1972, when HLA-B27 was correlated with ankylosing spondylitis [28]. Since then, HLA associations have been made for over 100 diseases, including many ocular­ diseases and systemic diseases with ocular manifestations. HLA-B27 associated diseases associated with anterior uveitis in children are the so-called seronegative­ spondyloarthropathies, including juvenile ankylosing spondylitis (AS), juvenile reactive arthritis (Reiter syndrome), and arthropathies associated with inflammatory bowel disease (IBD)[29]. Extraarticular manifestations distinguish between these spondyloarthropathies, which by definition do not have positive rheumatoid factor.

19.4.2.2  Clinical Findings/Natural History

HLA-B27 is present in only 1.4–8% of the general population; however, 50–60% of patients with acute iritis may be HLA-B27 positive [30]. About 20–30% of children with juvenile AS and juvenile reactive arthritis develop uveitis; patients with inflammatory bowel disease develop uveitis about 2–9% of the time [31, 32]. In addition to a strong association with HLAB27, the seronegative spondyloarthropathies are characteristically associated with a strong family history, onset of disease in late childhood or adolescence, and more boys than girls affected. Many children will develop lumbosacral spine disease and sacroiliitis.

Similarly to adults, the uveitis associated with juvenile spondyloarthropathies is acute in presentation, symptomatic, and unilateral (Fig. 19.2). Symptoms include a painful red eye with photophobia, increased tearing, and blurred vision. Clinical signs include an intense anterior chamber cellular response with variable flare. Fine keratic precipitates and fibrin can often be found on the corneal endothelium. Cells can spill into

the anterior vitreous, and rarely a diffuse vitritis can develop. CME can occasionally develop [33]. Attacks usually resolve in less than 6 weeks with adequate treatment, and children rarely experience residual visual impairment. Recurrences, however, are common.

Pathophysiology/Genetics

In humans, the major histocompatibility complex (MHC) located on chromosome six genetically encodes the HLA system. Three classes of gene products are encoded within the MHC complex and play a role in determining immunity and self-recognition in virtually all cells. Class I molecules such as HLA-B serve as the antigen-presenting structure for CD8 or suppressor T cells. The sequence of HLA-B27 has been known since 1985 [34], but its exact role in triggering an inflammatory response that causes disease is not known. The theory of molecular mimicry postulates that an immune response initially mounted against a peptide from an infectious agent is subsequently directed against HLAB27 itself due to epitope similarities [35, 36]. A second theory suggests that the HLA allele confers an altered immune response to a triggering environmental antigen that directly results in tissue damage, causing the disease [37]. There are many other theories with varying degrees of support, and in the future animal models will likely advance our understanding of this disease.

Diagnosis/Treatment/Complications

Treatment with frequent topical corticosteroids and a dilating drop are usually effective in controlling HLA-B27 associated anterior uveitis. The frequency of corticosteroids­ drops can be rapidly adjusted as the