CHAPTER

11

Pamela F. Weiss

Juvenile Idiopathic Arthritis

OVERVIEW OF PEDIATRIC RHEUMATIC DISEASE ENCOUNTERED BY THE PEDIATRIC ORTHOPAEDIC SURGEON Joint pain is a common childhood complaint. Each year, as many as 1% of all children will be evaluated by a physician for joint pain (1). Approximately 15% of healthy children reported on a health questionnaire that they had episodes of musculoskeletal pain (2). Further, healthy children in day care centers have approximately one painful episode every 3 hours, arising from play, disciplining, or interaction with peers (3). The orthopaedic surgeon is often the first specialist to encounter the child with joint, limb, or back pain. In a study of subspecialty referrals of juvenile arthritis, most children with pauciarticular juvenile rheumatoid arthritis (JRA) (62%) were referred to orthopaedic surgeons prior to referral to pediatric rheumatology care (4). Among children who are evaluated by a physician for pain in the joints, only 1 in 100 will eventually be diagnosed as having arthritis, but among those who present to an orthopaedist, the frequency of arthritis is surely higher. Accordingly, it is important that the orthopaedic surgeon be able to identify the most likely cause of the pain and either initiate treatment or refer the patient to an appropriate medical specialist. The purpose of this chapter is to provide the orthopaedic surgeon with an in-depth understanding of the presentation, differential diagnosis, and management of children with arthritis. With this framework, the orthopaedic specialist should be able to identify children with juvenile arthritis and to differentiate arthritis from benign pains of childhood, psychogenic pain syndromes, benign musculoskeletal back pain, infection, malignancy, or other systemic autoimmune diseases (lupus, dermatomyositis, and vasculitis). Infectious, malignant, congenital, mechanical, or traumatic causes of arthralgias and arthritis are presented in order to contrast the symptoms with those of juvenile arthritis; detailed presentations on these conditions can be found elsewhere in this text.

CLASSIFICATION OF JUVENILE ARTHRITIS Juvenile arthritis is a term for persistent arthritis lasting >6 weeks of unclear etiology. A diagnosis of juvenile arthritis is made by taking a thorough history, performing a skilled and comprehensive physical examination, utilizing directed laboratory tests and imaging procedures, and following the child over time. Over the past several decades, there have been three sets of criteria utilized for the diagnosis and classification of juvenile arthritis (Table 11-1). The first set of criteria was proposed in 1972 by the American College of Rheumatology (ACR) and defined three major categories of JRA: oligoarticular (pauciarticular), polyarticular, and systemic (5).The ACR JRA criteria exclude other causes of juvenile arthritis, such as spondyloarthropathies [JAS, inflammatory bowel disease (IBD)-associated arthritis, and related diseases], juvenile psoriatic arthritis, arthritis associated with other systemic inflammatory diseases [systemic lupus erythematosus (SLE), dermatomyositis, sarcoidosis, etc.], and infectious or neoplastic disorders. The second set of criteria was formulated in 1977 by the European League Against Rheumatism (EULAR) and coined the term juvenile chronic arthritis (JCA) (6). JCA is differentiated into the following subtypes: pauciarticular, polyarticular, juvenile rheumatoid [positive rheumatoid factor (RF)], systemic, juvenile ankylosing spondylitis (JAS), and juvenile psoriatic arthritis. The ACR and EULAR criteria, although similar, do not identify identical populations or spectra of disease. However, they have often been used interchangeably, leading to confusion in the interpretation of studies relating to the epidemiology, treatment, and outcome of juvenile arthritis. In 1993, The International League of Associations of Rheumatologists (ILAR) proposed (7) and revised (8) criteria for the diagnosis and classification of juvenile arthritis (Table 11-2). The term juvenile idiopathic arthritis (JIA) has been proposed as a replacement for both JRA and JCA. The

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TABLE 11-1

349

Comparison of JRA, JCA, and JIA Classifications JRA

JCA

JIA

Committee Age at onset Disease duration Onset types

ACR 6 wk Pauciarticular Polyarticular Systemic

EULAR 3 mo Pauciarticular Polyarticular RF-negative Juvenile rheumatoid arthritis Systemic Juvenile psoriatic arthritis Juvenile ankylosing spondylitis

Exclusions

Juvenile psoriatic arthritis Juvenile ankylosing spondylitis Inflammatory bowel disease Other forms of juvenile a­ rthritis

Other forms of juvenile arthritis

ILAR 6 wk Oligoarticular, persistent Oligoarticular, extended Polyarticular RF-negative Polyarticular RF-positive Systemic Psoriatic arthritis Enthesitis-related arthritis Other forms of juvenile arthritis

RF, rheumatoid factor.

