Patient reports loss of vision in left eye over 2 weeks

Posterior segment exam found severe vitritis with an area of retinal whitening nasally and an area of focal chorioretinal atrophy temporally.

Catherine A. Cox

Jordana F. Goren

A 45-year-old man was referred to the retina service for 2 weeks of cloudy vision in the left eye. The patient reported decreased vision in the left eye with “black hairs floating by” as well as “peripheral flickering.” The patient denied any ocular pain or tearing, but he reported some intermittent mild redness. He denied any history of similar episodes or any constitutional symptoms such as night sweats or fevers.

Ocular history was unremarkable. Medical history was significant for borderline hypertension and a remote history of appendectomy. The patient was not on any prescription medications. Social history was remarkable for recent travel through Great Britain and France. The patient reported drinking socially but denied any history of smoking or IV drug use.

On examination, the patient’s visual acuity without correction was 20/80 in the right eye with pinhole improvement to 20/25 and count fingers at 2 feet in the left eye without improvement using a pinhole. The right pupil was reactive without an afferent pupillary defect. The left pupil demonstrated minimal reaction to light with a relative afferent pupillary defect. IOPs were 16 mm Hg and 14 mm Hg, respectively. Extraocular movements were full in both eyes.

Anterior segment examination was notable for mild nuclear sclerosis in the right eye. The left eye demonstrated trace conjunctival injection, inferior non-granulomatous keratic precipitates, 3+ anterior chamber cell without hypopyon and trace nuclear sclerosis. Posterior segment examination of the right eye was unremarkable, while the left eye demonstrated severe 4+ vitritis with an area of retinal whitening nasally, as well as an area of focal chorioretinal atrophy temporally. There was also some vitreous clumping inferiorly without evidence of retinal vasculitis (Figure 1). Additional testing was notable for an elevated ESR of 45, positive CMV and HSV IgG, positive FTA-Abs, and reactive RPR. Toxoplasmosis IgM and IgG were both found to be negative; however, repeat testing for toxoplasmosis IgG was positive 4 days later. HLA-B27 and PPD testing were negative. Chest x-ray demonstrated a small nodule in the left lung projecting over the left anterior sixth rib.

Figure 1: Color fundus mosaic photograph of the left eye demonstrating a hazy view secondary to vitritis with an area of nasal retinal whitening likely representing necrosis. Note the absence of retinal vasculitis. Images: Goren JF, Krishnan C, Duker JS

What is your diagnosis?

Vision loss and panuveitis

The differential diagnosis of panuveitis with retinal whitening includes syphilis, toxoplasmosis, Vogt-Koyanagi-Harada syndrome, sympathetic ophthalmia, sarcoidosis, toxocariasis, tuberculosis, viral retinitis and bacterial endophthalmitis. Many of the infectious causes of posterior uveitis can be diagnosed with the previously mentioned blood tests.

Vogt-Koyanagi-Harada syndrome and sympathetic ophthalmia both have a characteristic history and pattern on fluorescein angiography, and in our patient’s case, there were no additional clinical symptoms or history of ocular trauma to suggest either of these diagnoses. Sarcoidosis is associated with elevated ACE and serum lysozyme levels, as well as hilar adenopathy on chest x-ray. Given the absence of hilar adenopathy on chest x-ray and low clinical suspicion, sarcoidosis was felt to be lower on the differential diagnosis, and therefore additional testing was not pursued. Tuberculosis can be ruled out with a negative PPD, and although the chest x-ray showed a solitary nodule, the appearance and location of this nodule was not consistent with tuberculosis. Given the patient’s laboratory testing and clinical picture, a diagnosis of syphilitic uveitis was made.

Discussion

Syphilitic uveitis is caused by infection with the spirochete Treponema pallidum. Syphilis is generally considered a sexually transmitted disease; however, it may be acquired through blood transfusion or contact with an infected lesion. Ocular syphilis is relatively uncommon and can be seen during the secondary or tertiary stages, typically between 2 and 6 months after initial infection. The most common ocular finding is uveitis; this is seen in 2.5% to 5% of patients with secondary or tertiary syphilis.

Syphilis causes disease only in humans. The bacteria can invade intact mucosa through tight junctions within the endothelium or via a skin abrasion. It then invades locally and disseminates throughout the body via the blood or lymphatic system. Syphilitic uveitis results in diffuse or focal lymphocytic infiltration of tissues surrounding the blood vessels of affected organs, which may include the iris, ciliary body and/or choroid.

