juvenile%20idiopathic%20arthritis
JUVENILE IDIOPATHIC ARTHRITIS
Juvenile idiopathic arthritis was formerly known as juvenile rheumatoid arthritis or juvenile chronic arthritis.
It presents as chronic joint swelling, pain with functional limitation for at least 6 weeks of unknown cause that starts before 16 year of age.
It is the most common autoimmune-autoinflammatory disease in children.
Around half of the children with juvenile idiopathic arthritis may have active disease until adulthood.

Principles of Therapy

  • Objectives in treating children w/ juvenile idiopathic arthritis (JIA)
    • To achieve disease remission
    • To control pain
    • To preserve range of motion, muscle strength & function
    • To control systemic complications
    • To foster normal nutrition, growth, & physical & psychological development
  • Management approach is customized based on the disease subtype & severity, occurrence of poor prognostic factors & response to treatment
  • Tuberculosis (TB) infection should be ruled out prior to starting anti-tumor necrosis factor (TNF)-α; testing for hepatitis B & C should be done prior to giving Methotrexate or anti-TNF-α in children w/ risk factors for infection
  • Immunization status must be updated prior to receiving treatment
    • Live vaccines should not be given in patients who is taking glucocorticoids or disease modifying antirheumatic drugs (DMARDs)
    • Inactive vaccines are not contraindicated
    • Yearly immunization w/ influenza is recommended 

Pharmacotherapy

Analgesic

  • Paracetamol may be considered for short-term use in treating persistent juvenile idiopathic arthritis (JIA) pain in children & adolescents
  • In addition to Paracetamol, Codeine may be given to manage moderate articular pain

Non-steroidal Anti-inflammatory Drugs (NSAIDs)

  • Considered the 1st-line drug for the treatment of inflammation & associated pain in children w/ JIA
    • Used for the initial management of pain, stiffness & inflammation
  • Exert anti-inflammatory, analgesic & antipyretic effects w/ long-term safety when used appropriately
    • Anti-inflammatory effects in JIA patients is noted after 4-6 weeks of constant administration
  • NSAID monotherapy is recommended for patients w/ low disease activity, w/ no joint contractures & features of poor prognosis, & during the clinical evaluation of possible systemic arthritis
    • Continued use w/o additional therapy for >2 months is discouraged in patients w/ active arthritis regardless of presence of poor prognostic features; continued use for >1 months in patients w/ active fever is not advised
  • Patients w/ systemic arthritis w/ active arthritis & w/o active systemic features may be started on NSAID monotherapy w/ or w/o intraarticular corticosteroids if w/ low disease activity & w/o poor prognostic features
  • Studies have shown that effectivity & tolerability of selective COX-2 inhibitors (eg Celecoxib, Meloxicam) are similar to the non-selective NSAIDs (eg Naproxen)
  • Use of NSAIDs alone seldom induce remission of polyarticular or systemic-onset JIA

Corticosteroids

Intra-articular

  • Use for joint injections in active arthritis is recommended regardless of disease activity level, prognostic features, joint contractures, concomitant therapy or JIA treatment group
  • Triamcinolone hexacetonide is commonly used for joint injections due to its superior efficacy
    • Improvement of arthritis may be noted after at least 4 months of use & may be repeated as needed
    • Intensification w/ systemic therapy may be needed when patient improved clinically for only a short duration of time

Systemic

  • Recommended as initial therapy for patients w/ systemic arthritis that have active fever & MD global assessment ≥7 but has no active arthritis
    • Started in patients w/ systemic arthritis that have active fever after 2 weeks of NSAID use

Biologic Disease Modifying-Antirheumatic Drugs (DMARDs)

  • Target specific cytokines (eg interleukin-1, interleukin-6) or interfere w/ specific cell function through depletion of B cells or suppression of T cell activation

Anti-tumor Necrosis Factor-α (Anti-TNF-α)

