arthritis juvenile idiopathic arthritis

8/13/2019 Arthritis Juvenile Idiopathic Arthritis

1/6

22 JAAPA january 2011 24(1) www.jaapa.com

Melissa Isennock, MPAS, PA-C; John M. Grosel, MD

J uvenile idiopathic arthritis (JIA)also known as

juvenile rheumatoid arthritis (JRA), although JRA isnow an outdated termis considered the most com-mon rheumatic disease in children younger than 16years.1 The condition has a wide variety of manifes-

tations, often making it difcult to identify. A timely diagno-sis is important because JIA may cause signicant short- andlong-term disability. Since the diagnosis is clinicala diagno-sis of exclusionpractitioners who maintain a high index ofsuspicion are more likely to recognize JIA early.

Juvenile idiopathic arthritis is dened as arthritis ofunknown etiology with symptoms that persist for at least 6weeks. The condition is diagnosed before age 16 years, andits symptoms cannot meet the diagnostic criteria for otherknown conditions. Several classications and presentationsof the disorder exist, and treatment varies. JIA may persistinto adulthood, and in these cases, clinicians should be pre-pared to provide long-term care and should consider likelycomorbidities.

DIAGNOSTIC CATEGORIESThe classication criteria developed by the InternationalLeague of Associations for Rheumatology is the most fre-quently used system to diagnose juvenile idiopathic arthritis(Table 1 ). This system identies ve major subtypes of thecondition, and an undifferentiated arthritis category if cri-teria for multiple subtypes or no subtypes are met. Factorscommon to all the subtypes include joint swelling and gaitdisturbances.2

Juvenile idiopathic arthritis is the most common systemicdisease associated with uveitis in childhood, so patients

Juvenile idiopathic arthritis: Can yourecognize this complex diagnosis?The v i ble m ifest tio s of jIa m ke di g osi g it co side ble ch lle ge fo cli ici s,b t e l , i divid lized t e tme t c dec e se the lo g-te m seq el e of the dise se.

CME LEARNING ObJECTIvESIde tif isk f cto s fo d p ev le ce of ve ile idiop thic th itisu de st d the v iet of p ese t tio s of jIareview the medic l d s gic l t e tme t optio srecog ize lo g-te m effects of the dise se

EARN CATEGORy I CME CREDIT b e di g this ticle d the ticle begi i g o p ge 42 d s ccessf llcompleti g the posttest o p ge 48. S ccessf l completio is de ed s c m l tive sco e of t le st 70%co ect. This m te i l h s bee eviewed d is pp oved fo 1 ho of cli ic l C tego I (P e pp oved) CMEc edit b the aaPa. The te m of pp ov l is fo 1 e f om the p blic tio d te of j 2011.

Figure 1. Changes associated with JIA

j e

i f e r

n .

G e

t r y

Synovial membrane

Normalknee joint

Synovial uid

Cartilage

Capsule

In amed synovialmembrane

Synovitis

Thinned cartilage

Bone erosion

JIA-affectedknee joint


2/6

www.jaapa.com january 2011 24(1) JAAPA 23

often present with both conditions. Anterior uveitis mayoccur in patients with all subtypes of JIA who have a posi-tive serum antinuclear antibody (ANA) test result but is

most common with oligoarticular JIA.3

Uveitis is initiallyasymptomatic with permanent damage occurring at theonset of symptoms, so JIA patients benet from an ophthal-mologic consultation.

