Diagnosis, Workup and Treatment
The patient underwent 24-2 Humphrey visual field testing which revealed scattered peripheral defects in the right eye and a dense inferior defect in the left eye, confirming Amsler testing. Optical coherence tomography disclosed borderline optic nerve retinal nerve fiber layer thickening in the superior quadrants bilaterally and mild disruption of RPE and photoreceptor layers of the central macula in the left eye. No subretinal fluid or cystic changes were evident at that time. An MRI of the brain and orbits demonstrated old cerebellar infarcts and was negative for any acute ischemic changes, masses or inflammatory lesions.
In the context of his macular findings on OCT, the patient was referred to the Retina Service for further evaluation. In the two-week interval between visits, the patient’s vision worsened from 20/40 to 20/80 in the right eye and improved from 20/400 to 20/40 in the left eye. A juxtapapillary Hollenhorst plaque and cotton wool spot without retinal whitening was noted in the right eye. The following day, the patient was admitted by his cardiologist for a previously scheduled coronary angiography for symptoms of worsening angina. Angiography revealed complete blockage of two coronary grafts not amenable to endovascular stenting, and carotid Doppler ultrasound was negative for significant carotid stenosis.
The patient was lost to follow up for one month following his admission for coronary angiography and over this interval his vision painlessly declined to count fingers in each eye. Re-examination at the slit lamp showed new findings of +1 anterior chamber cell and + 2 vitreous cell. Funduscopy now revealed yellow, creamy, indistinct chorioretinal infiltrates localized to both maculae and fluorescein angiography disclosed leakage of both discs and late hyperfluorescence in the areas of chorioretinal infiltration (See Figure 1). OCT demonstrated disruption of the inner segment ellipsoid band, nodular RPE changes, and submacular fluid in the left eye (See Figure 2).
That day, the patient was admitted to the Ophthalmology Service for further workup and treatment. Erythrocyte sedimentation rate and C-reactive protein were both elevated, to 110 and 1.1, respectively. Pulsed IV steroids were empirically initiated. Given the patient’s negative review of systems, a broad, extensive workup was obtained to investigate potential diagnoses including sarcoidosis; rheumatoid arthritis; systemic lupus erythematosus; HIV; syphilis; Lyme disease; Wegener’s granulomatosis; polyarteritis nodosa; and monoclonal gammopathies.
After two days of treatment with IV methylprednisolone, the patient’s vision improved to 20/200 in the right eye and 20/30 in the left eye. His hospital course was complicated by transiently uncontrolled hypertension and an episode of angina for which serial troponins were negative. He was discharged on 80 mg of oral prednisone daily with instructions to follow up with the Retina Service. Prior to this follow-up, his treating physician was notified that his workup yielded positive rapid plasma reagin (RPR) and fluorescent treponemal antibody absorption (FTA-ABS) reactivity consistent with syphilis infection. Human immunodeficiency virus testing was negative. The patient was subsequently re-admitted for two weeks of treatment with intravenous penicillin. Following this treatment course, his macular edema and subretinal fluid resolved and vision substantially improved to 20/25 in each eye.
As Sir William Osler said, “He who knows syphilis knows medicine.”1 Known as the “great mimicker,” the sexually transmitted spirochete Treponema pallidum can clinically declare itself in any organ system, not uncommonly leading clinicians down a false diagnostic pathway before the actual diagnosis is known.2 It is estimated that there are approximately 12 million new cases of syphilis annually, 90 percent of which occur in developing countries.3 Between 1990 and 2000, the annual rate of primary and secondary syphilis in the United States declined 87 percent to its lowest recorded level.4 However, in 2004 the rate of syphilis resurged 28 percent, primarily in men.5 In more recent years, younger men and men who have sex with men (in which rates of HIV infection are higher) have accounted for 67 percent of all syphilis cases in the United States.6
Acquired syphilis is conventionally divided into four stages. Primary stage is characterized by a painless chancre at the site of inoculation two to six weeks after infection.7 Secondary syphilis manifests 10 weeks following infection with non-specific symptoms of malaise and fatigue as well as a disseminated rash involving the palms and soles. Latent syphilis is clinically undetectable and can last for decades until the onset of tertiary syphilis, which is characterized by highly morbid cardiovascular and neurologic manifestations.
