• Clinical science

Juvenile idiopathic arthritis (Juvenile rheumatoid arthritis)

Abstract

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 involve joint inflammation lasting more than six weeks. It is classified into various types based on the pattern of joint involvement, the presence of extra-articular manifestations (e.g., uveitis, rashes, 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 oligoarthritic 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

  • Annual incidence: 4–14 cases per 100,000 children
  • Prevalence: 1/1000 children
  • Sex: >
  • Age of onset: < 16 years

References:[1]

Epidemiological data refers to the US, unless otherwise specified.

Etiology

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

References:[1][2]

Pathophysiology

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

References:[3]

Clinical features

  • Arthritic symptoms: red, swollen joints, early morning stiffness, limited or painful joint movement
  • Synovial thickening
  • Fever and other extra-articular manifestations; (e.g., uveitis, rashes, nail changes, lymphadenopathy, hepatosplenomegaly) may be present depending on the type of JIA (see “Subtypes and variants” below).
  • Certain children may present with nonspecific features such as excessive crying, lethargy, decreased scholastic performance, and/or growing pains.

References:[1]

Subtypes and variants

Type of JIA Epidemiology Definition Pattern of joint involvement

Extra-articular manifestations

Laboratory findings Treatment Prognosis

Relative frequency of each type

Peak incidence Sex

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
    • Persistent oligoarthritis: arthritis involving ≤ 4 joints throughout the course of the disease
    • Extended oligoarthritis: arthritis involving > 4 joints after 6 months of disease onset
  • Asymmetrical pattern
  • Large, weight-bearing joints (knee and ankle) are usually affected.
  • ESR
  • RF negative
  • ANA positive (∼ 70% of cases)
Mostly good

Seronegative polyarticular JIA

30% of cases

1–4 years and 6–12 years (bimodal incidence)

> (3:1 for the first age peak and 10:1 for the second)

  • Arthritis involving more than ≥ 5 joints within 6 months of disease onset
  • Symmetrical or asymmetrical
  • ESR
  • RF negative
  • ANA positive (∼ 40% of cases)
Variable clinical course and a high risk of functional limitation
Seropositive polyarticular JIA

< 10% of cases

9–12 years

> (10:1)

Persistent disease with periodic exacerbation and a high risk of progressive joint destruction
Systemic JIA (Still's disease)

< 10% of cases

2–4 years

=

  • Arthritis involving ≥ 1 joint AND
  • intermittent fever that lasts for at least two weeks with fever spikes occuring on at least 3 consecutive days AND
  • ≥ 1 extra-articular manifestation
  • Polyarthritis
The clinical course is highly variable; complete remission occurs in 40–50% of cases.
Psoriatic JIA

< 10% of cases

7–10 years

> (2:1)

  • Arthritis and psoriasis OR
  • Arthritis and ≥ 2 of the following features:
    • Dactylitis
    • Nail changes (pitted nails, onycholysis)
    • Psoriasis among first-degree relatives
  • Asymmetrical
  • Chronic anterior uveitis*
  • Nail changes
  • Psoriatic skin lesion often appear after the onset of arthritic symptoms
  • ANA positive (in 50% of cases)
  • HLA-B27 may be positive
  • RF negative
  • NSAIDs and intra-articular steroid injections
Mostly good

Enthesitis-related JIA

10% of cases

9–12 years

<

  • Arthritis with enthesitis
  • Asymmetrical
  • HLA-B27 positive (in 80% of cases)
  • RF negative
Mostly good
Undifferentiated arthritis

All forms of JIA that do not fit clearly into one of the types mentioned above

*The incidence of anterior uveitis increases when antinuclear antibodies (ANA) are present.

This list is based upon the ILAR classification criteria for juvenile idiopathic arthritis. The complete classification also contains additional exclusion criteria for each type of JIA. A detailed description of each type is beyond the scope of this learning card.

The affected joints are often stiff in the mornings or after longer periods of inactivity (e.g., sitting). Mobility improves with movement and is less impaired later in the day!

References:[4][4][3][1][5][6][7][8][9][10][11][12]

Diagnostics

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

Type of RF Frequency of ophthalmological screening
Risk stratification Age at diagnosis < 6 years Age at diagnosis > 6 years
ANA -ve
  1. Semiannually for another four years
  2. Thereafter, annually for life
  • Annual screening
ANA +ve
  1. Every 3 months for the first 4 years
  2. Semiannually for the next three years
  3. Thereafter, annually for life
  1. Semiannually for another two years
  2. Thereafter, annually for life
  • Annual screening

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!
References:[13][1][5][14]

Differential diagnoses

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

References:[1]

The differential diagnoses listed here are not exhaustive.

Treatment

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.

  • Definitive therapy
    • First-line
      • NSAIDs
      • Local intra-articular steroids (e.g., triamcinolone) are indicated in the case of active arthritis.
    • Second-line
      • Disease-modifying antirheumatic drugs (DMARDs)
        • Therapy with DMARDs should be started as early as possible in the case of high disease activity.
        • The DMARD of choice is determined on an individual basis with methotrexate being used in most cases.
      • Biologic agents: (e.g., etanercept; , adalimumab; , anakinra; , tocilizumab) are indicated if the response to DMARDs is poor.
      • Systemic glucocorticoid therapy (oral, IV)
        • Rarely used in children because of the risk of catabolic side effects (osteoporosis, growth impairment)
        • A short course of systemic glucocorticoid therapy may be prescribed in the following situations:
          • Severe systemic involvement (e.g., severe serositis; see Still's disease)
          • As bridge therapy to control severe arthritic symptoms while DMARDs are being initiated if adequate symptomatic relief is not obtained with NSAIDs.
          • Acute anterior uveitis
          • Macrophage activation syndrome
  • Supportive therapy
    • Physiotherapy: to prevent joint deformities
    • Surgery, splints, and/or orthotics: to correct limb length discrepancy and/or joint deformities

References:[1][15][16]

Complications

  • Joint destruction → joint subluxation, joint deformities (e.g., swan-neck, boutonniere deformities)
  • Limb length discrepancy
  • Growth retardation
  • Chronic anterior uveitisblindness
  • Pericarditis, pleuritis
  • Macrophage activation syndrome (MAS)

References:[1]

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) . However, most cases (∼ 95%) resolve by puberty.
  • Factors associated with a poor prognosis
    • Early onset
    • Prolonged active systemic disease
    • Hip and/or wrist involvement
    • Polyarthritis
    • Symmetrical disease
    • Presence of RF
    • Presence of anti-CCP antibodies

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

References:[17][1]

last updated 11/19/2018
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