Oligoarthritis Up to four joints may be affected at diagno-sis; the disease is said to be extended if it progresses to affectmore than four joints after the rst 6 months and to be

persistent if not more than four joints are affected through-out the course of the disease. The large joints of the lowerextremities (the knees and ankles) are most likely to beaffected.1 Oligoarthritis is the most common presentation of

juvenile idiopathic arthritis.2 Pol arthritis This classication includes rheumatoid

factor (RF)-negative or RF-positive arthritis involving veor more joints in the rst 6 months of disease. Two ormore positive RF test results at least 3 months apart in therst 6 months are required for disease to be classied asRF-positive JIA.2

S stemic-onset ju enile idiopathic arthritis (soJIA) Alsoknown as Still disease , soJIA is dened as 6 weeks of arthri-tis with intermittent fever that spikes daily or twice daily,usually each evening, for at least 2 weeks. Other symptomsmust include at least one of the following: characteristicevanescent erythematous rash, generalized lymphadenopa-thy, organomegaly, and serositis. Laboratory ndings notrequired for classication may include neutrophilia, throm-

bocytosis, and mild anemia, as well as an elevated ESR andelevated levels of C-reactive protein (CRP), liver transami-nases, serum ferritin levels, D-dimers, and aldolase. Thepattern of arthritis is split equally between oligoarticularand polyarticular, most frequently involving the knee, wrist,and ankle. The sacroiliac joint is least often involved. 2 Nosignicant sex bias has been identied in this subtype, andthe age at diagnosis peaks at ages 0 to 5 years, with 2 years

being the most common. 4Psoriatic and enthesitis-related arthritis Less common

diagnoses include arthritis and enthesitis with two of the fol-lowing symptoms: sacroiliac (SI) joint tenderness; presenceof HLA-B27 antigen; onset of arthritis in a male older than 6years; acute uveitis or history of ankylosing spondylitis; or sac-

roiliitis with inammatory bowel disease, Reiter syndrome, oracute anterior uveitis in a rst-degree relative. Psoriatic arthritisis arthritis and psoriasis with two of the following: dactylitis,

nail pitting, or a rst-degree relative with psoriasis.2

EPIDEMIOLOGyEvidence suggests that children of European ancestry are atan increased risk of developing all subtypes of juvenile idio-pathic arthritis except rheumatoid factor-positive polyarticularand systemic arthritis; the risk is highest for the extendedoligoarticular and psoriatic subtypes. Compared to childrenof European descent, black and Indian children are at a lowerrisk of all but RF-positive polyarthritis; those of Asian originare less likely to develop all but enthesitis-related arthritis;and American Indians are at an increased risk of developingpolyarthritis and extended oligoarticular subtypes. Females ofEuropean descent and non-European descent were more likelythan males to have JIA. 5

A 2007 CDC study found that approximately 294,000US children had some form of J IA or another rheumatolog-ic condition, which translates to 1 in 250 children youngerthan 18 years. Juvenile idiopathic arthritis incidence varies

by place and time, suggesting a possible environmentalcomponent.6 Estimates of JIA incidence range from 4 to14 per 100,000 children per year, and prevalence rangesfrom 9 to 113 per 100,000 population. Such a wide range isattributable to a lack of population-based studies, popula-tion differences, and environmental factors. 7 Mortality is anaverage of one death per million people per year. 6

DIAGNOSIS Juvenile idiopathic arthritis is a clinical diagnosis. The chiefsymptoms are varied, and primary care providers (PCPs)frequently refer children with JIA and soJIA (enthesitis-relatedand psoriatic not included) to orthopedic surgeons basedon the symptoms that manifest. 8 Thus, orthopedic surgeonsare more likely to refer these patients to a rheumatologist forfurther evaluation. Health care providers should be cognizantof the variety and onset of symptoms in order to better under-stand which referral each patient requires.

A retrospective chart review conducted by McGhee andcolleagues found musculoskeletal pain to be the most com-mon presenting complaint in children referred to rheuma-

KEy POINTSj ve ile idiop thic th itis (jIa) is th itis of k ow etiolog th t m st be di g osed b ge 16 e s. S mptoms m st be p ese tfo t le st 6 weeks.jIa h s ve s bt pes: oligo tic l , pol tic l , s stemic, e thesitis- el ted, d pso i tic th itis. E ch s bt pe h s v i gp ese t tio s d lifelo g seq el e.joi t swelli g d g it dist b ces e st o gl co el ted p ese ti g compl i ts i p tie ts with jIa. L bo to v l es e otspeci c d se ve o l s ppo tive ole i di g osis.T e tme t m i cl de exe cise the p , nSaIDs, co ticoste oids, dise se-modif i g ti he m tic d gs, t mo ec osis f ctoblocke s, d eve s ge . M ew t e tme ts e c e tl de i vestig tio , i cl di g i te le ki ecepto t go ists.


