Early Juvenile Idiopathic Arthritis

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The Need for Early Aggressive Treatment of JIA

In the last decade there has been an evolution in the understanding of the clinical course and long-term outcomes for JIA. Initially remission rates up to 60% were described in JIA.3 However, subsequent studies noted much lower rates with 33% at 10 years for JIA in general4 and 44% at 15 years for enthesitis-related arthritis (ERA).5 More tellingly, clinical remission off medications at 5 years was sustained in only 6% of JIA patients. Although a significant number of patients diagnosed with

Clinical presentation of early JIA

Children with JIA tend to be stoic and manifest symptoms according to their age and developmental level. They may exhibit joint inflammation only by difficulty moving following a period of inactivity or focus on compensatory technique to perform a task.17, 18, 19 In assessing children for arthritis, it is important to review any change in age-appropriate activities. Flexion contracture, weakness, and muscle atrophy may develop early.

The pattern of early joint involvement is characterized by

Pathogenesis of JIA

T cells are important in initiating the immune response in JIA, though some B cell dysregulation has also been postulated.34, 35, 36, 37 Several inflammatory cytokines play a prominent role, including tumor necrosis factor α (TNF-α),34, 38 interleukin (IL)-1,39, 40 and IL-6, resulting in cartilage destruction, joint-space narrowing, and erosions.41, 42

Similar to adult arthritis, in JIA there is persistent cellular inflammatory infiltrate in the synovium with neovascularization, pannus

Laboratory markers

The diagnosis of JIA is made clinically with established laboratory markers of little diagnostic value, though they play a role in identifying JIA patients at risk for specific complications. The presence of antinuclear antibody (ANA) identifies children at highest risk for eye involvement. ANA-positive patients are primarily female, with early age of disease onset, asymmetric arthritis, lower total joint involvement over time, and at increased risk of chronic iridocyclitis.4, 45, 46 RF

Imaging

Advances in imaging techniques—in particular MRI—allows the ability to detect changes early in the disease course and before observed symptoms making it a useful adjunct in early diagnosis.53, 54 MRI can detect the earliest stages of bone erosions.55 Systemic gallium scintigraphy has also been suggested to detect early JIA.56 Ultrasound may be helpful for enthesitis.57

Effects of early disease activity

Localized growth disturbances are common9 and occur in 10% to 48% of JIA patients during the first 2 to 3 years of disease.47 They are seen primarily at sites of inflammation with overgrowth due to hyperemia and accelerated growth maturation or impaired growth resulting from destruction of the growth center and premature closure of the epiphysis resulting in leg length discrepancies and micrognathia.9, 58, 59

At diagnosis, periarticular osteopenia is the most common radiographic change seen;

Prognosis and outcomes

The course and outcome of JIA cannot be predicted by baseline features. However, disease inactivity within the first 5 years is associated with lower number of restricted joints, less cumulative articular damage, and better functional and radiographic outcome. Targeting remission through aggressive therapeutic interventions provides better outcome.15

Therapy and treatment response within the first 6 months of disease is a factor in improved long-term outcome. In a retrospective study of JIA

Predictors of disease activity and prognosis

Because the response within the first 6 months seems to play a role in long-term outcome, identifying predictors of early inactive disease and risk factors for persistent disease in JIA is paramount. In a prospective study of patients a median of .65 months after diagnosis and 6 months after disease onset, a shorter duration from disease onset to diagnosis, younger age, and patients with oligoarticular JIA (46%) correlated with inactive disease at 6 months. Notably, only 33% of patients

Management

The goals of JIA management include inactive disease with subsequent clinical remission, normal growth and development, preservation of psychosocial integrity, participation in normal activities, and prevention of long-term complications associated with the disease and its treatment. It is a multidisciplinary approach that includes pharmacologic administration, physical and occupational therapy, and psychological support,44, 74 which should be included in the management as early as possible.

Medications

Similar to adult studies, there seems to be a window of opportunity early in the disease course that improves outcomes with the concept that there is a narrow time frame in which resetting of active disease is easiest to achieve. The use of DMARD therapy early in the disease suppresses disease activity with beneficial effects. The advent of biologics has made this even more attainable.8, 13, 44, 75

NSAIDs had traditionally been the foundation of therapy. It remains an important initial

Intraarticular corticosteroids

Intraarticular corticosteroid (IAS) injection has beneficial long-lasting effects with suppression of synovial inflammation and reversion of pannus formation without deleterious effects to the articular cartilage or linear growth.80 Its early use has also been associated with less leg-length discrepancy.29 The use of IAS is an effective initial therapeutic modality, particularly in oligoarticular JIA in which there is high-to-moderate joint disease activity and/or poor prognostic factors and in

Anti-TNF Agents

Anti-TNF agents have greatly affected the ability to achieve rapid disease improvement and effective disease control. Etanercept given by subcutaneous (SC) injection at a dose of .8 mg/kg weekly or .4 mg/kg twice weekly is effective and well-tolerated.86, 87, 88 A randomized double-blind placebo-controlled trial of polyarticular JIA patients showed a 74% response rate during the 3 month open label phase with significant difference in disease flare in the double blind portion (81% placebo vs 7%

Combination therapy

Combination therapy may be more effective than monotherapy.88, 119 Concomitant use of MTX with IAS results in longer disease remission in the injected joint.85 The Aggressive Combination Drug Therapy in Very Early Polyarticular Juvenile Idiopathic Arthritis (ACUTE-JIA) trial was a multicenter randomized, open-label clinical trial that evaluated aggressive combination therapy in early polyarticular JIA patients who were DMARD naïve and had arthritis for more than 6 months. Patients were

Summary

JIA is an immunoinflammatory disease of childhood that is distinct from adult arthritis but has a burden of disease with significant impact well into the adult years. It is now recognized that a considerable number of JIA patients will have active disease or sequelae of disease that persists into adulthood. Although longstanding disease is a risk factor for irreversible damage and functional disability, the changes begin early in the disease process. In addition, there are several

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