Samatha Madhavarapu

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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,

 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.

 Vital signs:
 HEENT : Normal
 Heart , Lungs ,Abdomen: Normal
 Skin: No rash
 R knee: decreased extension, no swelling, no redness, no warmth.
 Other Jts: FROM.

 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

 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

 Rheumatic &
Inflammatory Diseases
 Seronegative
Spondyloarthropathies
 Infectious Illnesses
 Reactive Arthritis
 Immunodeficiencies
 Metabolic Disorders
 Bone & Cartilage
Disorders
 Neoplastic Disorders
 Hematologic Disorders
 Pain Syndromes

 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.

 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

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Characteristic
Onset Types
Age of onset of arthritis
ACR ELAR ILAR
3 6
< 16 yr <16 yr
6
<16 yr
Duration of arthritis
Juvenile Ankylosing
Spondylitis
>= 6 wk
Doesn’t include
>= 3mn >= 6wk includes Includes
Juvenile Psoriatic Arthritis Doesn’t include includes includes
Inflammatory Bowel
Disease
Doesn’t include
Exclusion of other diseases YES includes includes
YES YES

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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

 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

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Synovitis: Villous hypertrophy & edema of subsynovial 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.

 Onset insidious or abrupt
 Morning stiffness and gelling
 Easy fatiguability
 Joint pain and swelling, limited joint movt, mild /non erythematous.

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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

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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

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Arthritis with visceral involvement
Characteristic intermittent spiking fevers to >/= 39c 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

 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

 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)

 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.
 synovial inflammation, early minimal changes seen
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Serositis
DEXA
: osteopenia

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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

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Used to treat all subtypes of JRA (40-60% children show improvement).
Mean duration for anti-inflammatory effect in JRA-
30 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.

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Safest, most efficacious, least toxic of of 2 nd line 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.

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For overwhelmingly inflammatory 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%

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Etanercept: Only one approved for 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

 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

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Child with oligo: esp. girls, onset< 6yrs age –chronic 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 8.9x10
3 /mcL (8.9x10
9 /L) with 40% polymorphonuclear leukocytes, 45% lymphocytes, and 15% monocytes; hemoglobin of 11.0 g/dL (110.0 g/L); platelet count of 472.0x10
3 /mcL
(472.0x10
9 /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