JIA and
Other
Rheumatic
Diseases in
Children
Norma Liburd,
RN-BC, MN
Objectives
Define Juvenile Idiopathic
Arthritis (JIA) and discuss
the diagnostic criteria.
Identify the subtypes of JIA
and discuss characteristics
of each.
Name at least one NSAID,
one biologic and one
DMARD used in the
treatment of JIA.
A few more Objectives
Discuss three school related problems
students with JIA have and intervention
strategies for each.
Identify the criteria for classification of
systemic lupus erythematosus.
Name the most common type of juvenile
localized scleroderma.
Discuss the criteria for diagnosis of
juvenile dermatomyositis, and treatment
approaches
Overview of JIA
New classification criteria proposed by the
Pediatric Task Force of the International
League of Associations for Rheumatology
(ILAR) in 1997
Chronic arthritis in childhood – one of the
more frequent chronic illnesses of
childhood.
An important cause of short and long-term
disability
Chronic arthritis
in childhood: JIA
It’s not a single disease, but a group of
related, genetically heterogeneous,
phenotypically diverse
immunoinflammatory disorders affecting
joints and other structures, possibly
activated by contact with an external
antigen or antigens.
JRA - Incidence/Prevalence
Published series are difficult
to interpret due to
classification, methodologies,
heterogeneity
Incidence: (per year)
1/100,000 in Japan
20/100,000 in Norway
Prevalence:
– 10 /100,000 in France
– 400/100,000 in Australia
– 113/ 100,000
Arthritis Foundation:
300,000 children in the US
have chronic arthritis.
.
JRA – Classification Criteria
JRA – American College of Rheumatology 1970
three types of onset: oligo (pauciarticular),
polyarticular, & systemic in the first 6 months of
onset
JCA Juvenile Chronic Arthritis (European League
Against Rheumatism) 1977
JIA Juvenile Idiopathic Arthritis proposed by the
Pediatric Task force of the International League of
Associations for Rheumatology ILAR (1993) –
developed to achieve homogeneity within disease
and categories.
Sex Ratio
All types of JIA:
– Girls: Boys 2:1
Oligo JIA:
– Girls: Boys 3:1
JIA with uveitis
– Girls: Boys
5-6:1
Poly JRA:
– Girls: Boys 3:1
Systemic JRA:
– Girls: Boys approx. 1:1
JIA outcomes: Mortality
Disease associated death rate is
< 1% in Europe
< 0.3% in North America
These numbers represent a
4 Fold to 14 fold Increase in Mortality Rate
Compared with General Population
Causes are cardiac, infection & macrophage activation syndrome
JRA outcome: functional abilities
Author
Year Published
Followup in
years (mean)
Poor Function
Bunim
1959
10
31%
Laaksonen
1966
>16
48%
Ansell
1976
>15
23%
Hill
1976
(14.5)
33%
Hanson
1977
5-25 (10)
28%
Stoeber
1981
10-22 (15)
41%
Levinson
1991
15-20
17%
Zak
2000
28
11%
Classification Criteria for JIA
Age at onset <16 years
Duration of Arthritis: 6 weeks
Arthritis in one or more joints defined as
swelling or effusion, or presence of two or
more of the following signs: (in 1 or more
joints)
– Limitation of ROM
– Tenderness or pain on motion
– Increased heat
Exclusion of other diseases
Diagnostic Studies
Diagnostic Tests
There is no lab test that diagnoses JIA
The H&P should determine the labs, not
the reverse
– CBC
– Rheumatoid factor
– Antinuclear Antibody (ANA) – with titer
– ESR or CRP
– Anti-CCP (anti-cyclic citrullinated protein)
Radiologic Studies
X-rays
Soft tissue swelling
Osteoporosis
Periosteal new bone
formation
Epiphyseal overgrowth
Marginal erosions
Narrowing of
cartilaginous
space
Joint subluxation
Bony fusion
Dexascans
Osteopenia
Osteoporosis
Etiology
Immune mediated disease
– Abnormal immunoregulation
– Abnormal cytokine production in the
inflammatory pathway (TNF, IL-6, IL-2R,
IL-1alpha)
Complex genetic predispositions
– HLA associations
Environmental triggers
– Infections
– Trauma
– Stress
Synovial lining is a thin membrane enclosing the joint space. The joint space
contains fluid that bathes the joint and reduces friction on motion.
