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SAMJ: South African Medical Journal

versión On-line ISSN 2078-5135
versión impresa ISSN 0256-9574

SAMJ, S. Afr. med. j. vol.105 no.12 Cape Town dic. 2015

http://dx.doi.org/10.7196/samj.2015.v105i12.10223 

CONTINUING MEDICAL EDUCATION
ARTICLE

 

Juvenile idiopathic arthritis - an update on its diagnosis and management

 

 

C ScottI; N BriceII

IMB ChB, FCPaed (SA), Grad Cert Paed Rheum (UWA). Paediatric Rheumatology, Institute of Child Health, Red Cross War Memorial Children's Hospital and University of Cape Town, South Africa
IIMB ChB, Dip HIV Man (SA), FCPaed (SA). Paediatric Rheumatology, Institute of Child Health, Red Cross War Memorial Children's Hospital and University of Cape Town, South Africa

Correspondence

 

 


ABSTRACT

Juvenile idiopathic arthritis (JIA) is the most common form of chronic arthritis in children and the most common cause of musculoskeletal disability in children. Early diagnosis may be challenging, but it is essential to ensure good outcomes. This review proposes an approach to the investigation and diagnosis of JIA. It also gives a summary of the latest available evidence-based treatment for this disease.


 

 

Musculoskeletal (MSK) complaints are very common in children, who present to general practitioners, paediatricians and orthopaedic surgeons. Studies have reported that they may occur in 4 - 30% of the community. A Scottish study showed that 1 in every 58 children presenting to a paediatric accident and emergency unit had limping as their primary complaint, and a survey of adolescents in British Columbia revealed that MSK complaints were viewed as the most common health concern after acne.[1-4] The differential diagnosis for a child presenting with MSK pain ranges from dreadful to completely benign (Table 1).

 

 

An accurate diagnosis of juvenile idiopathic arthritis (JIA) depends on a good clinical approach, clues derived from the history and examination, and pattern recognition, which will assist the clinician in making the diagnosis. A thorough history and examination are the most important tools to make the diagnosis of JIA, where early diagnosis and treatment have been shown to directly improve outcomes.[5] Children are constantly growing and developing, and changing milestones, anatomy and physiology increase the difficulty of making the diagnosis of JIA.

 

Methods

This brief review summarises the available and relevant evidence on the diagnosis and management of JIA in the South African (SA) context and is intended to assist the non-specialist in the identification, management and referral of these patients. Sources of relevance were drawn from published medical literature (searched via Medline), authoritative texts and online resources on paediatric rheumatology.

 

Epidemiology

JIA is the most common chronic MSK condition in children and the most common cause of MSK disability. Although it is perceived as a rare disease it is no less common than many other childhood diseases such as epilepsy and diabetes, and community-based studies indicate that a prevalence of between 1 and 4 per 1 000 children is affected.[6] The wide variation in prevalence rates between studies could in part be accounted for by differences in study design and lack of standardised definitions of JIA in earlier studies. Under-diagnosis and delays in presentation are thought to account for the low prevalence in hospital- and clinic-based studies.

 

Terminology and classification

JIA is the World Health Organization (WHO)'s accepted terminology for children <16 years of age who have chronic arthritis (lasting >6 weeks) and in whom no other specific cause of arthritis can be identified.[7] The terms juvenile chronic arthritis and juvenile rheumatoid arthritis are outdated and no longer preferred. Studies from developing countries such as SA and India appear to suggest that polyarticular JIA is more prevalent in these populations than oligoarticular JIA, which predominates in populations in Europe and the USA.[8]

For the purpose of classification, JIA is divided into 7 heterogeneous subtypes with specific clinical and pathophysiological characteristics (Table 2). Knowledge of patterns of JIA is useful in making an accurate diagnosis. A swollen knee and uveitis in a young girl, for instance, is typical of oligoarticular JIA. An older boy with Achilles insertion pain or arthritis of the first metatarsophalangeal joint is typical of juvenile enthesitis-related arthrtitis (ERA). Dactylitis and asymmetrical large-and small-joint arthritis are seen in patients with psoriatic arthritis, whereas symmetrical small-joint involvement in an older girl is typical of rheumatoid factor (RF)-positive polyarticular JIA.

