Table 19.2  Guidelines for ophthalmologic examinations in children with juvenile rheumatoid arthritis

Recommended Screening Schedule for JRA Patients Without Known Iridocyclitis

Adapted from American Academy of Pediatrics Section on Rheumatology and Section on Ophthalmology.. Pediatrics. 1993;92:295–296.

Pathophysiology

The pathophysiology behind JRA and the associated uveitis is not completely understood, but appears to be autoimmune in nature. This is supported by the presence of autoantibodies and the clinical response to immunosuppressive therapy. ANA antibodies are the most frequently associated with JRA-associated uveitis [19], and are directed against a variety of antigens, particularly histone H1 [20]. Further supporting the autoimmune nature of JRA-associated uveitis, other autoantibodies have been reported that react with iris epithelium, ciliary body epithelium, and retinal pigment epithelium [21, 22]. These antibodies are present in the sera of patients with JRA with and without uveitis. It is unclear whether any of these autoantibodies represent a pathologic mechanism or merely reflect an immune response to ocular tissue damage by other mechanisms. Histologic study of eyes removed after years of chronic disease demonstrate an intense inflammatory infiltrate in the iris and ciliary body consisting predominantly of lymphocytes and plasma cells [23, 24]. The true pathophysiology behind JRA-associated uveitis requires further investigation.

Diagnosis/Treatment

Since arthritis precedes the onset of uveitis in 85–90% of patients, most children with JRA are referred to ophthalmology by a pediatrician or rheumatologist and are asymptomatic from the ocular standpoint. When the ocular disease presents initially, determining the etiology of the uveitis is more challenging, and a

relatively broad differential diagnosis for uveitis in children should be considered. A thorough ocular and systemic history and review of systems can help narrow the potential etiologies.

Initial laboratory testing can include syphilis serologies, lyme titers, angiotensin-converting enzyme, and serum lysozyme. Notably, sarcoidosis in children presents more like an arthritic disease than what is commonly seen in adults (see Sect. 19.4.4). Additionally, lyme disease can present with arthritis and uveitis.

Anti-nuclear antibody (ANA) status should be determined, since it is unlikely for a child with JRA to not have ANA to develop uveitis [19]. HLA B27 and rheumatoid factor testing can also be helpful as it can be present in patients with the polyarticular onset JRA.

The mainstay of initial treatment for JRA associated uveitis is topical corticosteroids, with more severe cases requiring systemic or periocular corticosteroids. Short-acting mydriatic agents are used to keep the pupil mobile and prevent the formation of posterior synechiae. More recently, other immunomodulators such as methotrexate and infliximab have been used [25].

Genetics

For oligoarthritis, HLA associations include -A2, -DR5, -DR8, -DR11, and -DP2.1 [16]. Children with HLA-DR1 or HLA DR-4 rarely develop ocular disease [26].

Complications

Complications are common, and largely depend on the extent of damage at first diagnosis [27]. Undertreatment or overzealous treatment with steroids can also lead to complications. Prolonged inflammation can lead to band keratopathy, cataract formation, and glaucoma secondary to steroid use, chronic inflammation, posterior synechiae, vitreous debris, chronic hypotony, amblyopia, phthisis, and CME. In addition, there are potential complications from systemic immunosuppressive therapy, depending on the specific drug utilized.

19.4.2  HLA-B27-Associated Uveitis

19.4.2.1  Historical Context

The first association between a human leukocyte antigen (HLA) with an inflammatory disease was made in