Ocular syphilis is an uncommon manifestation of the disease, but is often instructive of the underlying diagnosis. Accounting for approximately 4 percent of all cases of uveitis,8 syphilitic uveitis may manifest at any stage of disease, occurring in 2.5 to 5 percent of patients with tertiary syphilis.7 Although posterior uveitis is the most common way for ocular syphilis to present, a large variety of presenting signs have been described in both HIV-positive and HIV-negative patients, including keratitis; gummous iris nodules; focal retinitis; multifocal choroiditis; phlebitis; arteritis; papillitis; and serous and exudative retinal detachments.6,7,9
Our case is consistent with the distinct clinical entity acute syphilitic posterior placoid chorioretinitis (ASPPC). First described by J. Donald Gass, MD, in 1990, ASPPC is caused by large, placoid, yellowish lesions at the level of the pigment epithelium in the macula and juxtapapillary areas.10 Patients with ASPPC tend to have concomitant HIV infection and, in a recent series, nearly 60 percent of patients had bilateral involvement.11 On fluorescein angiography, early central hypofluorescence is typically noted prior to late hyperflourescence in the affected macula.12 Leakage at the disc can also be noted. OCT findings have been more recently described and include disruption of the inner segment ellipsoid band, nodular thickening of the RPE with loss of the linear outer segment/RPE junction, and occasionally, loss of the external limiting membrane, accumulation of subretinal fluid and punctate hyperreflectivity in the choroid.11
The crux of diagnosing ocular syphilis is serologic testing. Given the association with non-granulomatous uveitis, it has been recommended that syphilis serological testing be obtained even in the absence of suggesting clinical findings.13 Serologic diagnosis relies upon both treponemal and non-treponemal testing.7,9 Non-treponemal tests including the Venereal Disease Laboratory Report (VDRL) and RPR card test have utility in screening for active disease and antibody quantification to gauge therapeutic response. Treponemal tests such as the FTA-ABS test are used for confirmation of prior or current infection. Lumbar puncture for cerebrospinal fluid analysis is indicated in patients with ocular syphilis as it can detect subclinical neurologic involvement and can thus be predictive of morbidity and mortality.14 In cases where serologic testing is unreliable, such as with patients with collagen vascular disease, advanced age, or HIV infection, direct treponeme visualization with dark-field microscopy or polymerase chain reaction-based analysis of intraocular fluids can be performed.15,16 Any patient with confirmed syphilis should be also tested for HIV, as risk factors for both diseases are similar and the presence of a chancre greatly increases risk of acquiring or transmitting the disease.7
Acquired syphilis with ocular involvement should be treated as neurosyphilis with intravenous penicillin G 3 to 4 million units daily for 10 to 14 days.17 Although alternative treatments with ceftriaxone and azithromycin have been proposed in patients with a penicillin allergy, there is limited evidence to guide dosing and duration of treatment.7 Thus, penicillin-desensitization is recommended in these patients.17
In the case described, the patient’s atypical presentation led clinicians down multiple diagnostic pathways before the underlying diagnosis of syphilis was revealed. Reflecting the indolent course of his disease, it was not until two months after the initial presentation that the patient demonstrated any signs of ocular inflammation (anterior, posterior and chorioretinal). Abrupt changes in vision and an elevated ESR prompted immediate empiric treatment with intravenous steroids. Ultimately, serologic testing confirmed the diagnosis of ASPPC and the patient was successfully treated with intravenous penicillin.
The key to timely, accurate diagnosis of ocular syphilis is a high level of clinical suspicion, which is confirmed with serologic testing. In this case, the indolent course with bilateral involvement, delayed presence of ophthalmic inflammation and ultimately positive serology alerted the treating physicians to the possibility of ocular syphilis.
The author would like to thank Nicolas Biro, MD, of the Neuro-ophthalmology Service and Rajiv Shah, MD, and Carl Park, MD, of the Retina Service for their time and assistance in preparing this case report.
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