Juvenile Rheumatoid Arthritis (JRA) Or Juvenile Chronic Arthritis

1. Juvenile Rheumatoid Arthritis (JRA)Or Juvenile Chronic Arthritis

2. It is autoimmune disease of unknown etiology. Pathophysiology: The common underlying findings in JRA is the presence of chronic inflammation of the joint synovium (synovitis) in which the synovium becomes thickened and hypervascular with infiltration by lymphocytes. This inflammation leads to production and release of tissue proteases and collagenases, which if left untreated lead to tissue destruction, especially of the articular cartilage and underlying bony structures. Epidemiology: JRA is the most common chronic rheumatologic disease of childhood. The disease has two peaks, one at age of 1-3yr, and another peak at ages 8-12 yr, but it can occurs at any age group. Girls are affected more commonly than boys especially in pauciarticular type of JRA.

3. Clinical features: A. Symptoms: JRA presented with gradual onset of swelling and effusion in the affected joint. The child may develop pain and stiffness of the joint (especially at morning) and limit the use of affected joint. B. Clinical signs: On physical examination, signs of inflammation are present, including joint tenderness, erythema, effusion, with limitation of range of motion due to pain, swelling or contracture from lack of use. If JRA affect lower extremity joints, a leg length discrepancy may be present if the arthritis is asymmetric.

4. C. Chronic iridocyclitis or uveitis: All children with JRA are at risk of development of chronic iridocyclitis or uveitis, but the risk is increased in: a. Presence of HLA-DR5, HLA-DR6, and HLA-DR8 tissue types. b. Positive ANA. c. Young girl with pauciarticular JRA. The uveitis can be asymptomatic until the point of visual loss, so any children with JRA should have regular ophthalmologic screening with a slit-lamp examination to identify anterior chamber inflammation and start prompt treatment for any active disease. Clinical classification of JRA: JRA can be divided into three subtypes: pauciarticular, polyarticular, and systemic onset JRA.

5. A. Pauciarticular JRA: It’s defined as the presence of arthritis in less than 5 joints within first 6 months from diagnosis It's characterized by: 1. It's the most common form of JRA, accounting for approximately 50% of cases. 2. Presence in young children, with a peak at age 1-3yr, and another beak at ages 8-12 years. 3. It affect medium-sized to large joints, and most commonly affect knee, followed by ankle and wrist joints. 4. It's unusual to affect small joints, such as the fingers or toes, and neck and hip joints involvement also uncommon. 5. There's no any clinical signs of systemic inflammation (e.g. fever, weight loss, or FTT) or any laboratory evidence of systemic inflammation (e.g. increased WBC counts or ESR).

6. B. Polyarticular JRA: It's defined as the presence of arthritis in 5 or more joints within the first 6 months of diagnosis. It's characterized by: 1. Accounting for 40% of cases of JRA. 2. It's symmetric arthritis, which can affect any joint, but typically involved the small joints of the hands and feet, ankle, wrist and knee. 3. Cervical spines can be involved, leading to fusion of the spine overtime. 4. Can present with evidence of systemic inflammation e.g. malaise, low-grade fever, growth retardation, anemia of chronic disease and elevated markers of inflammation (WBC count and ESR).

7. 5. Can affect any age group, with a peak in early child hood and another peak in adolescence. 6. Positive rheumatoid factor (RF) in adolescent patients (in this case the JRA will follow coarse similar to that of adult rheumatoid arthritis with poor prognosis). C. Systemic-onset JRA: It's accounting for 10% of cases, in which the arthritis preceded by clinical and laboratory signs of systemic inflammation by 6 weeks to 6 months. The arthritis is typically polyarticular and can be extensive and resistant to treatment, placing children at high risk for long-term disability.

