Transcript JRA - SBH Peds Res

Samatha Madhavarapu
21 m/o F with limping
HPI
• Intermittent limp of R leg started 6 weeks ago.
• Constant limp since 3 days
• Worse upon awakening
• Stiffness in R knee.
• Transient warmth and redness +
• Not able to bear weight initially, improves over 2 hrs.
• Was outdoors in Upstate at BBQ 8 weeks ago
• No fever, rash, recent URI
• No trauma, diarrhea,
HPI Contd…
 PMH: None
 FH: grand father has seizure disorder. No bone/joint
problems
 Immunizations: UTD
 NKDA
 Meds: Tylenol PRN pain.
 Labs done 6 weeks ago: wbc7.6, 33.9/66.3, ESR 18, xray
R knee Normal.
Physical Exam
Vital signs:
HEENT : Normal
 Heart , Lungs ,Abdomen: Normal
Skin: No rash
R knee: decreased extension, no swelling, no redness,
no warmth.
Other Jts: FROM.
LABS
BMP: 136/4.9/ 101/22/12/0.4/139/10.5
Total Protein/ Albumin: 7.5/4.7
LFT: 0.2/01, 38/19, 244
CBC: 7.3/ 12/36.3/392
ESR: 15
Other Labs
 CRP: 0.2
 ANA negative
 Lyme Ab titre: 1.2
 Anti CCP antibody: 8.3
 HLA B 27: Negative
 RF: 10.0
 Ultrasound of Knees: Small R knee jt effusion
DD of Arthritis/extremity pain in
Children
 Rheumatic &
Inflammatory Diseases
 Seronegative
Spondyloarthropathies
 Infectious Illnesses
 Reactive Arthritis
 Immunodeficiencies
 Metabolic Disorders
 Bone & Cartilage
Disorders
 Neoplastic Disorders
 Hematologic Disorders
 Pain Syndromes
Juvenile Rheumatoid Arthritis
 JRA most common rheumatic disease of childhood
 Synovitis of peripheral joints manifested as swelling
 JRA is not a single disease, but a category of diseases.
 It is a diagnosis of exclusion.
Criteria for Classification of JRA
 Age of onset: < 16 yrs
 Arthritis in > or = 1 joint
 Duration of the Disease: > or = 6 weeks
 Onset type is defined by type of articular involvement
in the first 6 months after onset:
 Poly arthritis: > or = 5 inflamed joints
 Oligo arthritis: < or = 4 inflamed joints
 Systemic Disease: arthritis with intermittent fever
Classification of Chronic Arthritis in
Children
 ACR, ELAR & ILAR classification
 Only ACR criteria have been statistically
validated.
Characteristic
ACR
ELAR
ILAR
Onset Types
3
6
6
Age of onset of arthritis
< 16 yr
<16 yr
<16 yr
Duration of arthritis
>= 6 wk
>= 3mn
>= 6wk
Juvenile Ankylosing
Spondylitis
Doesn’t
include
includes
Includes
Juvenile Psoriatic Arthritis
Doesn’t
include
includes
includes
Inflammatory Bowel
Disease
Doesn’t
include
includes
includes
Exclusion of other diseases
YES
YES
YES
Etiology
• Unknown
• Immunogenetic Susceptibility (Specific HLA
subtypes)
• External Triggers
- Viruses( EBV, Parvo virus B19, Rubella)
- Host hyperreactivity to specific self antigens(type 2
collagen)
- Enhanced T-cell reactivity to bacterial
/mycobacterial heat shock proteins
Epidemiology
 Incidence of JRA: 13.9/100,000
Sex:
 Pauci and poly articular disease more in girls
 Systemic onset –equal frequency in boys and girls
Race:
 Prevalence of JRA lower in Urban African – American
compared to Caucasians
 Oligo 40% newly diagnosed cases in Caucasians.
