Pediatric JRA

Tan May Vern @ Rachel

1000614239

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Definition
 JRA – Juvenile Rheumatoid Arthritis (also known as
Juvenile Chronic Arthritis)
 Recently, changed to Juvenile Idiopathic Arthritis (JIA)
 To avoid confusion with the adult rheumatoid arthritis

[Journal of American Medical Association – Juvenile Idiopathic Arthritis]

 Definition : Definite arthritis of unknown aetiology,

onset before age 16 years, persists for 6 weeks (Pediatric
Protocol 2nd Edition)
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Etiology
 Most common chronic rheumatologic disease of childhood –
prevalence 1:1000
 Two peaks
 Ages 1-3 years
 Ages 8-12 years (broader peak)

 Girls > Boys (especially in pauciarticular form)

 95% of children with JRA have a disease that is clinically and

immunogenetically distinct from rheumatoid arthritis in adult
 Newly presenting JRA is rare
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Pathophysiology
 Autoimmune disease with unknown etiology

Presence of chronic synovitis (inflammation of the joint synovium)

Synovium thickened + hypervascular infiltration by lymphocytes + inflammatory

cytokines

Inflammation  production and release of tissue proteases and collagenases

Tissue destruction (particularly articular cartilage)

Underlying bone structures

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Clinical Presentation
 Typically present with joint swelling with accompanying
effusion
 May develop pain and stiffness in the joint

 Limitation of joint usage and movement

 Morning stiffness and gelling also can occur in the joint

 Can be followed in response to therapy
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Physical Examination
 Signs of inflammation
 Joint tenderness
 Joint warmth
 Erythema
 Joint effusion

 Limited range of movement – pain, swelling or contractures

(lack of use)
 Bony abnormalities surrounding bone – due to presence of active
growth plate  bony proliferation and localized growth disturbance

 Lower extremity joint – leg-length discrepancy may be noted if arthritis is

asymmetric
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Extra-articular features
 Chronic Iridocyclitis or uveitis
 Higher risk in those with positive antinuclear antibody (ANA)
 Highest risk in :-
 Young girls + pauciarticular JRA and positive ANA
 Incidence ard 80%
 Usually asymptomatic until the point of visual loss
 IMPORTANT – regular opthalmologic screening with a slit-lamp examination 
identify anterior chamber inflammation
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 Other features :
 General – fever, pallor, anorexia, LOW
 Growth disturbances
 General – growth failure, delayed puberty
 Local – limb length/size discrepancy, micronagthia
 Skin – subcutaneous nodules, rash (systemic psoriasis,
vasculitis)
 Enthesitis
 Others – hepatomegaly, spleenomegaly, lymphadenopathy,
serositis, muscle atrophy/weakness
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Types
 At least seven different forms of the disease

 Mainly three subtypes

 Pauciarticular (Oligoarthritis)
 Polyarticular (Polyarthritis)
 Systemic Onset
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Pauciarticular JRA
 Definition : Presence of arthritis fewer than 5 joints within the first 6
months from diagnosis
 Most common form – approx 50% of cases

 Young children
 Peak age : 1-3 years
 Broader peak : 8-12 years

 Affects medium-sized to large joints

 Knee  Ankle  Wrist
 Unusual for small joints ie fingers or toes
 Neck and hip involvement – uncommon
An affected knee in a patient with pauciarticular juvenile rheumatoid arthritis. Note sizeable effusion, bony proliferation, and
flexion contracture.

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 May be otherwise well

 No evidence of any systemic inflammation – ie fever, weight
loss or failure to thrive
 No laboratory evidence of systemic inflammation – ie elevated
WBC count or ESR)
 Usually have positive Antinuclear Antibody (ANA)
 Higher risk of uveitis
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Polyarticular JRA
 Describes children with arthritis in 5 or more joints within the first 6 months
of diagnosis
 Accounts for about 40% of cases

 Present at any age

 Peak in early childhood
 Second peak in adolescence – differ from the children in first peak  positive
Rheumatoid factor
 Most likely represent a subgroup with true adult rheumatoid arthritis (RA) – clinical
course and prognosis similar to the adult RA

 Tend to have symmetrical arthritis – affecting any joint

 Typically the small joints – hands, feet, ankles, wrists and knees
 Cervical spine can be involved  fusion of spine
Polyarticular juvenile idiopathic arthritis, showing swelling of the wrists, metacarpal and interphalangeal joints and early
swan-neck deformities of the fingers.