With onset of inflammation, the synovial lining thickens and secretes more fluid, which may remain
in the joint and cause swelling. The inflamed lining produces warmth, swelling, and pain.
As inflammation progresses, the synovial lining grows over the cartilage and starts to erode it. As
inflammation continues, changes include marked erosion of cartilage, cystic changes and thinning
of the bone.
Classification Criteria
1. Systemic
2. Oligoarthritis
a. Persistent
b. Extended
3. Polyarthritis (rheumatoid factor negative)
4. Polyarthritis (rheumatoid factor positive)
5. Psoriatic arthritis
6. Enthesitis-related arthritis
7. Undifferentiated arthritis
a. Fits no other category
b. Fits more than one category
From Petty RE, Southwood TR, Baum J et al: Revision of the proposed classification criteria
for juvenile idiopathic arthritis: Durban, 1997, J Rheumatol 25:199-1994, 1998.
JIA Subtypes
Systemic Onset (5-15%)
Polyarticular Onset (20%)
– Rheumatoid Factor Positive
– Rheumatoid Factor Negative (85%)
Oligoarthritis (50-80%)
Juvenile psoriatic arthritis (7%)
Enthesitis related arthritis
Undifferentiated
Systemic JIA
Definition:
– Arthritis with, or preceded by, daily fever
of at least 2 weeks’ duration
– Fevers are quotidian (daily) for at least
3 days and is accompanied by one or
more of the following:
Evanescent, non-fixed, erythematous rash
Generalized lymph node enlargement
Hepatomegaly and/or splenomegaly
Serositis
Quotidian fever
Intermittent fever of
systemic JIA in a 3year-old girl. The
fever spikes usually
occurred daily in the
late evening to early
morning (quotidian
pattern), returned to
normal or below
normal, and were
accompanied by
severe malaise,
tachycardia, and
rash.
Systemic JRA
Rash – Salmon colored
– Maculopapular –
flat to slightly raised
– Trunk and
extremities
– Migratory
– Pruritic 5%
– Fleeting
– Persistent with
fever spike
Overview of Systemic JIA
10-15% of all JRA patients
Broad peak of onset 1-5 years
M:F 1:1
Variable number of joints
Il-6 is elevated and correlates with disease activity
Extraarticular symptoms:
– Fever 100 %
– Rash 95%
– Hepatosplenomegaly, 85%
– Lymphadenopathy 70%
– Pericarditis 35%
– Pleuritis 20%
Macrophage Activation Syndrome
Rare devastating complication of systemic JIA.
Etiology is uncertain.
Demonstration of macrophages ingesting other
hematopoietic cells in marrow is diagnostic
Early recognition is life-saving
– Looks somewhat like a flare up of systemic JRA but is different enough to allow for
early recognition)
Associated with CMV, EBV, changes in meds
Mortality 10-20%
Macrophage Activation Syndrome
Acute onset of fever with
–
–
–
–
–
–
–
Bruising, purpura, mucosal bleeding
Enlarged lymph nodes, liver, spleen
Elevated AST, ALT, PT, PTT, fibrin D-dimer
Elevated ferritin & triglycerides
Abrupt fall in WBC & platelets
Fall in ESR
Fall in fibrinogen, clotting factors
Often progresses to fatal DIC, hepatic
failure, encephalopathy
Treatment: IV steroids, cyclosporin
Polyarticular JIA - RF negative
Five or more joints in
the first 6 months of
disease
Asymmetric joint
involvement
Large joints of knees,
wrists, elbows and
ankles often affected
Morning stiffness, joint
pain
Intermittent low-grade
fever
Polyarticular - RF positive
Arthritis affecting 5 or more joints in the
first 6 months of disease.
Similar to adult RA
Females with onset in adolescence
Rheumatoid nodules
Early onset of erosive synovitis
Symmetric joint involvement
Small joints of hands or feet are affected
TMJ: micronathia
Cervical spine may be affected
Rheumatoid Nodules
Occur in 5-10% of children
with JIA
Most frequently on elbow
Pressure points, digital flexor
tendon sheaths, Achilles
tendons, bridge of nose in
child who wears glasses
Firm or hard, usually mobile,
nontender.
Solitary or multiple, may
change in size, may last
months to years.
