Syphilis cases caused by Treponema pallidum are rising in Germany, across Europe, and worldwide, fuelling a resurgence of ocular disease. Once largely confined to patients with HIV, this condition is now observed in broader populations and can mimic other retinal disorders, complicating the diagnosis.

At the 25th Euretina Congress 2025 in Paris, France, experts confirmed that ophthalmologists are often the first to detect cases, making early recognition and treatment essential for preventing vision loss.

In Europe, clinicians increasingly refer to acute syphilitic posterior placoid chorioretinitis (SPPC), a distinctive pattern that helps differentiate syphilis from ocular tuberculosis, as confirmed by Vishali Gupta, MD, Advanced Eye Centre, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

Rising Prevalence

According to Nicholas Jones, MD, former honorary professor of ophthalmology at the University of Manchester, Manchester, England, syphilis rates in England soon approached the levels last seen during World War II, when nearly 18,000 cases were reported annually.

By 2024, this figure is expected to rise to approximately 10,000. In Germany, the Robert Koch Institute, the country’s national public health agency, recorded 8305 cases by 2022, the highest number on record.

Jones attributed this surge mainly to effective antiretroviral therapy, which has lowered the fear of HIV among high-risk groups. “The reasons for these changes in incidence are multifactorial, but the main driver is the effectiveness of highly active antiretroviral therapy, which has removed the fear of HIV among the populations most at risk of acquiring syphilis,” he said.

Clinical Presentation

Similar to tuberculosis, syphilis is known as a “great mimicker” of the eye, often resembling other ocular conditions and complicating diagnosis.

Jones noted that distinct inflammatory patterns usually enable clear diagnosis. Acute uveitis is rare. Most patients show posterior choroidal inflammation with retinal involvement during secondary or latent infections, although ocular signs can also appear in the primary stage and are increasingly seen in tertiary diseases.

Ocular syphilis is suspected in patients with uveitis who have any of these signs or risk factors:

• Mucosal ulcers or skin rashes, particularly on the palms or soles
• Headache, tinnitus, or hearing loss
• History of sexually transmitted infection or HIV
• Retinitis or retinal vasculitis
• Uveitis unresponsive to steroid therapy

According to Jones, approximately 1% of patients with early syphilis develop uveitis. Of these, 56% were bilateral, 4% were granulomatous, 66% had retinitis, 20% presented with panuveitis, and 6% had papillitis.

About 94% of patients were men, over two thirds were men who have sex with men, and one third were HIV-positive. Patients were aged 20-75 years, with an average age of 40 years. “Even older patients can develop syphilitic uveitis and should not be overlooked,” Jones warned.

“Iritis alone is truly unusual,” he emphasised. “The hallmark of syphilis is retinitis,” he said.

It can be difficult to define, which helps distinguish it from viral retinitis, which is the key differential diagnosis. Punctate satellite lesions, which often appear to float in front of or next to the inflamed retina during funduscopy, are characteristic.

Vasculitis, when present, is usually nonocclusive. Localised necrotising inflammation occurs only occasionally, is not limited to patients who are HIV-positive, and often involves severe inflammation of the vitreous humour.

Polymerase chain reaction and testing of aqueous or vitreous samples can confirm syphilis and rule out viral causes of uveitis.

Testing for Toxoplasma, mycobacteria, herpesviruses, and fungi is recommended in immunodeficient patients. Retinal detachment can occur in late presentations with extensive scarring, potentially causing night blindness.

New Manifestations

“Since case numbers have risen, we have observed different variants of clinical presentation,” Jones reported. These can resemble multiple evanescent white dot syndromes, with small white spots at the posterior pole, or acute zonal occult outer retinopathy, a rare peripheral retinal disorder with electroretinogram deficits but minimal visible changes.

“The major concern now is SPPC,” Jones highlighted. In Manchester, SPPC accounts for approximately half of all syphilitic uveitis cases.

It predominantly affects men and men who have sex with men but is not associated with HIV, which does not influence prognosis.

The SPPC appears to be a phenomenon in Europe. In regions with high syphilis prevalence, such as South Africa, the prevalence is unknown. “My hypothesis is that placoid retinopathy results from a new mutation in Treponema pallidum SS14 Omega,” Jones said.

Distinguishing From Tuberculosis

Gupta noted that SPPC can be clinically overlooked. “It is best visualised with autofluorescence.” Typically, it presents as a single, large, sharply demarcated, plaque-like lesion at the posterior pole, differentiating it from tuberculosis, where chorioretinitis is usually multifocal.

Tuberculosis often manifests as granulomatous and anterior uveitis. “If a patient primarily shows retinal involvement, it is likely syphilis,” Gupta said.

“They are like identical twins, but these twins can not only imitate each other — they can also mimic other ocular infections.”

Jones added that ophthalmologists often detect syphilis first. Although patients with syphilis may be referred for blurred vision, in most cases, an ophthalmologist identifies the disease. “The ophthalmologist is crucial for diagnosis; otherwise, it may be missed.”

“About half of patients experience systemic symptoms,” Jones emphasised, advising clinicians to ask about headache, malaise, flu-like symptoms, weight loss, and mucocutaneous symptoms.

“Patients rarely volunteer information about rashes, so you need to ask and examine for them directly.”

He noted that examining the oral mucosa, palms, and skin is not too intrusive, but clinicians should remember that these rashes are infectious.

Differential diagnoses for uveitis with palmoplantar lesions include keratoderma blenorrhagicum in reactive arthritis or pustular psoriasis, although these conditions usually present with other forms of uveitis.

“Almost 10% of patients with ocular syphilis also have otosyphilis.” Jones added that there is a specific association between these two.

Diagnosis and Treatment

Active syphilis requires:

• A positive T pallidum-specific test, such as the Treponema pallidum hemagglutination test
• A non-T pallidum-specific but quantitative test, such as Venereal Disease Research Laboratory with a titre > 1:8

Jones emphasised: “You must be able to interpret serology correctly.” False positives can occur in patients with Lyme disease, tuberculosis, lymphoma, acute viral exanthems, autoimmune disorders, liver cirrhosis, and malaria.

Sexually transmitted disease specialists should be consulted to rule out coinfections, trace contacts, and guide treatment, following the neurosyphilis protocol.

Treatment with penicillin or cephalosporin is highly effective for more than 2 weeks. If systemic antibiotics are delayed, intravitreal ceftazidime may be initially administered. “It is immensely rewarding to help patients. Early diagnosis, initiation of treatment, and resolution are essential. Even patients with macular involvement can recover fully, both clinically and functionally, with early treatment,” Jones said.

This story was translated from Medscape’s German edition.