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 Can present with evidence of systemic inflammation

 Signs & Symptoms : malaise, low-grade fever, growth retardationie malaise, low-
grade fever, growth retardation
 Laboratory evidence : anemia of chronic disease, elevated markers of
inflammation – WBC, ESR
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Systemic-Onset JRA
 Small subgroup – 10% do not present with onset of arthritis but preceding systemic
inflammation
 Clinical features
 Typical recurring spiking fever – usually once or twice/day – can occur for several weeks to months
 Rash – typically morbilliform and salmon colored
 May be evanescent and occur only at times of high fever
 Rarely urticarial in nature
 Serositis – pleuritis, pericarditis
 Hepatosplenomegaly – 70% of children

 Significant constitutional symptoms – malaise and failure to thrive

 Laboratory findings – show inflammation

 Elevated WBC count, ESR, CRP and platelet count
 Anemia
Salmon-pink rash.

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 Arthritis follows systemic inflammation 6 weeks to 6

months
 Typically polyarticular in nature
 Can be extensive and resistant to treatment
 Children at highest risk for long-term disability
Feature Pauciarticular Polyarticular Systemic Onset

No of joints <5 (1-4) ≥5

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Varies, usually ≥5

Types of joints Medium to large Small to medium Small to medium

Gender Girls > Boys Girls > Boys Girls = Boys

predominance (esp younger children)

Systemic features None Some constitutional Prominent

Uveitis +++ + +

ANA positivity ++ + -

RF positivity - + (in older children -

with early onset RA)

Outcomes Excellent, >90% Good, >50% complete Variable, depends on

remission remission, some risk extent of arthritis
for disability
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Investigations
 Pauciarticular JIA – usually no laboratory abnormalities
 Polyarticular and Systemic-onset disease – elevated acute
phase reactants and anemia of chronic disease
 Laboratory investigations
 Full Blood Count
 ANA – identify patients at higher risk for uveitis
 Rheumatoid factor – identify children with early onset
adult RA
 Diagnostic arthrocentesis – exclude suppurative arthritis
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 Radiography
 Early stages – normal bone x-ray
 Later stages
 Peri-articular osteopenia (decreased mineralization)
 Growth centers may be slow to develop
 Accelerated maturation of growth plates
 Evidence of bony proliferation
 Late findings – erosion of bony articular surfaces
 Cervical spine involvement – fusion C1-4 may occur
 Atlantoaxial subluxation may be demonstrable
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Differential Diagnosis
Monoarthritis Polyarthritis
Acute 1. JIA - Polyarticular
1. Acute rheumatic fever 2. Reactive arthritis
2. Reactive arthritis 3. SLE
3. Septic arthritis/ osteomyelitis 4. Connective tissue diseases -
4. Early JIA sarcoidosis
5. Malignancy- leukemia, neuroblastoma 5. Inflammatory bowel disease
6. Hemophilia 6. Immunodeficiency syndromes
7. Trauma 7. Mucopolysaccharide

Chronic
1. JIA - Pauciarticular
2. Chronic infections: TB, fungal,
sarcoidosis
3. Bone malignancy
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Common D/Dx
 Systemic Lupus Erythematosus

 Rheumatic Fever

 Leukemia

 Kawasaki Disease
Juvenile 1. Gender : Type-dependent
2. Age : 1-16 years
Rheumatoid
Arthritis
3.
4.
Arthralgia : Present
Morning stiffness : Present
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5. Rash : Butterfly discoid
6. Joint involvement : Pauciarticular, Polyarticular (small joints)
7. Erosive arthritis : Present
8. Eye involvement : Iridocyclitis, uveitis
9. Other clinical manifestiations : Serositis (systemic onset), hepatosplenomegaly
10. Laboratory Investigations :
• Total WBC count - Increased
• ANA – Positive (50%)
• Rheumatoid factor – Positive (10%)(Polyarticular)
11. Pathogenesis : Autoimmune

Systemic Lupus 1. Gender : F>M

2. Age : 10-20 years
Erythematosus 3. Arthralgia : Present
4. Morning Stiffness : Present
5. Rash : Butterfly, discoid
6. Joint involvement : Monoarticular, Pauciarticular, Polyarticular (small joints)
7. Erosive arthritis : Non-erosive arthritis
8. Eye involvement : Retinitis, uveitis
9. Other clinical manifestiations : Proteinuria, serositis, oral ulcers, seizures
10. Laboratory Investigations :
• Total WBC count – Decreased
• ANA - Positive
• Rheumatoid factor - Positive
• Others - complement, Ab to double-stranded DNA
11. Pathogenesis : Autoimmune
Rheumatic Fever 1. Gender : M=F
2. Age : 5-15 years
3. Arthralgia : Present
4. Morning stiffness : No
5. Rash : Erythema marginatum
6. Joint involvement : Polyarticular – large joints, migratory
7. Erosive arthritis : Rare
8. Eye involvement : None
9. Other clinical manifestiations : carditis, subcutaneous nodules, chorea
10. Laboratory Investigations :
• Total WBC count – Normal to increased
• ANA - Negative
• Rheumatoid factor - Negative
• Others -  ASO anti-DNase B
11. Pathogenesis : Group A streptococcus

