Hypertensive Disc Edema or Ocular Syphilis? A Case Report of the Great Masquerader Open Access

Syphilis is a sexually or congenitally transmitted disease caused by the spirochete bacteria Treponema pallidum. Although syphilis is effectively treated with penicillin, in the USA, there has been a significant increase in prevalence of primary and secondary syphilis, particularly in females [1]. The disease may remain undetected and progress through primary, secondary, latent, and tertiary stages, ultimately toward multi-organ involvement, including the neurological system. Neurological complications of syphilis, termed neurosyphilis, can occur at any stage of syphilis, though historically associated with tertiary syphilis [2]. Hallmark conditions of neurosyphilis are syphilitic meningitis, meningovascular syphilis, tabes dorsalis, and syphilitic dementia [2]. Ocular syphilis can occur at any stage and has also been increasingly reported in the USA. Notably, ocular syphilis is more prevalent among HIV-positive patients; thus, individuals diagnosed with ocular syphilis should be tested for HIV if they have not already undergone screening. Ocular syphilis presents with a range of symptoms and can affect various ocular structures, ordinarily presenting with posterior uveitis or panuveitis, although optic nerve involvement has also been documented [3]. In this report, we describe a deceptive case of ocular syphilis that led to significant visual loss and discuss the implications for screening. The CARE Checklist has been completed by the authors for this case report, attached as online supplementary material (for all online suppl. material, see https://doi.org/10.1159/000545491).

A 38-year-old female with no known past medical history presented to the emergency department with a 7-month history of blurry vision,floaters, flashes, and photophobia in both eyes. Her symptoms intensified and progressed with a new pressure-like ocular pain that began 2 days prior to her presentation. On arrival, her blood pressure was 191/105, prompting an evaluation for end-organ involvement which included an assessment by ophthalmology. The patient was found to have isolated Frisen grade 1 disc edema in the left eye and the presumptive diagnosis at the time was hypertensive emergency with ocular end-organ involvement. CT head was unremarkable with no intracranial hemorrhage, mass effect, or midline shift. Additionally, CT angiography of the head and neck did not demonstrate any significant stenosis or large vessel occlusion. Of note, the patient underwent screening for sexually transmitted diseases per hospital guidelines, which included syphilis enzyme immunoassay. The patient was discharged upon resolution of the hypertensive episode, prior to the final reports of her infectious screening tests.

She presented to the ophthalmology clinic 5 days later given her continued blurred vision. In clinic, visual acuity in the right eye was 20/300, improved to 20/200 with pinhole, and 20/400 in the left eye without improvement with pinhole. Intraocular pressure was 21 mm Hg right eye and 22 mm Hg left eye. Pupils were equal, round, and reactive without an afferent pupillary defect. Fundoscopic exam revealed perimacular pallor in both eyes, right more than left (Fig. 1). There was nasal disc elevation in the right eye and grade 1 optic disc edema in the left eye. OCT nerve was performed to better visualize and quantify optic disc edema, which showed a falsely elevated retinal nerve fiber layer thickness, likely skewed by the presence of disc edema (Fig. 2). OCT of the macula was also done to investigate the perimacular pallor seen on fundoscopy, and it depicted ellipsoid zone disruption in both eyes along with hyperreflective, pyramidal deposits temporal to the fovea OD and sub-foveal OS in the outer retina and retinal pigment epithelium (Fig. 3). By the time of this encounter, the patient’s infectious panel drawn in the emergency department had concluded, and the patient was informed of her positive syphilis screening test and confirmatory reflex rapid plasma regain test. The patient was instructed to present to the emergency department from clinic for treatment of syphilis.

Upon her second presentation to the emergency department, treatment with IV penicillin G was initiated, and she was subsequently admitted. Further questioning with her partner present revealed that her partner tested positive for syphilis several years prior but did not inform the patient. STD testing panel also revealed positive HIV-1 by enzyme-linked immunosorbent assay with CD4 count of 294 cells/μL and a viral load of 3,200 RNA copies/mL, in addition to a trichomonas infection. For these, the patient was started on Biktarvy and metronidazole. Lumbar puncture was performed and revealed positive CSF VDRL and pleocytosis. Patient did not return to the ophthalmology clinic for follow-up.

