2. JRA is the most frequent chronic arthritis of children. The evidence of its was discovered from remained skeleton from 1000 years ago. It was prescribed at first in the 1800s, and its criteria established in 1973. 1

3. Historically, until recently, the terms JRA (in USA), and JCA ( In Europe),were used; but recent literatures use JIA instead of them because of : Only 5-10% of JRA patients have characteristic of adult-RF positive RA, so usage of rheumatoid term may be confusing. The JRA classification criteria focuses the pattern of onset, not the course and progression. 2

4. Epidemiology. The true prevalence of JRA is not determined, but estimates about 1 to 2 per 1000.. The incidence is about 10 to 20 cases per 100000 children.. It was reported from all of the world and all ethnics.. Prevalence and in incidence in Iran were not precisely defined. 3

5. 135791113 10 20 30 40 50 Total Girls Years Patient Number Boys 4

6. Classically,JRA subdivided to : 1. Oligoarthritis 2. polyarthritis 3. Systemic onset-disease Its diagnosis requires to. Onset before 16 th birthday. Objective arthritis in≥ 1joints. Exclusion of other causes of childhood arthritis for ≥ 6 weeks 5

7. Oligoarthritis Arthritis in < 4 joints Persistent type extended type at any time during the onset or course of the disease In first 6 months of disease but > 5 joints after 6 months It is the most common type of JRA (60%) 6

8. Manifestations The typical child with oligoarticular JRA is a girl who is:. Often the family notices that the child "walks funny" in the morning, but after a little while seems fine.. Usually begins at 1-4 years of age. limping without complaint. and unusual after 7 years. 7

9. . They are often ANA positive( 65-85%). They have the greatest risk of uveitis than other types of JRA (30-50%).. Arthritis usually occurs in large joints Knee Ankle Wrist Elbow fingers,toes,hip Early hip or small joints involvement are unusual 8

10. . Systemic manifestations are characteristically absent (other than uveitis). 9

11. . Uveitis is the most common complication.. Leg length discrepancy is another complication (due to increased blood flow to the inflamed joint).. Persistent form has the best articular outcome of all JRA forms; many cases are benign and resolving within six months. Course & Prognosis 10

12. . Up to 50% of oligo JRA progress to extended form (30% in first 2 years). Persistent form Extended form wrist, hand or ankle Involvement Symmetric ArthritisArthritis >1 jointESR Positive ANA Risk Factors 11

13. Polyarthritis JRA. It is more frequent in girls than boys (3:1).. It Is an arthritis in > 5 joints during the first 6 months; and is second most common type of JRA (30%).. It has a bimodal distribution of the age at onset although may occur at any age < 16. 1-3 years8-10 years 12

14. Poly JRA RF+RF- (majority) Usually Girl Later onset HLA-DR4+symmetric small joint involvement erosion Subcutaneous nodules prognosis 13

15. Manifestations. Large joints generally ( knee, wrist,…) involve, but small joints (hand, foot) too.. Often the child does not complain pain,but has pain on motion.. Systemic symptoms or sign is not dominant features, but fever, organomegaly & adenopathy may be present. 14

16. . Apophyseal joint involvement (neck pain), C1-C2 subluxation & TM joint involvement(micrognathia) may also occur.. Uveitis also occurs as in oligoJRA but less often (5%).. Many children in the younger age group are ANA positive. 15

17. Course & Prognosis Onset at later age Early involvement of small joints (hand, foot) Hip involvement Resistance to treatment Systemic manifestations Erosions RF+ Nodules Prognosis. Prognosis is better for RF- poly JRA than RF+ form, except uveitis that is more common in former. Arthritis Rheum. 2007 Feb

18. Systemic-onset Disease 10% of JRA A child typically 1-6 years (girls=boys), with:. Fever for ≥ 2 weeks, that is quotidian for ≥ 3 days (usually afternoon or evening).. Characteristic rash Macule or maculopapule Transient Non pruritic May occur at any site (trunk, proximal of limbs) and Koebner phenomenon 17