TABLE 11-2

Criteria for Classification of JIA

JIA Subtype

Exclusionsa

Oligoarthritis  Persistent  Extended Polyarthritis RF-negative Polyarthritis RF-positive

1–5

Systemic

1–4

Psoriatic

2–5

Enthesitis-related

1, 4, 5

Undifferentiated

1–5 1–3, 5

Inclusion Criteriab ≤4 joints during disease course >4 joints after the first 6 mo Arthritis affecting ≥5 joints during the first 6 mo Arthritis affecting ≥5 joints during the first 6 mo, plus RF positivity on two occasions more than 3 mo apart Arthritis with or preceded by daily fever of at least 2 weeks’ duration, accompanied by one or more of the following:   Evanescent, nonfixed erythematous rash   Generalized adenopathy   Hepatomegaly or splenomegaly  Serositis Arthritis and psoriasis, or arthritis and at least two of the following: a. Dactylitis b. Nail abnormalities (pitting or onycholysis) c. Family history of psoriasis in a first-degree relative Arthritis and enthesitis, or arthritis or enthesitis with at least two of the following: 1. SI joint tenderness and/or inflammatory spinal pain 2. Presence of HLA-B27 3. Family history of HLA-B27–associated disease in a first-degree ­relative 4. Onset of arthritis in a male after the age of 6 yr Children with arthritis of unknown cause that persists ≥6 wk Does not fulfill criteria for any of the other categories Fulfills criteria for ≥1 of the other categories

aExclusions: 1, psoriasis in the patient or a first-degree relative; 2, arthritis in an HLA-B27 positive male beginning after the sixth birthday; 3, ankylosing spondylitis, enthesitis-related arthritis, sacroiliitis with IBD, Reiter syndrome, or acute anterior uveitis in a ­first-degree relative; 4, IgM RF on at least two occasions more than 3 mo apart; 5, presence of systemic JIA. bInclusion criteria for all subtypes: 1, age at onset 50,000 (70), neutrophil predominance, low glucose (100 mm/hour. However, most children with oligoarticular and some with polyarticular JIA will have a normal ESR and CRP. The addition of a CRP test can be helpful in situations in which infection is strongly suspected, because the short half-life of this acute-phase protein results in a rapid decline in concentration with effective antibiotic treatment, whereas the ESR may continue to rise. In addition, serologic testing for Lyme is appropriate in the setting of monoarthritis if the patient is from a Lyme endemic area. The ANA titer is a measure of serum antibodies that can bind to one of many potential antigens present in the nucleus of normal human cells. ANA titer at a dilution of >1 to 40 is considered positive. The presence of an elevated ANA is not diagnostic of JIA and should not be used as a screening test for arthritis. ANA can be positive in up to 20% of the normal population and may be induced by illness or be present in firstor second-degree relatives with SLE (120, 121). Unless there is a high index of suspicion of JIA, a positive ANA test results in unnecessary subspecialty referrals and parental anxiety.

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A

B

FIGURE 11-6.  Reflex sympathetic dystrophy in a child with a 1 month history of hand swelling and pain. A: Right hand after 1 month of symptoms. B: Technetium-99m bone scan showing diffuse increased isotope uptake in the affected hand. C: Right hand after 3 weeks of intensive physical therapy and psychotherapy.

C

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A

359

B FIGURE 11-7.  Polyarticular JIA with wrist and finger involvement. A: At 6 years of age, there is periarticular osteopenia and diffuse swelling of the wrist and fingers. B: At 20 years of age there is significant carpal and carpometacarpal fusion.

FIGURE 11-8.  Systemic JIA with prolonged arthritis resulting in severe osteopenia and destructive changes in the hand and wrist, with severe ulnar deviation.

