1. Yackov Berkun, Hadassah Mnt Scopus Rheumatic diseases in children

2. 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

3. 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

4. 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

5. 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

6. 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

7. 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

8. 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

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

10. 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

11. מפרק נפיחות נוזל, היפרטרופיה, בצקת ללא אודם הגבלה בתנועה כאב לא חד ביטוים בתינוק 11 Berkun, JIA

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

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

18. Uveitis- hypopion, synechiae 18 Berkun, JIA

19. Uveitis, Keratic precipitates 19 Berkun, JIA

20. Uveitis, compl. Band kerathopathy 20 Berkun, JIA

21. Uveitis, compl. Synechae 21 Berkun, JIA

22. Slit lamp exam

23. Oligoarthritis, outcome March 2010 Berkun, JIA 23

24. 24 Berkun, JIA Oligoarthritis, outcome

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

26. 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

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

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

29. 29 Berkun, JIA Rash

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31. Rash 31 Berkun, JIA

32. Koebner 32 Berkun, JIA

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34. SoJIA, clinical features, rash Evanescent nonfixed erythematous Trunk חיוורון היקפי מופיעה עם חום Koebner phenomena 34 Berkun, JIA March 2010

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

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

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

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

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

40. 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

41. Disease courses Berkun, JIA 41 Persistent polyarthritis (50%) Monocyclic, remission within 2–4 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%)

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

43. Polyarticular, fingers 43 Berkun, JIA

44. Finger tenosynovitis 44 Berkun, JIA

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

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

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52. Micrognatia 52 Berkun, JIA

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

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

55. 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

56. Nail pitting 56 Berkun, JIA

57. Dactylitis 57 Berkun, JIA

58. 58 Berkun, JIA March 2010

59. 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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61. XR לשלול טראומה, תהליך אחר הרחבת המרווח דלדול עצם כיב בעצם תת סחוסית איבוד סחוס -הצרות sacroiliitis 61 Berkun, JIA

62. Tecnecium scan 62 Berkun, JIA

63. Treatment Nonsteroidal anti-inflammatory (NSAIDs) Berkun, JIA63

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

65. 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

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

67. 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

68. 68 Berkun, JIA

69. 69 Berkun, JIA Orencia

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

71. Treatment, splint 71 Berkun, JIA