  • Recommended in patients w/ ≤4 arthritic joints who have received glucocorticoid joint injections & 3 months of maximum tolerated dose of Methotrexate that have moderate or high disease activity & features of poor prognosis
    • Also given to patients who have received glucocorticoid joint injections & 6 months of Methotrexate that have high disease activity w/ no features of poor prognosis
    • Also recommended in patients w/ enthesitis-related arthritis who were given glucocorticoid joint injections & a trial of Sulfasalazine (w/o prior Methotrexate) & have moderate or high disease activity w/o considering the prognostic features
  • In patients w/ ≥5 arthritic joints, anti-TNF-α is recommended in patients who have received the maximum tolerated dose of Methotrexate or Leflunomide for 3 months & have moderate or high disease activity regardless of prognostic features
    • Also used in patients w/ low disease activity who have received Methotrexate or Leflunomide for 6 months, irrespective of prognostic features
    • Changing from 1 anti-TNF-α to another may be advised in patients w/ moderate or high disease activity who have used the current anti-TNF-α for 4 months, regardless of poor prognostic factors
    • In patients who have received Abatacept for 3 months & have high disease activity w/ features of poor prognosis & in patients who have received Abatacept for 6 months & have moderate or high disease activity w/ or w/o features of poor prognosis, switching to anti-TNF-α is recommended
  • Recommended more readily in patients w/ active sacroiliac arthritis
    • Given to patients w/ active sacroiliac arthritis who have received an adequate trial of NSAIDs & have high disease activity & poor prognostic features
    • Also recommended in patients who were maintained on Methotrexate for 3 months w/ high disease activity irrespective of prognostic factors, or w/ moderate disease activity w/ poor prognosis, or in patients given 6 months of Methotrexate w/ moderate disease activity w/ no poor prognostic features
    • Also given to patients w/ moderate or high disease activity who have used Sulfasalazine for 3 months, irrespective of prognostic features, or to patients w/ low disease activity & poor prognostic features who were on 6 months of Sulfasalazine
  • In patients w/ systemic arthritis w/ active arthritis & w/o active systemic features, anti-TNF-α is recommended to be initiated or added if patient received Methotrexate for 3 months, w/ moderate or high disease activity w/ or w/o poor prognostic features
  • When used up to the maximum recommended dosing regimen, may show response in 2-4 weeks in some patients
    • Usually cause significant improvement in symptoms, signs &/or lab parameters w/in 12-24 weeks
    • BMD was noted to improve after treatment w/ anti-TNF-α agents even in patients w/ incomplete disease control
  • Adalimumab & Infliximab appear to be more effective in JIA-associated uveitis than Etanercept
  • Some studies indicate that anti-TNF-α dose may be decreased when patients are in remission or in low disease activity, w/o losing its efficacy
  • Adalimumab
    • A fully human, IgG, monoclonal anti-TNF antibody
    • Approved to reduce signs & symptoms of moderate-severe active polyarthritis in patients ≥4 years old
    • May be used alone or in combination w/ Methotrexate
  • Etanercept
    • Soluble TNF p75 receptor fusion protein that binds to & inactivates TNF-α
    • First anti-TNF-α to be approved for use in JIA
    • A standard therapy given to patients w/ arthritis that did not respond to Methotrexate
    • May be used in children as young as 2 years old for treating moderate-severe polyarticular JIA
    • Shown to be less effective in patients w/ systemic-onset JIA than in patients w/ other forms of JIA
    • Should not be given to children w/ infection or history of recurrent infections
    • Can be used continuously for up to 8 years, as indicated by its long-term safety profile
      • Exacerbation & worsening of the disease are the 2 most common serious adverse effects noted beyond 4 years of use
  • Infliximab
    • A chimeric human/mouse monoclonal antibody that binds to soluble & membrane-bound TNF-α
    • Use in JIA needs further study because of its potential adverse effects (eg infusion reactions, development of antibodies)

Anti-Cytotoxic T Lymphocyte–Associated Antigen-4 Immunoglobulin

  • Abatacept
    • A fully human, soluble fusion protein that contains the extracellular domain of the cytotoxic
      T lymphocyte-associated antigen 4 (CTLA-4) & the Fc component of IgG1
    • Selectively inhibits the costimulatory signal needed for T-cell activation
    • Approved for the management of patients w/ moderate-severe polyarticular JIA
    • Recommended as an alternative management in patients w/ ≥5 arthritic joints who were maintained for 4 months on anti-TNF-α & have high disease activity, irrespective of poor prognostic features, or moderate disease activity w/ poor prognostic features
    • Also advised as another treatment approach in patients given ≥1 consecutive anti-TNF-α & have moderate or high disease activity, irrespective of prognostic factors, or low disease activity w/ poor prognostic features
    • Given to patients w/ systemic arthritis that has no active systemic features, who have received Methotrexate & anti-TNF-α & w/ high disease activity, regardless of prognostic features, or patients w/ moderate disease activity & features of poor prognosis
    • May be as effective as anti-TNF-α agents as shown by different studies; However, maximum efficacy was noted a few weeks later

