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Middle-age man experiences unilateral sudden-onset vision loss
Both eyes featured small non-granulomatous keratic precipitates in the corneal endothelium, and the right eye had RPE changes with a semicircular yellow placoid subretinal macular lesion.
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A 44-year-old man with no significant medical or ocular history was referred by an outside optometrist to Ophthalmic Consultants of Boston for sudden-onset painless decreased vision of the right eye that began 4 days before presentation. At that time, the patient was also experiencing fevers, fatigue, 3 weeks of painless sores on the roof of his mouth, and spots on his palms and soles. His primary care physician obtained blood work, including CBC, ESR, BMP, HIV, Lyme, rheumatoid factor, RPR, ANCA and ANA, which were all negative except for an ANA titer of 1:80. The patient was then referred to rheumatology.
The patient denied smoking and IV drug use. He was homosexual but denied any history of sexually transmitted diseases. The patient initially attributed the sudden-onset decreased vision in his right eye to an ocular migraine. However, when his symptoms did not improve, he sought treatment with a local optometrist who subsequently referred him to Tufts New England Eye Center’s uveitis specialist.
Examination
Upon examination at Tufts, the patient’s best corrected visual acuity was 20/200 in the right eye and 20/20 in the left eye. Pupils were equal, round and reactive with no relative afferent pupillary defect. IOP was 20 mm Hg in the right eye and 19 mm Hg in the left eye. There were bilateral conjunctival granulomas in the inferior fornix. The corneal endothelium had diffuse small non-granulomatous keratic precipitates bilaterally. The anterior chamber showed 1+ cell in the right eye and 0.5+ cell in the left eye. There was posterior synechiae in the right eye and 2 to 3+ nuclear sclerotic cataracts in both eyes. There was 1+ vitreous cell in the right eye and 0.5+ vitreous cell in the left eye.
Images: Bierman L, Rifkin L
On dilated fundus exam, the optic nerves were pink and sharp with small cups. In the right macula, there were retinal pigment epithelium changes with a semicircular yellow placoid subretinal macular lesion. There was a small flat choroidal nevus inside the superior arcade. Left eye fundus exam was unremarkable. OCT of the macula and color and autofluorescence fundus photos at presentation are shown in Figures 1 and 2.
What is your diagnosis?
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Vision loss, uveitis
Despite an initially negative RPR, panuveitis with a yellow macular placoid lesion with a curvilinear edge in the setting of a patient with mouth sores and spots on hands and soles, along with constitutional symptoms, is highly suspicious of syphilitic uveitis. Ocular syphilis is the “great imitator” and must be high on the differential. Untreated acquired syphilis is characterized by a painless chancre that originates at the site of inoculation and resolves spontaneously within 3 months; therefore, patients often do not seek treatment. Secondary syphilis can then occur 1 to 2 months later and manifests as lymphadenopathy and a generalized maculopapular rash that oftentimes is predominant on the palms and soles. If left untreated, tertiary syphilis can occur 1 year to decades later. This stage is characterized by gumma, cardiovascular syphilis and neurosyphilis. Uveitis can occur at any of the three stages of the infection.
Other etiologies high on the differential include sarcoidosis, tuberculosis and an idiopathic condition. Sarcoidosis should be considered in the differential in any patient presenting with intraocular inflammation, as it has numerous presentations and can affect any ocular tissue. Often sarcoid has cutaneous involvement including orbital and eyelid granulomas. Anterior uveitis can occur with mutton-fat keratic precipitates, Koeppe nodules and/or snowballs in the anterior vitreous. Posterior segment involvement can include snowball clumps of vitreous cell and nodular granulomas in the optic nerve, retina and/or choroid, and can even result in occlusive retinal vascular disease.
Ocular disease from tuberculosis can also manifest in many ways. Tuberculous uveitis is classically a chronic granulomatous disease. The most common presentation is disseminated choroiditis, which presents as multiple discrete yellow lesions in the posterior pole, with or without macular edema. There can be varying degrees of vitritis, multifocal choroiditis and serpiginous-like choroiditis, among many other manifestations. Retinal involvement is usually secondary to extension from the choroid.
For this patient, a workup was performed that included serum ACE, lysozyme, FTA-ABS, repeat RPR, Quanti-FERON levels and a chest X-ray. While waiting for test results, the patient was started on topical steroids four times daily in both eyes. Testing came back with a repeat RPR of 1:128 as well as a positive FTA-ABS.