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Children who have a positive ANA in the absence of systemic inflammation and arthritis are unlikely to subsequently develop a significant autoimmune disease (120, 122). In children with an established JIA diagnosis, the frequency of ANA positivity is greatest in young girls with oligoarticular disease, and represents an increased risk for anterior uveitis (123). If JIA is suspected on the basis of a history and physical exam, positive ANA should prompt an immediate referral to an ophthalmologist for a slitlamp examination to evaluate for the presence of uveitis. The RF is an autoreactive IgM, anti-IgG that is commonly used to help diagnose adult RA. In contrast to adults with RA, RF positivity is infrequent in children with JIA. Therefore, like the ANA, RF is not a good screening test for JIA. When present, it is most commonly associated with polyarticular JIA. RF is associated with a higher frequency of erosive synovitis and a poorer prognosis (124, 125). Anti-citrullinated cyclic peptide (anti-CCP) antibodies have a sensitivity and specificity of 48% and 98%, respectively, for adult RA (126). Additionally, adult CCP-positive RA patients have a more aggressive disease course manifested by joint erosions and destruction (127, 128). Anti-CCP antibodies are mainly detected in polyarticular RF-positive JIA patients and are of limited diagnostic value. However, in a child with established polyarticular disease, seropositivity for anti-CCP antibodies may portend a more destructive disease course and, therefore, help to identify patients who might benefit from more aggressive therapy at diagnosis. The presence of HLA-B27 is strongly associated with transient reactive arthritis, IBD, and ERA. The high familial occurrence of AS is directly related to the presence of HLAB27 (129). Although HLA-B27 is found in approximately 8% of the white population, it can be useful in the diagnosis of

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A

B FIGURE 11-9.  The cervical spine in a child with polyarticular JIA. A. At 6 years of age, there are no radiographic abnormalities. B. At 21 years of age there is ankylosis of C2–C5.

ERA. It is especially important in boys above the age of 6, where there is a family history of HLA-B27–associated illness, or SI joint or spinal inflammatory pain.

Synovial Fluid Analysis.  Arthrocentesis with synovial fluid analysis and culture should be performed in all children

with an acute arthritis accompanied by fever or in children for whom the diagnosis is unclear. In JIA, synovial fluid is type II, or inflammatory. The appearance is typically yellow and cloudy with decreased viscosity. Leukocyte counts are generally between 15 and 20,000 cells/mm3; however, they may range as high as 100,000 cells/mm3 (130–132). There is typically a neutrophil predominance (130).

Synovial Biopsy.  A synovial biopsy should be performed if the diagnosis remains unclear after laboratories, imaging, and synovial fluid analysis. Biopsy is particularly helpful if a diagnosis of tuberculosis, PVNS, or sarcoidosis is being considered.

TREATMENT RECOMMENDATIONS Medications.  The fundamental purpose of pharmacologic therapy is to achieve pain control, decrease inflammation, prevent joint destruction, and to maintain remission. The medications used are individualized for each patient, depending on their subtype of arthritis, degree of inflammation, and previous pharmacologic response. FIGURE 11-10.  CT scan of SI joints in a child with JAS showing erosions and sclerosis of the SI joints. (Courtesy of D. Ruben BurgosVargas.)

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Nonsteroidal Anti-Inflammatory Drugs.  NSAIDs are the initial therapeutic intervention in many children with JIA. NSAIDs provide both analgesia and anti-inflammatory effects. NSAIDs affect the biosynthesis of prostaglandins by direct inhibition of cyclo-oxygenase (COX) (133). There are two i­soforms

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rare (134). Gastroduodenal injury is more frequent in children who are receiving high doses, or more than one NSAID at a time (135). The use of aspirin in JIA is no longer recommended because of the risk of Reye syndrome. In the United States, the most commonly used NSAID for JIA is naproxen (10 to 20 mg/kg/d). In children with fevers, serositis, or pericarditis associated with systemic arthritis, reactive arthritis, or JAS, indomethacin is often the most effective NSAID (51). The doses of NSAIDs in children are based on body weight, and are often proportionally greater than in adult rheumatic diseases (Table 11-6). Preparations that come in a liquid form and have once- or twice-daily dosing are preferred. Children on long-term NSAID therapy should have a complete blood count, renal and liver function tests, and urine analysis at baseline, within 6 weeks of therapy initiation, and every 6 to 12 months thereafter. The average time required for a therapeutic response to NSAIDs is 2 to 12 weeks (136). Therefore, an NSAID is usually tried for several weeks before another is substituted. Approximately 50% of children respond to the first NSAID; of those who do not respond, 50% respond to an alternate NSAID (137). Nearly two-thirds of children with juvenile arthritis are inadequately treated with NSAIDs alone (138). These children require additional pharmacologic interventions.