Oligoarticular JIA
Arthritis in 1 to 4
joints during the first
6 months of disease
Girls 1 to 4 years
Knees, ankles,
elbows
Painless swelling of
joints is common
Uveitis: insidious,
subacute
15-20% have uveitis
JIA: Oligo – persistent
No more than 4 joints affected throughout the
disease course
JIA: Oligo - extended
Affects a total of more than 4 joints after the
first 6 months of disease.
At least 1/3 of children with Oligoarticular
arthritis fall into this category
Outcome is more typical of RF+ polyarticular
disease
Uveitis in JIA
Intraocular
inflammation affects
iris and ciliary body
Usually insidious and
may be asymptomatic
Activity of eye does
not parallel joint
disease
Slit lamp exam
detects anterior
chamber inflammation
Girls, ANA + and
onset before age 7 at
higher risk
Prognosis of Uveitis in JIA
Very good in 25% of cases
25% may require surgery for cataracts and/or
glaucoma
50% require prolonged treatment for moderate to
severe chronic inflammation; however, the
prognosis is generally good
Complications: cataracts
20%, glaucoma 20%,
band keratopathy 16%
(end stage scarring)
Uveitis in JIA
Usually occurs after onset of arthritis. Highest
risk is within 2 years of onset of arthritis.
Majority develop eye disease within 5-7 years
after onset
65% have bilateral involvement, unilateral may
progress to bilateral
Treatment includes topical steroids, SQ
Methotrexate, IV Remicade; SQ Humira and
Enbrel.
Slit Lamp Exam – JIA
Guidelines
Rheumatology & Ophthalmology sections of the
American Academy of Pediatrics, 1993
Oligoarticular ANA+
<7
years at Dx
Oligoarticular ANA+ 7 or
older at Dx
Oligoarticular ANA <7
years at Dx
Oligoarticular ANA –
<7 years at Dx
Systemic
Q 3-4 months for 7
years, then yearly.
Q 4-6 months for 7 yrs,
then yearly.
Q 4-6 months for 4 yrs,
then yearly.
Yearly.
Guidelines for ophthalmological screening of
children with JIA
JIA Onset
ANA
Onset < 7 yrs
Onset ≧ 7 years
Oligo
Positive
Every 3-4 months
Every 4-6 months
Oligo
Negative
Every 4-6 months
Every 4-6 months
Polyarthritis
Positive
Every 3-4 months
Every 4-6 months
Polyarthritis
Negative
Every 4-6 months
Every 4-6 months
Systemic
Neg or pos
Every 12 months
Every 12 months
High risk – screen every 3 months
Moderate risk – screen every 4-6 months
Low risk: screen every 12 months
All patients considered to be at low risk 7 yr after onset of arthritis; should have yearly
ophthalmological exams indefinitely.
All patients are considered to be at low risk 4 years after onset of arthritis, should have yearly
ophthalmological exams indefinitely.
All high risk patients are considered to be at medium risk 4 years after onset of arthritis.
Modified from Yancy C, et.al, The Guidelines of the Rheumatology and ophthalmology sections of the
AAP. Pediatrics 92:295-296, 2003.
JIA: Psoriatic Arthritis
Arthritis and psoriasis or
Arthritis with 2 of the following:
– Dactylitis - sausage like
swelling of toe or finger
– Nail pitting
– Psoriasis in a first degree
relative (parents, siblings)
Slightly more females
Symmetrical involving large
and small joints
JRA: Spondyloarthropathy
JIA: Enthesitis related arthritis
Arthritis and enthesitis
Arthritis or enthesitis with at least 2 of the
following:
– Sacroiliac joint tenderness and/or
inflammatory lumbosacral pain
– Presence of HLA-B27
– Onset of arthritis in a male after age 6 years
– Ankylosing spondylitis, Enthesitis Related
Arthritis, Sacroiliitis with inflammatory bowel
disease, Reiter’s syndrome or acute anterior
uveitis in a first-degree relative.
