Overview of Juvenile Idiopathic Arthritis Pediatric Rheumatology Red Team Resident Teaching Series

Juvenile Idiopathic Arthritis One of the more common chronic childhood diseases almost as common as childhood-onset diabetes mellitus at least 4 times more common than sickle cell disease or cystic fibrosis at least 10 times more common than leukemia, hemophilia, chronic renal failure, or muscular dystrophy

Differential Diagnosis for JIA Acute (within 72 hours) Infection: Septic arthritis, Rheumatic fever Malignancy: Leukemia, Neuroblastoma Toxic Synovitis Blood disorders: Hemophilia, Sickle Crisis (dactylitis) Trauma Chronic (more than 4 weeks) Infection: TB, Lyme disease, Parvovirus, Rubella Pigmented villonodular synovitis (PVNS) Other rheumatic diseases (SLE, Sarcoid, vasculitis)

CRITERIA FOR THE DIAGNOSIS OF JUVENILE IDIOPATHIC ARTHRITIS Age of onset < 16 years Arthritis (swelling or effusion, limitation of motion, tenderness or pain on motion, and/or increased heat) in one or more joints Duration of disease 6 weeks or longer Onset type defined by type of disease in the first 6 months: Polyarticular: 5 or more inflamed joints Oligoarticular: < 5 inflamed joints Systemic arthritis: Characteristic fever Exclusion of other forms of arthritis

Juvenile Arthritis Breakdown Oligoarticular JIA (50-60%) Polyarticular JIA (30-35%) Systemic JIA (5-10%) Enthesitis Related Arthritides (5-15%) Juvenile Ankylosing Spondylitis Reactive Arthritis IBD associated arthritis Juvenile Psoriatic Arthritis ILAR (International League of Associations for Rheumatology) Classification of JIA

Case History #1 2 yo girl presents with a 4 week history of limping. Mom notices she wants to be carried out of bed in morning and cannot fully straighten her right leg. But by the afternoon she is running around. ROS: No fevers. No rash. No recent illnesses. PE: normal vitals, right leg with swelling, limitation of motion and pain on passive motion and right ankle with swelling Labs: Normal CBC, ESR 25, ANA positive

Oligoarticular JIA Fewer than 5 joints Peak onset between 2-4 years Tends to affect larger joints and lower extremities Asymmetric joint involvement Peak onset between 2-4 years One knee is the most common presentation (50%) Highest risk of uveitis among the JIA types Girls:Boys - 3:1 Labs may be normal or mild elevation of acute phase reactants ANA positive (<1:640) in 65-85% Rheumatoid Factor usually negative Ankle or wrist arthritis and symmetric arthritis predictive of erosions

Uveitis Up to 21% of oligoarticular and 10% of polyarticular patients ANA positive JIA patients are at higher risk of uveitis Highest risk of uveitis: ANA+ young girls with oligoarticular disease Usually asymptomatic Can occur anytime

Uveitis - Complications cataracts glaucoma visual impairment, including blindness posterior synechiae band keratopathy

Case History #2 14 yo girl presents with hand and feet pain over 6 weeks. It is difficult for her to write in school and run during her basketball practices. She feels that her hands are more stiff in the mornings. ROS: Fatigue. Occasional low grade fevers. No rash. No recent illnesses PE: normal vitals, MSK – bilateral wrists, MCPs, PIPs, knees, ankles, and feet swollen and tender to palpation Labs: WBC 7K, Hgb 12, Plt 500 K, ESR 51, ANA negative, RF positive, anti CCP antibody positive

Polyarticular JIA 5 or more joints involved Age of onset: biphasic Girls:Boys – up to 5:1 Usually symmetric joints involving the large and small joints Can see boutonnière and swan neck deformities Rheumatoid Factor positive patients onset in late childhood or adolescence rheumatoid nodules (5-10%) early erosive disease chronic course persisting into adulthood Can see systemic symptoms of mild fever, fatigue

Poly JIA – Laboratory Usually have elevated acute phase reactants Rheumatoid Factor (RF) Associated with worse prognosis Anti Cyclic Citrullinated Peptide antibodies (anti-CCP antibodies) up to 75% of children with RF+ poly JIA have positive anti CCP antibodies

Case History #3 10 yo boy presents with 2 weeks of high spiking fevers (>103), rash, joint pains, and body aches. When the fever is down, he feels fine. ROS: positive for chest pain, headaches, sore throat PE: T 38.0 HR 120 BP 120/75 HEENT- cervical LAD Skin- salmon colored evanescent rash on arms/legs Lungs- crackles at bases MSK – bilateral shoulders, elbows, wrist, hips, and knees swollen and painful on movement Labs: Infectious evaluation negative; PPD neg; ESR 105 WBC 25K Hgb 10 Plt 800K AST 60 ALT 75 ANA negative Radiology: CXR shows bilateral pleural effusions

Keobner phenomenom

Systemic Juvenile Idiopathic Arthritis (SJIA) Girls:Boys - 1:1 Peak age of onset is variable Characteristic features: fever 39°C or higher for >2 weeks and salmon colored rash Arthritis joint involvement variable or may be just arthralgias Child looks ill during fever, but well when afebrile Other features include carditis, pleuritis, pneumonitis, CNS, anemia, DIC, “macrophage activation syndrome” Rash in 80% of patients Labs: Elevated ESR, CRP, WBC, Platelets, Ferritin, d-dimers, AST, and ALT. Anemia, low Albumin, ANA and RF negative Uveitis is rare Prognosis guarded

SJIA Quotidian Fever Curve Fever occurs on a once to twice daily basis, usually during the same time of day each day, spiking to approximately the same temperature each time. The temperature will often become hypothermic after a fever, prior to return to a normal temperature.