3/6

tology. In order of frequency, other complaints includedabnormal laboratory test results, joint swelling, fever, gaitdisturbance, rash, fatigue, and morning stiffness. No patient

with isolated musculoskeletal pain had juvenile idiopathicarthritis, thus making such pain a poor diagnostic criterion;especially as an isolated complaint, it generally was caused

by mechanical or overuse syndromes instead. The mostreliable manifestations of JIA include joint swelling and gaitdisturbances, usually a limp most prominent after periodsof rest that improves with activity. 8

Laboratory values were nonspecic. Neither ANA norrheumatoid factor tests had the ability to identify patientswith juvenile idiopathic arthritis, and though the ESRseemed to be more specic, the positive predictive valuewas low.8 Overall, the timely diagnosis of JIA is most likelywith a good history and physical examination, while labora-tory tests should serve merely a supportive role.

Imaging studies, including conventional radiography andMRI, are useful for ruling out other possible diagnosesand monitoring the progression of the disease or responseto treatment. In general, however, ndings on imaging arenonspecic and are not considered diagnostic in JIA. 9

TREATMENTOligoarticular arthritis often responds to NSAIDs and gluco-corticoid intra-articular injections. Polyarticular arthritis oftenrequires the use of disease-modifying antirheumatic drugs(DMARDs), injections, and/or tumor necrosis factor (TNF)

blockers. Systemic onset often requires oral glucocorticoids anda DMARD. Several new and alternate agents are available. 1

A generalized approach to treatment that can help thehealth care provider to identify when further treatmentchanges are best left to a rheumatologist while stillmaintaining an active role in patient care is shown inAn approach to the treatment of rheumatoid arthritis. 10 Certain patients are best managed by a team that mayinclude several specialists, including a rheumatologist,orthopedist, occupational therapist, physical therapist, psy-chiatrist, and others as indicated by the patients specicsymptoms.

Exercise therap Patients with juvenile idiopathic arthri-tis tend to be less active than healthy children, leading todeconditioning and functional deterioration. Exercise pro-grams for these patients are varied and may include endur-ance training, strength training, or a combination of both. 11

Although very few controlled trials on exercise therapyexist, an exercise regimen, tailored to the patients capabili-ties, is generally recognized as an integral part of the overalltreatment plan. None of the studies found that exercisetherapy exacerbated arthritis. 11

NSAIDs These agents work by inhibiting the cyclooxygenase(COX) pathway of arachidonic acid metabolism and thus pre-vent formation of inammatory prostaglandins. In oligoarticular

JIA, NSAIDs may be used as monotherapy. A recent surveyof 129 pediatric rheumatologists found that 72% would use anNSAID as rst-line treatment.12 Many NSAIDs are available in

CME Juvenile arthritis


TABLe 1. Classi cation of ju enile idiopathic arthritis 2,13

Oligoarthritis

a th itis i 1-4 oi ts d i g st 6 mo Pe siste t: ot mo e th 4 oi ts th o gho t dise se co se

Exte ded: mo e th 4 oi ts fte st 6 mo

Excl sio s: 1-5

Pol arthritis

a th itis i 5 o mo e oi ts d i g st 6 mo

rhe m toid f cto (rF)-positive o eg tive

Excl sio s: rF-positive, 1-3,5; rF- eg tive, 1-5

S stemic-onset ju enile idiopathic arthritis

a th itis i 1 o mo e oi ts fo 6 wk

2 wk of feve with t le st 3 d of q otidi p tte

O e o mo e of the followi g: ev esce t e them to ssh, ge e lized l mph de op th , hep tomeg l d/o

sple omeg l , se ositis

Psoriatic arthritis

a th itis d pso i sis Or

a th itis d t le st 2 of the followi g: d ct litis, il pitti go o chol sis, pso i sis i st-deg ee el tive

