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Management of the Upper Extremity in Juvenile Rheumatoid Arthritis Dane Glueck, MD, and Harris Gellman, MD Abstract Juvenile rheumatoid arthritis is a multifaceted disease. Average age of onset is 6 years, with peaks between 1 and 4 and between 9 and 14 years. Girls are affected more frequently than boys. Nonsteroidal anti-inflammatory drugs are the standard first line of therapy. Second-line therapy of antirheumatic drugs may be used early for progressive disease. Intra-articular corticosteroid injections should be considered to preserve joint mobility and muscle strength when medical treatment fails to con-trol synovitis or when marked functional impairment exists. Historically, surgery has been a last resort, but in appropriate patients, it should be considered soon after failure of conservative management. However, when possible, reconstructive sur-gery should be delayed until completion of skeletal growth. J Am Acad Orthop Surg 2005;13:254-266 Juvenile rheumatoid arthritis (JRA), frequent in JRA,2 and large joints are the most common major connective more commonly involved than small tissue disease in children, affects joints. nearly 250,000 individuals in the Because small children are often United States.1 Its incidence of ap- unable to effectively communicate proximately 16 per 100,000 is equiv- their pain, diagnosis may be difficult. alent to that of type I diabetes and In one third of patients, JRAremains childhood cancer.2,3 Average age of active beyond adolescence; another onset is 6 years, with peaks between third have intermittent exacer-ages 1 and 4 and between 9 and 14 bations.8-11 Furthermore, children years. Girls are affected more fre- with JRA frequently have increased quently than boys. Upper extremity stiffness, loss of motion, and joint involvement can lead to loss of ankylosis compared with their adult function and independence as well counterparts.6 However, JRA often as self-esteem. Wrist or hand prob- hasamildercoursewithagreaterre-lems are reported in 66% of patients mission rate (between 50% and 70%) with JRA; radiographic changes oc- than does adult RA.6,12-16 cur in 93% of these by 5 years after onset.4-6 Diagnostic and classification crite- Pathophysiology ria are shown in Table 1.7 The onset, laboratory data, and course of JRA The synovial tissue that lines joints differ markedly from those of rheu- is the target for inflammation in JRA, matoid arthritis (RA) in adults. Rheu- althoughthecauseofthesynovitisand matoid factor (RF) is present in only the inciting agent or agents are un-20% of patients with JRA compared known. Immunologic mechanisms, with80%ofadultswithRA.Oligoar- suchasimmunecomplexdisease,may thritis and systemic onset are more perpetuate the synovitis, but expla- nations for the chronicity of synovial inflammationremaintobeascertained. Persistent synovitis in an individ-ual joint results in joint damage. Be-cause articular cartilage does not re-generate, this destruction is often permanent. Inflammatory synovial proliferation spreads as a pannus, destroying articular surfaces and leading to the direct involvement of bone at the articular margins. This proliferation causes a rise in joint pressure, with obvious swelling. Persistent inflammation results in contracture, fibrosis, and ankylosis of the joints, while muscle spasm may increase immobility. Inflamma-tion and increased local blood sup-ply may lead to hypertrophy of the joint and premature closure of the epiphyseal plate. Ultimately, the combination of joint destruction, Dr. Glueck is Orthopaedic Resident, Department of Orthopaedic Surgery, University of Kentucky, Lexington, KY. Dr. Gellman is Voluntary Clin-ical Professor, Department of Orthopaedic Sur-gery, University of Miami, FL, and University of Arkansas, Little Rock, AR. None of the following authors or the departments withwhichtheyareaffiliatedhasreceivedanything of value from or owns stock in a commercial com-pany or institution related directly or indirectly to the subject of this article: Dr. Glueck and Dr. Gellman. Reprint requests: Dr. Gellman, Broward Hand Center, Suite 305, 3100 Coral Hills Drive, Coral Springs, FL 33065-4137. Copyright 2005 by the American Academy of Orthopaedic Surgeons. 