FIGURE 11-11.  Iritis in oligoarticular JIA. Posterior synechiae with an irregular pupil.

Corticosteroids.  Intra-articular corticosteroid injections

of the COX enzyme. COX-1 is constitutively expressed and is involved in gastric cytoprotection, maintenance of renal perfusion, and platelet aggregation. COX-2 is upregulated at sites of inflammation. Most NSAIDs inhibit both COX isoforms, with consequential side effects such as GI toxicity or renal hypoperfusion. NSAIDs are generally safe and well tolerated in most children. Abdominal pain, nausea, and vomiting are the most common side effects, and gastrointestinal­hemorrhage is

TABLE 11-6

361

have been shown to be safe and effective in controlling the synovitis in JIA (139, 140). A recent decision analysis reported that initial intra-articular injection, rather than a trial of NSAIDs, is the optimal treatment for monoarthritis (141). In order to avoid a singled intra-articular injection, 3.8 children need to be treated with an initial trial of NSAIDs; the cost of initial therapy with NSAIDs was an expected additional

NSAIDs for the Treatment of JIA

Drug TID medications Indomethacin (Indocin)a,b Salicylsalicylic acid (Aspirin)b Ibuprofen (Motrin, Advil, etc.)a,b Tolmetin (Tolectin)b BID medications Sulindac (Clinoril) Choline magnesium trisalicylate (Trilisate)a Naproxen (Naprosyn)a,b Diclofenac sodium (Voltaren) Celecoxib (Celebrex)b Daily medications Nabumetone (Relafen) Meloxicam (Mobic)a,b Feldene

Dosage (mg/kg/d)

Maximum Daily Dose (mg)

2–3 80–100 45 30–40

200 5200 3200 1800

4–6 50–65 15–20 2–3 4–6

400 4500 1000 150 400

20–30 0.25 0.25–0.4

2000 15 20

aLiquid bU.S.

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preparation available. Food and Drug Administration (FDA)-labeled for use in children.

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6.7 months of active arthritis (141). Further, early intra-articular corticosteroid injections are associated with less leg-length ­discrepancy (LLD) in young children with oligoarthritis (142). Triamcinolone hexacetonide (1 mg/kg for large joints and 0.5 mg/kg for medium joints) is the most commonly used agent and often provides long-term control of inflammation. The most frequent adverse consequence of intra-articular corticosteroids is the development of subcutaneous atrophy at the site of injection. Other side effects of intra-articular injections include infection, chemical irritation, and periarticular calcifications. Systemic corticosteroids can be used for rapid control of severe arthritis. However, long-term use should be restricted to those children who have severe arthritis or systemic features that do not respond to other interventions.

Methotrexate.  The efficacy of methotrexate in JIA is well established (143, 144). It is a folic aid analogue, a competitive inhibitor of dihydrofolate reductase, and an inhibitor of purine biosynthesis. Methotrexate is typically given at a dosage of 0.5 to 1 mg/kg/wk or 15 mg/m2/wk (with a maximum of 25 mg) once weekly, either orally or by subcutaneous injection (145, 146). The most common side effects of methotrexate are nausea, fatigue, and liver transaminitis. Supplementation with folic acid (1 mg/d) can usually prevent gastrointestinal complications. Subcutaneous methotrexate should be considered for children who require doses >20 mg or who have significant gastrointestinal toxicity with the oral formulation. The average timecourse for clinical response to methotrexate is 6 to 8 weeks. Children on methotrexate should have a complete blood count and liver function tests at baseline, within 6 weeks of therapy initiation and then every 2 to 3 months thereafter.