Excl sio s: 2-5

Enthesitis-related arthritis

a th itis d e thesitis, Or

a th itis o e thesitis with t le st two of the followi g:s c oili c oi t te de ess d/o i mm to l mbos c lp i ; HLa-B27 positive; th itis i m le > 6 ; c tes mptom tic te io veitis; histo of k losi g spo d litis,e thesitis- el ted th itis, s c oiliitis with i mm to boweldise se, reite s d ome, o c te te io veitis i st-deg ee el tive

Excl sio s: 1, 4-5

Undifferentiated arthritis

a th itis f l lli g c ite i i o e of bove c tego ies, Or

a th itis f l lli g c ite i i 2 o mo e bove c tego ies

Exclusions

1. Pso i sis o histo of pso i sis i st-deg ee el tive

2. a th itis i HLa-B27-positive m le begi i g fte 6th bi thd

3. a k losi g spo d litis, e thesitis- el ted th itis, s c oiliitiswith i mm to bowel dise se, reite s d ome, o c te

te io veitis i st-deg ee el tive

4. IgM he m toid f cto o 2 o mo e occ sio s 3 mo p t

5. S stemic ve ile idiop thic th itis i the p tie t


4/6


liquid form for children who cannot swallow pills. The efcacyof NSAIDs is not known to be high, however, and many chil-dren experience side effects, most often abdominal pain.

Recent studies have shown that celecoxib, a COX-2inhibitor, may prevent COX-1 inhibition-related side effectssuch as GI ulcers, upset, and bleeding without lesseningefcacy. Research has shown that chronic use is safe in chil-dren.12 Although NSAIDs can be useful in JIA, especiallythe oligoarticular form, they are often not effective as thesole therapy. Additionally, if the disease is progressive atdiagnosis, which may include joint contractures or muscleatrophy, initiation of more aggressive therapy is advisable. 13

Glucocorticoids Oral steroids remain a powerful anti-inammatory option, but their large side-effect prole warrantscaution when using them. While they are excellent for control-ling systemic manifestations in patients with systemic-onset

juvenile idiopathic arthritis, glucocorticoids should be avoidedfor patients in other classications unless being used as a

bridge to new treatment or for patients who are experiencingterrible pain and functional restriction. 1 Once improvementis seen, oral steroids should be tapered to the lowest effectivedose or discontinued completely as quickly as safety allows.

Intra-articular corticosteroid injections are a common treat-ment method for adult rheumatoid arthritis (RA), but theyare not typically used in children because of concern abouteffects on cartilage and local suppression of limb growth. 13 Recent understanding that intra-articular steroids are safe andwell-tolerated may increase their use in children.

Patients with oligoarticular JIA are most likely to useinjections, especially if NSAIDs fail to provide completesymptom control. Triamcinolone hexacetonide, a long-acting preparation, is the drug of choice. Injections can beused as often as every 3 months but should not be admin-istered more than three times per year per joint. 1

Disease-modif ing antirheumatic drugs The most com-monly used DMARD is methotrexate, but sulfasalazine andleunomide are also used. Methotrexate, a folate antagonist,is often the second-line agent in JIA after NSAID failure.Supplementation with folic acid may lessen GI upset, the mostcommon side effect, without altering efcacy. 1

Methotrexate has proven to be both safe and efcacious,and those patients who have a 70% response rate to treat-ment tend to continue to have the best 5-year disease con-trol.13 Although maximum doses have increased over time,higher doses of the drug do not show an increase in efcacyor adverse effects.14

Tumor necrosis factor lockers Etanercept, iniximab,and adalimumab comprise the TNF blockers. Etanercept has

been proven to be effective in controlling pain and swelling,especially in patients with disease that was unresponsive toother therapies; it may also delay radiologic progression of thedisease.1 This drug has demonstrated sustained improvementin signs and symptoms of juvenile idiopathic arthritis andmaintains its safety prole over time. A recent study found thatthe risk of severe adverse effects 8 years into therapy was nohigher than at the beginning of treatment. 15