Leukemia 1. Gender : M=F

2. Age : 2-10 years
3. Arthralgia : Present
4. Morning stiffness : No
5. Rash : No
6. Joint involvement : Monoarticular, Pauciarticular, Polyarticular (small joints)
7. Erosive arthritis : No
8. Eye involvement : No
9. Other clinical manifestiations : Thrombocytopenia, hepatosplenomegaly
10. Laboratory Investigations :
• Total WBC count – Increased or neutropenia ± blasts
• ANA - Negative
• Rheumatoid factor - Negative
• Others – Bone marrow examination
11. Pathogenesis : Acute lymphoblastic leukemia
Kawasaki Disease 1. Gender : M=F
2. Age : < 5 years
3.
4.
Arthralgia : Present
Morning stiffness : No
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5. Rash : Diffuse maculopapular (non-specific), desquamation
6. Joint involvement : Polyarticular – small joints
7. Erosive arthritis : No
8. Eye involvement : Conjunctivitis, uveitis
9. Other clinical manifestiations : fever, lymphadenopathy, swollen hands/feet, mouth
lesions
10. Laboratory Investigations :
• Total WBC count - Increased
• ANA - Negative
• Rheumatoid factor -Negative
• Others –Thrombocytosis,  immune complexes
11. Pathogenesis : Unknown
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Management
 Multidisciplinary approach

 Aim of treatment – minimize the effects of inflammation

1. Control of pain
2. Prevention of loss or restoration of range of motion
3. Restoration of function
4. Promotion of normal growth and development

 Result : Acceptable Quality of Life

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Aspects of Management
 Minimum of five aspects of care
1. Pharmacologic management
2. Physical management
3. Psychosocial care
4. Nutritional aspects
5. Group of nonrheumatologic aspects of medical care

 Coordination of these components is vital for success of management

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1. Pharmacologic Mx
 No medication currently available is universally effective or without adverse
side effects
 Until recently, efficacy was generally limited to improving signs and symptoms
of disease
 Medical treatment of JRA can improve quality of life and physical function, and
limit deformity and disability
 Still, treatment remains ameliorative rather than curative

 The pharmacotherapeutic approach to the child with JRA, even early in the
illness, depends on the disease course and treatment preferences of the patient
and their families
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Specific Agents
1. NSAIDs

2. Second-line agents
a) Methotrexate
b) Sulfasalazine
c) Leflunomide
d) Hydroxychloroquine
e) Thalidomide
f) D-Penicillamine
g) Parenteral Gold
h) Oral Gold
i) Intravenous Immune Globulin
j) Cytotoxic Drugs (Azathioprine, Chlorambucil, Cyclosporine)

3. Glucocorticosteroids

4. Immune Response Modifiers (Biologics)

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1. NSAIDs
 Does not alter the natural history of JRA

 Action – anti-inflammatory
 Lessen stiffness and pain
 Increase range of motion

 Alone are sufficient in ¼ of all patients with JRA – mostly pauciarticular

type
 Ibuprofen as effective as aspirin
 Better safety profile – less toxicity
 Convenient – twice daily (Aspirin – 4 times)

 Based on the survey of Brunner, there is a clear preference for naproxen

 Dosed twice daily
 Liquid and pill form
 Limit usefulness in fair-skinned individual - pseudoporphyria
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 Favourable initial response in over half of patients on the first NSAID

prescribed
 In clinical practice – lack of efficacy can often be traced to poor patient
compliance.

