A 23-year-old white female presented to the office after experiencing a red, painful left eye for approximately one week. Additionally, she reported photophobia and a radiating left, frontal headache. Neither artificial tears nor acetaminophen had provided significant relief. Her ocular history included bilateral myopia as well as a small-angle, constant left esotropia with mild amblyopia in that eye.
Her best-corrected visual acuity was 20/20 OD and 20/30 OS. Pupil testing, motility testing and confrontation fields were all normal. Biomicroscopy of the right eye was essentially unremarkable, but the left eye displayed 3+ injection of the bulbar conjunctiva with a notable circumlimbal flush. Additionally, the anterior chamber demonstrated grade 2+ cells and flare. Fine keratic precipitates were also evident on the corneal endothelium, most notably inferior. Intraocular pressure (IOP) was 16mm Hg OD and 12mm Hg OS. A dilated fundus examination was unremarkable.
The patient was diagnosed with acute, idiopathic anterior uveitis in her left eye. Treatment included cycloplegia (5% homatropine twice daily in each eye) and liberal use of topical corticosteroid drops (0.05% difluprednol every two hours in the left eye for the first 72 hours). The condition was brought under control in a matter of weeks; cycloplegia was discontinued and the steroid drops were slowly tapered until cells were no longer evident in the anterior chamber.
Although the patient responded well and the episode appeared singular, we discussed the implications of idiopathic anterior uveitis, as well as the potential for a systemic etiology.
We recommended she obtain a physical examination as a precautionary measure, with medical testing to follow as determined by her primary care physician. Several weeks later, she reported that serologic testing had come back positive for human leukocyte antigen-B27 (HLA-B27).
|Characteristic cells and flare presentation in a patient with acute anterior uveitis. |
This column reviews some of the diagnostic and management challenges associated with uveitis, as well as with HLA-B27.
Anterior uveitis is heralded by a constellation of clinically observable findings, typically including deep perilimbal injection of the conjunctiva and episclera, keratic precipitates along the corneal endothelium, variable corneal edema and “cells and flare” within the aqueous.1 “Cells” represent free-floating leukocytes, liberated from the iris vasculature in response to inflammation, while “flare” refers to plasma proteins suspended in the aqueous, giving rise to a hazy or smoky appearance. The classic presentation typically involves an individual 20 to 60 years of age, complaining of unilateral ocular pain, photophobia, and tearing.2,3
While circumstances that spark the development of uveitis vary, its resultant events stimulate a localized inflammatory state impacting the iris, ciliary body and cornea. Cytokines mediate numerous tissue changes, among them vasodilation and increased vasopermeability.4,5 As cellular debris and large molecular weight proteins accumulate in the aqueous, negative sequelae become increasingly likely, including synechiae, secondary glaucomas and neovascularization of the iris and angle.4-6 Unmanaged, the condition is potentially sight-threatening from a variety of pathogenic mechanisms.
Numerous etiologies may be implicated in anterior uveitis, ranging from trauma to widespread infection to generalized ischemic disorders.7-12 Some of the more well-known systemic etiologies include rheumatoid arthritis, systemic lupus and Lyme disease.11,12 Medical testing is generally not undertaken for isolated episodes; however, if the presentation is bilateral, severe, recalcitrant or recurrent, the patient should obtain testing to investigate for potential underlying systemic conditions (Table 1).
Imaging studies are also part of the medical workup. X-rays of the sacroiliac joint are useful in diagnosing ankylosing spondylitis, while a chest radiograph helps identify tuberculosis or sarcoidosis infiltration into the pulmonary system.14 Unfortunately, these tests are time-consuming and expensive. Rather than taking a “scatter-shot” approach, we prefer to comanage patients with an internist or rheumatologist who can choose the most appropriate tests.
Table 1. Systemic Tests
Human Leukocyte Antigen-B27
HLA proteins, often found on white blood cells, are encoded by genes of the major histocompatibility complex.15-17 While their specific functions are diverse, they are principally implicated in the immune response and inflammatory pathways.16 Researchers classify HLAs into different types (e.g., HLA-A, HLA-B, HLA-C), and those types into further, numbered versions, or alleles (e.g., HLA-A24, HLA-B13). The HLA-B27 serotype is strongly linked with the seronegative spondyloarthropathies group of autoimmune diseases.15-18 In these conditions, blood tests may reveal a positive HLA-B27 result. However, rheumatoid factor and antinuclear antibody are characteristically negative. The most prevalent of these conditions is ankylosing spondylitis; other known disorders include reactive arthritis, spondylitis associated with inflammatory bowel disease (including Crohn’s disease and ulcerative colitis), psoriatic arthritis and juvenile idiopathic arthritis. Additionally, HLA-B27+ individuals may manifest inflammation localized solely to the uveal tract, known clinically as isolated acute anterior uveitis.17,19
For our patient, identification of the HLA-B27 serotype resulted in mixed emotions. While we were somewhat relieved at having discovered an underlying cause, we were greatly concerned about her future. Would she be likely to suffer additional recurrences of uveitis? Could she potentially develop any of the systemic illnesses mentioned? What steps can she take now to help prevent potential complications later on? While these questions are difficult to answer with absolute certainty, the reality is that individuals who are HLA-B27+ have a high tendency toward recurrent anterior uveitis; of even greater concern is the fact that about 50% will develop an associated spondyloarthropathy during their lifetime.20 Unfortunately, the only known prophylactic measure that can lessen the severity of complications associated with HLA-B27+ disorders is diligence. Proactive care with the PCP or managing rheumatologist, as well as regular evaluations by the eye care provider, are all that we can presently recommend for individuals like our patient.
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3. Miserocchi E, Fogliato G, Modorati G, Bandello F. Review on the worldwide epidemiology of uveitis. Eur J Ophthalmol. 2013;23(5):705-17.
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12. Barisani-Asenbauer T, Maca S, Mejdoubi L, et al. Uveitis- a rare disease often associated with systemic diseases and infections- a systematic review of 2619 patients. Orphanet J Rare Dis. 2012;7:57.
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15. Chang J, McCluskey P, Wakefield D. Acute anterior uveitis and HLA-B27. Surv Ophthalmol. 2005;50(4):364-88.
16. Chang J, McCluskey P, Wakefield D. Acute anterior uveitis and HLA-B27: what’s new? In: Pleyer U, Forrester, JV (Eds). Uveitis and Immunological Disorders: Progress III. Berlin and Heidelberg: Springer-Verlag; 2009. pp. 9–18.
17. Gouveia EB, Elmann D, Morales MS. Ankylosing spondylitis and uveitis: overview. Rev Bras Reumatol. 2012;52(5):742-56.
18. Smith WM. Gender and spondyloarthropathy-associated uveitis. J Ophthalmol. 2013:928264.
19. Monnet D, Moachon L, Dougados M, Brézin AP. Severe uveitis in an HLA-B27-positive patient with ankylosing spondylitis. Nat Clin Pract Rheumatol. 2006;2(7):393-7.
20. Wakefield D, Chang JH, Amjadi S, et al. What is new HLA-B27 acute anterior uveitis? Ocul Immunol Inflamm. 2011;19(2):139-44.