Iniximab is a chimeric monoclonal anti-TNF-alpha antibody. 1 Although adults with rheumatoid arthritis are cur-rently treated with iniximab, further studies of the risks and

benets in pediatric patients are required. Adalimumab is afully human monoclonal anti-TNF-alpha antibody admin-istered by SC injection every 2 weeks. Studies show thatadalimumab improves signs and symptoms of the diseaseand can be given with or without methotrexate to achievethese improvements. The combination of adalimumab plusmethotrexate exhibited the most desirable end point. Themost common side effects include infections and injection-sitereactions, although the size and length of the study were notsufcient to identify the risk of rare adverse events. 16

Interleukin receptor antagonists Interleukin-1 (Il-1) has been linked to the pathogenesis of JIA. Thus anakinra, arecombinant Il-1 receptor antagonist, is being investigated forsafety and efcacy. It has been shown to reduce the symp-toms of RA in adults, especially when disease-modifyingantirheumatic drugs do not offer adequate control.

One study found 58% of patients showed a greater than30% disease improvement when anakinra was given indaily SC injections. The highest improvements were seenin patients with systemic onset, followed by those witholigoarticular and polyarticular subtypes. Fewer patients inthe treatment group had disease ares compared to those inthe placebo group. The most common adverse effects wereinjection-site reactions, headache, and upper respiratorytract infections.17

Research remains preliminary for anakinra in the treat-ment of juvenile idiopathic arthritis, but it does seem toproduce improvements and short-term adverse effects areminimal. However, more research is necessary before thedrug will be added to the formulary for JIA.

Surger Some patients will have progressive joint degen-eration, and in such cases medication may no longer beenough to prevent disability or pain. Surgery has been apossible treatment for some time, but the efcacy of eachoption differs. Nonarthroplasty choices such as synovec-tomy or osteotomy are no longer indicated, as they haveproduced inconsistent results. The hip is a frequentlyaffected and problematic joint in JIA, and bone sparingstrategies like bipolar hemiarthroplasty have been suggestedand tried. Although these methods provide clinically signi-cant improvement for patients, they have not been shownto be as effective or durable as total hip arthroplasty. Thisprocedure is proven to provide relief from unremitting painfor most patients, and the outcomes are better than withhemiarthroplasty. Although there is concern for acetabularcomponent loosening and failure, for some patients theremay be no other choice to relieve pain. 18

LONG-TERM SEQUELAEPatients with juvenile idiopathic arthritis, especially soJIA,develop chronic impairment. The disease course may bemonophasic, meaning one episode that lasts less than 24months. Other possible courses are polycyclic, relapsing-


5/6


CME Juvenile arthritisALgoriThM. An approach to the treatment of rheumatoid arthritis

R h e u m a

t o l o g

i s t

P r i m a r y c a r e p

h y s

i c i a n

Initiate therapy Begin patient education Start DMARD therapy within 1 mo Consider NSAID Consider local or low-dose systemic corticosteroids Start physical therapy or occupational therapy

Establish diagnosis early Document baseline disease activity and damage Estimate prognosis

Periodically assess disease activity

Adequateresponse with

decreaseddisease activity

Inadequate response(ongoing active

disease after 3 mo ofmaximal therapy)

Change or add DMARDs

MTX Othermonotherapy

Othermonotherapy

Combinationtherapy

Failure ofDMARDs

Symptomaticor structural

joint damage

Surgery

Combinationtherapy

Combinationtherapy

No previousMTX treatment Suboptimalresponse to MTX

BiologicDMARDs

Monotherapy

Key: DMarD, dise se-modif i g ti he m tic d g; MTX, methot ex te.ad pted with pe missio f om ODell jr. The pe tic st tegies fo he m toid th itis. n E gl j Med. 2004;350(25):2591-2602.