 NSAIDs – must be taken on a consistent basis for better response

 If NSAID is not adequately effective after a 2-3 mth trial, alternative NSAID
can be tried
 Combining NSAID should be done with caution – synergy may occur in
toxicity but not necessarily efficacy
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 Precautions
 Most common side effect : abdominal pain and anorexia
 Can cause clinically significant GIT side effects
 Best taken with food to minimize gastric irritation
 Any patients on chronic NSAID therapy should be monitored for adverse renal, hepatic,
and gastrointestinal effects
 Children and parents should be aware of signs and symptoms of gastric ulcer and
gastrointestinal bleeding – uncommon but important side effects of NSAIDs
 Investigations
 Routine urinalysis (every 3-6 mths) – occasional occurrence of interstitial nephritis and
renal papillary necrosis
 Elevations of serum levels of liver enzymes – AST and ALT – measured every 3-6 mths
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 Contraindications :
 Tolmetin and indomethacin in cardiac dysfunction  hemodilution effect
 Aspirin in patients with asthma
 Any salicylate in G6PD deficiency, influenza and varicella infections – association
with Reye syndrome

 Availability of the new selective COX-2 inhibitors – reduce GIT consequences – but ultimate
usefulness of these agents in JRA remains to be determined
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2. Second-line agents
 Approximately ¾ of children with JRA will not respond
adequately to an NSAID alone
 Thus treatment with a second-line drug should then be
considered
 Referred to as Disease-modifying Antirheumatic Drugs
(DMARDs)
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(a) Methotrexate (MTX)

 Drug of choice for polyarthritis following inadequate
response to NSAIDs
 Relatively safe for at least several years of treatment at a
dose of 10mg/m2/week
 Firm evidence that MTX may actually slow or halt the
progression of bony destruction in adult RA
 Route
 Oral
 Both subcutaneous and intramuscular routes are equally
effective for higher doses or in patients with poor absorption
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 MTX has a number of significant safety concerns, thus

clinicians wish to taper or discontinue MTX as soon and as
rapidly as possible
 Common adverse effects
 Oral ulcers
 Gastrointestinal disturbances
 Bone marrow suppression (lesser extent)
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(b) Sulfasalazine
 Plays a minor role in children with poly- or pauciarticular JRA

 NEVER given to children with systemic-onset – relatively high rate of

development of serum sickness
 Brunner et al. found that only 5% of 195 children with JRA on second-line
agents were given sulfasalazine
 Contraindications
 Hypersensitivity to sulfa drugs or salicylates
 G6PD deficiency
 Elevated liver enzymes or hematocytopenia
 Systemic-onset JRA
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 S/E :
 Intolerance
 Potential toxicity to liver and bone marrow
 Nausea, diarrhea, vomiting
 Stevens-Johnson syndrome – rare but potential serious
complication
 Transient infertility in males
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(c) Hydroxychloroquine
 Maintains a minor role as second-line agent

 Given to 10% of children on DMARDs

 Most severe side-effects – retinal toxicity (dose-related)

due to drug deposition and macular degeneration
 Visual field and colour vision evaluations should be obtained
prior to, and every 6 to 12 months after, initiating
hydroxychloroquine therapy

 Skin may acquire a muddy appearance due to dermal

accumulation of the drug
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3. Glucocorticosteroids
 Prednisolone and related drugs have continued to play an important role in
the management of the systemic manifestations of JRA
 Every attempt should be made to keep the dose, frequency and duration of
steroid administration to a minimum
 If possible, should be given in the morning rather than night to minimize
growth suppression
 Two routes
 Systemic
 Intra-articular
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 Adverse side-effects of Glucocorticosteroids

 Infectious illness – Varicella infection
 Immunization should be considered for all nonimmune
patients
 If immunization not feasible, varicella zoster immune
globulin should be given to a nonimmune child on long-term
steroids within 48 hours of known exposure to chickenpox
 Acyclovir given at the onset significantly decreases the
disease severity
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(a) Systemic Corticosteroids

 High-dose IV hydrocortisone or methylprednisolone – usually restricted to
children with life-threatening complications – severe pericarditis, or DIC due to
macrophage activation syndrome
 Oral prednisone – systemic-onset JRA, especially those with pericarditis and
fever
 Daily or twice daily in a dose of 0.5-2.0mg/kg
 Low dose
 Moderately well-controlled disease
 Controlling symptoms during a flare-up of polyarticular disease
 While waiting for the onset of therapeutic effect of the DMARDs

 Long-term S/E : Growth suppression, significant trabecular bone loss (higher

dose), immunosuppresion, central nervous system effects, cataracts, protein
wasting and myopathy
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(b) Intra-articular Glucoorticosteroids

 Injection directly into inflamed joints is of considerable
benefit in the management of children with limited arthritis
 When treatment of NSAIDs has failed to completely control the
disease
 Intolerant to NSAIDs

 Eg Triamcinolone acetonide and triamcinolone

hexacetonide
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4. Immune Response Modifiers

