A 64-year-old woman with hypertension, diabetes, and prior stroke presented with one month of intermittent blurry vision and headaches. Exam revealed bilateral optic disc swelling concerning for papilledema. Brain MRI and venography were normal. Lumbar puncture (LP) showed normal opening pressure but lymphocytic pleocytosis and elevated protein, favoring papillitis over papilledema. She was discharged on acetazolamide.

Three weeks later, she returned with worsening vision. Repeat LP showed marked lymphocytic pleocytosis (450 cells/µL), elevated protein (116 mg/dL), and normal glucose. Empiric steroids and plasmapheresis were started for presumed autoimmune etiology, with transient improvement. Infectious evaluation revealed serum RPR 1:16 and positive CSF VDRL, confirming neurosyphilis. HIV and Lyme testing were negative. She was treated with high-dose IV penicillin, resulting in substantial visual recovery and near-complete resolution of papillitis.

Neurosyphilis can mimic autoimmune diseases, complicating diagnosis, especially when presenting as bilateral papillitis (optic neuritis specifically affecting the optic nerve head). The diagnosis should be considered in patients with unexplained optic disc swelling and lymphocytic CSF pleocytosis to ensure timely diagnosis and treatment.