6/6


remitting, or persistent. A polycyclic course is uncommon.Patients who had a polyarticular onset are more likely to havea persistent disease course. Patients at higher risk for persistent

diseasewho were thus likely to have a poorer outcomehadactive arthritis and persistent fever at 3 months from diagno-sis and an elevated ESR with corticosteroid treatment at 6months from diagnosis. 19 These predictors are useful becausesuch patients require more aggressive treatment to avoid dis-ability; they can also provide patients and families with a betteridea of the likely individual disease course.

JIA is not solely a disease of childhood, and 31% to55% of patients have active disease 10 years after diagno-sis. Adults with the condition have been found to havehigher levels of physical disability, pain, fatigue, andunemployment.20

Ps chosocial effects Chronic pain and illness are well-known to cause depression and anxiety. Juvenile idiopathicarthritis can affect physical growth; furthermore, many of thesepatients are on long-term steroid therapy, which also causesimpaired development. Short stature is often considered a dis-advantage in social and psychological realms.

Patients with long-term disease may have lower academicor employment levels, are more likely to be single, andexhibit delayed independence. Severity of illness does notnecessarily predict level of disability. Boys, children fromsingle-parent or low-income families, and children whoare older at diagnosis are at greatest risk. The quality of apatients social support network correlates with psychoso-cial outcome.21

Transition from pediatric to adult care is an importantconsideration, and delay of this transfer may affect entryinto adulthood. The practitioner may wish to foster thepatients personal responsibility for health care in order topromote independence.

Although chronic illness and JIA do not guarantee psy-chosocial disability, it is important to consider the psycho-logical effects of long-term disease. A less obvious effect ofthe illness, it is no less important for the long-term healthof the patient.

Mortalit Patients with juvenile idiopathic arthritis haveincreased mortality compared to the general population. Onestudy found a fourfold increase in its cohort of JIA patients,none of whose deaths occurred in childhood. Deaths occurredfrom complications of other autoimmune diseases, especiallyin patients with polyarticular or systemic onset JIA. 20 This sug-gests that JIA is involved in broader immune system dysregu-lation in some patients; therefore, a higher index of suspicionfor related diagnoses in JIA patients is warranted.

CONCLUSION Juvenile idiopathic arthritis is a more common illness than may be expected, and it can be a difcult diagnosis for cliniciansto make. Given the wide range of manifestations, a thoroughhistory and physical examination to determine the likelihoodof JIA in a patient with suspicious complaints is invaluable.Laboratory values act as a supportive measure or tool to rule

out other diagnoses. Treatment is varied. An individualizedcare plan must be developed by determining the most effectiveagents and modalities for the patient and, if the disease course

progresses, by implementing more aggressive approaches totreatment. JIA is a chronic illness, so the practitioner can better serve

patients by remaining aware of the diseases potential effects onquality of life both physically and mentally. Being cognizant ofsuch effects allows for a better overall treatment plan and maymake a difference in a patients current and future health. JAAPA

Melissa Isennock w s st de t i the M iett College Pa p og mwhe this ticle w s w itte . John Grosel is ssist t p ofesso ithe M iett Pa p og m d st ff diologist fo M iett Im gi g, I c,M iett , Ohio. The tho s h ve i dic ted o el tio ships to disclose

el ti g to the co te t of this ticle.

DRUGS MENTIONEDAdalimumab (Humira)Anakinra (Kineret)Celecoxib (Celebrex)Etanercept (Enbrel)In iximab (Remicade)

REFERENCES 1. Weiss JE, Ilowite NT. Juvenile idiopathic arthritis.Rheum Dis Clin N Am.2007;33 (3):441-470.2. Petty RE, Southwood TR, Manners P, et al. International League of Associations for Rheumatol-

ogy classi cation of juvenile idiopathic arthritis, second revision, Edmonton, 2001.J Rheuma- tol.2004;31(2):390-392.

3. Thorne JE, Woreta F, Kedhar SR, et al. Juvenile idiopathic arthritis-associated uveitis: incidenceof ocular complications and visual acuity loss.Am J Ophthalmol. 2007;143(5):840-846.