 

 

Pathophysiology

The cause of JIA is not known, although it is accepted that some type of interplay between environmental factors (e.g. infections or the gut microbiome) and complex genetic factors leads to a disturbance in the balance between immune tolerance and inflammation. Certain human leukocyte antigen (HLA) (class I and II) and non-HLA genes have been associated with different types of JIA.[9] Some subtypes of JIA appear to be more autoimmune in their pathophysiology than others, with adaptive and humoral immunity playing a major part. RF-positive polyarticular JIA, for instance, is strongly associated with the presence of antibodies against RF and cyclic-citrullinated peptide (CCP), and CD4 T-cells play a role in propagating the inflammatory response. Systemic JIA, however, is an autoinflammatory disease driven by abnormalities of the innate immune system, with neutrophils and macrophages playing the major pathogenic roles.

 

Approach to diagnosis

Taking a history in a child with suspected JIA

A good history with appropriate focus on the relevant symptoms and signs of JIA and other conditions in the differential diagnosis is very important in diagnosing JIA. Table 3 summarises the relevant aspects of history-taking in a patient with suspected JIA.

Examination

A child presenting with joint pain or MSK symptoms should have a full examination of all systems and not just of the MSK system. A basic paediatric examination, including anthropometry and vital signs (as well as blood pressure), is crucial. This not only helps to diagnose or exclude non-rheumatic illnesses that may present with MSK pain, but also to find signs associated with many of the rheumatic diseases. Red flag signs for malignancy include the following: fever, malaise, weight loss, pallor, petechiae, nocturnal bone pain, constant symptoms, unexplained bruising and lymphadenopathy.

It is important to note that children with JIA (or their parents) do not always report pain or limitation in their joints, especially the younger age groups. It is crucial that a thorough examination is undertaken to identify all active joints.

The MSK examination should start with the screening examination known as the paediatric gait arms legs spine (PGALS). This validated screening tool has been designed to facilitate the rapid initial assessment of a child with MSK pain. It is quick and easy to do and easily accepted by patients. The PGALS starts with 3 screening questions and moves to several manoeuvres that are specifically choreographed to reveal abnormalities in the MSK system in children. It is summarised in Table 4 and is published here with permission from the authors.[10]

 

 

If an abnormality is identified on PGALS, a full MSK examination should be undertaken, including a thorough examination of all joints. Guidelines on specific joint examinations can be viewed online (see Online resources below). This web-based resource is focused on providing information to non-rheumatologists on the examination and management of rheumatic diseases. Specific points of interest in the examination of children with JIA are given in Table 5.

 

 

Laboratory investigations

Laboratory investigations in JIA are used mainly to exclude other diagnoses or to investigate complications of JIA or its treatment. The minimum investigations are given in Table 6.

 

 

Conventional radiography

Radiographs in children with MSK disease are a standard firstline investigation that is widely available and affordable. In the context of the diagnosis of JIA, radiographs are useful in excluding other causes of MSK pain, e.g. fractures or other bony lesions such as osteomyelitis or tumours. They can also give specific information on joint space narrowing, bone erosions, joint alignment, subluxation or ankylosis. It is important to note that the absence of abnormalities on X-ray examination does not exclude acute or chronic arthritis.

Other imaging modalities are summarised in Table 7.

 

 

Treatment of JIA

Early recognition of JIA and referral to specialist and multidisciplinary services for management improves the prognosis. In all cases the goal of treatment is complete disease remission and normal physical and social development. The many new medications currently available for the treatment of JIA make this achievable.

Non-pharmacological therapy

Physiotherapy and occupational therapy are essential in the management of JIA. These therapies improve joint range of motion and mobility and thereby prevent permanent deformity. They can help manage pain and encourage children to exercise within the limits of their abilities. This physical activity is safe and important in improving the quality of life of children with JIA. Social workers and mental health experts are often also needed to address the psychosocial impact of pain and chronic illness on the child and family unit.

Pharmacological therapy

Non-steroidal anti-inflammatory drugs (NSAIDs)

NSAIDs are used for the management of joint pain and stiffness. All NSAIDs are equally effective and choice depends on cost, tolerability, dosing schedule and formulation. Gastrointestinal side-effects are common and patients requiring long-term NSAIDs should have regular renal and liver function monitoring.

