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BACKGROUND Chronic Arthritis in Childhood characterized as Juvenile Rheumatoid Arthritis JRA or JIA Age of onset < 16 years of age. 2

JRA – Classification Criteria  JRA – American College of Rheumatology 1970 three types of onset: oligo (pauciarticular), polyarticular, & systemic in the first 6 months of onset  JCA Juvenile Chronic Arthritis (European League Against Rheumatism) 1977  JIA Juvenile Idiopathic Arthritis proposed by the Pediatric Task force of the International League of Associations for Rheumatology ILAR (1993) – developed to achieve homogeneity within disease and categories.

Chronic arthritis in childhood: JIA  It’s not a single disease, but a group of related, genetically heterogeneous, phenotypically diverse immunoinflammatory disorders affecting joints and other structures,.

Overview of JIA Chronic arthritis in childhood – one of the more frequent chronic illnesses of childhood.  An important cause of short and long-term disability

JRA - Incidence/Prevalence  Incidence: (per year) 1/100,000 in Japan 20/100,000 in Norway  Prevalence:  10 /100,000 in France  400/100,000 in Australia .

What Is Juvenile Rheumatoid Arthritis?  Arthritis is a disease in a person’s joints that cause swelling and pain where the bones meet each other, resulting in stiffness and loss of motion  Juvenile Rheumatoid Arthritis is arthritis in children under 16 years old with inflammation lasting at least 6 weeks

Sex Ratio  All types of JIA:  Girls: Boys 2:1  Oligo JIA:  Girls: Boys 3:1  JIA with uveitis  Girls: Boys 5-6:1  Poly JRA:  Girls: Boys 3:1  Systemic JRA:  Girls: Boys approx. 1:1

Etiology  Immune mediated disease  Abnormal immunoregulation  Abnormal cytokine production in the inflammatory pathway (TNF, IL-6, IL-2R, IL- 1alpha)  Complex genetic predispositions  HLA associations  Environmental triggers  Infections  Trauma  Stress

Who Gets JRA?  About 1 child in every 1,000 develops some type of juvenile arthritis.  Approximately 75,000 children in the U.S.  Can affect children at any age, but uncommon in the first six months of life  Peak of Age” 1-3 and 8-12 years

Why Do Kids Get JRA?  Cause is unknown  Research suggests a genetic predisposition  Triggered by an environmental factor, such as a virus  JRA is an autoimmune disease  Immune system mistakes healthy cells for harmful ones.  Body releases chemicals to fight healthy cells causing pain and swelling.

CLASSIFICATION OF JRA  ACR Criteria  Age at onset: < 16 years of age;  Arthritis - swelling or effusion or the presence of 2 or more of the following signs:  Limitation of range of motion,  Tenderness or pain on motion and  Increased heat in one or more joints;  Duration of disease > 6 weeks;  Onset type is defined by the type of disease in the first 6 months:  Oligoarticular (Pauciarticular) < 5 inflamed joints;  Polyarticular: > 5 inflamed joints;  Systemic onset: arthritis with characteristic fever.  Exclusion of other forms of childhood arthritis. 13 Modified from JT Cassidy, JT Levinson, RM Laxer, CB Lindsley. Textbook of Pediatric Rheum. 2005

BACKGROUND  Pathogenesis and Etiology of JRA: Multi-factorial  Genetic, Hormonal, Immunologic.  Heterogeneity of JRA  At least 3 primary types of onset of JRA:  Pauciarticular (Oligoarticular)  Polyarticular and  Systemic 14

Types of Juvenile Rheumatoid Arthritis  There are three types JRA.  Pauciarticular: fewer than five joints are affected. Usually knees and large joints.  Polyarticular: affects five or more joints. Joints on both sides of body are affected. Smaller joints like hands or toes.  Systemic JRA: affects many parts of the body. Heart, lungs and liver could be affected as well.

Systemic JIA  Definition:  Arthritis with, or preceded by, daily fever of at least 2 weeks’ duration  Fevers are quotidian (daily) for at least 3 days and is accompanied by one or more of the following:  Evanescent, non-fixed, erythematous rash  Generalized lymph node enlargement  Hepatomegaly and/or splenomegaly  Serositis

Quotidian fever Intermittent fever of systemic JIA in a 3- year-old girl. The fever spikes usually occurred daily in the late evening to early morning (quotidian pattern), returned to normal or below normal, and were accompanied by severe malaise, tachycardia, and rash.

Systemic JRA  Rash -  Salmon colored  Maculopapular – flat to slightly raised  Trunk and extremities  Migratory  Pruritic 5%  Fleeting  Persistent with fever spike

Overview of Systemic JIA  10-15% of all JRA patients  Broad peak of onset 1-5 years  M:F 1:1  Variable number of joints  Il-6 is elevated and correlates with disease activity  Extraarticular symptoms:  Fever 100 %  Rash 95%  Hepatosplenomegaly, 85%  Lymphadenopathy 70%  Pericarditis 35%  Pleuritis 20%

Signs/symptoms  Limping  Stiffness when awakenin  Reduced activity level  Persistent fever  Joint swelling

Polyarticular - RF positive  Arthritis affecting 5 or more joints in the first 6 months of disease.  Similar to adult RA  Females with onset in adolescence  Rheumatoid nodules  Early onset of erosive synovitis  Symmetric joint involvement  Small joints of hands or feet are affected  TMJ: micronathia  Cervical spine may be affected