8. Manifestations of systemic inflammation are: 1. Typical recurrent spiking fever, usually once or twice a day, which can occur for several weeks to months. 2. Morbilliform, salmon colored rash which may be occur only at time of fever and rarely this rash could be urticarial in nature. 3. Serositis, e.g. pleuritis and pericarditis, occurs in half of patients . 4. Hepatosplenomegaly occurs in 70% of cases. 5. Constitutional symptoms, including malaise and FTT. 6. Laboratory findings of inflammation e.g. elevated WBC count, ESR,CRP, platlate count and anemia.

9. Investigations of JRA: 1. Elevated acute phase reactant (ERS, PCR, WBC counts) and anemia of chronic disease especially in systemic-onset and polyarticular JRA. 2. Complete blood count to exclude leukemia, should be done in all children with joint or bone pain. 3. ANA titer in all patients with pauciarticular JRA to identify patients at high risk of uveitis. 4. Rheumatoid factor assay, especially in adolescent with polyarticular JRA. 5. Diagnostic arthrocentesis (synovial fluid aspiration and examination) to exclude suppurative arthritis. Synovial fluid in JRA have WBC count of 50,000 to 100,000/c.mm, predominantly lymphocytes with negative Gram stain and culture, while in suppurative arthritis , synovial WBC count much higher than 100,000/c.mm, predominantly neutrophils, with positive Gram stain and culture for causative M.O.

10. 6. Radiological findings: Bone X-ray is normal at early stage of JRA, but latter develop the following findings: a. Periarticular osteopenia resulting from decreased mineralization. b. Slow development of growth centers. c. Accelerated maturation of growth plates with evidence of bony proliferation to the surrounding tissues. d. Erosions of bony articular surfaces as late findings. e. If the cervical spine is involved, fusion of C1-4 may occur, and atlantoaxial subluxation may occur.

11. Differential diagnosis: 1. Connective tissue diseases e.g. SLE, juvenile dermatomyocytis, and scleroderma with arthritis. 2. Infectious arthritis e.g. bacterial arthritis, viral arthritis, fungal arthritis and Lyme disease. 3. Reactive arthritis e.g. poststreptococcal arthritis, rheumatic fever and HSP. 4. Orthopedic disorders e.g. traumatic arthritis. 5. Hematological and oncologic disorders e.g. leukemia, lymphoma, sickle cell disease, thalassemia, malignant and benign tumors (of bone, cartilage or synovium), metastatic bone diseases. 6. Miscellaneous e.g. rickets, and arthritis associated with IBD.

12. Treatment: Aims of treatment: 1. Suppression of inflammation. 2. Preserving joint function. 3. Preventing deformities. 4. Preventing blindness. I. First line treatment: 1. NSAIDs e.g. naproxen, ibuprofen, indomethacin and others, apart of aspirin, are the first choice in treatment of JRA. 2. Systemic corticosteroids e.g. prednisolone, used only in severe systemic-onset JRA with internal organs involvement or for significant active arthritis causing inability to movement. Corticosteroids used as bridging therapy until other medications take effects. 3. Intra-articular corticosteroid may be helpful in pauciarticular JRA.

13. II. Second line medications: e.g. hydroxychloroquine and sulfasalazine used in patients with arthritis not fully controlled by NSAIDs alone. III. Methotrexate, orally or subcutaneously, become the drug of choice for polyarticular and systemic-onset JRA which not respond to first and second lines medications. IV. For patients who don't respond to NSAIDs, 2nd line medications, or methotrexate, there are recent agents are available to control arthritis by blocking inflammatory cascade, these medications include etanercept and infliximab.

14. Complications of JRA: 1. Loss of function of involved joint secondary to joint contracture or bony fusion or loss of joint space. 2. Visual loss or blindness secondary to untreated associated uveitis. Prognosis: JRA have excellent prognosis, with an overall 85% complete remission rate especially in children with pauciarticular JRA. Poor prognostic signs: 1. Systemic-onset disease. Thank you for your attention 2. Positive rheumatoid factor. 3. Poor response to therapy. 4. Presence of erosions on X-ray.