Anti-CD20

  • Rituximab
    • A chimeric monoclonal antibody to CD20 that causes selective depletion of CD20-positive B cells which may produce anti-inflammatory effects in arthritis
    • Recommended as an alternative treatment option in patients w/ ≥5 arthritic joints who have received anti-TNF-α & Abatacept consecutively & have high disease activity, w/o considering the prognostic features, or in patients w/ moderate disease activity w/ poor prognostic features
      • More appropriate to use in patients w/ positive rheumatoid factor (RF)

Interleukin-1 Receptor Antagonist

  • Anakinra
    • A recombinant human interleukin-1 receptor antagonist
    • Recommended in all patients w/ systemic arthritis that has active fever & features of poor prognosis, regardless of current therapy
    • Also given to all patients w/ systemic arthritis that develops or continue to have fever while receiving systemic glucocorticoids
    • May be added or started in patients w/ systemic arthritis but has inactive systemic features, after receiving Methotrexate & have moderate or high disease activity, irrespective of poor prognostic features
    • Also advised in patients w/ high or moderate disease activity who have received Methotrexate & anti-TNF-α or Methotrexate & Abatacept, regardless of prognostic factors
    • In patients w/ systemic arthritis but w/ inactive systemic features, initiation of Anakinra may be less appropriate later in the disease course than near the disease onset
    • May be switched to anti-TNF-α agents in patients w/ moderate or high disease activity, irrespective of poor prognostic features; however unmasking of latent systemic disease activity is possible when Anakinra is discontinued
  • Canakinumab
    •  A recombinant human monoclonal interleukin-1β antibody
    •  Recommended as an alternative treatment for >2 years old patients w/ systemic arthritis w/ active systemic features & w/ continued disease activity despite therapy w/ glucocorticoids, Methotrexate & other first-line drugs
    •  Also recommended as an alternative treatment option in patients w/ systemic arthritis w/o active systemic features & w/ >4 arthritic joints after receiving DMARD combined w/ Anakinra, Tocilizumab, Abatacept, or an anti-TNF-α agent
  •  Rilonacept
    •  Further studies are needed to prove the efficacy of Rilonacept in JIA patients
      • Studies have shown uncertain/inappropriate effects of Rilonacept in patients w/ systemic arthritis w/ or w/o systemic features  

Interleukin-6 Receptor Antagonist

  • Tocilizumab
    • A humanized monoclonal antibody that inhibits the cytokine IL-6
    • Recommended for children & adolescents ≥2 years old w/ active systemic JIA who had responded inadequately to NSAIDs, systemic corticosteroids & Methotrexate
    • May also be given to children & adolescents ≥2 years old w/ refractory systemic onset of JIA & polyarticular JIA

Non-Biologic Disease-Modifying Antirheumatic Drugs (DMARDs)

Methotrexate

  • Recommended as the initial therapy for patients w/ ≤4 arthritic joints that have high disease activity & features of poor prognosis
    • Also given to patients w/ high disease activity w/o features of poor prognosis & to patients w/ moderate disease activity w/ features of poor prognosis after initial glucocorticoid injection
    • After repeated glucocorticoid injections, Methotrexate may be started in patients w/ moderate disease activity w/o features of poor prognosis or in patients w/ low disease activity w/ features of poor prognosis
  • In patients w/ ≥5 arthritic joints, Methotrexate may be given as initial treatment for patients w/ high disease activity regardless of poor prognostic factors & for patients w/ moderate disease activity & features of poor prognosis
    • After 1 months of NSAID use, Methotrexate may be started in patients w/ low disease activity & features of poor prognosis or in patients w/ moderate disease activity w/o features of poor prognosis if NSAID was used for 1-2 months
  • Recommended for patients w/ systemic active arthritis but w/ no active systemic features after ≤1 months of NSAID use irrespective of poor prognostic features
    • Not appropriate for initial treatment of patients w/ active fever & w/o active arthritis
  • Effective at relatively low oral dose, has relatively fast onset of action & acceptable toxicity (ie absence of risk for oncogenicity & production of sterility)
  • Response is usually observed after ≥3 months of use & is advised to be continued for ≥1 year after achieving remission
  • May be continued while starting anti-TNF-α (ie Etanercept, Adalimumab) in patients who had partial clinical response to previously given Methotrexate
  • Folic acid at 1 mg/day should be given concomitantly to decrease gastrointestinal irritation & mucosal toxicity w/o decreasing Methotrexate’s effectivity
  • Adolescents taking Methotrexate should be advised to avoid alcohol, smoking & pregnancy