19. . Arthritis wrists, knees, and ankles is most typical hand, hip, cervical spine,.. and may occur with other symptoms or weeks to months later.. Visceral involvement Hepatomegaly, hepatitis Splenomegaly Generalized adenopathy Pericarditis Rarely: pulmonary fibrosis, CNS disease Uveitis is rare in systemic disease 18

20. Leukocytosis, thromboytosis, anemia &ESR, abnormal LFT common ANARF Rarely + 19

21. Course & Prognosis The typical child with systemic onset relative quiescence of 4-6 months period of fever, rash & varying degree of arthritis systemic manifestations But up to 50% evolve chronic polyarthritis The long term prognosis is determined by the severity of arthritis 20

22. Poor prognostic sign Those with > 6 months of fever, thrombocytosis & need for corticostreoid Life-threatening complication : Macrophage activating syndrome 21

23. Chronic disease activity may take several different forms Continue with fever and rash for years, but little progression of their arthritis Persistent systemic manifestations with progressive arthritis Resolution of the fever & rash, but have a destructive arthritis 22

24. Ocular involvement. Uveitis is a serious complication of JRA. The frequency of it differs by subtype Oligo 23 > poly> systemic

25. Risk factors Age at onset of arthritis Duration of disease ANA+ Subtype of JRA Uveitis is often initially silentScreening is necessary Girls 24

26. Screening Subgroup Frequency Any JRA category except SJRA ≤ 6 years at onset, ANA + Any JRA category except SJRA ≤ 6 years at onset, ANA - Any JRA category except SJRA ≥ 7 years at onset, ANA +/- SJRA Every 3-4 months for 4 years, then every 6 months for 3 years, then annually Every 6 months for 4 years, then annually Every 6 months for 4 years, then annually Annually 25

27. JRA Immunologic Factors Genetic Factors Environmental Factors Familial Predisposition (especially in Oligoarticular form) HLA II genes (DR1,..) Non HLA-genes Ethnicity (European descent > Asian or black) Differ in Incidence and subtype Arthritis Rheum. 2007 Jun (Especially oilgo & poly forms) B cells RF (poly forms) ANA (oligo forms) Immune complex complement activation Differ between oligo form & other forms NK cell activity Immunologic Factors Changes in TH1& TH2 cytokines TNF-α, IL-1, IL-6 & IL-18 IL-10 Regulatory T-cells (in persistent form of oligo and not extended form) Activity of systemic JRA Rubella EBV Influenza Chlamydia May be explain seasonal variations Environmental Factors A trigger (such as an infectious agent) Physical Trauma Psychological Factors 26

28. Management. Management of JRA has many components, that pharmacotherapy has is only one of which.. Treatment in most children is prolonged over many years.. Because of the impact of disease on family and child, they mast be regard in management. 27

29. . Keeping the child with JRA out of the hospital. The best management is carried out by multi disciplinary team 28

30. Aim of treatment Control of pain Prevention of loss or restoration of range of motion promotion of normal growth Considering psychological aspects 29

31. So a comprehensive management needs physical & occupational therapy Psychologcal care Nutritional aspects pharmacologic management 30

32. Growth Retardation & Osteopenia Disease Effect Nutrition Drug side Effects Mechanical Problems Control of disease 31

33. Pharmacologic management Oligoarthritis Poor response to NSAIDS Good respoonse to intra-articular corticostroids. Not responder to local injections. Extended Type. Small Joint Involvement Treat like Polyarthritis 32

34. Polyarthritis. Treat Like adult RA. MTX should be prescribed early 33

35. Systemic-onset Disease. Systemic corticosteroids use for arthritis, fever & serositis.. Other DMARDS recommend like in polyarthritis; IVIG occasionally prescribe for systemic manifestations.. Anakinra recently prescribe as a first DMARD. 34

36. Uveitis Initial Therapy: Corticosteroids eye drop with mydriasis Severe Disease Dependency to Corticosteroids Immunosuppressive Therapy Mtx is the cornerstone of treatment 35