254 Journal of the American Academy of Orthopaedic Surgeons Dane Glueck, MD, and Harris Gellman, MD Table 1 Juvenile Rheumatoid Arthritis Diagnostic Criteria and Subtype Classification 1. Age of onset <16 years 2. Arthritis in one or more joints, defined as swelling or effusion or the presence of two or more of the following: limited range of motion, tenderness or pain on motion, or with increased heat 3. Duration of disease: >6 weeks 4. Type of disease onset during the first 6 months classified as: a. Polyarthritis: five or more joints b. Pauciarticular disease: (oligoarthritis) four or fewer joints c. Systemic disease: arthritis with intermittent fever 5. Exclusion of other forms of juvenile arthritis Reproduced with permission from Cassidy JT, Levinson JT, Brewer EJ Jr: The development of classification criteria for children with juvenile rheumatoid arthritis. Bull Rheum Dis 1989;38:1-7. soft-tissue damage, immobilization, antinuclear antibodies, and certain and growth deformity produces a human leukocyte antigens may assist devastating effect.2 in classifying patients.18 Affected Chronic inflammation of the jointsareswollen,stiff,painful,warm, synovium is characterized by limited in motion, and occasionally B-lymphocyte infiltration and expan- erythematous. Two or more of these sion. The presence of macrophages objective signs are necessary to war-and signs of T-cell invasion are asso- rantthedesignationofarthritis.7 The ciated with the release of cytokines, joint fluid in patients with JRA con-which evoke synoviocyte prolifera- tainsincreasednumbersofcells,pre-tion. Short-term cytokine imbalance dominantly polymorphonuclear leu-in acute inflammation is normal, but kocytes; cell counts may range prolonged imbalance is seen pri- between 10,000 and 100,000/mm3. marily in chronic idiopathic inflam- Synovial fluid glucose levels, how- matory disease, such as JRA. ever, may be decreased. Scola et al17 found the synovium In addition to the joints, other or-in patients with JRA to contain mes- gan systems may be involved in senger RNAfor vascular endothelial JRA, with patterns of organ involve-growthfactor,angiopoietin1,andre- ment differing in subgroups. Possi-spectivereceptors.Thisdiscoverysug- ble extra-articular manifestations gests that induction of angiogenesis include iridocyclitis of early child-by products of lymphocytic infiltra- hood pauciarticular disease; rheu-tion may be involved in the persis- matoid nodules and rheumatoid tence of disease. The resulting thick- vasculitis of seropositive disease; enedpannuscausesjointdestruction. fevers, rash, polyserositis, hepa-In many patients, the predominance tosplenomegaly, lymphadenopathy, ofcytokinesassociatedwithtissuede- anemia, and leukocytosis in ad-struction,includinginterleukin-6and vanced rheumatoid disease.19 tumornecrosisfactor,suggeststhepos- sibility of improved responsiveness to specific biologic agents targeting Presentation these factors.17 No laboratory test is diagnostic for The three typical modes of onset are JRA, although the presence of RFs, pauciarticular, polyarticular, and Vol 13, No 4, July/August 2005 systemic. Each has a distinct pattern of joint involvement and prognosis. The pauciarticular form, with four or fewer joints affected, is the most common, seen in 40% to 50% of pa-tients with JRA.1 Large joints, such as the elbow, commonly have asym-metric involvement.1-3 Few extra-articular manifestations occur, with the exception of chronic uveitis. Pos-itive test results for antinuclear antibodies or iridocyclitis may be seen in the early childhood pauci-articular form. Later childhood pre-sentation more commonly involves sacroiliitis and a positive HLA-B27 test result. The polyarticular form affects 35% of patients with JRA. The onset is insidious, with progressive joint involvement. Large joints, such as the shoulders, elbows, and wrists, are most commonly affected. Poly-articular onset is divided into two forms based on the presence (sero-positive) or absence (seronegative) of RF. The seronegative form in-volves minimal joint destruction and responds well to physical ther-apy.4 In contrast, the seropositive form is rapidly progressive, leading to ruptured tendons and joint de-struction within 6 to 12 months (Fig. 1). Presentation is similar to that in the adult form and more commonly affects patients older than age 8 years. The seropostitive form is more likely to require surgery and to continue into adulthood.3 Systemic disease (Still’s disease) accounts for 10% to 20% of patients withJRAandmaypresentatanyage. This form typically involves high in-termittent fever and extra-articular manifestations, such as rash, myal-gias, and hepatosplenomegaly, that persist for 2 to 6 months. Persistent arthritisofmultiplejoints,bothlarge andsmall,beginswithinthefirstfew months. Nearly one third of children withthesystemicformofJRAwilllat-er have chronic arthritis, which be-comes the primary manifestation of the disease.1 255 Management of the Upper Extremity in Juvenile Rheumatoid Arthritis Figure 1 Anteroposterior radiograph of a right hand seropositive for juvenile rheuma-toid arthritis, with destruction of the radio-carpal joint. Note the spontaneous fusion of the thumb metacarpophalangeal joint, and growth arrest and shortening of the distal ulna. General Management Treatmentrequiresamultidisciplinary teamincludingasocialworker,occu-pationalandphysicaltherapists,nurse, pediatricrheumatologist,ophthalmol-ogist, and orthopaedic surgeon. Par-entsmustrealizetheneedfordevoted, long-termtherapy.Theprimarygoals of treatment include decreasing pain and inflammation, maintaining mo-tionandfunction,sustainingsatisfac-torygrowthanddevelopment,andpre-venting deformity.20 Inconsideringthelong-termram-ifications