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Yackov Berkun, Hadassah Mnt Scopus Rheumatic diseases in children

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Juvenile rheumatic diseases A wide range of conditions Inflammatory, mechanical, behavioral or psychological May present with symptoms localized to the musculoskeletal system MS symptoms common in childhood 15% occasional limb pains 5% chronic MS pain, daily activities Lasting for 3 months or more Berkun, JIA 2

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Juvenile rheumatic diseases Juvenile idiopathic Arthritis Vasculitis Kawasaki disease Henoch-Schonlein purpura Autoinflammatory FMF Panniculitis CRMO/SAPHO syndromes PFAPA Connective tissue SLE Juvenile dermatomyositis Inflammatory bowel disease Mixed connective tissue disease Linear scleroderma Progressive systemic sclerosis 3

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Mechanical/orthopedic Infection/post-infective Viral rubella, measles, mumps, parvo, hepatitis Reactive arthritis Rheumatic fever Septic arthritis Transient hip synovitis Hematological Idiopathic pain syndromes Other Berkun, JIA 4

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Introduction, JIA Most frequent chronic inflammatory disease of childhood One of the more common chronic illnesses of childhood and an important cause of disability First series 1890, George Stil 1897 Group of disorders defined by ILAR criteria 1997 Berkun, JIA 5

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Epidemiology All races and geographic areas Prevalence: 0.1-4/1000 Chronic disease /1000 Epilepsy 3 DM 1 CP 1.3 JIA 2 6 Berkun, JIA

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Objectives To recognize symptoms and signs of clinical subgroups of JIA To understand laboratory and radiology studies helpful when considering the diagnosis To be familiar with the differential diagnosis To understand the general approaches to treatment 7 Berkun, JIA

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JRA American College of Rheumatology Revised Criteria Age of onset < 16 years Arthritis of one or more joints Duration of disease > 6 weeks (EULAR 12) Other conditions which present with arthritis in childhood must be excluded 8 Berkun, JIA

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ILAR classification Criteria, Durban 1997 Oligoarthritis persistent extended Systemic Polyarticular RF+ Polyarticular RF- Psoriatic arthritis Enthesitis-related arthritis (ERA) Other Berkun, JIA 9

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Oligoarthritis Most common 40-60% of JIA 4 or fewer joints in the first 6 months Insidious onset Age 1-3 years Monoarthritis 50% Large joints Knee 50%, ankle, elbow Asymmetric Systemic symptoms absent Uveitis 30% 10 Berkun, JIA

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Oligoarthritis, Laboratory CBC, ESR normal ANA 60-80% 16 Berkun, JIA March 2010

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30% ANA Asymptomatic 50% at diagnosis Within 5 years Bilateral in 2/3 Loss of vision 10% Uveitis 17 Berkun, JIA

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Uveitis- hypopion, synechiae 18 Berkun, JIA

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Uveitis, Keratic precipitates 19 Berkun, JIA

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Uveitis, compl. Band kerathopathy 20 Berkun, JIA

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Uveitis, compl. Synechae 21 Berkun, JIA

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Slit lamp exam

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Oligoarthritis, outcome March 2010 Berkun, JIA 23

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24 Berkun, JIA Oligoarthritis, outcome

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ILAR classification Criteria, Durban 1997 Oligoarthritis persistent extended Systemic onset Polyarticular RF+ Polyarticular RF- Psoriatic arthritis Enthesitis-related arthritis (ERA) Other Berkun, JIA 25

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Systemic onset JIA 10% of JIA Female 40-50% Prominent systemic symptoms fever, rash, lymphadenopathy, hepatosplenomegaly, pericarditis, pleuritis Arthritis may be absent for months to years Uveitis uncommon 26 Berkun, JIA

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Fever 2 weeks 39 0 Quotidian Spikes 1-2/d 27 Berkun, JIA SoJIA, clinical features, fever