 Blacks with JRA were older and less likely to test positive
for ANA or to have uveitis, more likely to test positive for
Ig M RF
Pathogenesis
• Synovitis: Villous hypertrophy & edema of subsynovial
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tissues.
Vascular endothelial hyperplasia
Infiltration of mononuclear and plasma cells.
Pannus formation with erosion of cartilage and bone.
Recriutment of T-cells specific to synovial non specific
antigens., facilitated by specific HLA types.
Clinical Features
 Onset insidious or abrupt
 Morning stiffness and gelling
 Easy fatiguability
 Joint pain and swelling, limited joint movt, mild /non
erythematous.
Oligoarthritis/Pauciarticular
• Affects 4 or fewer joints
• Typically larger joints (knees, ankles, wrists).
• Starts with 1 joint
• Monoarticular involvement of hip, upper extremity
large joints never presenting sign in JRA.
• If knee is affected-limping+, esp morning
• Chronically- atrophy of extensor muscles of thigh,
tight hamstrings & knee flexion contractures.
• Associated with HLA-DR8
Polyarthritis/Polyarticular
• Minimum 5 joints should be effected.
• Both large & small jts of upper and lower extremities
• Resembles adult RA and HLA profile.
• Associated with HLA –DR4
• Rheumatoid nodules in severe form
• Micrognathia- chronic TM joint disease
• C-Spine involvement- atlantoaxial subluxation
Systemic Onset
• Arthritis with visceral involvement
• Characteristic intermittent spiking fevers to >/= 39c
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for >/= 2 weeks.
Febrile episode assoc with evenescent (< 1 hr)
macular rash, linear or circular, salmon colored ,2-5
mm, over trunk & proximal extremities.
Koebner Phenomenon+
Arthralgia, myalgia
Hepatosplenomegaly,Lymaphadenopathy
Serositis/pericardial effusion
Photophobia (uveitis), irregular iris due to synechiae
Labs
 CBC with diff:
Lymphopenia,Thrombocytosis,microcytic anemia.
Neutropenia is uncommon.
 ESR:
- Always elevated with systemic JRA.
- Usually elevated with polyarticular but within
reference range in pauci articular.
- When elevated, ESR helps to monitor success of
medical treatment
Labs contd
 ANA:
Positive in 40-85% with oligo/poly articular
Unusual with systemic onset
Titers do not correlate with disease severity.
Associated with increased risk of uveitis
 RF: Rare in systemic JRA.
Marker of persistence of polyarticular JRA into
adulthood, devpt of rheumatoid nodules and poor
functioning.
 Total protein and albumin: levels are often decreased
during active disease
 ALT test: to exclude hepatitis (viral or autoimmune)
prior to starting NSAIDS
 U/A: to r/o infection (trigger of JRA or transient
postinfectious arthritis) and nephritis (seen in pts with
SLE)
Imaging
X-ray:
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When 1 jt is affected , to r/o osteomyelitis or
septic arthritis.
 Soft tissue swelling, regional osteoporosis,
osteopenia, sub chondral bone erosions, narrowing
of cartilage spaces, fusion of nueral arches.
MRI
 synovial inflammation, early minimal changes seen
Echo cardiography: Serositis
DEXA: osteopenia
X rays
Management
 Multidisciplinary Team for care of children
 Core Team:
 Parents and Child
 Pediatric Rheumatologist
 Pediatrician
 Nurse
 Social Worker
 Physical Therapist
 Occupational Therapist
 Nutritionist
 Ophthalmologist
 Main goal: maximize daily functioning , minimize
drug toxicity
 Key predictor of long term outcome is early
diagnosis and referral to rheumatology team.
 Diet: Include 3 servings of calcium rich foods
 Activity: more active, better the prognosis
NSAIDS
• Used to treat all subtypes of JRA (40-60% children
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show improvement).
Mean duration for anti-inflammatory effect in JRA30 days
Most with pauci and few with poly respond to NSAID
alone .
