Juvenile idiopathic arthritis

Table 1 Classification of subtypes of juvenile idiopathic arthritis[12]

Systemic arthritis

Definition: Arthritis in one or more joints with or preceded by fever of at least 2 wk’ duration that is documented to be daily (“quotidian”) for at least 3 d, and accompanied by one or more of the following:

1 Evanescent (non-fixed) erythematous rash

2 Generalized lymph node enlargement

3 Hepatomegaly and/or splenomegaly

4 Serositis

Exclusions: 1 to 4

Oligoarthritis

Definition: Arthritis affecting one to 4 joints during the first 6 mo of disease. Two subcategories are recognized:

1 Persistent oligoarthritis: Affecting not more than 4 joints throughout disease course

2 Extended oligoarthritis: Affecting a total of more than 4 joints after the 6 mo of oligoarticular disease

Exclusions: 1 to 5

Polyarthritis (Rheumatoid factor negative)

Definition: Arthritis affecting 5 or more joints during the first 6 mo of disease; a test fot RF is negative.

Exclusions: 1 to 5

Polyarthritis (Rheumatoid factor positive)

Definition: Arthritis affecting 5 or more joints during the first 6 mo of disease; 2 or more tests for RF at least 3 mo apart during the first 6 mo of disease are positive.

Exclusions: 1, 2, 3, 5

Psoriatic arthritis

Definition: Arthritis and psoriasis, or arthritis and at least two of the following:

1 Dactylitis

2 Nail pitting or onycholysis

3 Psoriasis in a first-degree relative

Exclusions: 2, 3, 4, 5

Enthesitis related arthritis

Definition: Arthritis and enthesitis, or arthritis or enthesitis with at least two of the following:

1 The presence or a history of sacroiliac joint tenderness and/or inflammatory lumbosacral pain

2 HLA-B27 positivity

3 Onset of arthritis in a male over 6 yr of age

4 Acute (symptomatic) anterior uveitis

5 History of ankylosing spondylitis, enthesitis-related arthritis, sacroiliitis with inflammatory bowel disease, reactive arthritis, or acute anterior uveitis in a first-degree relative

Exclusions 1, 4, 5

Undifferentiated arthritis

Definition: Arthritis that fulfills criteria in no category or in 2 or more of the above categories

Exclusion criteria for JIA

1 Psoriasis or a history of psoriasis in a first-degree relative

2 Arthritis in an HLA-B27 positive male following his 6th birthday

3 History of ankylosing spondylitis, enthesitis-related arthritis, sacroiliitis with inflammatory bowel disease, reactive arthritis (Reiter’s syndrome), or acute anterior uveitis in a first-degree relative

4 The presence of IgM rheumatoid factor on 2 or more occasions at least 3 mo apart

5 The presence of systemic JIA in the patient

JIA: Juvenile idiopathic arthritis; HLA: Human leukocyte antigen.

Table 2 American College of Rheumatology pediatric core set criteria for improvement in juvenile idiopathic arthritis[52]

Criteria
1	Physician’s global assessment of overall disease activity by VAS
2	Parent of patient global assessment of overall well-being by VAS
3	Functional ability
4	Number of joints with active arthritis
5	Number of joints with limited range of motion
6	Erythrocyte sedimentation rate
ACR Pediatric 30 response	A minimum of 30% improvement from baseline in a minimum of 3 out of 6 components, with a worsening by > 30% in no more than one component
ACR Pediatric 50 response	Requires 50% improvement in 3 out of 6 components with worsening of 30% in no more than one component
ACR Pediatric 70 response	Requires 70% improvement in 3 out of 6 components with worsening of 30% in no more than one component

VAS: Visual analogue scale 0-10 cm. ACR: American College of Rheumatology.

Table 3 Preliminary clinical criteria to define the inactive disease status and clinical remission in oligoarticular, polyarticular and systemic onset juvenile idiopathic arthritis[53,54] arthritis[52]

Criteria

1 No active synovitis

2 No fever, rash, serositis, splenomegaly, or generalized lymphadenopathy attributable to juvenile idiopathic arthritis

3 No active uveitis

4 Normal erythrocyte sedimentation rate and/or C-reactive protein

5 Physician’s global assessment of disease activity indicates no active disease

6 Morning stiffness no more than 15 min

Inactive disease:

All criteria must be met

Clinical remission on medication:

Six continuous months of inactive disease on medication

Clinical remission off medication:

Twelve continuous months of inactive disease off all anti-arthritis and anti-uveitis medications

Table 4 Biologic agents used in the treatment of juvenile idiopathic arthritis

Drug	Target	FDA approval for JIA	Administration	Dosage
Etanercept	TNF-α	Polyarticular JIA ages 2 yr and older	Subcutaneous injection	0.8 mg/kg per dose once a week, maximum 50 mg/dose
Adalimumab	TNF-α	Polyarticular JIA ages 4 yr and older	Subcutaneous injection	24 mg/m2 every 2 wk, maximum 40 mg/dose
Infliximab	TNF-α	No	Intravenous infusion	6-10 mg/kg per dose week 0, 2 and 6; then every 4 to 8 wk
Anakinra	IL-1	No	Subcutaneous injection	1-2 mg/kg per day, maximum 100 mg/dose
Canakinumab	IL-1	Systemic-onset JIA ages 2 yr and older	Subcutaneous injection	2-4 mg/kg every 4 wk
Rilonacept	IL-1	No	Subcutaneous injection	2.2-4.4 mg/kg once a week
Abatacept	Cytotoxic T-lymphocyte- associated antigen 4	Polyarticular JIA ages 6 yr and older	Intravenous infusion	10 mg/kg week 0, 2 and 4; then every 4 wk, maximum 1000 mg/dose
Rituximab	CD20	No	Intravenous infusion	750 mg/m2; two doses 2 wk apart or 375 mg/m2; four doses, weekly × 4, maximum 1000 mg/dose
Tocilizumab	IL-6	Polyarticular JIA ages 2 yr and older	Intravenous infusion	8 -12 mg/kg every 2 wk

TNF-α: Tumor necrosis factor-alpha; IL-6: Interleukin-6; JIA: Juvenile idiopathic arthritis.