Antitumor Necrosis Factor Agents.  Although the etiology and pathogenesis of juvenile arthritis are still unclear, macrophage-derived cytokines, such as tumor necrosis factor-a, appear to play a critical role in the induction and perpetuation of the chronic inflammatory process in JIA. Etanercept (Enbrel) is a soluble protein containing the extracellular domains of a p75 human TNF receptor attached to the Fc portion of a type 1 human immunoglobulin. Etanercept binds TNF-a in circulation and prevents subsequent cell activation. A multicenter placebo-controlled, double-blinded trial showed it to be effective in the treatment of juvenile arthritis that was resistant to initial therapy with methotrexate (147, 148). Further, the safety and efficacy of etanercept is maintained for up to 8 years (149). Etanercept is given subcutaneously at a dose of 0.8 mg/kg/wk. Infliximab (Remicade) is a chimeric, monoclonal anti– TNF-a antibody that binds both soluble and membrane-bound TNF-a. Infliximab has been shown to be efficacious in combination with methotrexate for the treatment of refractory juvenile arthritis (150) and chronic inflammatory uveitis (151). However, recently, a double-blinded, randomized trial did not show a statistically significant difference between children treated with methotrexate plus placebo versus methotrexate plus infliximab (149). Infliximab is given intravenously at a ­dosage

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of 3 to 10 mg/kg/dose; higher doses are often used for the treatment of refractory uveitis. Higher doses (≥6 mg/kg/dose) are also associated with less frequent adverse events, infusion reactions, and induced antibodies to the drug itself, ANA and double-stranded DNA (149). Adalimumab (Humira) is a fully human monoclonal anti–TNF-a antibody that binds soluble and membranebound TNF-a. Adalimumab alone or in combination with methotrexate was well tolerated and effective in treatmentrefractory RA (152), juvenile arthritis (153), and treatmentrefractory JIA-associated uveitis (154). Adalimumab is given subcutaneously at a dose of 24 mg/m2 (maximum dose 40 mg) every other week (153). The major adverse events associated with the use of anti– TNF-a agents are an increased risk of infection, coccidiomycosis, and reactivation of latent tuberculosis (155). Prior to the onset of therapy, patients should have a documented negative PPD.

Sulfasalazine.  Sulfasalazine has been used extensively in Europe, and increasingly in North America for the treatment of JIA. It was developed on the idea that RA was caused by an infection; therefore, it has both antibacterial and anti-­inflammatory properties. A randomized, double-blind, placebo-controlled trial showed that sulfasalazine is both safe and effective for the treatment of oligo- and polyarticular juvenile arthritis (156). It is typically given in an enteric-coated form at a dose of 50 mg/kg/d in two divided doses. Serious side effects have been noted in children with systemic arthritis, and the routine use of sulfasalazine is not recommended for this subgroup (157, 158). Side effects occur in up to 30% of patients (159) and include cytopenias, severe allergic reactions such as Stevens Johnson syndrome, hypogammaglobulinemia, and IgA deficiency. Children taking sulfasalazine should have a complete blood count, liver function tests, and urinalysis at baseline and every 2 to 3 months thereafter. Immunoglobulin levels should be monitored every 6 months. Abatacept.  Abatacept (Orencia) is a fully human monoclonal antibody (MRA) that consists of the extracellular domain of the CTLA-4 receptor attached to the Fc portion of the immunoglobulin receptor. CTLA-4 competitively binds CD-80/86 and blocks T-cell co-stimulation. Abatacept is efficacious and safe in TNF-resistant adult RA (160). In a double-blinded, randomized controlled trial, children with methotrexate-resistant or TNF-resistant JIA who were treated with abatacept had a statistically significant decrease in the occurrence of and increased time to disease flare (161). Abatacept is given at a dose of 10 mg/kg every 4 weeks. The major adverse events are infusion reactions and infection (161). Anti-Interleukin 1 Agents.  Anakinra (kineret) is an IL-1 receptor antagonist. It has been shown to be safe and efficacious in combination with methotrexate for adult RA (162). A recent randomized, placebo-controlled trial showed that anakinra was safe and well tolerated at a dose of

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CHAPTER 11  |  Juvenile Idiopathic Arthritis

1 mg/kg/d (maximum 100 mg) but did not significantly reduce disease flares in children with polyarticular JIA (163). In JIA, it has been anecdotally used for systemic JIA, although there are no randomized controlled trials published at this time. The major side effects of anakinra are injection site reactions and infection.

Anti-Interleukin 6 Agents.  IL-6 is a key inflammatory cytokine in RA and JIA. Anti–IL-6 receptor MRA has been studied for the treatment of systemic JIA in open label phase II trials. These preliminary trials have demonstrated that MRA is safe, well tolerated, and resulted in improvement in symptoms and inflammatory markers (164, 165). Tocilizumab (RoActemra or Actemra) is a recombinant humanized MRA that acts as an IL-6 receptor antagonist. A recent doubleblinded trial demonstrated that Tocilizumab monotherapy was superior to methotrexate monotherapy in RA, with a rapid improvement in symptoms and a favorable safety profile (166). Tocilizumab trials in children have not been published yet.

