• Clinical science

Juvenile idiopathic arthritis (Juvenile rheumatoid arthritis)

Summary

Juvenile idiopathic arthritis (JIA; formerly called juvenile rheumatoid arthritis) is a broad term for childhood rheumatic diseases that begin before the age of 16 and are characterized by joint inflammation that lasts more than 6 weeks. It is classified into various types based on the pattern of joint involvement, the presence of extra-articular manifestations (e.g., uveitis, rash, nail changes, lymphadenopathy, hepatosplenomegaly), laboratory findings, and disease prognosis. Oligoarticular JIA, which is the most common type, presents with asymmetric involvement of up to four joints (with the knee joint most often affected). Nearly half of all cases of oligoarticular JIA are associated with anterior uveitis, which may be diagnosed by slit-lamp examination. Laboratory tests such as ESR, rheumatoid factor (RF), antinuclear antibodies (ANA), and the HLA-B27 antigen test are used to classify and determine the prognosis of JIA. Treatment of JIA is similar to that of adult rheumatoid arthritis and involves the use of NSAIDs, intra-articular steroid injections, and disease-modifying antirheumatic drugs (DMARDs) such as methotrexate. Systemic glucocorticoid therapy should be avoided because of the risk of growth impairment.

Epidemiology

  • Prevalence: 1:1000 children [1]
  • Sex: >
  • Age of onset: < 16 years of age

Epidemiological data refers to the US, unless otherwise specified.

Etiology

  • Idiopathic
  • Immunological predisposition (different HLA associations) [2]
  • Possibly triggered by a viral or bacterial infection
  • Exposure to antibiotics during childhood may increase the risk of JIA.

Pathophysiology

Autoimmune and/or autoinflammatory disease → chronic synovial inflammation with infiltration of plasma cells, B lymphocytes, and T lymphocytes joint capsule hyperplasia growth of fibrovascular connective tissue (pannus) → invasion of the articular surface → loss of joint function [3]

Clinical features

For the exact pattern of joint involvement and specific extra-articular symptoms, see “Subtypes and variants” below.

The affected joints are often stiff in the morning or after longer periods of inactivity (e.g., sitting). Joint stifness improves with movement and decreases later in the day.

Subtypes and variants

Classification of juvenile idiopathic arthritis [3][4]
Type of JIA

Relative frequency

Peak incidence Sex Definition Pattern of joint involvement

Extra-articular manifestations

Laboratory findings Treatment Prognosis

Oligoarticular JIA

  • Most common form (accounts for 50% of all JIA cases)
  • 2–4 years
  • > (3:1)
  • Arthritis involving ≤ 4 joints within 6 months of disease onset
  • Asymmetrical pattern
  • Large, weight-bearing joints (knee and ankle) are usually affected.
  • ESR
  • Negative RF
  • Positive ANA (∼ 70% of cases)
  • Mostly good [5]

Seronegative polyarticular JIA [6]

  • 30% of cases
  • 1–4 years and 6–12 years (bimodal incidence)
  • >
  • Arthritis involving more than ≥ 5 joints within 6 months of disease onset
  • ESR
  • Negative RF
  • Positive ANA (∼ 40% of cases)
  • Variable clinical course and a high risk of functional limitation
Seropositive polyarticular JIA [6]
  • < 10% of cases
  • 9–12 years
  • > (10:1)
  • Symmetrical
  • ESR
  • Positive RF
  • Persistent disease with periodic exacerbation and a high risk of progressive joint destruction
Systemic JIA (Still disease)
  • < 10% of cases
  • 2–4 years [7]
  • =
  • Arthritis involving ≥ 1 joint AND
  • Intermittent fever that lasts for at least two weeks with fever spikes occurring on at least 3 consecutive days AND
  • ≥ 1 extra-articular manifestation
  • Monoarthritis, oligoarthritis, and polyarthritis possible (most commonly affects ≥ 2 joints) [8]
  • Often involves knees, ankles, and wrists
  • The clinical course is highly variable.
  • Complete remission occurs in 40–50% of cases.

A prerequisite for the diagnosis of all forms of JIA is that arthritic symptoms begin before the age of 16 and last ≥ 6 weeks.

Diagnostics

The clinical diagnosis of JIA can be supported by a number of diagnostic tests.

Laboratory tests

Blood tests are used to classify JIA, assess the prognosis, and rule out other similar conditions (see “Subtypes and variants” above).

Imaging tests

  • Ultrasound [11]
    • Used to detect synovial hypertrophy and intraarticular fluid collections
    • Best imagistic tool for the detection of early bone erosions
  • X-ray [12]
    • May be used for the identification of JIA complications
    • Should not be performed routinely

Other diagnostic tests

Anterior uveitis that occurs with JIA may be asymptomatic (especially in the case of chronic anterior uveitis). However, untreated anterior uveitis is associated with a high risk of developing glaucoma, cataracts, and optic nerve damage. Therefore, early detection via slit lamp examination and swift initiation of treatment are of paramount importance.

Differential diagnoses

The differential diagnosis of JIA includes other causes of nonsuppurative arthritis in children: [14]

The differential diagnoses listed here are not exhaustive.