related to the child’s phys-icalandemotionaldevelopment,itis inappropriatetoassumethatthedis-ease will be mild and that remission is likely to occur.21 Early joint dam- age is common, and a limited oppor-tunity may exist in which to prevent permanent damage.15,16 More aggres-sive approaches may be warranted in children with poorer prognoses, such asthosewithseropositivediseaseand those with systemic disease with a rapidlyevolvingpolyarticularcourse. An aggressive approach also may be justified in young children with a rapidly evolving conversion from the pauciarticular to polyarticular form21,22 (Fig. 2, Table 2). Medical Management Currently, an initial trial of non-steroidal anti-inflammatory drugs (NSAIDs)for6to8weeksisthestan-dard first line of therapy.12,21,23 As a result of the potential for Reye’s syn-drome, use of salicylate has marked-lydecreased.21,23,24 Disease-modifying antirheumatic drugs, such as meth-otrexate, gold penicillamine, and sul-fasalazine, are now being used ear-lierthanpreviouslyasasecondchoice for progressive disease.12,21,24 These drugs are considered remittent be-cause they can slow the disease pro-cess; however, their use seldom leads to complete remission. Although disease-modifying antirheumatic drugs decrease inflammation, they are not categorized as anti-inflammatorybecausetheydonotde-crease prostaglandin production, re-lieve pain directly, or reduce fever. Gold salts have been used for the treatment of arthritis for more than 50 years. The mechanism of action is unclear, but apparently they interfere with white blood cell functions that result in joint damage and inflamma-tion,thusslowingdestruction(Fig.2). Gold has been shown to be as effec-tive in the treatment of children as it is in adults.25 Penicillamine Penicillamineisachelatorofheavy metals that have accumulated in the body.Although its mechanism of ac- tion in RAis not known, it is thought to alter the white blood cell function that results in joint damage. Penicil-lamine is administered orally, begin-ning with a low dose, then gradual escalation. When the treatment is ef-fective, patients must stay on this course indefinitely. Side effects are similar to those associated with gold salts, most commonly rashes, mouth sores, loss of taste, and gastrointes-tinal upset. Protein in the urinalysis can be an early sign of renal toxicity. Penicillamine may be used in con-junctionwithNSAIDsandiseffective in approximately 30% of patients.21-24 Hydroxychloroquine Hydroxychloroquineisusedinpa- tients with RA who do not respond well to NSAIDs. It has few side ef-fects and does not require blood test monitoring.Hydroxychloroquineap-pears to interfere with immune cell function and is reported to be effec-tive in approximately 30% of patients with JRA.21-24 One rare but serious side effect associated with hydroxy-chloroquine is deposition of the drug in the retina, with the potential for visual impairment; therefore, an oph-thalmologic examination is recom-mended every 6 months. Hydroxy-chloroquine may be taken in conjunction with NSAIDs, and they are often prescribed together. Methotrexate Methotrexatehasbecomethedrug of choice to treat patients with RA when NSAIDs fail. Methotrexate works faster than other remittent drugs, often bringing improvement in weeks rather than months. It is an antimetabolite, interfering with the metabolism of folic acid. The drug is thoughttoinhibitimmunesystemac-tivity and reduce inflammation; it also may slow the rapid growth of cells in the synovial membrane that lines the joints.14,23,24,26 Methotrexate can be adminis-tered orally or subcutaneously ac-cording to a strict dosage schedule.14 256 Journal of the American Academy of Orthopaedic Surgeons Dane Glueck, MD, and Harris Gellman, MD Initial considerations • Mode of onset • Rate of progression • Patient’s current age Ability to comply with postoperative therapy? Time to cessation of skeletal growth • Adequate passage of time to allow for remission Initial management Medical Four or fewer joints Multiple joints involved involved (pauciarticular) (polyarticular, systemic) Physical/occupational therapy • Splinting and traction • Gentle active or active-assisted exercise • Night resting splints • Dynamic splints/ serial casting Psychosocial • Patient/parent education • Counseling: psychosocial and academic Surgical consult and evaluation • NSAIDs • Intra-articular corticosteroids (every 4-6 mo) Intra-articular corticosteroid injection (every 4-6 mo) NSAIDs (6-8 wk) High-dose NSAIDs (6-8 wk) Methotrexate Other advanced medical treatment (second-line drugs, eg, gold salts, infliximab) Continued pain and decreased function despite medical treatment and physical and occupational therapy. Presence of the following: • Wet synovitis • Joint destruction • Joint space narrowing • Growth abnormalities • No contraindications to surgery Surgery Early • Joint synovectomy/ tenosynovectomy • Soft-tissue releases and realignment Late (in the presence of severe joint destruction or improper