Corticosteroids

Systemic oral and parenteral corticosteroids are used in the treatment of JIA, usually as bridging therapy while disease-modifying anti-rheumatic drug (DMARD) regimens take effect. They are particularly useful in severe polyarthritis and systemic JIA. Importantly, they do not induce remission, and care should always be taken to minimise exposure, given the potential side-effects of long-term use. Concurrent calcium and vitamin D supplementation is necessary to prevent osteopenia.

Intra-articular steroid (IAS) injections have been shown to induce sustained remission when used as monotherapy or in conjunction with methotrexate.[11] Triamcinolone hexocetonide is thought to have superior efficacy to methylprednisolone acetate. IAS injections are usually well tolerated, but in young children should preferably be done under sedation or general anaesthetic. Subcutaneous atrophy at the injection site can occur in approximately 2% of cases.[12]

Disease modifying anti-rheumatic drugs

DMARDs are used as maintenance therapy to control disease activity. They are safe and effective in children and their use ideally limits the need for long-term NSAIDs and corticosteroids. Early introduction of DMARDs has been shown to decrease disease severity and improve prognosis. Table 8 summarises the important prescribing details of synthetic DMARDs.[13-15]

Biologic agents

The advent of biologic agents has significantly enhanced the treatment options for children with JIA and made complete disease remission an achievable outcome. The choice of agent depends on JIA subtype, but patient preference with regard to route and frequency of admission should also be considered. These agents are expensive and access to them requires careful motivation to the healthcare system involved. Table 9 summarises the important prescribing details of biologic DMARDs.[16-21]

 

Conclusion

JIA is not a rare disease and the complications of untreated JIA are significant. All physicians dealing with children should know when to suspect or diagnose this condition and perform the relevant investigations. Early appropriate referral will improve outcomes in patients with this disease. The modern arsenal of investigations and management greatly improves the outcome of patients with JIA. Other causes of joint pain or MSK morbidity in children range from benign to potentially life threatening.

 

Practice points

  • MSK complaints are very common in children.

  • Early and correct diagnosis and referral of patients with JIA are important.

  • JIA is predominantly a clinical diagnosis based on pattern recognition.

  • RF has no value in screening for patients with JIA.

  • Remission can be achieved in the majority of patients using traditional DMARD therapy.

  • Targeted cytokine therapy such as tumour necrosis factor inhibitors offers good therapeutic options to those not responding to traditional DMARDs.

 

References

1. De Inocencio J. Epidemiology of musculoskeletal pain in primary care. Arch Dis Child 2004;89(5):431-434. [http://dx.doi.org/10.1136/adc.2003.028860]        [ Links ]

2. Foster HE, Cabral DA. Is musculoskeletal history and examination so different in paediatrics? Best Pract Res Clin Rheumatol 2006;20(2):241-262. [http://dx.doi.org/10.1016/j.berh.2005.11.001]        [ Links ]

3. Goodman J, McGrath P. The epidemiology of pain in children and adolescents: A review. Pain 1991;46(3):247-264. [http://dx.doi.org/10.1016/0304-3959(91)90108-A]        [ Links ]

4. Fischer S, Beattie T. The limping child: Epidemiology, assessment and outcome. J Bone Joint Surg Br 1999;81(6):1029-1034. [http://dx.doi.org/10.1302/0301-620X.81B6.9607]        [ Links ]

5. Albers HM, Wessels JA, van der Straaten RJ, et al Time to treatment as an important factor for the response to methotrexate in juvenile idiopathic arthritis. Arthritis Rheum 2009;61(1):46-51. [http://dx.doi.org/10.1002/art.24087]        [ Links ]

6. Manners PJ, Bower C. Worldwide prevalence of juvenile arthritis: Why does it vary so much? J Rheumatol 2002;29(7):1520-1530.         [ Links ]

7. Petty RE, Southwood TR, Manners P, et al. International League of Associations for Rheumatology classification of juvenile idiopathic arthritis: Second revision, Edmonton, 2001. J Rheumatol 2004;31(2):390-392.         [ Links ]