PHYSICAL AND OCCUPATIONAL THERAPY All children with prolonged arthritis should be evaluated by a physical and/or occupational therapist to provide an ­appropriate teaching and treatment program. Most treatment programs for JIA will include active and passive range-ofmotion exercises, strengthening, and other modalities such as use of hot paraffin for relief of hand stiffness. Swimming has the advantage of providing muscle strengthening and active range of motion without significant weight bearing. Splinting may be used for maintaining alignment, providing rest, and reducing flexion contractures. For children with severe flexion contractures, a dynamic tension splint or serial casting can be used to correct the contracture. Physical therapy for range of motion in JAS is primarily to prevent loss of mobility and poor functional positioning.

Surgical Interventions.  For most children with JIA, orthopaedic surgery has a limited role in the management plan. With early detection and aggressive medical management, the majority of children with JIA have a satisfactory outcome without significant disability. However, for those children with persistent arthritis despite medical therapy, continued pain, or progressive leg-length discrepancy, there is often significant benefit from individualized orthopaedic surgical intervention. Surgical intervention in JIA presents unique challenges to the management team. The small size of children and their growth potential must be taken into consideration. Also, in the postsurgical period, prolonged immobilization can lead to decreased strength and range of motion. Intensive physical therapy is frequently required during the recovery period. There is no universal agreement about which procedures are indicated for the treatment of complications of JIA. However, the overall goal is to provide symptomatic relief and improved functioning.

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363

Synovectomy.  Synovectomy may be indicated in JIA for relief of persistent joint pain, swelling, and loss of range of motion related to synovial hypertrophy. Several recent studies suggest that arthroscopic synovectomy for treatment-refractory monoarthritis only partially effective JRA and that recurrence was common (167, 168). In one study, two-thirds of children relapsed within 24 months of the procedure (167), and in a second study, 67%, 95%, and 100% of children with oligo-, poly-, and psoriatic JIA relapsed after an average of 1 year (168). Predictors of a good response were normal inflammatory markers and short disease duration at the time of the procedure (167).

Soft-Tissue Release.  Soft-tissue release may be useful in a child with a severe contracture of the knee or hip that is resistant to splinting or serial casting. Reports have demonstrated various results. The most recent publications have shown only a modest benefit (169, 170).

Arthrodesis.  Arthrodesis may be indicated for severe joint destruction of the ankles or cervical spine secondary to prolonged synovitis. After puberty, a fixed and painful deformity of the ankle may be corrected by a triple arthrodesis. Occasionally, in children with isolated damage of the subtalar or talonavicular joint, a single joint fusion may be appropriate (171). Although many children with JIA have cervical spine arthritis and atlantoaxial instability, there is no consensus on the indications for prophylactic fusion. In many cases, a simple cervical orthosis may stabilize the neck and prevent further subluxation. However, fusion of the cervical spine (C1–C2) is indicated in children who have progressive neurologic involvement (172, 173). Epiphysiodesis.  An appropriately timed epiphysiodesis can be successfully used to correct leg-length discrepancies in oligoarticular JIA (174, 175). The discrepancy can be predicted using the method of Moseley (92). Simon et al. (175) reported that 15 such patients were followed up to skeletal maturity and showed satisfactory results.

Total Joint Arthroplasty.  Total joint arthroplasty is indicated for children with JIA who have severe destructive joint changes with functional impairment. The most common joints replaced are the hip and knee, followed by the shoulder and elbow. Cemented hip replacements may reduce pain and improve functional ability; however, there is a significant rate of loosening and need for subsequent revision (176, 177). A recent study has suggested that bipolar hemiarthroplasty of the hip, with a 79% 10-year survival, may be an alternative to conventional joint arthroplasty (178). Results of total knee arthroplasty in JIA have been encouraging, with few revisions required (179–183). Cementless total knee arthroplasty has been used in selected cases (184). Recent studies have confirmed the efficacy of the procedure by reporting an overall 99% survival for nonconstrained anatomically graduated components prosthesis with cementless fixation (183).

