ABSTRACT

Pediatric uveitis may be a serious health problem because of the lifetime burden of vision loss due to severe complications if the problem is not adequately treated. Juvenile idiopathic arthritis (JIA)-associated uveitis is characterized by insidious onset and potentially blinding chronic anterior uveitis. Periodic ophthalmologic screening is of utmost importance for early diagnosis of uveitis. Early diagnosis and proper immunomodulatory treatment are essential for good visual prognosis. The goal of treatment is to achieve enduring drug-free remission. The choice of therapeutic regimen needs to be tailored to each individual case. One must keep in mind that patients under immunomodulatory treatment should be monitored closely due to possible side effects. Local and systemic corticosteroids have long been the mainstay of therapy; however, long-term corticosteroid therapy should be avoided due to serious side effects. Steroid-sparing agents in the treatment of JIA-associated uveitis include antimetabolites and biologic agents in refractory cases. Among the various immunomodulatory agents, methotrexate is generally the first choice, as it has a well-established safety and efficacy profile in pediatric cases and does not appear to increase the risk of cancer. Other classic immunomodulators that may also be used in combination with methotrexate include azathioprine, mycophenolate mofetil, and cyclosporin A. Biologic agents, primarily tumor necrosis factor alpha inhibitors including infliximab or adalimumab, should be considered in cases of treatment failure with classic immunomodulatory agents.

Introduction

Despite advances in diagnosis and treatment, uveitis, especially in the pediatric age group, continues to be a serious health problem due to complications that may lead to blindness. Ocular involvement has particular importance in extra-articular manifestations of pediatric rheumatic diseases because of its high incidence and morbidity. Juvenile idiopathic arthritis (JIA) is the most common pediatric rheumatic disease with both articular and ocular involvement.^1,2,3,4,5

In the United States of America, 6% of all reported uveitis cases are pediatric, and approximately 80% of these are related to JIA.^6,7In Turkey, JIA and Behçet’s disease are the most common systemic diseases among pediatric uveitis cases, and the reported incidence of JIA varies between 3.3% and 30.4%.^8,9,10,11

JIA is characterized by chronic arthritis beginning before the age of 16 and is the leading cause of arthritis in pediatric patients. It occurs more frequently in female children, with a reported female to male ratio of 3:2. The International League of Associations of Rheumatology (ILAR) classification system defines 7 subtypes of JIA which feature varying rates and types of uveitis. Approximately 78-90% of patients with JIA-associated uveitis have oligoarticular (≤4 joints) manifestation and 90% of these patients are antinuclear antibody (ANA) positive. Between 7-14% of the patients have polyarticular (≥5 joints) and 2-6% have systemic (systemic symptoms as well as articular involvement) manifestations. The average age of uveitis onset in JIA patients is 6-8 years old. In the majority of patients uveitis appears within 4-7 years of arthritis onset. However, uveitis occurs prior to arthritis in about 6% of cases and is only noticed if an eye exam is performed when the arthritis is diagnosed.^{12,13,14,15,16}Therefore, it is imperative that all patients diagnosed with JIA undergo ophthalmologic examination and regular screening depending on the disease type. Oligoarticular and polyarticular JIA patients with arthritis onset at or before age 6, with arthritis for 4 years or less or positive for ANA should undergo an ophthalmologic examination every 3 months. Screening intervals for patients at lower risk of uveitis should be 6 to 12 months.¹⁷The diagnosis may be overlooked due to a lack of obvious ocular symptoms like redness, pain or light sensitivity, because some pediatric patients are unable to sufficiently communicate, or due to the chronic course of the disease. As a result, serious sight-threatening complications such as band keratopathy, cataract, glaucoma or hypotony may be observed at presentation.^1,18,19,20

Patients with a consistently high degree of flare in the aqueous humour, which indicates the protein level, are at greater risk of complications. Risk factors for a poor prognosis are early age of uveitis onset, male gender, ANA positivity, short interval between arthritis and uveitis onset, oligoarticular manifestation and presence of ocular complications at time of presentation. Furthermore, patients with onset of arthritic involvement in early childhood are at high risk of chronic severe uveitis. In contrast, patients with arthritis onset at a later age exhibit recurrent acute anterior uveitis attacks and have a better prognosis.^18,21The early diagnosis and correct treatment of these pediatric patients is critical for a good visual prognosis.

Cases of JIA-associated uveitis typically exhibit anterior uveitis characterized by iris and ciliary body involvement and is often bilateral. As a patient’s arthritis and uveitis may follow different courses, the activity in each area of involvement should be evaluated independently, and treatment should be planned for each individual in cooperation with a pediatric rheumatologist. The results of numerous studies in the literature related to this topic can be used as the basis for a specific treatment algorithm for pediatric uveitis patients.^6,7,22