Treatment

Definitive therapy

First-line therapy [15]

Second-line therapy

Supportive therapy

  • Physiotherapy: to prevent joint deformities
  • Surgery, splints, and/or orthotics: to correct limb length discrepancy and/or joint deformities

Most drugs that are used to treat adult rheumatoid arthritis may be used to treat JIA as well (see “Therapy” in “Rheumatoid arthritis”). However, certain forms of therapy (e.g., systemic glucocorticoid therapy) should, as a rule, be avoided in children.

Complications

We list the most important complications. The selection is not exhaustive.

Prognosis

The clinical course and prognosis are highly variable (see “Subtypes and variants” above) . Most cases (∼ 95%) resolve by puberty.

  • Factors associated with a poor prognosis [15]
    • Early onset
    • Prolonged active systemic disease
    • Hip and/or wrist involvement
    • Polyarticular involvement
    • Symmetrical disease
    • Presence of RF
    • Presence of anti-CCP antibodies

Early disease onset is associated with a greater degree of growth impairment and deformity.

  • 1. U.S. Department of Health & Human Services. Juvenile idiopathic arthritis. https://ghr.nlm.nih.gov/condition/juvenile-idiopathic-arthritis#statistics. Updated August 17, 2020. Accessed September 29, 2020.
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  • 3. Van Meer A. Juvenile Idiopathic Arthritis. http://www.pathophys.org/jia/. Updated February 19, 2017. Accessed February 19, 2017.
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  • 6. Verbsky J, Oberle E, Harris J. Polyarticular juvenile idiopathic arthritis – epidemiology and management approaches. Clin Epidemiol. 2014: p. 379. doi: 10.2147/clep.s53168.
  • 7. Mullin AH, Nataraj D, Ren JJ, Mullin DA. Inhaled benzene increases the frequency and length of lacI deletion mutations in lung tissues of mice. Carcinogenesis. 1998; 19(10): pp. 1723–33. doi: 10.1093/carcin/19.10.1723.
  • 8. Genetic and Rare Diseases Information Center. Systemic onset juvenile idiopathic arthritis. https://rarediseases.info.nih.gov/diseases/10966/systemic-onset-juvenile-idiopathic-arthritis. Updated January 1, 2007. Accessed August 13, 2020.
  • 9. Mahmud SA, Binstadt BA. Autoantibodies in the Pathogenesis, Diagnosis, and Prognosis of Juvenile Idiopathic Arthritis. Frontiers in Immunology. 2019; 9. doi: 10.3389/fimmu.2018.03168.
  • 10. Hamooda M, Fouad H, Galal N, Sewelam N, Megahed D. Anti-cyclic citrullinated peptide antibodies in children with Juvenile Idiopathic Arthritis. Electronic physician. 2016; 8(9): pp. 2897–2903. doi: 10.19082/2897.
  • 11. Wakefield RJ, Gibbon WW, Conaghan PG, et al. The value of sonography in the detection of bone erosions in patients with rheumatoid arthritis: a comparison with conventional radiography. Arthritis Rheum. 2000; 43(12): pp. 2762–2770. pmid: 11145034.
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  • 13. Singhal O, Kaur V, Singhal M, Machave Y, Gupta A, Kalhan S. Arthroscopic synovial biopsy in definitive diagnosis of joint diseases: An evaluation of efficacy and precision. International Journal of Applied and Basic Medical Research. 2012; 2(2): p. 102. doi: 10.4103/2229-516x.106351.
  • 14. Kim KH, Kim DS. Juvenile idiopathic arthritis: Diagnosis and differential diagnosis. Korean Journal of Pediatrics. 2010; 53(11): p. 931. doi: 10.3345/kjp.2010.53.11.931.
  • 15. Beukelman T, Patkar NM, Saag KG, et al. 2011 American College of Rheumatology recommendations for the treatment of juvenile idiopathic arthritis: initiation and safety monitoring of therapeutic agents for the treatment of arthritis and systemic features. Arthritis Care Res. 2011; 63(4): pp. 465–482. doi: 10.1002/acr.20460.
  • 16. Ringold S, Weiss PF, Beukelman T, et al. 2013 Update of the 2011 American College of Rheumatology recommendations for the treatment of juvenile idiopathic arthritis. Arthritis Rheum. 2013; 65(10): pp. 2499–2512. doi: 10.1002/art.38092.
  • 17. Schiappapietra B, Varnier G, Rosina S, Consolaro A, Martini A, Ravelli A. Glucocorticoids in juvenile idiopathic arthritis. Neuroimmunomodulation. 2015; 22(1-2): pp. 112–8. doi: 10.1159/000362732.
  • Cunha BA. Fever of unknown origin caused by adult juvenile rheumatoid arthritis: The diagnostic significance of double quotidian fevers and elevated serum ferritin levels. Heart Lung. 2004; 33(6): pp. 417–421. doi: 10.1016/j.hrtlng.2004.07.002.
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases. Questions and Answers about Juvenile Arthritis. https://www.niams.nih.gov/health_info/juv_arthritis/. Updated June 1, 2015. Accessed February 19, 2017.
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last updated 10/13/2020
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