JRA: Spondyloarthropathy
JIA: Enthesitis related arthritis
Primarily affects boys 8 years and older
Affects large joints of lower extremities
Heel pain and Achilles tendonitis
Sacroiliitis (90% of cases)
Iritis (20% of cases) generally acute
process
Low grade fevers
Decreased appetite
Medications
NSAIDs
DMARDs:
Methotrexate, Plaquenil,
Sulfasalazine
Biologic response
modifiers
Glucocorticosteroids
Miscellaneous
NSAIDS
FDA approved for
pediatric use
– Aspirin
– Tolmetin
– Naproxen
– Ibuprofen
– Indomethacin
– Meloxicam (Mobic)
– Celebrex
Common NSAIDS in JIA
Naproxen
Ibuprofen
Indomethacin
Tolmetin
Meloxican
Piroxicam
Celecoxib
Nabumetone
(Relafen)
ASA
mg/kg/day
10-20
30-40
1.5-3.0
20-30
0.25
0.2-0.3
6-12
30
Max
1000
2400
200
1800
15
20
400
2000
80-100
3200
Methotrexate
Standard dose: 10-15 mg/m2 or 0.3-0.6
mg/kg/week, subQ
Improvement seen in 6-8 weeks, but may
take up to 6 months.
Labs every 6 weeks: CBC, CMP
No alcohol
Used for treatment of uveitis (4-6 months
to determine efficacy)
Meds: Targeting inflammation
Meds: Biologic Agents:
Target against cytokines involved in
inflammation: TNF , IL-1Ra, IL-6
Enbrel
(Etanercept):
approved for JRA
– 0.4 mg/kg twice per
week SQ injections
– Improvement by third
to fourth dose
– Hold for suspected
bacterial infection,
varicella
– Site reactions
– Binds to TNF
Biologic Agents:
Remicade (Infliximab) - infusion, risk of
anaphylaxis, dose may need to be
increased depending on response, used in
refractory uveitis as well
3 mg/kg IV weeks 0, 2 and 6 (may  dose
to 10 mg/kg)
Improvement can be seen after first dose
Labs every 4-8 weeks (CBC, CMP)
Not approved for children
Biologic Agents:
Anakinra (Kineret) – (blocks IL-1 which
stimulates synoviocytes and chondrocytes
to produce small inflammatory mediators –
leading to cartilage destruction and bone
erosions.
– Used in systemic JRA (but not approved)
– Daily, very painful, SQ injections, rotation of
sites is important
Biologics
Actemra (Tocilizumab) 8 mg/kg
– ACTEMRA is indicated for the treatment of
active systemic juvenile idiopathic arthritis in
patients 2 years of age and older who have
responded inadequately to previously therapy
with NSAIDS and steroids.
--Given every 2 weeks
by IV, over one hour.
--Dosing interval can
be shortened to every
week if condition
warrants.
Biologics
Humira (adalimumab) TNF blocker: approved
for children ages 4 to 17
Dose: 15mg (33 lbs) to <30 kg (66 lbs): 20 mg
every other week
Dose: 30kg or more: 40 mg every other week
Humira pen – or prefilled syringe
Painful injections, but can add lidocaine to buffer
the pain (Hershey study).
Can shorten interval to weekly (with auth)
Biologics
Orencia (Abatacept) T-lymphocyte modulator
IV over 30 minutes: at 0, 2 4
weeks, then every 4 weeks
Approved for children 6 and
older as monotherapy or with
methotrexate
<75 Kg: 10 mg/Kg
If over 75 Kg: follow adult
dosing
Approved for adults: weekly SQ
self injection
Glucocorticosteroids
IV Solumedrol and daily oral Prednisone
systemic flares ~ pericarditis or persistent Sx
temporary measure until DMARD is effective
Joint injections - usually under sedation
– Triamcinolone hexacetonide (Aristaspan)
long acting steroid
Works best with large joints
Miscellaneous Treatment
Thalidomide: 2 mg/kg/day
– Mechanism of action probably by effects on TNF
and other inflammatory cytokines
– Very rigorous patient monitoring
Bone Marrow Transplant
– Experimental for severe autoimmune disease
unresponsive to conventional therapy
– Autologous stem cell transplant being evaluated
in small number of children
– Infections ~ very risky – high death rate
PT/OT - Overall goals
Maintain or restore
functional ROM in joints
Strengthen muscles
surrounding affected joints
- to enable joints to
remain in a functional
position
Assist child to perform
activities in ways as close
to normal as possible
– so they do not feel
“different” from peers.
PT/OT - Management in JIA
Splint fabrication