Samatha Madhavarapu

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: NoneFH: grand father has seizure disorder. No

bone/joint problems Immunizations: UTDNKDAMeds: Tylenol PRN pain.Labs done 6 weeks ago: wbc7.6, 33.9/66.3,

ESR 18, xray R knee Normal.

Physical ExamVital signs:HEENT : NormalHeart , Lungs ,Abdomen: NormalSkin: No rashR knee: decreased extension, no swelling, no

redness, no warmth.Other Jts: FROM.

LABSBMP: 136/4.9/ 101/22/12/0.4/139/10.5Total Protein/ Albumin: 7.5/4.7LFT: 0.2/01, 38/19, 244CBC: 7.3/ 12/36.3/392ESR: 15

Other LabsCRP: 0.2ANA negativeLyme Ab titre: 1.2Anti CCP antibody: 8.3HLA B 27: NegativeRF: 10.0Ultrasound of Knees: Small R knee jt effusion

DD of Arthritis/extremity pain in Children

Rheumatic & Inflammatory Diseases

Seronegative Spondyloarthropathies

Infectious IllnessesReactive ArthritisImmunodeficiencies

Metabolic DisordersBone & Cartilage

DisordersNeoplastic DisordersHematologic

DisordersPain Syndromes

Juvenile Rheumatoid ArthritisJRA most common rheumatic disease of

childhoodSynovitis of peripheral joints manifested as

swellingJRA 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 classificationOnly 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 girlsRace: 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 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 FeaturesOnset insidious or abruptMorning stiffness and gellingEasy fatiguabilityJoint 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 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

LabsCBC 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 contdANA:Positive in 40-85% with oligo/poly articularUnusual with systemic onsetTiters do not correlate with disease

severity.Associated with increased risk of uveitisRF: 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)

ImagingX-ray: 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

ManagementMultidisciplinary Team for care of childrenCore Team:Parents and ChildPediatric RheumatologistPediatricianNurseSocial WorkerPhysical TherapistOccupational TherapistNutritionistOphthalmologist

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 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.

Methotrexate• Safest, most efficacious, least toxic of of 2nd

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.

• 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%

Glucocorticoids

Anti TNF alpha • 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

SulphasalazineImproved 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 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 ARTHRITIShttp://www.youtube.com/watch?v=NqyB-

cTxvs8