Discussion
Syphilis can mimic a wide range of ocular disorders. Most commonly, though, it will present as uveitis. Currently, syphilitic uveitis accounts for 1% to 2% of all uveitis patients. Uveitis can occur in all three stages of the disease. It can be granulomatous or non-granulomatous, unilateral or bilateral, and it can affect the anterior, intermediate or posterior segment. Despite the diverse presentation, there are some distinctive patterns that occur in syphilis, including posterior placoid chorioretinitis and superficial retinal precipitates in the setting of panuveitis. Superficial retinal precipitates appear small and creamy white in color. Posterior placoid chorioretinitis consists of yellowish placoid lesion(s) near the macula in uniform distribution of outer retinal and inner choroidal inflammation. The lesions form a discrete oval or circular area in the posterior pole, as in our patient. These characteristics are thought to be pathognomonic of secondary syphilis. This can also be accompanied by a small amount of retinal fluid and disruption of the ellipsoid zones. Neuro-ophthalmic manifestations include Argyll Robertson pupil, ocular motor nerve palsies, optic neuropathy and retrobulbar optic neuritis.
Nonspecific and commonly used tests for syphilis include Venereal Disease Research Laboratory (VDRL) and rapid plasma reagin (RPR), which quantify the amount of serum anti-cardiolipin antibodies by flocculation. The VDRL test can become positive 4 to 5 weeks after infection, but it can sometimes become negative due to the prozone phenomenon, a false negative from high antigen titers interfering with antibody-antigen lattice formation necessary to visualize a positive flocculation test. Also, it is important to keep in mind that up to 30% of patients can develop a negative test over time. Therefore, a negative VDRL test does not rule out the diagnosis of syphilis. In addition, RPR can be negative in very early or late syphilis. Therefore, a negative RPR also does not rule out syphilis. More specific testing includes FTA-ABS, which measures the amount of serum antibodies specifically directed against treponemal antigens. Therefore, VDRL and RPR are more appropriate for screening large populations with a lower risk of syphilis, and if on the differential, a specific test such as FTA-ABS should be employed as well. Testing cerebrospinal fluid for neurosyphilis in a patient with ocular syphilis is debated in the literature, but all patients with syphilis should be tested for HIV given the high rate of coinfection.
Treatment of ocular syphilis is considered the same as for neurosyphilis. Treatment entails high-dose IV penicillin of 18 million units to 24 million units of penicillin G per day for 10 to 14 days. If the patient is allergic to penicillin, ceftriaxone, oral doxycycline or azithromycin may be used. Ocular prognosis is favorable, unless treatment is delayed more than 12 weeks or visual acuity is very low at the start of treatment.
Clinical course continued
The patient was immediately started on topical prednisolone four times a day in both eyes, and his primary care physician and rheumatologist were immediately alerted to the high suspicion for syphilitic placoid. Once the RPR and FTA-ABS came back positive, the patient was indeed treated for syphilis. Upon return to the ophthalmology clinic 1 week after his initial visit, the patient’s visual acuity in the right eye had improved from 20/200 to 20/70, the keratic precipitates on the corneal endothelium in both eyes had resolved, there were no cell in the anterior chamber, and the vitritis had improved with 0.5 cell in the right eye and no cell in the left eye. There was a dramatic resolution of the macular placoid lesion, as seen in Figures 3 and 4. He was tapered off the topical prednisone and will be seen again in clinic in 1 month.
- References:
- Benson CE, et al. J Ophthalmic Inflamm Infect. 2015;doi:10.1186/s12348-015-0045-0.
- Bollemeijer JG, et al. Invest Ophthalmol Visual Sci. 2016;doi:10.1167/iovs.15-17906.
- Davis JL. Curr Opin Ophthalmol. 2014;doi:10.1097/ICU.0000000000000099.
- Fu EX, et al. Retina. 2010;doi:10.1097/IAE.0b013e3181cdf3ae.
- Gorovoy IR, et al. Sex Transm Dis. 2013;doi:10.1097/OLQ.0000000000000048.
- For more information:
- Lauren Bierman, MD, and Lana Rifkin, MD, can be reached at New England Eye Center, Tufts University School of Medicine, 750 Washington St., Box 450, Boston, MA 02111; website: www.neec.com.
- Edited by Jessica Moon, MD, and Emily C. Wright, MD. They can be reached at the New England Eye Center, Tufts University School of Medicine, 750 Washington St., Box 450, Boston, MA 02111; website: www.neec.com.