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Arthritis polyarticular May be absent in 20% Berkun, JIA 28

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29 Berkun, JIA Rash

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Rash 31 Berkun, JIA

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Koebner 32 Berkun, JIA

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SoJIA, clinical features, rash Evanescent nonfixed erythematous Trunk Koebner phenomena 34 Berkun, JIA March 2010

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SoJIA, clinical features, general Serositis Pericarditis 35 Berkun, JIA

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Lymphadenopathy Hepatosplenomegaly Berkun, JIA 36 SoJIA, clinical features, general

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Systemic JIA, criteria Arthritis + fever > 2 wks Quotidian > 3 days +1 of evanescent nonfixed erythematous generalized lymphadenopathy hepato/ splenomegaly serositis 37 Berkun, JIA

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SoJIA, laboratory WBC , Hgb , platelets to ESR Ferritin ANA and RF negative 38 Berkun, JIA

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Complications Heart tamponade Malnutrition Osteoporosis Joint deformity Amyloidosis Growth retardation Berkun, JIA39

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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 Berkun, JIA 40

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Disease courses Berkun, JIA 41 Persistent polyarthritis (50%) Monocyclic, remission within 24 years (40%) Relapsing polycyclic Flares systemic + mild arthritis (10%) Poor outcome Systemic features> 0.5 years, thrombocytosis, polyarthritis incl. hip involvement Mortality (2.8% to 14%)

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ILAR classification Criteria, Durban 1997 Oligoarthritis persistent extended Systemic Polyarticular RF- Polyarticular RF+ Psoriatic arthritis Enthesitis-related arthritis (ERA) Other Berkun, JIA 42

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Polyarticular, fingers 43 Berkun, JIA

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Finger tenosynovitis 44 Berkun, JIA

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Polyarticular disease, laboratory WBC , Hgb , platelets WNL to ESR to ANA 25% 46 Berkun, JIA

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Polyarthritis RF+ 5-10% Age >10 years Symmetric Rheumatoid nodules Vasculitis Lung 47 Berkun, JIA March 2010

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Micrognatia 52 Berkun, JIA

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ILAR classification Criteria, Durban 1997 Oligoarthritis persistent extended Systemic Polyarticular RF- Polyarticular RF+ Psoriatic arthritis Enthesitis-related arthritis (ERA) Other Berkun, JIA 53

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Psoriatic arthritis Arthritis and psoriasis Dactylitis sausagelike swelling of finger Nail pitting Onycholysis Family history Anterior uveitis, symptomatic 54 Berkun, JIA

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Psoriasis Typical 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

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Nail pitting 56 Berkun, JIA

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Dactylitis 57 Berkun, JIA

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Enthesitis related arthritis Enthesitis - inflammation at the insertion of tendons, ligaments, or joint capsules to the bone Arthritis lower limb, hip, intertarsal Male >8y Later SIJ, axial involvement HLA B27 Familial history Anterior uveitis, symptomatic 59 Berkun, JIA

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XR , - sacroiliitis 61 Berkun, JIA

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Tecnecium scan 62 Berkun, JIA

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Treatment Nonsteroidal anti-inflammatory (NSAIDs) Berkun, JIA63

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Treatment, Corticosteroids Uncontrolled or life-threatening SoJIA Local uveitis, Intra-articularlar Berkun, JIA

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Treatment, Methotrexate Most 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

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Choy EH. N Engl J Med. 2001;344:907916. Inhibition of Cytokines Activation of anti-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

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Biologicals Berkun, JIA 67 Anti TNF Etanercept Enbrel Infliximab Remicade Adalimumab Humira Anti-IL-1; anakinra Anti-IL-6 (tocilizumab) T cell co-stimulation inhibitor abatacept

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69 Berkun, JIA Orencia

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Rilonacept (IL-1 receptor) Canakinumab. Anakinra- IL-1 receptor antagonist Berkun, JIA 70

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Treatment, splint 71 Berkun, JIA