JUVENILE RHEUMATOID ARTHRITIS (JRA)

(JUVENILE CHRONIC ARTHRITIS-JCA)

DIAGNOSIS AND TREATMENT

Omondi Oyoo FACR

 Our task now is
not to fix the
blame for the past,
but to fix the
course for the
future
 TOPICS

INTRODUCTION
EPIDEMIOLOGY
DIAGNOSIS
TREATMENT
CLINICAL OUTCOME
FUTURE
TREATMENTS
 ASSUMPTIONS
IN PREPARING TALK

 AUDIENCE PREDOMINANTLY NON RHEUMATOLOGISTS

 SINCE THE TALK IS IN THE MORNING, AUDIENCE IS

PHYSICALLY STRONG AND MENTALLY ALERT

 TALK WILL BE BOTH QUANTITATIVE AND QUALITATIVE

– COVERING BOTH BASICS AND STRESSING KEY CONCEPTS
JRA- Introduction

most common childhood

arthritis
common childhood chronic
illness
JRA- Introduction

Cause
unknown
Associated with
– abnormal immunoregulation
– abnormal cytokine
production
– ? latent viral infection
JRA- Introduction

Requirements for
diagnosis
combination of data
from
– history
– physical examination
– laboratory testing
JRA- Introduction

Different from adult RA

in
clinical course
immunogenetic
association
functional out come
JRA- Introduction

5-10% JRA
rheumatoid factor
positive
poly articular
beginning in
adolescence
resembles adult
onset RA
 JRA- Epidemiology

overall 10-20 cases per 100,000

population
between 57-113/1000 children
younger than 16 years in the U.S.A.
(urban white)
26/100,000 – urban blacks U.S.A
Sweden 26/100,000
Finland 18.2 cases/ 1000 population
 JRA- Epidemiology

50% of JRA have disease that persist

into adulthood
age of onset 1-3 years
girls account for majority of patients
(twice as often as boys)
44% concordance rate in identical
twins
4% concordance rate in dizygotic
twins
 JRA- Epidemiology

U.S.A prevalence
70,000-100,000 case in a
population under 16
35,000-50,000 people over
age16 have active JRA
 JRA- Epidemiology

Comparison with other diseases

 same number of children as juvenile
diabetes mellitus
 4 times more than sickle cell anemia
 10 times more than hemophilia,
acute lymphocitic leukemia, chronic
renal failure or muscular dystrophy
 JRA- Diagnosis

Diagnostic criteria
 onset at less than 16 years of age
 persistent arthritis in one or more
joints for at least 6 weeks.
 exclusion of other types of
childhood arthritis
 JRA- Diagnosis

AMERICAN COLLEGE OF RHEUMATOLOGY DIAGNOSTIC CRITERIA

FOR CLASSIFICATION OF JUVENILE RHEUMATOID ARTHRITIS
_____________________________________________________________
•Age at onset younger than 16years
•Arthritis in one or more joints defined as swelling or effusion, or the presence of
two or more of the following signs: limitation of range of motion, tenderness or
pain on motion, and increased heat
•Duration of disease of  6 weeks
•Type of onset of disease during the first 6 months classified as
-Polyarthritis- 5 joints or more
-Oligoarthrits- 4 joints or fewer
-Systemic disease with arthritis and intermittent fever
•Exclusion of other forms of juvenile arthritis
______________________________________________________________
 JRA- Diagnosis

Four key points

arthritis
• swelling
• effusion
• limitation of motion
- tenderness
- pain on motion
- joint warmth
(arthralgia is not sufficient to satisfy this
definition )
 JRA- Diagnosis

Four key points(cont)

arthritis must persist for at least 6
weeks (ACR) (EULAR- 12 weeks)
other causes of chronic arthritis
must be excluded.
no specific laboratory or other
test can establish the diagnosis of
JRA
JRA- Diagnosis

Sub division of JRA

Systemic (sJRA) –10%
Polyarticular (po JRA) –
30%
Pauciarticular (pa JRA)
– 60%
 JRA- Diagnosis

Systemic onset JRA (sJRA)

– 10% of childhood JRA
– peak age 1-6 years
– boys and girls equally
affected
– daily/twice daily intermittent
fever
– characteristic JRA rash
JRA- Diagnosis

JRA rash
– pale pink
– blanching
– characterised by small macules
on maculopapules
– transient (minutes to a few
hours)
– non pruritic in 95% of cases
– commonly seen on the trunk
 JRA- Diagnosis