Syphilis is considered a “great masquerader” as it can present with almost any type of ocular inflammation including iritis, keratic precipitates, conjunctivitis, episcleral or scleral inflammation, and interstitial keratitis. Dilated iris capillaries, also known as roseola, may also be seen and are considered a characteristic feature. Syphilis can also present more posteriorly with vitritis, retinitis, central retinal vein occlusion, uveal effusion, subretinal neovascular membrane, papillitis, periphlebitis, uveitis, serous and exudative retinal detachment, and chorioretinitis. In HIV-positive patients, syphilis may present as acute syphilitic posterior placoid chorioretinitis with yellow or gray lesions in the macular or juxtapapillary regions. Additional ocular manifestations include cataract, glaucoma and pupillary abnormalities such as Argyll Robertson pupil seen in late syphilis.

Given the varying presentations of syphilis, a high level of clinical suspicion is required to make the diagnosis. In early primary or secondary syphilis, the diagnosis can be made via dark-field microscopy or immune-fluorescent staining of active skin lesions. Serologic testing includes non-treponemal tests such as VDRL and RPR, which measure antibody to cardiolipin cholesterol antigen. Specific treponemal tests, such as FTA-Abs and hemagglutination assay (MHA-Tp), directly measure antibody to T. pallidum and can be used to confirm the diagnosis. When neurosyphilis is suspected, the patient should also be evaluated by lumbar puncture.

In 1999, the World Health Organization estimated that there were 12 million new cases of venereal syphilis worldwide. Syphilis is generally more concentrated in populations of lower socioeconomic status, as well as in those with poor hygiene, multiple sexual partners and/or limited access to care. In 2008, there were 13,500 reported cases of primary and secondary syphilis in the United States, with 63% of these cases being among homosexual men.

Treatment

Treatment regimens for syphilis are dependent on the stage of disease; however, penicillin G is the preferred medication for all stages. Neurosyphilis is treated with aqueous crystalline penicillin G of 18 million to 24 million units per day divided into 3 million to 4 million units via IV every 4 hours or via continuous infusion for 10 to 14 days. Patients may alternatively be treated with procaine penicillin 2.4 million units intramuscularly daily plus probenecid 500 mg by mouth four times a day for 10 to 14 days. After initiation of antibiotic therapy, steroids are generally added to blunt the inflammatory response due to bacterial cell death. All patients with neurosyphilis should also be tested for HIV and monitored closely for treatment failure.

Figure 2: Color fundus mosaic photograph of the left eye demonstrating marked improvement of vitritis as well as resolution of the previously noted area of nasal retinitis/necrosis after 1 week of antibiotic therapy.

Our patient was admitted to the hospital on the infectious disease service and was started on IV penicillin G. During his hospitalization, he was found to be HIV positive. The patient was not started on HAART at this time in order to avoid worsening of his symptoms from immune reconstitution syndrome. After appropriate counseling, he was sent home with a PICC line to complete his course of penicillin therapy. At a 1-week follow-up visit to the retina service, his retinitis had completely resolved and the patient was started on oral prednisone (Figure 2). HAART was implemented approximately 2 months later. At a 1-year follow-up visit, best corrected visual acuity was 20/30 in the right eye and 20/40 in the left eye. In the left eye, there was no remaining evidence of retinitis or vitritis, but a small macular epiretinal membrane and temporal chorioretinal scar were noted.

References:

• Aldave AJ, King JA, Cunningham ET Jr. Ocular syphilis. Curr Opin Ophthalmol. 2001;12(6):43-41.
• Browning DJ. Posterior segment manifestations of active ocular syphilis, their response to a neurosyphilis regimen of penicillin therapy and the influence of human immunodeficiency virus status on response. Ophthalmology. 2000;107(11):2015-2023.
• Centers for Disease Control and Prevention. Sexually Transmitted Disease Surveillance 2004. U.S. Department of Health and Human Services. http://www.cdc.gov/std/stats04/toc2004.htm. September 2005.
• Chao JR, Khurana RN, Fawzi AA, Reddy HS, Rao NA. Syphilis: reemergence of an old adversary. Ophthalmology. 2006;113(11):2074-2079.
• Cunningham ET Jr. Uveitis in HIV positive patients. Br J Ophthalmol. 2000:84(3):233-235.
• Tamesis RR, Foster CS. Ocular syphilis. Ophthalmology. 1990;97(10):1281-1287.
• Yanoff M, Duker JS. Ophthalmology. 3rd ed. Philadelphia: Elsevier; 2009.

• Jordana F. Goren, MD, MS, Chandrasekharan Krishnan, MD, and Jay S. Duker, MD, can be reached at New England Eye Center, Tufts University School of Medicine, 800 Washington St., Box 450, Boston, MA 02111; 617-636-4219; fax: 617-636-4866; website: www.neec.com.
• Edited by Catherine A. Cox, MD, and Jordana F. Goren, MD, MS. Drs. Cox and Goren can be reached at New England Eye Center, Tufts University School of Medicine, 800 Washington St., Box 450, Boston, MA 02111; 617-636-4219; fax: 617-636-4866; website: www.neec.com.