Hydroxychloroquine

  • Used as additional drug to treat chronic arthritis in older children
    • Usually added to NSAID regimen; rarely given as monotherapy
  • Therapeutic response is rarely seen before 2-3 months of therapy; should be discontinued if no improvement after 6 months of use
  • Eye exam (ie test of color vision & visual fields) should be performed before therapy
  • Not recommended for children <4 years old

Leflunomide

  • May be used as an alternative to Methotrexate
  • One of the treatment options for patients w/ ≥5 arthritic joints that have high disease activity & features of poor prognosis
    • May also be given as initial treatment for patients w/ high disease activity w/ no poor prognostic features & for patients w/ moderate disease activity w/ poor prognostic features after a brief trial of NSAIDs
  • Therapeutic effects may be noted 4 weeks after starting the therapy & continues until 5 months of treatment
  • Studies have shown cases of severe liver injury in rheumatoid arthritis patients who used Leflunomide

Sulfasalazine

  • Recommended for patients w/ enthesitis-related arthritis w/ moderate or high disease activity after glucocorticoid joint injection or NSAID use, regardless of features of poor prognosis
  • Effects are noted w/in 4-8 weeks after starting the therapy
  • Generally not advisable to children w/ active systemic JIA due to increased hypersensitivity reactions

Non-Pharmacological Therapy

Nutritional Therapy

  • Calcium intake in children w/ juvenile idiopathic arthritis (JIA) should be monitored & daily intake be increased
    • Patient’s w/ JIA have been shown to have low bone mineral density (BMD) regardless of steroid use
    • Pathologic fractures have been noted in 15-26% of children w/ JIA
  • Calcium plus vitamin D is advised in some patients especially those on corticosteroids
    • Corticosteroid causes bone loss which further increases the risk of osteoporosis & osteopenia
    • Steroids reduce calcium absorption & increase urinary calcium loss that leads to bone resorption
  • Evaluate & ensure appropriate protein & caloric intake

Orthotics Management

  • Splints & foot orthotics may be recommended on an individualized basis
    • Benefit of splints depends on the patient’s age, type of orthosis used & the location of the joint affected

Physical Activity

  • Provides important general health benefits & may improve disease outcomes w/o causing disease exacerbation
  • Reduces loss of proteoglycans & cartilage damage, optimizes BMD, & decreases obesity risk that may worsen joint load
  • A minimum of 6 weeks exercise program may provide:
    • Improved aerobic fitness
    • Better muscle strength & function
    • Lesser disease activity
    • Improved self-efficacy, energy level & quality of life
    • Decreased pain & use of medicines
  • Aquatic exercises promote range of motion, strength & fitness w/ lower stress on joints
  • Weight bearing exercise should be recommended to develop optimal bone width & density
  • Moderate fitness & strengthening exercises are recommended for children w/ JIA
    • If patient has well controlled disease & have adequate physical activity, competitive or impact sports may be an option
    • Patients w/ moderate-severe impairment or active joint inflammation should be advised to limit activities w/in pain thresholds & then gradually return to full activity after disease exacerbation
  • Children w/ neck arthritis should have x-ray screening for C1-C2 instability before joining any contact sports
  • Use of appropriately fitted mouth guards & eye protection should be recommended during activities

Thermotherapy

  • Heat &/or cold may be advised for relief of JIA symptoms
    • Heat treatments (eg heat packs, deep heat ultrasound, warm baths) may be helpful in lessening joint rigidity, pain & muscle spasms, & increasing joint flexibility
      • Morning warm bath or shower may help decrease stiffness & pain
    • Massage, which is often given w/ heat therapy, may help ease pain, reduce anxiety, promote relaxation, & prevent adhesions in subcutaneous tissues
    • Cold treatment (eg cold packs) causes vasoconstriction in joints w/ inflammation & may help in pain relief
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