8. Weakley K, Esser M, Scott C. Juvenile idiopathic arthritis in two tertiary centres in the Western Cape, South Africa: University of Cape Town; 2011. Pediatr Rheumatol Online J 2012;10(1):35. [http://dx.doi.org/10.1186/1546-0096-10-35]        [ Links ]

9. Prakken B, Albani S, Martini A. Juvenile idiopathic arthritis. Lancet 2011;377(9783):2138-2149. [http://dx.doi.org/10.1016/S0140-6736(11)60244-4]        [ Links ]

10. Foster HE, Kay LJ, Friswell M, Coady D, Myers A. Musculoskeletal screening examination (pGALS) for school-age children based on the adult GALS screen. Arthritis Rheum 2006;55(5):709-716. [http://dx.doi.org/10.1002/art.22230]        [ Links ]

11. Zulian F, Martini G, Gobber D, Agosto C, Gigante C, Zacchello F. Comparison of intra-articular triamcinolone hexacetonide and triamcinolone acetonide in oligoarticular juvenile idiopathic arthritis. Rheumatology (Oxford) 2003;42(10):1254-1259. [http://dx.doi.org/10.1093/rheumatology/keg358]        [ Links ]

12. Scott C, Meiorin S, Filocamo G, et al. A reappraisal of intra-articular corticosteroid therapy in juvenile idiopathic arthritis. Clin Exp Rheumatol 2010;28(5):774-781.         [ Links ]

13. Beresford M, Baildam E. New advances in the management of juvenile idiopathic arthritis - 1: Non- biological therapy. Arch Dis Child Educ Pract Ed 2009;94(5):144-150. [http://dx.doi.org/10.1136/adc.2008.144576]        [ Links ]

14. Gowdie PJ, Shirley M. Juvenile idiopathic arthritis. Pediatr Clin North Am 2012;59(2):301-327. [http://dx.doi.org/10.1016/j.pcl.2012.03.014]        [ Links ]

15. Takken T, van der Net JJ, Helders PP. Methotrexate for treating juvenile idiopathic arthritis. Cochrane Database Syst Rev 2001;(4):CD003129. [http://dx.doi.org/10.1002/14651858.cd003129]        [ Links ]

16. Beresford M, Baildam E. New advances in the management of juvenile idiopathic arthritis - 2: The era of biologicals. Arch Dis Child Educ Pract Ed 2009;94(5):151-156. [http://dx.doi.org/10.1136/adc.2009.170860]        [ Links ]

17. Giannini E, Ilowite N, Lovell D, et al. Long-term safety and effectiveness of etanercept in children with selected categories ofjuvenile idiopathic arthritis. Arthritis Rheum 2009;60(9):2794-2804. [http://dx.doi.org/10.1002/art.24777]        [ Links ]

18. Katsicas MM, Russo RA. Use of adalimumab in patients with juvenile idiopathic arthritis refractory to etanercept and/or infliximab. Clin Rheumatol 2009;28(8):985-988. [http://dx.doi.org/10.1007/s10067-009-1162-7]        [ Links ]

19. Quartier P, Allantaz F, Cimaz R, et al A multicentre, randomised, double-blind, placebo-controlled trial with the interleukin-1 receptor antagonist anakinra in patients with systemic-onset juvenile idiopathic arthritis (ANAJIS trial). Ann Rheum Dis 2011;70(5):747-754. [http://dx.doi.org/10.1136/ard.2010.134254]        [ Links ]

20. De Benedetti F, Brunner H, Ruperto N, et al Efficacy and safety of tocilizumab (TCZ) in patients with systemic juvenile idiopathic arthritis (SJIA): Tender 52-week data. Pediatr Rheumatol 2011;9(Suppl 1):164. [http://dx.doi.org/10.1186/1546-0096-9-S1-P164]        [ Links ]

21. Lovell DJ. Long-term efficacy and safety of adalimumab for up to 6 years in patients with juvenile idiopathic arthritis. ACR/ARHP scientific meeting, November 2011, Chicago, USA.         [ Links ]

 

 

Correspondence:
C Scott
chris.scott@uct.ac.za

 

 

Online resources
Paediatric musculoskeletal matters. User-friendly and elegant resource on paediatric musculoskeletal conditions for students or medical personnel working with children. Developed by Prof. Helen Foster from Newcastle University, UK: www.pmmonline.org

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