Oligoarticular JIA  Arthritis in 1 to 4 joints during the first 6 months of disease  Girls 1 to 4 years  Knees, ankles, elbows  Painless swelling of joints is common  Uveitis: insidious, subacute  15-20% have uveitis

Uveitis in JIA  Intraocular inflammation affects iris and ciliary body  Usually insidious and may be asymptomatic  Activity of eye does not parallel joint disease  Slit lamp exam detects anterior chamber inflammation  Girls, ANA + and onset before age 7 at higher risk

Prognosis of Uveitis in JIA  Very good in 25% of cases  25% may require surgery for cataracts and/or glaucoma  50% require prolonged treatment for moderate to severe chronic inflammation; however, the prognosis is generally good Complications: cataracts 20%, glaucoma 20%, band keratopathy 16% (end stage scarring)

JRA by the Type-of-Onset 32 Characteristic % Cases (F:M) # Joints Age at onset Systemic involvement Chronic Uveitis RF/ANA Prognosis Polyarticular 30 (3:1) > 5 Thru childhood, peak 1-3 yr Mild; unremitting articular involvement 5% 10%/40-50% moderately good Pauciarticular 60 (5:1) < 4 Early childhood, peak 1-2 yr None; uveitis (++) 5-15% Rare/75-85% Excellent except for eyesight Systemic 10 (1:1) Variable Thru childhood, no peak Systemic self- limited; chronic destructive arthritis ~50% Rare Rare/10% Moderate to poor JT Cassidy, RE Petty, RM Laxer, CB Lindsley. Textbook of Pediatric Rheumatology, 2005

33 Extra-Articular Manifestations of JRA Fever Rheumatoid rash Rheumatoid nodules Hepatosplenomegaly Lymphadenopathy Chronic uveitis Pericarditis Pleuritis Abdominal pain Polyarticular 30% Pauciarticular 0% Systemic 100% JT Cassidy, RE Petty. Textbook of Pediatric Rheumatology, 2001

How Is Juvenile Rheumatoid Arthritis Different From Adult Rheumatoid Arthritis?  Main Difference: Many people with JRA outgrow the illness, while adults usually have lifelong symptoms.  Studies estimate that by adulthood, JRA symptoms disappear in more than half of all affected children.  Unlike rheumatoid arthritis in an adult, JRA may affect bone development as well as the child's growth.

Diagnostic Tests  There is no lab test that diagnoses JIA The H&P should determine the labs, not the reverse  CBC  Rheumatoid factor  Antinuclear Antibody (ANA) – with titer  ESR or CRP  Anti-CCP (anti-cyclic citrullinated protein)

Radiologic Studies X-rays Soft tissue swelling Osteoporosis Periosteal new bone formation Epiphyseal overgrowth Marginal erosions Narrowing of cartilaginous space Joint subluxation Bony fusion Osteopenia Osteoporosis

CLINICAL MANIFESTATIONS of JRA 37

How Is JRA Diagnosed?  Complete health history  Physical examination to look for joint inflammation, rashes, nodules, signs of internal organ inflammation and/or eye problems  Laboratory tests to help rule out other diseases  Erythrocyte sedimentation rate  Hemoglobin and blood count testing  Urinalysis  X-rays  Tests of joint, blood and tissue fluids to check for infections or inflammation

46 PROGNOSIS OF JRA  Pauciarticular JRA  Boys may be affected in older childhood or adolescence; this may represent an early manifestation of a spondyloarthropathy.  Leg length discrepancy from asymmetric knee synovitis and bone growth may cause flexion contractures, gait abnormalities and long-term growth abnormalities.  Eye involvement as anterior uveitis, may lead to scarring or blindness in ~ 15-20% of children.

47 PROGNOSIS OF JRA  Polyarticular JRA and Systemic JRA  Active arthritis into adulthood: 50% to 70% of polyarticular or systemic onset JRA;  Long-term disabilities: 30% to 40% of children  May need major surgery (joint replacement).  Radiographic joint damage within 2 years;  Mortality rate: 0.4% to 2% (greater risk with systemic JRA than with polyarticular JRA).

Active Learning: X-Ray of Patient  One is normal, and one is a patient with JRA:  Can you determine the differences?

Treatment Options  Goal: Control symptoms, prevent joint damage, and maintain function  1. Non-steroidal Anti-Inflammatory Drugs (NSAIDS)  Motrin or Advil  2. Disease Modifying Drugs (DMARDS)  Hydroxychloroquine: Plaquenil  Sulfasalazine: Azulfidine  Methotrexate: Rheumatrex

Medications  NSAIDs  DMARDs: Methotrexate, Plaquenil, Sulfasalazine  Biologic response modifiers  Glucocorticosteroids  Miscellaneous

51 Evolving Treatment of JRA Paradigm shift…. The trend in managing JRA is much more aggressive treatment earlier in the disease course with the goal of preventing joint damage and slowing progressive articular damage. Since the 1990s and into the 2000s…

Surgery  Rarely used in the early course of disease  Function:  Relieve pain  Release joint contractures  Replace a damaged joint

Exercise  Target:  Shoulder  Neck  Lower leg  Chest  Hip  Knee