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Childhood Arthritis L 5/8/2015 Childhood Arthritis L. Nandini Moorthy, MD MS Associate Professor of Pediatrics, Div. of Rochester Epidemiology Program Project Rheumatology, RWJMS‐Rutgers, New database, an incidence of 13.9 cases of Brunswick, NJ juvenile rheumatoid arthritis (JRA) per 100,000 per year was reported Incidence rate estimates ranging from 0.008‐0.226 per 1000 children, and prevalence from 0.07‐4.01 per 1000 children 83,000 ED visits per year! A 2007 CDC study; Sacks JJ, Helmick CG, Luo YH, Ilowite NT, Bowyer S. Prevalence of and annual ambulatory health care visits for pediatric arthritis and other rheumatologic conditions in the United States in 2001–2004. Arthritis Care Res 2007;57(8):1439–1445. Nandini 2015 Genetics of JIA Complex genetic trait ‐ multiple genes interact to result in a specific phenotype. 1. Asthma Monozygotic twin concordance rates ‐25% and 40% 2. Congenital heart disease Prevalence of JIA among siblings of probands ‐ 15‐ to 30‐fold 3. Cerebral palsy greater than that of the general population 4. Diabetes HLA‐DR accounts for only about 17% of the genetic burden 5. Epilepsy of JIA, which suggests that other variants within and outside 6. Childhood arthritis the MHC play a role in susceptibility More children have arthritis than those with muscular dystrophy, cystic fibrosis and sickle cell combined. Histopathology PATHOGENESIS Hyperplastic Synovium Disequilibrium of Cytokines Pannus Arthroscopic view Nodular Tendonitis Pro-inflammatory Anti-inflammatory Feldmann M, et al. Cell. 1996;85:307‐310. 1 5/8/2015 Key Actions Attributed to Cytokines Objective arthritis in ≥ 1 joint(s) for ≥ six IL‐6 weeks Children ≤ 16 years ≥ 6 mo necessary to examine the clinical features [exception: SoJIA] IL‐6 Recognition of each phenotype early is critical! IL‐6 Poor growth, anemia Different courses, complications, treatments and prognosis… IL‐1 : Inflammation, bone & cartilage destruction 1. Oligoarthritis (50% of cases)‐ persistent and extended 2 year old Caucasian girl comes in limping to your office 2. Polyarthritis (30‐40% of cases) ‐RF‐ve and RF+ She has a swollen knee Mother noticed it a couple of weeks ago while 3. Systemic arthritis (10‐15% of cases) giving her a bath‐ she initially thought her girl was chubby 4. Psoriatic arthritis (usually –ve RF) Mother recalls she has been limping in the mornings for a few months and has asked to 5. Enthesis‐related arthritis be picked up (ILAR classification) Reviewed in TJAL, Classification of juvenile arthritis UpToDate, March 2015 Commonest subtype (›50%) • Swollen joint (warm, not red) 1‐5 years of age, peaks at 2‐3 yrs of age • Limp or an abnormal gait Girls > boys • Rarely complain of pain Walks funny in the mornings but then is alright • No constitutional symptoms Arthritis in ≤ four joints • Routine lab values ‐normal Commonly affects large joints (knees, • Frequently ANA +ve ankles, elbows) • Antibodies to dsDNA, Ro, La, Sm, Usually spares hips Rarely affects small joints of hands & feet RNP, and RF should be absent 2 5/8/2015 Two groups: Dactylitis (more typical of psoriatic arthritis) Persistent oligoarthritis ‐with 1‐4 joints affected during the 1st 6 months Children >9 yrs with arthritis involving the hips or knees and of disease enthesopathic symptoms (spondyloarthropathy) st Extended oligoarthritis ‐1‐4 joints affected during the 1 6 months of Neoplastic disease (ALL, neuroblastoma) disease who subsequently experience involvement of >4 joints. Infectious/post‐infectious/reactive Descriptors: If hip involved, consider: Age at onset . Toxic synovitis Pattern of joint involvement (large versus small joints, both large and . Legg Calve Perthes disease small joints with upper or lower limb predominance, and symmetric or . Osteoid osteoma asymmetric disease). Presence of ANA . Neoplasm Occurrence of uveitis . Spondyloarthropathy Reviewed in TJAL, Oligoarticular JIA UpToDate, March 2015 . SCFE Benign course and prognosis‐ many resolve within 6 mo NSAIDs approved for use in children with JIA: st st About 50% remit completely; Recurrences ~ 20% (1 year or 1 5 years) . Naproxen May progress to . Tolmetin . Persistent oligoarthritis . Meloxicam . Extended‐oligoarticular arthritis . Chronic destructive arthritis Celecoxib Risk factors in the 1st 6 mo that identify higher risk . Ibuprofen of progression to extended polyarthritis, Intra‐articular steroid injection (Remission more than 6 mo in form/erosions, persistent synovitis and disability: 82% of injections, Padeh et al) . >4 joints . Complications‐ infection, subcutaneous atrophy . Symmetric disease Methotrexate . Ankle or wrist involvement Biologic agents‐ Etanercept, Adalimumab . Laboratory evidence of inflammation Reviewed in TJAL, Oligoarticular JIA UpToDate, March 