J uvenile R heumatoid A rithritis ( JRA ) Prepared by: Dr. Lami’ Salah Directed by: Dr. Jareer Halazoon

1. Juvenile Rheumatoid Arithritis ( JRA ) Prepared by: Dr. Lami’ Salah Directed by: Dr. Jareer Halazoon

2. Is one of the most common Rheumatic diseases in children and a major cause of chronic disability. • It is characterized by idiopathic synovitis of the peripheral joints, associated with soft tissue swelling and effusion. • In the classification of American collage of Rheumatology JRA is regarded not as a single disease but as a category of disease with three principal types of onset:- • 1- Oligoarithritis or Pauciarticular disease (involvement of less than 5 joints) • 2- Polyarithritis (involvement of more than 5 joints) • 3- Systemic onset disease.

3. Etiology • Exact etiology is unknown although 2 events are considered necessary : 1- Immunogenetic Susiceptibility • 2- External triggers(environmental) • eg.: -certain viruses as - Parvovirus B19, • Rubella, EBV. • -Host Hyper-reactivity to specific self • antigens as type II collagen.

4. Enhanced T-cell reactivity to bacterial or mycobacterial heat shock proteins.

5. Epidemiology -Incidence is approximately 14/100000 children per year among children 15 years or younger with an overall prevalence of 113/100000 children. -Different Racial and ethnic groups appear to have varying frequencies of the subtypes of JRA, one study reported that black american children with JRA were:

6. Older at presentation. • Less likely to have elevated ANA titres or Uveitis.

7. Pathogenesis 1- Inflammation of synovial membrane synovitis which villous hypertrophy and edema of subsynovial tissues 2- There is marked increased in permeability of blood vessles and the synovial lining layer which lead to joint effusion that contain lymphocytes and plasma cells 3- The hyperplastic synovium spreads from the joint margins onto the cartilage surface, this “Pannus” of inflamed synovium damage the underlying cartilage….

8. Cartilage by blocking its normal route of nutrition and by the direct effects of cytokines on the chondrocytes. So the cartilage become thinned making the underlying bone more susceptible to any minor trauma.

9. Clinical Manifestations Initial symptoms include: 1- morning stiffness. 2- easy fatigability particularly after school in the early afternoon. 3- joint pain later in the day and joint swelling. 4- the involved joint often warm, lacks full range of motion and occasionally painful on motion but usually not erythematous.

10. In Oligoarithritis (Pauciarticular): • It predominantly affect joints of lower extremities (knees and ankles) • Involvement of upper extremity large joint is also seen but is not characteristic of this type. • Involvement of hip is almost never a presenting sign of this type, although it may occur later (particularly in Polyarticular JRA) and is often the first sign of deteriorating functional course.

11. In Polyarithritis (polyarticular) subtype: • It resembles the adult RA. • Is generally characterized by involvement of large and small joints, as many as 20-40 separate joints are often affected. • Rheumatoid nodules can be found on the extensor surfaces of elbows and over the achilles tendon and usually associated with more severe course. • Micrognathia reflects tempromandibular joint involvement

12. Cervical spine may be involved too, with risk of atlantoaxial sublaxation.

13. In Systemic Onset Disease: • manifested by arithritis and visceral involvement including: -Hepatosplenomegaly • -Lymphadenopathy • -Serositis which may lead to pericardial • effusion. • -it is characterized by fever with daily temperature spikes to at least 39 C, sometimes followed by mildly hypothermic temperature , for a minimum of 2 weeks

14. -each febrile episode is often accompanied by a faint, erythematous, macular Salmon colored rash which may be linear or circular from 2-5 mm distributed most commonly over the trunk and proximal extremities. -Koebner phenomena: it is cutaneous hypersensitivity to superficial trauma , is elicited by lightly running the edge of the examiners fingernail along the uninvolved skin, and is usually suggestive of Systemic Onset disease

15. Note: Some children will have persistent arthralgia despite repeated normal physical examination, although those children don’t fulfill the diagnostic criteria for JRA initially, the diagnosis of JRA may sometimes be established as long as 2 years after initial presentation

16. Diagnosis is usually clinical and supported with the lab findings Clinical Criteria for diagnosis include: 1-Age of onset less than 16 years. 2-Arithritis(swelling or effusion) , or presence of two or more of the following signs in one or more joints -limitation of full range of movement -tenderness or pain on motion. -increase heat. 3-Duration of disease of 6 weeks or longer

17. 4-Onset type is defined by type of disease in first 6 months. Polyarithritis: 5 or more inflamed joints. Oligoarithritis: less than 5 joints involved Systemic onset: arithritis with characteristic fever 5-Exclusion of other forms of juvenile arithritis.