In this case, we depict a unique presentation of ocular syphilis masked by presumed hypertensive emergency. The chronicity of the patient’s visual deterioration and lack of other signs of end-organ damage should have prompted a more thorough investigation for other secondary causes of disc edema. Furthermore, the lack of typical hypertensive retinopathy exam findings such as hemorrhages, arterial attenuation, arteriovenous nicking, beading in addition to negative head imaging indicate that the patient’s vision changes were likely due to other causes. Ocular syphilis is known as the “great masquerader” of various ocular conditions and typically presents as posterior uveitis or panuveitis, while optic neuritis, inflammatory disc edema, retinitis, retinal vasculitis, and retinal detachment have also been reported [4]. This case described optic neuritis without uveitis as a manifestation of ocular syphilis, a rare finding which emphasizes the importance of maintaining ocular syphilis as a potential cause of abnormal exam findings, especially in high-risk populations.

This patient was found to be coinfected with syphilis and HIV; HIV infection is commonly associated with syphilis, most likely due to their similar risk factors for contraction [5]. Furthermore, ocular syphilis is more frequently identified in HIV positive patients with some studies identifying coinfection with HIV in almost 50% of patients with ocular syphilis; therefore, any HIV infected patient with ocular complaints should be evaluated for syphilis, and vice versa [6]. HIV coinfection may also change the course and manifestations of ocular syphilis. Coinfected patients are more likely to experience more severe bilateral ocular disease and tend to present with ocular syphilis at a younger age than HIV-negative patients [7]. This is possibly due to the immunocompromised state accelerating the effect of syphilis infection on visual function [8]. The patient in our case was middle aged, further emphasizing the importance of screening for syphilis in young, sexually active patients with unexplained visual loss. The severity of HIV infection can affect the manifestation of ocular syphilis with lower CD4 counts (i.e., <200 cells/mm³) being found to correlate with posterior uveitis secondary to syphilis [6, 9].

Diagnostic criteria of neurosyphilis includes central nervous system or ophthalmic signs or symptoms in the presence of positive serologic testing, in combination with either positive Venereal Disease Research Laboratory (VDRL), elevated CSF protein >40 mg/dL, or increased WBC count >5 mononuclear cells/μL on CSF testing. Our patient was found to have reactive CSF VDRL titers, conclusive of a neurosyphilis diagnosis. In around 20%–70% of ocular syphilis cases, there is concurrent neurosyphilis, which has also been associated with HIV positive status [6, 10]. Given that ocular symptoms may often be the first noticeable symptom of syphilis, coupling unexplained visual changes with a detailed history and thorough review of systems is critical to avoid missing a diagnosis of neurosyphilis [10]. Treatment of ocular syphilis involves administration of IV penicillin G 18–24 million units per day for 10–14 days. Penicillin G is preferred over IM penicillin V for the treatment of ocular syphilis as neurosyphilis is assumed, and penicillin G demonstrates much superior CNS penetration [11].

Ocular syphilis is a difficult diagnosis to make given its wide range of presentations and exam findings. Our case was further complicated by a hypertensive episode which masked the cause of the patient’s visual symptoms. If not for our hospital’s policy to test patients who qualify for screening for syphilis and HIV, the patient’s neurosyphilis infection could have gone unnoticed as she was otherwise asymptomatic and unaware of her past exposure to syphilis. Therefore, physicians should have a lower threshold for suspicion for syphilis in sexually active patients living in endemic areas for syphilis who present with unusual visual changes. These patients should be promptly evaluated for syphilis in addition to neurosyphilis and HIV coinfection in order to mitigate permanent visual loss and other severe disease manifestations.

Ethical approval is not required for this study in accordance with local or national guidelines. Written informed consent was obtained from the patient for publication of the details of their medical case and any accompanying images.

The authors have no conflicts of interest to declare.

This study was not supported by any sponsor of funder.

Nicole Oska: investigation, writing – original draft, and writing – review and editing; Michael Saad: data curation, resources, and writing – review and editing; Hassan Tokko: supervision, validation, and writing – review and editing.

All data generated or analyzed during this study are included in this article and its online supplementary material files. Further inquiries can be directed to the corresponding author.