2015 Reviewed in TJAL, Oligoarticular JIA UpToDate, March 2015 Silent, chronic, anterior uveitis Permanent visual damage >15% of 1/3‐1/2 will have the following affected patients despite therapy. complications: –Mostly ANA positive girls (~ 20%) Systemic agents: . cataracts – Irreversible damage & blindness ▪ glucocorticoids . synechiae –Ophthalmologic monitoring (AAP schedule) ▪ methotrexate . glaucoma –+ve ANAs and <6 yrs at diagnosis ‐at the greatest risk of developing ▪ cyclosporine . band keratopathy uveitis ▪ mycophenolate . macular edema ▪ adalimumab . legal blindness ▪ Infliximab . male gender ‐ risk factor for a more ▪ rituximab poorer outcome Band keratopathy and synechiae 3 5/8/2015 Affected limb longer 11 to 36% with persistent oligoarticular JIA <1 cm are probably not clinically significant >1 cm‐associated with increased strain on the shorter leg, and perhaps accelerated degeneration of the contralateral hip. Growth retardation was more likely in children who required treatment with disease modifying rheumatic drugs Appropriate lift in the opposite shoe (DMARDs) than those who were treated with intra‐articular Orthopedic consultation before skeletal maturity glucocorticoid injections alone Stapling‐surgically close the distal tibial epiphysis in the leg which is longer and allow catch‐up growth on the opposite side. Risk factors: Knee is most commonly involved‐ since two‐thirds of . younger age at onset longitudinal growth occurs around this joint . elevated ESR Joint injection with glucocorticoids early in the course of oligoarticular JIA may prevent leg length discrepancies. Reviewed in TJAL, Oligoarticular JIA UpToDate, March 2015 2. The girl who is tired, and cannot button her shirt Risk generally small in patients with JIA •12 year old AA girl has been very tired for the last several months An increased risk in those with extended •She walks like grandma in the morning oligoarticular disease •Has difficulty getting ready in class •Fingers look puffy •Teacher says she gets tired while tired while writing 20% ‐20% of JIA Begins similarly to oligoarticular disease with 1‐2 joints affected Girls > boys Spreads to involve ≥5 joints during the 1st 6 mo after onset. 2‐5 years & 10‐14 years Often intercurrent infection precipitates a dramatic increase in symptoms Progressive involvement of >/=5 Rapid onset of polyarthritis –likely reactive arthritis joints in the first 6 months Relentlessly progressive with relapses with an increasing number of involved joints AM stiffness and fatigue Symmetrical involvement with the knees, wrists, and ankles most frequently affected see fig May have low‐grade fever Dactylitis followed by progression to polyarticular Fingers & toes exhibit both peri‐ disease over several months Do not appear systemically ill articular & soft‐tissue swelling Uveitis –ANA positive are at greater risk Ruddy: Kelley's Textbook of Rheumatology, 6th ed Tenosynovitis of flexor tendon Rare to see children <10 years of age with a +ve RF Reviewed in TJAL, Polyarticular juvenile idiopathic arthritis: Clinical manifestations and Arthritis intermittent or persistent sheaths diagnosis UpToDate, March 2015 4 5/8/2015 PoJIA‐ hand X‐ray •Soft‐tissue swelling ‐3rd MCP •Joint space is narrowed Rapid onset of inflammation in multiple joints •Extensive periosteal new bone formation Often many small joints of the hands and feet within 2‐3months of the 3rd metacarpal Pain in the small joints Commonly affected ‐ fingers, wrists, elbows, the cervical spine, hips, knees, and ankles +ve RF group: . female . severe disease . may be HLA‐DR4‐+ve and/anti‐CCP ab +ve, Most children RF‐ve: Early carpal fusion . Rare to have +ve CCP ab (more often in JIA) Reviewed in TJAL, Polyarticular juvenile idiopathic arthritis: Clinical manifestations and diagnosis UpToDate, March 2015 Hallmark of JIA posterior cervical fusion PoJIA‐Differential diagnosis Infectious Other rheumatic diseases Arthritis in >4 joints during the 1st 6 mo . Viral (parvo?) . Psoriatic arthritis Labs may be nl or suggest an inflammatory state: . Septic . Spondyloarthropathie . Elevated ESR (≥40 mm/hr) . Lyme . IBD . Anemia (Hgb≤11 g/dL) . Other . Celiac disease • Serum sickness . SLE . Hypergammaglobulinemia • Rarer causes . Dermatomyositis . +ve ANA (40‐50%) –younger . Malignancy . Sarcoidosis . 5‐10% RF + . Immunodeficiencies . Scleroderma . Leukocytosis . Vasculitis Flexion contractures OCULAR ‐ Uveitis (14%) Difficulty with ambulation . More likely in ANA +ve and RF –ve and < 6 yrs old Bony erosions and joint destruction Vertebral compression fractures Severe disability requiring total joint replacement VISCERAL‐ Internal organ involvement is rare . TMJ involvement Ruddy: Kelley's Textbook of Rheumatology, 6th
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