Yackov Berkun, Hadassah Mnt Scopus

Yackov Berkun, Hadassah Mnt Scopus

Rheumatic diseases in children

Juvenile rheumatic diseasesA wide range of conditionsInflammatory, mechanical, behavioral or

psychologicalMay present with symptoms localized to

the musculoskeletal systemMS symptoms common in childhood15% occasional limb pains5% chronic MS pain, daily activities

Lasting for 3 months or moreBerkun, JIA2

Juvenile rheumatic diseasesJuvenile idiopathic

ArthritisVasculitis

Kawasaki diseaseHenoch-Schonlein

purpuraAutoinflammatory

FMFPanniculitisCRMO/SAPHO

syndromesPFAPA

Connective tissueSLEJuvenile

dermatomyositisInflammatory bowel

diseaseMixed connective

tissue diseaseLinear sclerodermaProgressive

systemic sclerosis3

Mechanical/orthopedic Infection/post-infective

Viral rubella, measles, mumps, parvo, hepatitis

Reactive arthritis Rheumatic feverSeptic arthritisTransient hip synovitis

Hematological Idiopathic pain syndromesOtherBerkun, JIA4

Introduction, JIAMost frequent chronic inflammatory

disease of childhoodOne of the more common chronic

illnesses of childhood and an important cause of disability

First series 1890, George Stil 1897Group of disorders defined by ILAR

criteria 1997

Berkun, JIA5

EpidemiologyAll races and geographic areasPrevalence: 0.1-4/1000Chronic disease /1000

Epilepsy 3DM 1CP 1.3JIA 2

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ObjectivesTo recognize symptoms and signs of

clinical subgroups of JIATo understand laboratory and radiology

studies helpful when considering the diagnosis

To be familiar with the differential diagnosis

To understand the general approaches to treatment

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JRA American College of Rheumatology Revised Criteria

Age of onset < 16 yearsArthritis of one or more jointsDuration of disease > 6 weeks (EULAR 12)Other conditions which present with arthritis

in childhood must be excluded

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ILAR classification Criteria, Durban 1997

Oligoarthritis persistent extended

SystemicPolyarticular RF+Polyarticular RF-Psoriatic arthritisEnthesitis-related arthritis (ERA)Other

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Oligoarthritis Most common 40-60% of JIA4 or fewer joints in the first 6 monthsInsidious onsetAge 1-3 yearsMonoarthritis 50%Large joints

Knee 50%, ankle, elbowAsymmetric Systemic symptoms absentUveitis 30%

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מפרקנפיחות

, בצקת, היפרטרופיה נוזל אודם ללא בתנועה הגבלה חד לא כאב בתינוק ביטוים

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Oligoarthritis, Laboratory

CBC, ESR normalANA 60-80%

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30%ANAAsymptomatic50% at diagnosisWithin 5 yearsBilateral in 2/3Loss of vision 10%

Uveitis

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Uveitis- hypopion, synechiae

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Uveitis, Keratic precipitates

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Uveitis, compl. Band kerathopathy

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Uveitis, compl. Synechae

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Slit lamp exam

Oligoarthritis, outcome

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Oligoarthritis, outcome

ILAR classification Criteria, Durban 1997

Oligoarthritis persistent extended

Systemic onsetPolyarticular RF+Polyarticular RF-Psoriatic arthritisEnthesitis-related arthritis (ERA)Other

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Systemic onset JIA10% of JIAFemale 40-50%Prominent systemic symptoms

fever, rash, lymphadenopathy, hepatosplenomegaly, pericarditis, pleuritis

Arthritis may be absent for months to yearsUveitis uncommon

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Fever 2 weeks 390

QuotidianSpikes 1-2/d

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SoJIA, clinical features, fever

• Arthritis polyarticular• May be absent in 20%

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Rash

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Rash

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Koebner

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SoJIA, clinical features, rashEvanescent nonfixed erythematousTrunk היקפי חיוורון חום עם מופיעהKoebner phenomena

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SoJIA, clinical features, general

SerositisPericarditis

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LymphadenopathyHepatosplenomegaly

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• SoJIA, clinical features, general