spontaneous fusion) • Joint arthroplasty • Corrective osteotomy • Selective joint fusions Figure 2 General approach to treatment of patients with juvenile rheumatoid arthritis. NSAID = nonsteroidal anti-inflammatory drug. Vol 13, No 4, July/August 2005 257 Management of the Upper Extremity in Juvenile Rheumatoid Arthritis Table 2 Patients With Juvenile Rheumatoid Arthritis: Surgical Candidates Patients most likely to require surgery Positive rheumatoid factor polyarticular onset Rapidly progressing systemic onset Progression from pauciarticular to polyarticular manifestation (young patient) Indications for synovectomy Involvement of one or few joints Severe synovitis Failure of nonsurgical treatment No radiographic evidence of articular cartilage destruction Relative indications for synovectomy Severe pain Significant decrease in motion or joint contracture Along with the usual, less signifi- pension may be mixed with 1 mL of cant side effects, long-term metho- 1% lidocaine (without epinephrine) trexate use can cause liver damage; forjointinjections.Typically,between therefore, routine liver function tests 1 and 1.5 mL of the solution is used are required. Methotrexate may be for a wrist joint, between 0.3 and 0.5 taken in conjunction with NSAIDs. mL for finger joints, and 2 mL for el-Patients taking methotrexate are bows and shoulder joints. warned to avoid alcohol. Prognosis of patients with pauci-articular arthritis has improved with Infliximab the use of intra-articular corticoste-Infliximab is a monoclonal anti− roids.31,32PadehandPasswell32reported tumornecrosisfactor(TNF)chimeric fullremissionlasting>6monthsin82% antibody that has been shown to be of injected joints (246/300), with re-effectiveforadultswithRA,especially lief of joint contracture and the abil-whenusedinconjunctionwithmeth- itytodiscontinueoralmedicationsin otrexate to reduce the development 60% of patients. Further, using intra-of anti-TNF antibodies.27 articularcorticosteroidsasmonother-Infliximabhasbeenstudiedinsev- apyforpauciarticulararthritishasbeen eral open clinical trials in both poly- suggested.32 Injectionsmayberepeat- articular and systemic JRA and has ed as often as every 4 to 6 months. been found overall to have demon- Although rare, complications in-stratedefficacyinapproximately60% cludeskinatrophyandsubcutaneous of patients.Approximately 3% to 5% tissue/fat necrosis; these are usually of patients have had infusion re- minor and nonsystemic. All cortico-actionsorfrankallergicreactions,and steroidpreparationshavebeenfound 9% developed new autoantibodies.28 to be effective, but triamcinolone hexacetanide may be more effective Intra-articular Corticosteroids than methylprednisone.29 Whenmedicaltreatmentfailstocon-trol synovitis or when marked func- tional impairment exists, early use of Physical, Occupational, intra-articularcorticosteroidinjection and Psychosocial Therapy shouldbeconsideredtohelppreserve jointmobilityandmusclestrength.21,29,30 Thegoalsofphysicalandoccupation-One milliliter of betamethasone sus- al therapy include relief of pain and swelling, maintenance of and im-provement in motion, and preserva-tion of or improvement in strength and coordination.33 Heat and cold are commonly used to relieve pain and stiffness and to relax tissues. Heat, which is well tolerated by most pa-tients, acts by increasing collagen ex-tensibility while reducing muscle spasm. Cold is useful in acute exac-erbations and postoperatively to de-creasepainandswelling,allowingfor more aggressive therapy.34 Wrist splints help prevent joint deformity andcontracture.9,33 Rigidnightsplints maintainposition,andday(working) splints provide support during activity. During the acute phase, the joint is splinted in a comfortable position as close as possible to position of function. This decreases pain, in-flammation, and loading on joint surfaces while allowing gentle ac-tive or active-assisted range-of-motion (ROM) exercises. In the sub-acute phase, pain is usually less intense, allowing more aggressive therapy to improve mobility. Treat-ment goals during the chronic phase are to prevent or correct deformi-ty.9,35 To evaluate joint surfaces, ra-diographs should be taken before beginning aggressive therapy. Many children with chronic, de-bilitating disease have difficulty ad-justing to their disability. It is impor-tant to make sure that both the child as well as the family have the appro-priate psychosocial assessment and follow-up to cope with the effects of the disease. Often parents and chil-dren are alarmed by the diagnosis. Effective treatment usually begins with detailed education of the pa-tient and parents. Counseling needs are important, and the school should be actively involved.36 PatientswithRAcommonlyreport that stress often precedes flare-ups in disease activity. Psychosocial factors may also compromise adherence to treatmentprotocols,resultinginmod-ifications. Thus, parental monitoring 258 Journal of the American Academy of Orthopaedic Surgeons ... - tailieumienphi.vn