(Biologics)
 Etanercept is a TNF antagonist and the first immune
response modifier to be used in large numbers of children
with polyarticular course JRA
 This agent appears to be at least as effective as MTX and
has extremely good toxicity profile
 Russo et al. recently reported that etanercept was capable
of inducing a sustained response in 1/3 of 19 cases of
systemic JRA
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Management
 Drugs and dosage
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General Approach to Pharmacotherapy of

Pauciarticular JRA
 Children presenting with this form of JRA are no longer, without exception,
started on systemic therapy with NSAIDs
 Typically begins with NSAIDs, but may move quickly to more aggressive
therapy such as MTX
 MTX second-line drug of first choice – started quickly when NSAIDs fail
 Especially when progression to a polyarticular course is likely

 Intra-articular infections of long-acting glucocorticosteroids such as

triamcinolone hexacetonide and triamcinolone acetonide may be used
initially in a high proportion of patients
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General Approach to Pharmacotherapy of

Polyarticular JRA
 In patients with polyarthritis in whom the arthritis is destructive or poorly
controoled by NSAIDs, a second-line medication is added early in the
disease course
 MTX and sulfasalazine – two drugs of choice

 Intraarticular steroids are frequently used to bring inflamed joints under

control while waiting for the effects of second-line agents to be realized
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General Approach to Pharmacotherapy of Systemic

JRA
 General approach is more complex than other forms due to
the multiple manifestations that may be present
 NSAIDs, prednisone and intraarticular steroids typically
are used early in the disease
 MTX is also one of the mainstay of treatment in systemic
JRA
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2. Physical Management
 Physical therapy
 Goals
a) Maintenance or increase of joint range of motion
b) Maintenance or increase of muscular strength
c) Maintenance or increase of endurance for activities of daily living
d) Decrease of pain
e) Maintenance of neutral postural alignment
 Education to parents and patient regarding the importance of adherence to home
treatment and exercise program
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 Occupational Therapy
 Goals
 Improve efficiency of effort (energy conservation)
 Substitute certain activities for others (joint protection)
 Increase independence by the use of assistive aids and
techniques
 Use of splints to correct or prevent deformities, correct or
prevent contractures, and aid flexion and extension of
involved areas
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3. Psychosocial care
 Child’s self image
 Physical achievement and physical appearance
 Confidence

 School participation
 Participation in physical education – depending on child’s limitations
 Coordination with teachers

 Recreation
 Should participate in school and community recreation programs ie swimming, bicycling, and
low-impact sporting activities

 Family functioning
 Counseling is imporatant – chronic potentially disabling disease in a young children have
devastating consequences on the functioning of the family unit, ranging from depression and
guilt to divorce
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 Patient and Parent Education

 Financial Burden
 Financial condition of the family must be considered while
prescribing medications or when deciding to put the child on
splint or other orthoses
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Other medical aspects

1. Opthalmologist
 Referred for uveitis screening
 Slit-lamp examination – especially in females, pauciarticular type and those
with ANA positive
 Regular follow-up even if initial screening normal
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Complications
 Chronic Anterior Uveitis
 Asymptomatic
 Can lead to severe visual impairment
 Thus, regular ophthalmological screening using a slit lamp is indicated

 Flexion contracture of joints

 Joint held in most comfortable position  minimize intra-articular pressure
 Chronicity  joint destruction  joint replacement

 Growth failure – may be generalized from anorexia, chronic disease & steroid
therapy
 Amyloidosis
 Rare but serious complication  proteinuria  renal failure
Growth failure and marked genu valgum (knock knees) in an 8-year-old girl with juvenile idiopathic arthritis. For
comparison, her sister on the left is 4 years old.

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Outcomes
 Prognosis – excellent, overall 85% complete remission rate

 Pauciarticular type – tend to do well

 Polyarticular & Systemic-onset – functional disability

 Poor prognosis
 Systemic onset
 +ve Rheumatoid factor
 Poor response to therapy
 Presence of erosions on X-ray
 63

THANK YOU
References :

1. Illustrated Textbook of Pediatrics 3 rd Edition

2. Nelson Essentials of Pediatrics 5th Edition

3. Paediatric Protocols for Malaysian Hospital 2 nd Edition

4. Arthritis and Allied Conditions 15th Edition (Chapter 62 – Treatment of

Juvenile Rheumatoid Arthritis)

5. http://www.racgp.org.au/Content/NavigationMenu/ClinicalResources/R
ACGPGuidelines/Juvenileidiopathicarthritis/JIA_algorithm.pdf