Rofecoxib , celecoxib (selective Cox-2 inhibitors) ~
similar to naproxen effectiveness
Adverse : nausea, decreased appetite, abd pain. Less
gastritis.
Methotrexate
• Safest, most efficacious, least toxic of of 2nd line
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agents for JRA.
Used in 60% patients with poly JRA
Inhibits DHFR, purine synthesis.
Pts unresponsive to PO MTX benefit from SC or IM
administration.
Well tolerated in children.
Pts who respond well have improved growth,
functionality, radiographic improvement.
Glucocorticoids
• For overwhelmingly inflammatory
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or systemic illness.
Bridge therapy for those who did
not respond to conventional therapy
Ocular control of uveitis (drops or injections)
Intra articular use :initial therapy in pts with only 1 or
2 joint involvement
Improvement in symptoms in 2-3 days, which last for
at least 6 mo in 60% and 1yr in 45%
Anti TNF alpha
• Etanercept: Only one approved for
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children
Fusion protein with TNF receptor
monomer fused to Fc portion of Ig G1.
Administered SC twice weekly used in active
polyarticular JRA who fail MXT therapy.
JRA assoc-chronic uveitis that is inadequately
responsive to steroid therapy.
Not to be used with h/o chronic infections
R/o TB before starting rx
Sulphasalazine
 Improved joint inflammation & labs compared to
placebo.
 GI irritation and rash.
 Steven johnson in pts with active systemic JRA.
 CI in porphyria and G6PD deficiency
Systemic JRA
Prognostic features
• Child with oligo: esp. girls, onset< 6yrs age –chronic
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uveitis risk
Polyarticular: RF, rheumatoid nodules
Systemic onset: number of joints involved, duration
of inflammation, severity of arthritis.
Limb length discrepancy, contractures,
Disability continues into adulthood in 20%
Chronic pain syndromes.
Psychological complications.
 LIVING WITH RHEUMATOID ARTHRITIS
 http://www.youtube.com/watch?v=NqyB-cTxvs8
A 16-month-old boy is brought to your clinic because his mother says he
is "walking funny" today. She states that he has been walking for 4
months and is very active, but she is unaware of any trauma or falls. She
denies fever or other symptoms. He appears well and has normal vital
signs. Physical examination reveals mild tenderness to palpation over
the medial aspect of the lower leg just above the ankle. There is no
overlying bruising, erythema, or edema, and you can elicit full range of
motion in the hips, knees, and ankles.
Of the following, the MOST likely diagnosis is
a. Aneurysmal Bone Cyst
b. Ankle Sprain
c. Fracture
d. Osteomyelitis
e. Transient Synovitis
An 11-year-old girl presents 2 weeks after an office visit for a presumed viral
illness characterized by fever, malaise, and flushing of the cheeks. Today, her
mother notes that she no longer has a fever, but she complains of pain in her
knees and elbows. On physical examination, the left knee is slightly swollen and
warm but not erythematous. The girl reports pain on movement of both
elbows, but there are no physical findings on examination of the elbows or
other joints. The remainder of the physical examination findings are normal,
except for an oral temperature of 100.6°F (38.1°C). Results of laboratory studies
include a white blood cell count of 8.9x103/mcL (8.9x109/L) with 40%
polymorphonuclear leukocytes, 45% lymphocytes, and 15% monocytes;
hemoglobin of 11.0 g/dL (110.0 g/L); platelet count of 472.0x103/mcL
(472.0x109/L); and erythrocyte sedimentation rate of 20 mm/hr.
Of the following, the MOST likely pathogen to cause this child's
joint complaints is
a. Borrelia burgdorferi
b. Coxsackievirus
c. group A beta-hemolytic streptococci
d. influenza A virus
e. parvovirus B19
Acknowledgement
Dr. Jillian Parekh
Dr. Karen Sawitz
Questions???