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In a recent review, Connor and Morrey (185) evaluated the long-term outcome for 19 children (23 elbows) who had been managed with total elbow arthroplasty and followed up for at least 2 years. Only three (13%) had poor results caused by late complications: aseptic loosening, instability, and worn bushings (185).

COMPLICATIONS Uveitis.  Uveitis is one of the most severe extra-­articular complications of JIA. It is often asymptomatic and, if untreated, can lead to synechiae, cataracts, glaucoma, retinal detachment, and visual loss (Fig. 11-11). Significant predictors of ocular inflammation include JIA subtype, younger age at disease onset, and ANA positivity (186). Oligoarticular JIA has the highest cumulative incidence of uveitis, occurring in up to 25% and 16% of children with extended and persistent courses, respectively (186). Uveitis is much less frequent in polyarticular and systemic JIA patients, 4% and 1%, respectively. In ERA, ocular inflammation occurs in up to 7% of children; in two-thirds of children, it is manifested by pain, photophobia, and conjunctival erythema (186). Uveitis is present in up to 10% of psoriatic JIA patients and is typically asymptomatic (186). Although the overall incidence and severity of uveitis seem to be decreasing (187, 188), even a lowgrade chronic uveitis can result in a poor visual outcome (189). Current guidelines for ophthalmologic examination are based on age, ANA status, and type of JIA onset (190) (Table 11-7). Growth Retardation.  Chronic inflammation and corticosteroid therapy adversely impact the growth of children with TABLE 11-7

Guidelines for Initial Frequency of Screening Eye Exams in JIA Minimum Screening Frequency Age at Onset

JIA Onset Type Oligoarticular  ANA+  ANA− Polyarticular  ANA+  ANA− Systemic Psoriatic  ANA+  ANA− Enthesitis-related arthritis

6 months, and (c) crossing two or more percentiles on the height for age growth chart. Once remission is achieved and corticosteroid therapy is discontinued, as much as 70% have catch-up growth; however, the remaining 30% may have persistent growth retardation (192). Preliminary results of recombinant growth hormone look promising (193); however, use of growth hormone in the JIA population is not part of currently recommended routine therapy.

Osteoporosis.  Risk factors for osteoporosis in JIA include chronic corticosteroid use, physical inactivity, delayed puberty, and malnutrition (194). Recent studies have demonstrated that children with chronic arthritis are at risk for low volumetric bone mineral density and bone strength (195). Furthermore, a recent population-based study demonstrated an elevated risk of fracture in children with chronic arthritis (196). Careful attention to calcium and 25-OH vitamin D status may help minimize osteoporosis in the JIA population. Leg-Length Discrepancy.  Increased blood flow to inflamed joints also results in increased nutrient delivery to adjacent growth plates, resulting in increased bone growth. If arthritis is asymmetric in the lower extremities, this may result in LLD over time. LLD < 1 cm are probably clinically insignificant and may be a variant of normal. LLD > 1 cm, h ­ owever, may result in strain on the shorter leg and back. Early treatment of arthritis may prevent LLD. One study showed that early and continued use of intra-articular corticosteroid ­injections help prevent LLD and decrease the need for shoe lifts (142).

PEARLS AND PITFALLS • JIA has been proposed as a replacement for both JCA and JRA. • Oligoarthritis is the most common subtype of JIA. • Only 5% of RF-positive and 30% of RF-negative polyarticular JIA patients achieve long-term remission off medication. • Less than one-fourth of children with JAS have pain, stiffness, or limitation of motion of the SI or lumbosacral spine at disease onset. • Small joints of the toes are commonly involved in JAS and are seldom affected in other forms of JIA, with the exception of psoriatic arthritis. • Initial laboratory evaluation of arthritis should include a CBC, ESR, and CRP. Lyme ELISA should also be considered if living in a Lyme endemic area. • RF and ANA positivity are not diagnostic of JIA • Plain radiographs are useful in the initial evaluation for identifying osteopenia, fractures, or other bony lesions. • Radiographic features associated with JIA include soft-­ tissue swelling and widening of the joint space, generalized

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• • • •

osteoporosis, joint space narrowing, erosions, subluxation, and ankylosis. Screening flexion and extension films are recommended prior to anesthesia if cervical disease is suspected. ANA positivity is a marker of risk for JIA-associated uveitis. All children with JIA should be evaluated for uveitis at diagnosis and routinely thereafter. JIA patients are at risk for growth failure, osteoporosis, and LLD.

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