Systemic JIA, criteria Arthritis + fever > 2 wks Quotidian > 3 days +1 of

evanescent nonfixed erythematous generalized lymphadenopathy hepato/ splenomegaly serositis

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SoJIA, laboratory

WBC , Hgb , platelets to ESR Ferritin ANA and RF negative

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ComplicationsHeart tamponadeMalnutritionOsteoporosisJoint deformityAmyloidosisGrowth retardation

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Macrophage activation syndrome• Hemophagocytic lymphohistiocytosis• Life-threatening complication, cytokine

storm• NK cells dysfunction• Sustained fever, hepatosplenomegaly,

anemia, liver dysfunction, coagulopathy, CNS

• Early diagnosis• Aggressive treatment

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Disease courses

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Persistent polyarthritis (50%)Monocyclic, remission within 2–4 years

(40%) Relapsing polycyclic

Flares systemic + mild arthritis (10%)Poor outcomeSystemic features> 0.5 years,

thrombocytosis, polyarthritis incl. hip involvement

Mortality (2.8% to 14%)

ILAR classification Criteria, Durban 1997

Oligoarthritis persistent extended

SystemicPolyarticular RF-Polyarticular RF+Psoriatic arthritisEnthesitis-related arthritis (ERA)Other

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Polyarticular, fingers

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Finger tenosynovitis

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Polyarticular disease, laboratory

WBC , Hgb , platelets WNL to ESR to ANA 25%

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Polyarthritis RF+

5-10%Age >10 yearsSymmetricRheumatoid nodulesVasculitisLung

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Micrognatia

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ILAR classification Criteria, Durban 1997

Oligoarthritis persistent extended

SystemicPolyarticular RF-Polyarticular RF+

Psoriatic arthritisEnthesitis-related arthritis (ERA)Other

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Psoriatic arthritis

Arthritis and psoriasisDactylitis

sausagelike swelling of fingerNail pittingOnycholysisFamily historyAnterior uveitis, symptomatic

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PsoriasisTypical lesion -sharply

demarcated erythematous plaque covered by silvery white scales, on elbow

Initial eruptions- guttate distribution, often triggered by streptococcal infections

Scalp – 50%, beyond terminal hair

Nail pitting

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Dactylitis

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Enthesitis related arthritisEnthesitis - inflammation at the insertion

of tendons, ligaments, or joint capsules to the bone

Arthritis lower limb, hip, intertarsalMale >8yLater SIJ, axial involvementHLA B27Familial historyAnterior uveitis, symptomatic

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XR , תהליך טראומה לשלול

אחר המרווח הרחבת עצם דלדול סחוסית תת בעצם כיב- הצרות סחוס איבודsacroiliitis

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Tecnecium scan

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Treatment

• Nonsteroidal anti-inflammatory (NSAIDs)

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Treatment, Corticosteroids

Uncontrolled or life-threatening SoJIA

Local – uveitis, Intra-articularlar

Berkun, JIA

Treatment, MethotrexateMost widely used DMARD

Mostly in polyarticular disease

Oral, IM or SC

Adverse events/monitoring

stomatitis, leukopenia, nausea/ abdominal pain, anorexia,

malaise, fatigue, elevated hepatic enzymes, lung

Sulphasalazine

Berkun, JIA

Choy EH. N Engl J Med. 2001;344:907–916.

Inhibition of Cytokines

Activation ofanti-inflammatory pathways

Anti-inflammatory

cytokine

Suppression of

inflammatory

cytokines

Neutralization of cytokines

Soluble receptor

Monoclonal antibody

No signal

Receptor blockade

Monoclonal antibody

Receptor antagonist

No signal

Inflammatory cytokine

Normal interaction

Cytokine

receptor

Inflammatory signal

Biologicals

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Anti TNFEtanercept – EnbrelInfliximab – RemicadeAdalimumab – Humira

Anti-IL-1; anakinraAnti-IL-6 (tocilizumab)T cell co-stimulation inhibitor

abatacept

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Orencia

Rilonacept (IL-1 receptor) Canakinumab. Anakinra- IL-1 receptor antagonist

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Treatment, splint

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