Ocular Syphilis: the Great Imitator

Ocular syphilis, often dubbed the great imitator because it can present as several other conditions, continues to challenge clinicians with its diverse and often misleading presentations. With incidence rates rising annually,¹ optometrists are increasingly likely to encounter this elusive disease in practice. In my home state of New York, new cases of syphilis have steadily increased to reach more than 10,000 in 2022, after essentially no new cases were reported in 2000.²

This article presents five cases that show the diverse presentations of ocular syphilis and just how difficult it can be to detect this tricky, and increasingly common, disease.

CASE NO. 1: A MISDIAGNOSED KERATITIS

A 33-year-old Black man presented with bilateral eye pain persisting for 1 month.³ It was initially treated as conjunctivitis by a previous provider.

He had a pustular facial rash, and his vision was reduced to 20/70 OD and 20/60 OS. Examination revealed bilateral peripheral ulcerative keratitis. Workup later confirmed syphilis infection with HIV coinfection. The patient was initially treated with steroids but was transitioned to 4 million units of intravenous (IV) penicillin every 4 hours for 14 days after confirmation of syphilis infection, leading to remarkable visual recovery (20/20 OU).

CASE NO. 2: A TUMOR THAT WAS NoT

A 47-year-old Asian man was referred for a presumed intraocular tumor in his left eye.

An MRI had confirmed a 10 x 7.5-mm mass.⁴ He denied systemic symptoms, but blood work revealed a positive venereal disease research laboratory test, rapid plasma reagin test, and Treponema pallidum hemagglutination assay with negative inflammatory markers. He was diagnosed with syphilitic scleritis and treated with a 3-week course of IV penicillin, resulting in substantial resolution within 1 month (Figure 1).

CASE NO. 3: VISION LOSS IN A YOUNG woman

A 30-year-old overweight woman experienced progressive vision loss over 8 months. She had experienced stable, chronic headaches and a 30-pound unintentional weight loss.

Examination showed an edematous optic disc in the left eye and dense bilateral posterior subcapsular cataracts. The patient was referred for lumbar puncture, which returned normal results, and for blood work, which was positive for rapid plasma reagin and T pallidum particle agglutination.⁵

The patient was treated with IV penicillin and underwent cataract extraction, ultimately achieving 20/20 OU vision and resolution of the optic disc edema.

CASE NO. 4: ATYPICAL RETINAL NECROSIS

A 50-year-old man with a history of genital warts presented with profound bilateral vision loss and visual acuity of counting fingers OD and light perception OS. He was found to have suspected bilateral acute retinal necrosis and was empirically started on antivirals (Figure 2).

Testing revealed positive syphilis and Hepatitis C,⁶ with negative results for herpes simplex virus, cytomegalovirus, HIV, and TORCH (toxoplasmosis, other [including syphilis, varicella-zoster virus, and parvovirus B19], rubella, cytomegalovirus, and herpes simplex virus) diseases. After 2 weeks of IV penicillin, the patient’s vision improved modestly to 20/100 OD and remained at light perception OS.

CASE NO. 5: UNRESOLVED PANUVEITIS

A 60-year-old man reported bitemporal black-and-white spots in his vision and redness in both eyes. His IOPs were normal at presentation, 10 mm Hg OD and 12 mm Hg OS.

He was treated with topical steroids for panuveitis but returned 1 month later with worsened symptoms and elevated IOP (22 mm Hg OD and 21 mm Hg OS). Blood work confirmed a diagnosis of syphilis.⁷ After a 2-week course of IV penicillin and continued topical steroids, the patient regained 20/20 BCVA OU.

WHAT IS SYPHILIS?

Syphilis is caused by the T pallidum bacteria and is mainly spread through sexual contact. The bacteria penetrate intact skin and leave a small sore called a chancre upon initial infection, which is known as primary syphilis. If untreated, the disease will progress to secondary syphilis within approximately 6 weeks and will result in multiple rash-like lesions on mucous membranes. At this point, if left untreated, the disease will enter the latent phase and can reemerge as tertiary or neurosyphilis. While not contagious at this stage, it can cause serious illness or death if it is not swiftly addressed.⁸

Ocular syphilis generally occurs in the tertiary stage; as these cases illustrate, it can mimic inflammatory, infectious, and even neoplastic processes. Despite this challenge, misdiagnosis or delayed treatment can lead to irreversible vision loss, as seen in case No. 4. Patients should be tested for syphilis whenever there is an incidence of unexplained ocular inflammation. Both nontreponemal (eg, rapid plasma reagin, venereal disease research laboratory) and treponemal (eg, FTA-ABS, TPPA) tests are necessary to confirm a diagnosis. Spinal taps are not recommended when symptoms are present because of the accuracy of serologic testing. If a patient tests positive for syphilis, screening for HIV should be performed due to high rates of coinfection.⁸ Ocular manifestations of syphilis can occur at any stage of the disease; if encountered, the disease must be treated as neurosyphilis because of the potential for systemic complications and vision loss.

Optometrists are uniquely positioned to see signs such as an Argyll Robertson pupil, which will not constrict with light but will constrict with accommodation. We may also see a Hutchinson triad in children, interstitial keratitis, malformed teeth, and deafness. The CDC recommendation for treating presumed neurosyphilis is 3 to 4 million units of IV penicillin G every 3 to 4 hours for 10 to 14 days.⁸ The CDC does not formally endorse steroids when syphilitic uveitis is present, but they are often coadministered to control inflammation.

ARM YOURSELF WITH KNOWLEDGE

With rising rates and a diverse presentation of symptoms, awareness and early diagnosis is key to detecting and managing patients with ocular manifestations of syphilis. The cases in this article show the wide variety of presentations of ocular syphilis and just how important it is to consider syphilis as a differential, no matter how unlikely it may seem.