Other features of
sJRA
• growth delay • anemia
• osteopenia • leucocytosis
• diffuse lymphadenopathy • thrombocytosis
• hepatosplenomegaly • elevated acute
• pericarditis phase reactants
• pleuritis
JRA- Diagnosis

rare features in sJRA

– uveitis
– positive rheumatoid
factor
 JRA- Diagnosis

complications of sJRA
– pericadial tamponade
– severe vasculits

– prognosis determined by severity

of arthritis (may develop with fever
and rash or weeks or months after
onset of fever)
 JRA- Diagnosis

Poly articular onset (po JRA)

– arthritis in five or more joints
– seen in 30- 40% of patients with
JRA
JRA- Diagnosis

po JRA
– two distinct
diseases
• RF positive
• RF negative
 JRA- Diagnosis

RF positive po JRA

• almost always girls
• later disease onset (8 years old)
• HLA DR 4 positive
• symmetric small joint invovement
• risk of developing – nodules
- erosions
- poor functional outcome
• resembles adult onset RA
 JRA- Diagnosis

po JRA clinical manifestations

• fatigue
• anorexia
• growth retardation
• delay in sexual maturation
• osteopenia
• may develop at any age
• girls outnumber boys 3 to 1
 JRA- Diagnosis

Pauciarticular JRA (pa JRA)

– arthritis in four or fever joints
– two distinct clinical groups
– -early onset
– -late onset
 JRA- Diagnosis

Early onset pa JRA

- 1-5 years old
- girls : boys – 4 : 1
- ANA positive
- chronic eye inflammation (30-50% of
cases)
- best overall articular outcome
 JRA- Diagnosis

Early onset pa JRA eye involvement

- in 30 to 50% of patients
- involves anteria chamber
- no or minimal symptoms in 80% of affected
children
- severe changes include
- corneal clouding
- cataracts
- glaucoma
- partial or total visual loss
 JRA- Diagnosis

Late onset pa JRA

– more common in boys
– 50% HLA-B27 positive
– enthesitis/ tendinitis
– arthritis
– large joints (shoulder hips and knees)
- the spine
 JRA- Diagnosis

 pa JRA
– eye involvement ( rare)
- very sudden in onset
- painfull red eyes
- chronic complications less likely to
occur
JRA- Diagnosis
JRA- Diagnosis
JRA- Diagnosis
JRA- Diagnosis
 JRA- Treatment

Unique Pediatric Concerns in

treating JRA
 Patients are intimate members of family
- in house nurse, PT, OT, psychologist
- significant impact on sibs and parental
relationship
- maternal depression, separation/
divorce, monetary concerns may
distract from medical care
 JRA- Treatment

Unique Pediatric Concerns in treating

JRA (cont)
– Patients have a full time career- school!
– Growth/nutrition must be monitored
– Adolescence changes everything
- denial
- sex, drugs, rock & roll
– sports rule
- proactive enrollment in non-contact sports
- alternative roles
 JRA- Treatment

MANAGEMENT OF JUVENILE RHEUMATIOD ARTHRITIS

Basic program
Nonsteroidal anti-inflamatory drug
Physical and occupational therapy
Eduction and counseling of family and patient
Involvement of school and community agencies
Nutrition

Advanced drug therapy

Hydroxychloroquine, sulfaslazine, methotrexate
Gold compounds, D-penacillamine
Intra-articular steroids
 JRA- Treatment

MANAGEMENT OF JUVENILE RHEUMATIOD ARTHRITIS(cont)

Glucocorticoids

Immunosuppressive therapy

Experimental therapy
Orthopedic surgery
Preventive surgery
Reconstructive surgery
JRA- Treatment

Care involves
- family
- interdisciplinary health care
team
 JRA- Treatment

comprehensive care addressing

- education
- peer relationship
- self esteem
- social adjustment
- family dynamics
- vocational planning
- financial concerns
JRA- Treatment

treatment
– diagnosis to
satisfy
- patient
- parents
- extended family
- health care team
 JRA- Treatment

theraupetic goal
- relieving symptoms
- maintaining joint motion
- maintaining muscle strength
- preventing joint damage
- minimizing joint damage
- maximizing functional status
- promoting positive self image
- encouraging positive/ productive family
dynamics
JRA- Treatment

treatment programme
- physical
- social
- pharmacologic
- surgical
JRA- Treatment

physical
- range of motion
exercises
- splints
- joint protection
techniques
JRA- Treatment

social
- psychosocial adjustement
- school adaptation
- vocational issues
JRA- Treatment

pharmacologic
- articular
- ocular
- other manifestations
 JRA- Treatment

NSAIDS
- majority respond in two weeks
- 25% do not respond until 8 to 12 weeks
(average time 4 weeks)
- switch over to another NSAID if one type is
not giving good response
- Aspirin dose 75-90mg/kg/day
- Naproxen 15mg/kg/day
- Ibuprofen 35mg/kg/day
- Indomethacin 2-3mg/kg/day
- Tolmetin sodium 20-30mg/kg/day
 JRA- Treatment

problems associated with

NSAIDS
- anorexia
- abdominal pains
- coagulation disorders
- lever function
- renal function
- cns symptoms
 JRA- Treatment

