Ocular presentation of primary syphilis in a man with HIV

Abstract

The incidence of syphilis is rising, particularly among men who have sex with men. Ocular involvement, often manifesting as bilateral uveitis, typically occurs in later stages and is more severe and difficult to recognise in individuals living with HIV. We describe the case of a man with HIV infection who presented to our outpatient clinic with vision loss and a cutaneous maculopapular rash.

KEY MESSAGES.

• Early recognition of ocular syphilis and neurosyphilis is critical to prevent treatment delays.

• Delayed treatment may result in irreversible complications.

• Ocular symptoms and signs suggestive of syphilis should never be underestimated

Background

Syphilis cases are increasing, especially among men who have sex with men.¹ Ocular involvement is rare in the primary stage, typically occurring in the secondary or late latent stages.² The most common manifestation is uveitis, which is bilateral in over 50% of cases.³ Among patients with ocular syphilis, the proportion of people living with HIV is higher than in the general population; ocular involvement can be more severe and difficult to recognise in people living with HIV.⁴

Presentation, investigations and treatment

A man in his 50s, diagnosed with HIV in 2014 (nadir CD4+ 5/mm³), initially presented with oesophageal candidiasis from AIDS. He was treated with protease inhibitor-based antiretroviral therapy and, since 2020, with Bictegravir/Tenofovir Alafenamide/Emtricitabin. By 2024, his CD4+ count had risen to 343/mm³. He presented to our outpatient clinic with decreased visual acuity, blurred vision, bilateral conjunctival hyperaemia, and divergent strabismus (figure 1). Additionally, a non-pruritic erythematous maculopapular diffuse rash was observed on the trunk, abdomen and face, along with a non-painful ulcer in the anal region. Neurological examination revealed preserved consensual photomotor reflexes, a negative Lasegue’s sign and a slightly shortened stride with bradykinesia and stiffness in the left upper limb.

Figure 1. In the lower-right corner of the image, the presentation of ocular syphilis with bilateral conjunctival hyperaemia, divergent strabismus and blurry vision, before and after the treatment. Optical coherence tomography (OCT) (a,e), OCT-angiography (b,f), fluorescein (c,g) and indocyanine green (d,h) angiography of the right eye (a,b,c,d) and left eye (e,f,g,h) showing signs of placoid chorioretinal vasculitis. Lower lane: after appropriate treatment, there was the complete restoration of outer retinal layer (m) and resolution of the placoid lesion (n) in the left eye. Right eye showed persistence of macular oedema (i), but there was an improvement of the disaggregation of outer retinal layer (i) and slight resolution of the placoid lesion (i).

Among the serum serological tests, the Treponema pallidum haemagglutination assay (TPHA) was positive, while the venereal diseases research laboratory (VDRL) test was negative.

A brain CT scan was normal, showing no indirect signs of mass effect.

The eye examination revealed significantly decreased visual acuity bilaterally. The patient underwent a comprehensive ophthalmic examination, including optical coherence tomography (OCT), OCT angiography, fluorescein angiography and indocyanine green angiography (figure 1). The examinations showed conjunctival hyperaemia and papillary oedema bilaterally. The right eye manifested signs of vitritis, retinal vasculitis and cystoid macular oedema with disaggregation of the outer retina. The left eye showed a regular macula profile; however, there was significant disaggregation and irregularity of the outer hyper-reflective retinal layers. OCT-angiography and indocyanine angiography indicated significant closure of the choriocapillaris in the macular region of both eyes. The final diagnosis was posterior placoid chorioretinitis secondary to syphilis.

Cerebrospinal fluid (CSF) analysis revealed the following: cells 23.2/ mm³, protein 700 mg/L, lactate 1.5 mmol/L and positive TPHA. The diagnosis of neurosyphilis was established based on CSF testing positive for TPHA, along with pathological findings in chemical and physical examinations. Subsequently, intravenous crystallised penicillin G was administered for 14 days. 48 hours after the initiation of therapy, the skin rash disappeared, and visual acuity improved a few days later. The patient continued with ophthalmological follow-up visits and began systemic steroid therapy with prednisone.

At the follow-up visit, persistent macular oedema was noted, but the placoid chorioretinitis had completely resolved in both eyes (see figure 2 for timeline).

Figure 2. Timeline of case presentation. CSF, cerebrospinal fluid; TPHA, Treponema pallidum haemagglutination assay.

Discussion

Individuals living with HIV can exhibit neurological symptoms at an earlier stage of syphilis.⁵ The diagnosis of neurosyphilis is based on identifying pathological findings in the CSF, including the presence of pleocytosis, which may decrease over time, and a slight increase in protein levels. The VDRL test yields positive results in 30–70% of cases;⁶ in cases of negative results, treponemal tests on CSF are recommended. According to guidelines, CSF evaluation is advised for individuals exhibiting neurological symptoms and in cases of ocular involvement when cranial nerve dysfunction is present.⁷ A recent review by Xu et al analysing ocular syphilis in people living with HIV indicated that the most frequent eye involvement consisted of uveitis, with approximately 40% of subjects having a previous history of syphilis, characterised by protean manifestations.⁸ In our case, the individual had a CD4+ count of 343/mm³; however, both the choroid and the retina were involved, a condition typically seen with a CD4+ count below 200/mm³. This atypical presentation in someone with a higher CD4+ count makes the diagnosis more challenging, as ocular syphilis may not be immediately suspected in individuals with preserved immune function.⁹ We concur with the recommendation to avoid repeating the lumbar puncture, as the serum RPR titre can predict the efficacy of the therapy.¹⁰