There are several different types of JIA which can be classified by the number of joints involved. Specific types of JIA have higher associations with the development of uveitis. The American College of Rheumatology divides JIA into three categories based on number of joints involved: systemic, oligoarticular (persistent or extended), or polyarticular (Table 25.2). The International League of Associations for Rheumatology (ILAR) classification also includes Rheumatoid factor (RF) positive polyarthritis, RF negative polyarthritis, psoriatic arthritis, and enthesitis-related arthritis. Uveitis is most often associated with the extended oligoarthritis type of JIA in 25 % of patients followed by the persistent oligoarthritis type in 16 % [3]. Systemic JIA is rarely associated with uveitis.

Unlike most forms of uveitis, JIA uveitis is associated with an insidious onset of nongranulomatous anterior uveitis in a white, quiet eye. Children generally report no symptoms and may present to an ophthalmologist after failing a school vision screen or because of diagnosis of arthritis. Clinical signs include anterior uveitis with cells and flare. Anterior chamber cells are present when there is active inflammation, but most eyes with chronic inflammation may exhibit flare associated with leakage of proteins from the ciliary body vasculature. Inflammation is most commonly bilateral, but there can be unilateral inflammation or asymmetric involvement. Other common clinical features include band keratopathy, nongranulomatous keratic precipitates, posterior synechiae, and elevated intraocular pressure. Patients can have posterior segment involvement including vitritis, cystoid macular edema, and optic disc edema.

Patients with enthesitis-related arthritis who develop uveitis may present with symptoms of acute anterior uveitis, including pain, photophobia, redness, and blurred vision. These patients are generally male adolescent patients with positive HLA-B27.

The diagnosis of JIA uveitis is made based on careful history, physical exam, and ancillary tests. Patients and family members should be asked about a history of joint swelling or restriction of movements as well as family history of autoimmune diseases, especially inflammatory arthritis or psoriasis. Children with uveitis should have a thorough physical examination for evidence of joint disease, preferably by a pediatric rheumatologist. Serologic testing may be helpful in ruling out other entities for uveitis (Table 25.3). ANA positivity is a major risk factor for the development of uveitis in patients with oligoarticular arthritis, with up to 30 % of these patients developing uveitis. RF positivity is associated with a low risk for uveitis.

The differential diagnosis of uveitis with arthritis in children includes infectious and noninfectious entities. Lyme disease is an important infectious cause of uveitis and arthritis in children and serologic testing (both screening enzyme linked immunoassay and confirmatory Western blot) should be performed for patients who live in endemic areas. Cat scratch disease can also present with uveitis and Bartonella serologies should be obtained if the history is suggestive. Viral processes such as the herpes family of viruses can cause uveitis in children and should be considered in the differential diagnosis.

Other noninfectious causes of uveitis in the pediatric population include sarcoidosis, which can present with arthritis and anterior uveitis in children. Familial juvenile systemic granulomatosis, also known as Blau syndrome, can also present with arthritis and uveitis in children; however, the uveitis is most often a bilateral granulomatous panuveitis which differs from JIA uveitis. Tubulointerstitial nephritis with uveitis syndrome can present as bilateral anterior uveitis, often with fevers, malaise, and flank pain. Definitive diagnosis is made with renal biopsy demonstrating interstitial nephritis. Behcet’s disease can also present with uveitis and pauciarticular arthritis; diagnostic criteria include the presence of oral and/or genital ulcers. Behcet’s is rare in children and is characterized by more extensive vasculitis.

JIA uveitis is most often associated with a chronic course with 60–80 % of patients having inflammation lasting longer than 3 months. JIA is associated with a low incidence of remission of anterior uveitis [5]. The goal of treatment in JIA uveitis should be to eliminate active inflammation in order to prevent long-term ocular complications. While topical and systemic corticosteroids may be initial treatments for uveitis, they should be used sparingly due to significant side effects related to chronic exposure. Systemic nonsteroidal medications may be helpful for arthritis symptoms, but generally do not adequately control ocular inflammation. Patients diagnosed with JIA uveitis, particularly those with ocular complications at presentation and duration of uveitis greater than 3 months should be treated with steroid-sparing immunosuppressive therapies (Table 25.4). Methotrexate is the most commonly used first-line treatment for JIA uveitis and is effective for both joint and eye disease. Other anti-metabolite therapies such as azathioprine and mycophenolate mofetil and T cell inhibitors like cyclosporine have been used in JIA uveitis with variable results [6]. The advent of biologic response modifier therapies has had a significant impact on the treatment and control of ocular inflammation in JIA. In patients with severe disease that is recalcitrant to standard immunosuppressive therapy, TNF alpha inhibitors such as infliximab and adalimumab are safe and effective second-line treatments for JIA uveitis [7–9]. TNF inhibitors are usually used in conjunction with methotrexate for improved efficacy and to prevent the development of human anti-chimeric antibodies in patients treated with infliximab, although they can be used as monotherapy. Other biologic agents such as abatacept and rituximab have also been used in patients with severe JIA uveitis who have failed multiple immunosuppressive therapies [10, 11].