Macrophage Activation Syndrome Concern for Macrophage Activation Syndrome (MAS) (consumptive process) AKA secondary HLH High risk in patients with Systemic JIA Presents with hemorrhagic syndrome, HSM, LAD, fever See drop in ESR, Platelets, WBC Coagulopathy – increased PT/PTT, ↑LFTs, elevated d-dimers, ↓fibrinogen, DIC consumption like picture but also due to liver dysfunction High triglycerides, LDH, FERRITIN (usu > 10,000) Mental status changes and seizures Can be life threatening Also reported with: Polyarticular JIA, SLE, MCTD, JDM, Kawasaki’s, sarcoid

Case History #4 16 yo boy presents with lower back pain and bilateral heel pain that affects his basketball playing. He is also complaining of a red painful eye ROS: positive for fatigue, some weight loss PE: normal vitals HEENT – erythematous conjunctiva and sclera MSK – bilateral ankle swelling, heel tenderness, SI joint pain on palpation, and decreased lumbar flexion Labs: CBC normal ESR 50 ANA negative, RF negative, HLA-B27 positive

*Can have all or only some of the characteristics Enthesitis Related Arthritis (ERA)/Seronegative Enthesitis Arthritis (SEA)/ Spondyloarthropathies Refers to a group of rheumatic diseases that includes: Joints of axial skeleton Entheses Psoriasis Inflammatory bowel disease Infections *Can have all or only some of the characteristics

ERA/ Spondyloarthropathy HLA- B27 associated RF and ANA negative Adult form: inflammatory low back pain Juvenile form: ≤16 years old onset Asymmetric arthritis, usually lower extremities Peripheral enthesitis Age of onset – late childhood and adolescence Boys>Girls Arthritis – Axial joint involvement Enthesitis Iritis – red painful photophobic eye, usually unilateral

Enthesial evaluation

Iritis: Acute onset of a red, often painful eye

Case History #5 4 yo girl presents with a 3 week history of a swollen toe. No history of preceding trauma. ROS: benign PE: normal vitals Skin – dry scaly patches on hands and abnormal nails MSK – swollen left 3rd toe Labs: CBC normal, ESR 30, ANA positive

Juvenile Psoriatic Arthritis Psoriasis affects 1-3% of general population and 20-30% of those patients have associated arthritis Preceded, accompanied, or followed by psoriasis Half don’t manifest psoriasis until after joint presentation Age of onset for arthritis 7 to 11 years, with psoriasis between 9 to 13 years – preschool years and middle to late childhood Slightly more common in girls; M:F of 1:2.5. Eye Asymptomatic uveitis -15-20% and assoc with +ANA Symptomatic uveitis - rare in kids and assoc with +HLA-B27 Arthritis Dactylitis - implies underlying tendinitis (aka sausage digit) Can be aggressive and damaging Scattered, asymmetric oligoarthritis of large and small joints, most commonly knee, finger (but DIP is rare), toes. Pitting of the nails seen in 75% of children with disease.

Juvenile Arthritis Therapy Start with nonsteroidal antiinflammatory drugs (NSAIDS) If significant synovitis involving multiple joints persists for 3-6 months, or radiologic evidence of destructive disease is present consider initiation of DMARD (disease modifying antirheumatic drug). Methotrexate and sulfasalazine are most commonly used DMARDs. If significant synovitis persists despite DMARD consider adding biologic agent (TNF inhibitors, Tocilizumab, Abatacept). Steroids - Never proven to be disease modifying Moderate to high doses used for systemic JIA and severe uveitis (>1 mg/kg/day) Low doses for polyarticular JIA and ankylosing spondylitis (5-15 mg/day) Intraarticular steroid injections

Juvenile Arthritis Prognosis Oligoarticular JIA - Overall better outcome with less damage many will go into remission but subset of children will develop a polyarticular course 20-30% will get uveitis with the sequelae of blindness if unrecognized and untreated Polyarticular JIA – Guarded outcome with potential damage prognosis worse if RF+, small joint or hip involvement, or erosive disease patients who had not gone into remission by age 16 are likely to have chronic course Systemic JIA – Guarded outcome 50% will recover without problems Significant morbidity and mortality can occur with macrophage activation syndrome

Important Points to Remember Arthritis in children can be a symptom of a more systemic process (non rheumatologic and rheumatologic) OR a disease entity itself ANA is only helpful for helping to determine uveitis risk Rheumatoid Factor (RF) ONLY important in older children with > 4 joint involvement Don’t forget the eyes Toe swelling: think psoriatic arthritis One knee swelling: think Lyme arthritis Any child < 5 years of age with hip or back pain: be cautious! JIA pain is more insidious and less acute Very rare to have musculoskeletal sprain resulting in acute swelling in children < 3 years of age Xrays are important to rule out fracture or malignancies; not diagnostic of arthritis