The Role of the Ophthalmologist in the Prompt Diagnosis of Syphilis: Unmasking the Great Mimicker.

PURPOSE: Syphilis is a systemic sexually transmitted infection that often mimics autoimmune and neurological disorders, which can lead to diagnostic delays. We describe a series of four patients affected by ocular syphilis initially misdiagnosed as a systemic inflammatory condition to highlight the ophthalmologist's role in early detection and management, thereby preventing irreversible visual impairment. METHODS: We retrospectively reviewed four cases of ocular syphilis from 2022 to 2024, which were initially misdiagnosed as autoimmune or neurological diseases and thus inappropriately treated with immunosuppressive therapy. The patients underwent a full ophthalmic examination, including best-corrected visual acuity, slit-lamp biomicroscopy, fundus imaging, optical coherence tomography, and retinal angiography. Syphilis serologies were performed, and treatment included intravenous penicillin G or ceftriaxone (for penicillin-allergic patients). RESULTS: All patients tested positive for syphilis, with negative HIV screening. Initial misdiagnoses included systemic sarcoidosis, multiple sclerosis, psoriasis-like skin lesions, or unknown inflammatory conditions and were treated with unnecessary immunosuppressive therapy. Ocular findings varied from granulomatous panuveitis to retinal vasculitis, placoid chorioretinitis, and macular edema. Antibiotic therapy led to significant clinical improvement, but patients exhibited irreversible damage, such as decreased visual acuity, persistent color vision loss, retinal atrophy, and irreversible photoreceptor damage. CONCLUSION: Syphilis remains a great mimicker, frequently misdiagnosed as non-infectious systemic disease. Ophthalmologists play a critical role in identifying ocular manifestations and initiating appropriate serological testing. A delayed diagnosis increases the risk of irreversible damage. Given the rising incidence, greater awareness and interdisciplinary collaboration are essential to ensure timely diagnosis and management.