JUVENILE IDIOPATHIC ARTHRITIS Presented by: Samira Alesaeidi, MD

Definition An autoimmune, noninfective, inflammatory joint disease Arthritis in one or more joints Begins before the 16th birthday Persisting for 6 weeks or more Has no other known cause

EPIDEMIOLOGY Incidence: Age of onset: Female/male: 2/1 to 3/1 JIA criteria: 1/10,000 yr Age of onset: First peak: 1 to 3 years (girls > boys) Second peak: 8 to 10 years (boys > girls) Female/male: 2/1 to 3/1

Signs and symptoms The first manifestation: Limping Morning limp that improves with time Reduced reduced physical activity, and poor appetite or deformity, rather than pain or swelling Pain,  Morning stiffness, Toddler may no longer stand in the crib in the morning or after naps School absences

Extra-articular Eye disease: Photophobia  Associated with inflammation in the front of the eye UK guidelines 6 weeks of JIA being diagnosed or suspected Screening Slit lamp  features of inflammation cells in the AC Acute anterior uveitis with hypopyon Intraocular pressure, visual acuity (VA)

Extra-articular Leg length discrepancy, genu valgum Growth disturbance: may have reduced overall rate of growth Paradoxically: involve large joints grow faster Leg length discrepancy, genu valgum Muscle atrophy: muscle weakness Osteoporosis

CLASSIFICATION Juvenile Idiopathic Arthritis (ILAR) Oligoarticular JIA Polyarthritis (RF negative) Polyarthritis (RF positive) Systemic onset JIA Psoriatic arthritis Enthesitis-related arthritis Undifferentiated arthritis

Classification

Pathogenesis Trigger Genetic Background Abnormal Immune Response Disease

Triggering Factors ENVIRONMENT High parental income Being an only child Fetal exposure to smoking (JIA in girls) Infectious agent (virus, bacteria?)

Genetic Background HLA Non-HLA HLA-B27: spondyloarthropathy HLA-A: oligoarthritis DRB1: ANA-positive cases HLA-DRB1: eye disease Non-HLA Polymorphism: IL6, PTPN 22

Ag APC T Cell B Cell Tissue Damage CD40L Il-1β, TNF-α Il-6 CD40 ANA Serum immunoglobulins TNF, IL-1, IL-6, IL17 Collagenase ( from Pannus ) Circulating immune complexes Complement activation> PMN Tissue Damage

PATHOGENESIS Hallmark is the tumor-like expansion of inflamed synovial tissue (pannus) Histology Thickened synovium (highly vascular) Hyperplasia of synoviocytes in the lining layer Dense infiltrate of inflammatory cells ( T cells, macrophages, B cells and NKC)

CLINICAL FEATURES OF SUBTYPES OF JUVENILE IDIOPATHIC ARTHRITIS

OLIGOARTHRITIS The most common form (50-60%) F/M: 4/1 Age: before 6 years  four or fewer joints  If ANA+, patient need routine eye exam every 3 months

OLIGOARTHRITIS Clinical Manifestations Joints: knees and ankles, Small joints of the hand Temporomandibular joint Shoulders are rarely involved

OLIGOARTHRITIS Laboratory Features A positive ANA test (50% to 70%) Elevated ESR & CRP (mildly or moderately) Mild anemia A high ESR may predict progression to the extended subtype

Polyarticular 20-40 % of JIA Five or more joints Girl>boy Smaller joints are affected Symmetrical RF +: 20% of JIA, HLA-DRB1∗0401, 9-12 y, Uveitis: unusual RF - : ANA + in 40% of patients, Uveitis occurs in 5% to 20%

POLYARTHRITIS, RHEUMATOID FACTOR POSITIVE Clinical Manifestations Arthritis: Aggressive, symmetric PIP, MCP, wrists and large joints Felty's syndrome Rheumatoid nodules (10%) Uveitis: unusual

Systemic 10-20 % of JIA Arthritis, fever, salmon pink rash Male=Female Age: 2-4 y  Involves both large and small joints Fever and rash come and go May have internal organ involvement Hepatosplenomegaly, lymphadenopathy, serositis, hepatitis Polymorphism in macrophage migration inhibitory factor RF – ANA –

SYSTEMIC ARTHRITIS Laboratory Features Very high CRP and ESR leukocytosis (neutrophilia) Thrombocytosis Anemia Liver enzymes, ferritin, and coagulation screen may be abnormal in severe cases Polyclonal hypergammaglobulinemia RF and complement levels are normal or high

Treatment intra-articular corticosteroid MTX suppress joint inflammation TNF alpha blockers, such as etanercept Celecoxib

Oral steroids (short course ) Methylprednisolone (IV) Multiple joint injections

SYSTEMIC ARTHRITIS Mild: NSAIDs Treatment Mild: NSAIDs Indomethacin is helpful for fever and pericarditis Severe cases, non responders: steroids Prednisolon (0.5 mg/kg) Methylprednisolone (30 mg/kg bolus) DMARDS (methotrexate and cyclosporine) these are less effective than in polyarthritis

PRINCIPLES OF TREATMENT GROWTH DISTURBANCES Poor growth Pubertal delay Osteoporosis Bisphosphonates Calcium and vitamin D Physical therapy Stretches Muscle building Joint protection

OLIGOARTHRITIS Topical medications Uveitis : Topical medications Glucocorticoids and mydriatics Resistant to topical therapy or side effects Methotrexate and anti-TNF-α agents

PSORIATIC ARTHRITIS Arthritis and psoriasis or Arthritis and at least two Dactylitis Nail abnormalities (>/= 2 nail pits, onycholysis) Family history of psoriasis in a first-degree relative Oligoarticular Uveitis in 15% of children

ENTHESITIS-RELATED ARTHRITIS Arthritis and enthesitis or arthritis or enthesitis with >/= 2 of: (1) Sacroiliac joint tenderness, or inflammatory lumbosacral pain (2) Positive HLA-B27 (3) Onset of arthritis in a boy 6 years old or older (4) Acute anterior symptomatic uveitis (5) History of AS, ERA, sacroiliitis, IBD, Reiter's syndrome, or acute anterior uveitis in a first-degree relative

ENTHESITIS-RELATED ARTHRITIS Clinical Manifestations Enthesitis Patella Achilles' tendon Plantar fascia Arthritis Hips, knees, or ankles (symmetric or asymmetric) Spinal symptoms are rare (At onset) Acute anterior uveitis

Soft tissue swelling (a) Joint space widening (b) Periostitis (c) Radiographic changes Early changes Soft tissue swelling (a) Joint space widening (b) Periostitis (c)

Sublaxation Deformity Ankylosis Osteonecrosis

Abnormal increased uptake of TMJ (synovitis)

Osteopenia Growth arrest lines

Guidelines for screening eye exams in JIA > 7 years </= 6 years subtype Every 6 months for 4 years then annually Every 3-4months for 4 Years then every 6 months for 3 years Any category except sJIA ANA+ Any category except Sjia ANA- Annual Systemic