

Disease-modifying antirheumatic drugs (DMARDs) may be used in specific circumstances in oligoarticular JIA.

  • If the arthritis has extended to more than four joints—extended oligoarticular JIA.

  • Evidence of severe/erosive disease in any joint.

  • Relapse of injected joint—despite a further NSAID and/or a further joint injection.

If any of these three criteria are fulfilled, then a DMARD should be commenced. The first-line choice is methotrexate.

Methotrexate is an immunosuppressant that has revolutionised the treatment of children with JIA. It is an antineoplastic antimetabolite whose efficacy in JIA was first highlighted in 1992. Dose prescribed in current practice is 10–15 mg/m2.15 It can be given orally or subcutaneously. Side effects include nausea, abdominal pain, rashes and mouth ulcers. Methotrexate requires regular monitoring of patients’ white cell count and liver function.19 Long-term liver damage is not felt to be a problem in children, but they must be counselled about the dangers of excessive alcohol consumption. Methotrexate has teratogenic potential. Children and young adults should be regularly counselled about this. Once placed on systemic immunosuppressive therapy, patients should also avoid live vaccines.

Biological therapies

The term ‘biological’ refers to disease-modifying antirheumatic therapies whose action is directed against specific mediators of the immune inflammatory process—cytokines. They use either monoclonal antibodies or soluble cytokine receptors to selectively target and block individual components of the inflammatory cascade. Currently all, with the exception of Janus kinase inhibitors, are administered either intravenously or via subcutaneous injection. Many are given in co-administration with methotrexate to optimise their effect.19

In regard to their use in oligoarticular JIA, patients progress to these medications only when optimised methotrexate therapy has failed either due to ongoing disease activity or methotrexate side effect intolerance.18 Biologics targeting anti-tumour necrosis factor-α are the first line in the majority of patients with JIA who require progression to these therapies.19

Biological therapies and their use within JIA remain a relatively new therapeutic advancement, having been adopted for routine use by paediatric rheumatologists over the last two decades.19 The safety profile of these medications is favourable but ongoing study is required to fully establish long-term outcomes.

Conclusion

In this article, we have discussed the current classification (ILAR) of JIA, noting that oligoarticular JIA is the most common subtype. We have highlighted the salient points to be considered in the history and examination, in suspected oligoarticular JIA, with a reminder to never forget to refer these patients for uveitis screening on diagnosis. Treatment of oligoarticular JIA is best managed by the multidisciplinary team. Drug therapies involve NSAID initially, followed by intra-articular injections to the affected joints, with methotrexate and biological therapies reserved for severe cases or progression of joint involvement to extended oligoarticular JIA.

Key messages

  • The diagnosis of oligoarticular juvenile idiopathic arthritis (JIA) is a clinical diagnosis, reliant on a good history and thorough examination (with the use of ultrasound in unclear clinical cases).

  • Investigations are not required for the diagnosis of oligoarticular JIA to be made.

Ethics statements

Patient consent for publication

References

Footnotes

  • Correction notice This paper has been updated since it was published online. The table legends have been inserted.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Provenance and peer review Commissioned; externally peer reviewed.