18. Finding which may support the diagnosis 1- Inflammatory reflectors as : Raised CRP,Serum Ig, leukocytosis, thrombocytosis and ESR. NOTE: ESR could be normal propably when most activated lymphocytes responsible for disease have shifted from blood stream and entered the synovium.

19. 2- Hematological abnormalities: - anemia of chronic disease. - raised platelets count. - raised WBCs count. 3- Elevated ANA titres in 40% to 85% of children with Pauciarticular or Polyarticular JRA but unusual in Systemic Onset disease. Detectable ANA are usually associated with increased risk for the development of chronic Uveitis.

20. 4- Positive Rhuematoid Factor (RF) : - These are circulating auto-antibodies which have the Fc portion of IgG as their antigen. - The nature of the antigen means that they self aggregate into immune complexes and thus activate complement system and stimulate inflammation, causing chronic synovitis. -Transient production of RFs is an essential part of body`s normal mechanism for removing immune complexes, but in JRA they show much higher affinity and their production is persistent and occurs in the joint.

21. -These RFs can be of any Ig subclass (IgM, IgG, IgA) but the most common tests employed clinically detect the IgM RF. -The term sero-negative RA is used for patients in whom the standard tests for IgM RF are persistently negative, those tend to have more limited pattern of synovitis. -IgM RF is not diagnostic of JRA, nor its absence rule the diagnosis out , but is useful predictor of prognosis. -For example a persistently high titre of RFs in early disease implies more persistently active synovitis , more joint damage and greater disability eventually. -Other causes for elevated RF and ANA in childhood is viral infection as EBV.

22. 5- Bone mineral metabolism is often abnormal is children with JRA and predominantly affects appendicular cortical bones. a- Early radiographic changes include: -Soft tissue swelling. -Osteoparosis. -Periostitis about the affected joints. b- Regional epiphyseal closure maybe accelerated. c- Continued disease may lead to subchondral erosions and narrowing of cartilage space with varying degrees of bony destruction and fusion.

23. d-Late radiographic changes are seen in the hands and cervical spine most frequently at the level of C2-C3.

24. Differential Diagnosis: 1- Any rheumatic disease as: -SLE -Juvenile dermatomyositis -Sarcoidosis -Vasculitis 2- Trauma 3- Infection 4- Rheumatic fever

25. 5- Autoimmune hepatitis. Less Commonly: 1- Leukemia 2- DM 3- Cystic Fibrosis 4- Glycogen Storage disease

26. Treatment -the long term treatment of children with JRA is initiated and subsequently modified according to Disease subtype, Severity, and Response to therapy. -Aim of treatment is to establish the child in a pattern of adaptation that is as normal as possible and to accomplish this goal with minimal risk of adverse effects.

27. For example: -Most Children with Oligoarticular JRA respond to NSAIDs alone as a first line of treatment. -Most Polyarticular patients and some oligoarticular patients with aggressive disease require additional medications as a second line of treatment. -There is whats called “Therapeutic Pyramid” in which: we start with NSAIDs as a first line of treatment then precedes through the Sulfasalazine, Methotrexate and immunosuppressives (azathioprine, Cyclophosphamide) and experimental drugs.

28. -Glucocotricoids are used for the management of:- 1- overwhelming inflammatory or systemic illness. 2- in lower doses as for bridge therapy for children who did not respond, in addition to another drug such as methotrexate. 3- for ocular and intra-articular use. -Are very powerful anti-inflammatory drugs, but they maybe associated with tachyphylaxis and impose upon child the risk of severe toxicities as Cushing Syndrome , Growth retardation.

29. Methotrexate is considered the safest most effective and least toxic of currently available second line agents. • It can be given -Orally • -SC once weekly • Other aspects of management • Routine slit lamp eye examination for early detection of uveitis. • Dietary evaluation to ensure adequate Ca intake.

30. Prognosis: • Although the course of JRA is unpredictable , some general statement can be made concerning onset type and outcome.

34. Complications: • 1-Anemia: • -usually unresponsive to iron therapy and maybe exacerbated by GI bleeding due to the use of NSAIDs. • 2- SLE: • in children with polyarticular JRA particularly when they develop high titres of ANA • 3- Orthopedic Complication: • -bone deformity as leg discrepancy, secondary scoliosis, flexion contractures.

35. 4- Psychological Trauma: -As problems in school attendance and socialization.

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