Methotrexate(MTX) and NSAIDS

- in two thirds of patients with JRA
- 10mg/m2 BSA weekly
- mainly for sJRAor po JRA
- response 70-80%
non responders
• increase methotrexate dose to
1mg/kg/week (maximum 50mg/week)
 JRA- Treatment

problems with methotrexate

- oral ulcers
- nausea
- decreased appetite
- abdominal pains
- pulmonary complications
 JRA- Treatment

 oral gold – 0.15mg/kg/day efficacy

 d-penicillamine- 10mg/kg/day similar to
 hydroxychloroquine 5-7mg/kg/day
placebo
 JRA- Treatment

injectible gold
- 5mg test dose
- 0.75-1mg/kg weekly for 20 weeks
- maintenance every 2 weeks for 3
months
- every 3 week for 3 months
- every 4 weeks
- 50 –60% of patients improve
- high frequency of side effects
 JRA- Treatment

sulphasalazine
- encouraging results
- 40-60mg/kg/day
- A void in sJRA

 intravenous gamma globulins (IVGG)

• promising results in po JRA
 JRA- Treatment

glucocoticoids
- used in severe and life threatening
complications of sJRA
- used in resistant JRA
- often used in combination with other
drugs
- predisone dose 0.1-1mg/kg/day
 JRA- Treatment

INDICATIONS FOR SYSTEMIC STEROIDS IN sJRA

 Macrophage Activation Syndrome
 CNS involvement (rare) –seizures, lethargy,
meningismus
 Stridor with cricoarytenoid arthritis
 Interstitial pulmonary disease
 Myocarditis
 JRA- Treatment

INDICATIONS FOR SYSTEMIC STEROIDS IN

sJRA(cont)
 Moderate to severe pericarditis with
impairement of cardiac function
 Secondary amyloidosis
 Severe anemia
 Failure of standard therapy to relieve
symptoms sufficiently to allow comfortable
function
 JRA- Treatment

Intraarticular steroids
– in pa JRA
 JRA- Treatment

IMMUNO SUPPRESSIVE
THERAPY
– chlorambucil
– cyclophosphamide
– azathioprime
 JRA- Treatment

 IMMUNO SUPPRESSIVE THERAPY

– Used in
– secondary amyloidosis
- life threatening illness
- un remitting progression of arthritis and
disability
 JRA- Treatment

IMMUNO SUPPRESSIVE
THERAPY
– Problems
• leucopenia
• bone marrow supression
• malignancy
• mutagenic effects
• sterility and amenorhoea
 JRA- Treatment

eternecept
– in patients refractory to or
resistant to methotrexate
– dose 0.4mg/kg/dose (maximum
25mg twice weekly for three
months)
 JRA- Treatment

Ocular
– managed by experienced ophthalmologist
- early detection
- topical corticosteroid
- dilating agents
- frequent follow up
• severe cases- systemic/sub-tenon steroid injection
- chlorambucil
- cyclophsophamide
- NSAIDS
 JRA- Treatment

 other extra articular manifestation

- poor linear growth especially in sJRAand po JRA

- growth hormone therapy
– protein calorie malnutrition due to
- poor appetite
- catabolic drugs
- physical inactivity
- inflammatory medications
– dietary intervention
- adequate caloric and protein intake
- nocturnal enteral nasogastric supplemental feeding
JRA- Treatment

surgical
- synovectomy
- tenosynovectomy
- re-constructive surgery
 JRA- Outcome

 satisfactory for properly managed children is

approximately 85%
 about 30% of JRA patients have functional
limitation after 10 or more years
 mortality 0.29 –1.1 /100 patients (3 – 14 times
greater than the standardized U.S. children
population)
 ocular –85% have normal visual acuity
 15% with significant visual loss
 10% blinded in at least one eye.
JRA-Future Treatments

Anti TNF -- standard or elevated

doses
Anti IL –6
Anti IL –6 + Anti TNF -
Stem cell transplant
Pulse therapy to induce remission
- IV steroids + IV Cytoxan + MTX
Other combinations
 The very best
way to predict
the future is to
create it.
THANK YOU
FOR YOUR
ATTENTION