4. Behrens EM, Beukelman E, Gallo L, et al. Evaluation of the presentation of systemic onset juvenile rheumatoid arthritis: data from the Pennsylvania systemic onset juvenile arthritis registry(PASOJAR).J Rheumatol. 2008;35(2):343-348.

5. Saurenmann RK, Rose JB, Tyrell P, et al. Epidemiology of juvenile idiopathic arthritis in amultiethnic cohort.Arthritis Rheum. 2007;56(6):1974-1984.

6. Childhood arthritis. Centers for Disease Control and Prevention Web site. http://www.cdc.gov/arthritis/basics/childhood.htm#2. Updated June 25, 2010. Accessed December 1, 2010.

7. Rabinovich CE. Juvenile rheumatoid arthritis. eMedicine Web site. http://emedicine.medscape.com/article/1007276-print. Updated June 1, 2010. Accessed December 1, 2010.

8. McGhee JL, Burks FN, Sheckels JL, Jarvis JN. Identifying children with chronic arthritis basedon chief complaints: absence of predictive value for musculoskeletal pain as an indicator ofrheumatic disease in children.Pediatrics. 2002;110(2):354-359.

9. Miller E, Uleryk E, Doria AS. Evidence-based outcomes of studies addressing diagnostic ac-curacy of MRI of juvenile idiopathic arthritis.Am J Roentgenol. 2009;192(5):1209-1218.

10. ODell JR. Therapeutic strategies for rheumatoid arthritis. N Engl J Med. 2004;350(25):2591-2602.11. Takken T, van Brussel M, Engelbert RH, et al. Exercise therapy in juvenile idiopathic arthritis.

Cochrane Database Sys Rev.2008;16(2):1-27. 12. Foeldvari I, Szer IS, Zemel LS, et al. A prospective study comparing celecoxib with naproxen i

children with juvenile rheumatoid ar thritis.J Rheumatol.2008;36(1):174-182.13. Haines KA. Juvenile idiopathic arthritis: therapies in the 21st century.Bull NYU Hosp Jt Dis.

2007;65(3):205-211.14. Bartoli M, Taro M, Magni-Manzoni S, et al. The magnitude of early response to methotrexate

therapy predicts long-term outcome of patients with juvenile idiopathic arthritis.Ann RheumDis.2008;67(3):370-374.

15. Lovell DJ, Reiff A, Ilowite NT, et al. Safety and ef cacy of up to eight years of continuous etaner-cept therapy in patients with juvenile rheumatoid arthritis.Arthritis Rheum. 2008;58(5):1496-1504.

16. Lovell DJ, Ruperto N, Goodman S, et al. Adalimumab with or without methotrexate in juvenilerheumatoid arthritis.N Engl J Med.2008;359(8):810-820.

17. Ilowite N, Porras O, Reiff A, et al. Anakinra in the treatment of polyarticular-course juvenilerheumatoid arthritis: safety and preliminary ef cacy results of a randomized multicenterstudy.Clin Rheumatol. 2009;28(2):129-137.

18. Yun AG, Martin S, Zurakowski D, Scott R. Bipolar hemiarthroplasty in juvenile rheumatoidarthritis.J Arthroplasty.2002;17(8);978-986.

19. Singh-Grewal D, Schneider R, Bayer N, Feldman BM. Predictors of disease course and remissioin systemic juvenile idiopathic arthritis.Arthritis Rheum. 2006;54(5):1595-1601.

20. French AR, Mason T, Nelson AM, et al. Increased mortality in adults with a history of juvenilerheumatoid arthritis.Arthritis Rheum. 2001;44(3):523-527.

21. Turkel S, Pao M. Late consequences of chronic pediatric illness.Psychiatr Clin N Am. 2007;30(4):819-835.

Le unomide (Arava, generics)Methotrexate (Rheumatrex, Trexall, generics)Sulfasalazine (Azul dine, Azul dine EN-tabs, generics)Triamcinolone hexacetonide injection (Aristospan)

arthritis juvenile idiopathic arthritis

Documents