Ocular Syphilis

Syphilis has been a constant companion of mankind for many centuries and yet the exact origin of the disease remains unknown.¹ There are currently two main theories regarding the disease’s origin.² According to the New World theory, also referred to as the Columbian theory, syphilis was endemic to the Caribbean and was probably brought to Europe after the first visit by Columbus in 1492. The Old World Theory, or Pre-Columbian theory, hypothesizes that syphilis was endemic to Africa and was already present in Europe prior to the age of Columbus. Syphilis was first recorded in Europe between 1494 and 1495 after an outbreak in Naples, Italy, during a French invasion and the term “syphilis” was first used in 1530 by Girolamo Fracastoro, an Italian physician and poet.² Treponema pallidum, the causative spirochete, was first identified in 1905 at the Charité Clinic in Berlin by Schaudinn and Hoffmann. The history of ocular syphilis (OcS) is even more obscure, and it is uncertain when the first case of ocular involvement in syphilis was described.

Much has been written about the ability of ocular syphilis to mimic various presentations of ocular inflammation as well as the effect that HIV infection may have on both its presentation and diagnosis.^3–6 The diagnosis of OcS is usually presumptive based on a compatible clinical picture and positive serology results for syphilis, although some authors have investigated alternative methods using ocular fluid in an attempt to make a definitive diagnosis of OcS.^7–9

This issue of Ocular Immunology and Inflammation features three articles addressing different issues pertaining to ocular syphilis. Kaya and Ozdal¹⁰ reported the rare finding of subretinal hypopyon in a case of ocular syphilis. A 31-year-old man was initially diagnosed with toxic optic neuropathy since he had a medical history of drug addiction and bilateral optic disc edema. The patient was pulsed with intravenous corticosteroids for 3 days followed by oral prednisolone in the neuro-ophthalmology clinic. He presented again 2 weeks later with further decrease in visual acuity and this time with intraocular inflammation and worsening of the disc edema. Foci of diffuse retinitis and occlusive vasculitis were noted as well as a levelling subretinal hypopyon in the left eye, prompting a search for an infective cause. The Treponema pallidum hemagglutination assay (TPHA) result was positive, whereas HIV testing was negative. The patient’s visual acuity improved to 0.3 (20/63) OU after the initial cessation of systemic corticosteroids and appropriate treatment with intravenous penicillin. The authors discuss red flags that should have prompted a search for an infectious cause before initiating systemic corticosteroids treatment in this patient, as well as poor prognostic factors in ocular syphilis.

Kelgaonkar et al.¹¹ reported an unusual, novel appearance of syphilitic chorioretinitis resembling “beaded pearls on a string.” A 30-year-old man presented with gradual, painless, bilateral loss of vision for 4 months and nyctalopia for 5 months. On examination, the most noteworthy feature was that of multiple, sub-vascular, creamy white lesions extending to the extreme periphery in both eyes – although the lesions were larger and more extensive on the left. These lesions were clearly visible on fundus autofluorescence, and the authors described four distinct outer retinal patterns of these “beaded pearls” on OCT. The patient was newly diagnosed with HIV infection with a CD4+ cell count of 486 cells/mL and a positive TPHA test result. He was treated with intravenous ceftriaxone for 2 weeks, followed by 2 weeks of oral doxycycline and was also commenced on combined antiretroviral therapy. His BCVA improved to 20/40 after 1 month with resolution of the retinal lesions.

Green et al.¹² reported a case of presumed seronegative OcS in a patient with untreated HIV infection who responded well to empiric intravenous penicillin G. A 40-year-old man, known to have untreated HIV infection, type 2 diabetes mellitus and systemic hypertension, presented with acute-onset loss of vision in both eyes. He was found to have mild vitritis as well as peripapillary cotton wool spots and intra-retinal hemorrhages and placoid-like lesions in the posterior poles of both eyes. The authors were concerned about possible acute posterior placoid syphilitic chorioretinitis, but results of treponemal antibody tests (chemiluminescent microparticle immunoassay) were negative on more than one occasion. His HIV viral load was 3410 copies/mL and CD4+ count was 324 cells/mL. The patient was started empirically on oral valganciclovir for potential viral retinitis but his condition worsened despite antiviral treatment. Anterior chamber taps were performed in both eyes, but CMV, HSV, VZV, Toxoplasma gondii and Mycobacterium tuberculosis PCR results were all negative. A rapid plasma reagin test was also negative on day 5. Given the worsening retinitis on aggressive antiviral treatment and the high clinical suspicion for OcS, intravenous penicillin G was initiated empirically and the large subretinal deposits decreased in size the following day. Ten months after the initiation of penicillin, the patient’s visual acuities improved to 20/30 OD and 20/40 OS.

The remainder of the article provides a review of OcS and syphilis testing and serves to remind the reader that both the treponemal tests (TTs) and non-treponemal tests (NTTs) for syphilis are imperfect, with meaningfully less than 100% sensitivity and specificity, that such testing may be even less reliable in patient with HIV infection, and that empiric intravenous penicillin therapy should be considered in cases with features suggestive of OcS, even when serologic testing for syphilis is negative.