Spotlight Case: The Great Masquerader

Oussama Boundaoui, MD
Heena Patel, MD

Case history

A 51-year-old Caucasian man with HIV, maintained on highly active antiretroviral therapy (HAART), was referred by an urgent care center for a possible detached retina in the left eye. He had presented to the urgent care clinic 1 week prior with acute blurred vision in the left eye along with floaters. He denied photopsia or ocular pain. His last CD4 count was 600, and viral load was undetectable. Medical and social history showed he was sexually active (MSM) and was otherwise unremarkable, and review of systems was negative.

On exam, his vision was 20/30 and 20/70 (unimproved with pinhole) in the right and left eyes, respectively. Pupils were both symmetrically reactive without afferent pupillary defect, and intraocular pressures were normal. Stellate keratic precipitates were noted in both eyes, but the anterior segment was otherwise quiet, without acute or chronic signs of inflammation. Posterior segment exam on the right eye showed moderate-to-severe disc edema. The left eye likewise showed moderate-to-severe disc edema with peripapillary flame-shaped hemorrhages and multiple small subretinal placoid pigmented lesions distributed within the arcades throughout the macula. The peripheral retina appeared attached, and no vitritis was seen. 

SD-OCT of the right and left eyes showed disruption of the outer retinal segments and retinal pigment epithelium. Fluorescein angiography of both eyes revealed a characteristic “leopard pattern” of hypofluorescent placoid macular lesions in the early phase, with late phase hyperfluoresence. 

The patient was sent to the emergency department urgently to obtain stat neuroimaging, lumbar fluid analysis, and a laboratory panel for suspected infectious etiology.  Serum RPR testing for syphillis was reactive at 1:128, and confirmatory MHA-TP was likewise positive.  The patient was promptly admitted to the inpatient ward to start a 14-day IV penicillin course for neurosyphilis.

Fluorescein angiography of the patient’s right and left eyes demonstrate the characteristic “leopard spot” pattern seen in acute syphilitic posterior placoid chorioretinitis (ASPPC), with patches of hyperfluorescence and hypofluorescence.

Optical coherence tomography of both eyes (right eye shown) showed disruption of the outer retinal layers including the photoreceptor layer, IS/OS junction, and retinal pigment epithelium. The hyperreflective nodular thickening of the RPE and outer retina characteristic for ASPPC is also present.

What's your diagnosis? 

The Centers for Disease Control (CDC) recently issued a clinical advisory regarding ocular syphilis. Since December 2014, more than 24 cases of ocular syphilis have been reported across the United States, a majority of cases occurring in the MSM population. A few of these cases have resulted in blinding sequelae [1]. Ours is yet another case of ocular syphilis on the West Coast. 

Syphilis, coined “the great imitator” due to its variable presentations, has emerged as an important infectious cause of ocular morbidity in developing countries in Western Europe and the United States. Disease occurs from infection by the spirochete Treponema pallidum, involving the eyes typically during the secondary and tertiary stages of disease. 

Involvement may be unilateral or bilateral, affecting most ocular tissues from the conjunctiva to the optic nerve and extraocular cranial nerves. Uveitis is the most frequent presentation, with onset as early as 6 weeks following initial infection [2]. Uveitis may affect the anterior segment, posterior segment, or both. In the posterior segment, acute syphilitic posterior placoid chorioretinitis (ASPPC), described first by Gass, is characteristic[(3]. OCT findings in ASPPC demonstrate focal thickening and nodularity of the RPE with disruption of the overlying photoreceptor-ellipsoid junction [4]. 

Syphilitic posterior uveitis is considered neurosyphilis by most authorities; therefore it is critical to obtain lumbar puncture in cases of ocular, and especially posterior syphilitic uveitis[5]. To this effect, the CDC recommends performing a lumbar puncture to evaluate for neurosyphilis in all individuals with ocular syphilis, as the concurrence rate is high[6]. 

Co-infection with HIV is frequent. Berger reported a 42% prevalence of syphilitic eye disease in a group of 12 HIV-infected patients with neurosyphilis[7] . A more recent series in 2011 reviewing the clinical characteristics of 13 patients with posterior syphilitic uveitis revealed a co-infection rate of 83%, thought by the authors to be related to the steady decline in AIDS-related mortality[8].

Treatment of ocular syphilis is identical to that of neurosyphilis, consisting of 10–14 days of intravenous penicillin G therapy (18–24 million units IV daily)[9]. An alternative is 10-14 days of intramuscular procaine penicillin (2.4 million U IM daily) with probenecid (500 mg orally 4 times per day). Penicillin desensitization is advocated by many authors in cases of penicillin allergy[10].

Since submission of this case for publication, we diagnosed ocular syphilis in another sexually active (MSM) patient who presented with posterior uveitis, prompting further laboratory testing. His infectious disease work-up revealed newly-diagnosed HIV. 

Take-home points

In conclusion, with the reemergence of syphilis in the developed world, it is ever more imperative for the clinician to:

  • Maintain a reasonable degree of suspicion for ocular syphilis when evaluating patients with new or chronic cases of uveitis.
  • Undertake a thorough review of systems with a careful review of medical and sexual histories, as these may cue the physician to diagnose ocular syphilis in more susceptible populations such as MSM or HIV-infected patients.

This high index of suspicion on the part of the ophthalmologist will allow for early diagnosis and effective treatment of a potentially blinding infectious ocular malady.

Refrences

  1. CDC clinical advisory: Ocular syphilis in the United States. Centers for Disease Control and Prevention website. http://www.cdc.gov/std/syphilis/clinicaladvisoryos2015.htm.Updated February 8, 2016. Accessed April 16 2015.
  2. Kiss S, Damico FM,  Young L H.Ocular manifestations and treatment of syphilis. Semin  Ophthal.2005; 20(3):161-7.
  3. Gass JD , Braunstein, RA,  Chenoweth RG. Acute syphilitic posterior placoid chorioretinitis. Ophthal.1990; 97(10): 1288-1297.
  4. Burkholder B M, Leung TG, Ostheimer TA, Butler N J, Thorne JE,  Dunn J P. Spectral domain optical coherence tomography findings in acute syphilitic posterior placoid chorioretinitis. J Ophthalmic Inflamm Infect. 2014; 4(1): 2. doi: 10.1186/1869-5760-4-2.
  5. Chao JR, Khurana, RN, Fawzi AA, Reddy HS, Rao NA. Syphilis: reemergence of an old adversary. Ophthal. 2006; 113(11): 2074-2079.
  6. Mandelcorn ED. Infectious causes of posterior uveitis. Can J Ophthal.2013; 48(1): 31-39.
  7. Katz DA, Berger JR. Neurosyphilis in acquired immunodeficiency syndrome. Arch Neurol. 1989; 46(8): 895-898.
  8. Li SY, Birnbaum AD, Tessler HH, Goldstein DA. Posterior syphilitic uveitis: clinical characteristics, co-infection with HIV, response to treatment. Jap Ophthal. 2011; 55(5): 486-494.
  9. CDC Sexually transmitted disease treatment guidelines. Centers for Disease Control and Prevention website. http://www.cdc.gov/std/treatment/2006/default.htm. Updated March 4, 2010.
  10. CDC Sexually transmitted diseases treatment guidelines--2002. Centers for Disease Control and Prevention website. http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5106a1.htm. Updated May 3, 2002.

Financial disclosures

Dr. Boundaoui - None.

Dr. Patel - None.

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