To describe an unusual case of cerebral syphilitic gumma in a patient with multiple sclerosis (MS) being treated with Rituximab.

We present the case of a 23-year-old woman with a history of pediatric-onset, relapsing-remitting MS on anti-CD20 therapy complicated by hypogammaglobinemia, who developed a papular rash involving her back, trunk, and extremities. Laboratory evaluation revealed positive treponemal antibodies and rapid plasma reagent test (titer 1:16). She was diagnosed with secondary syphilis and treated with intramuscular penicillin. Four months later, she presented with a generalized tonic-clonic seizure and headaches. MRI of the brain revealed a new left frontal lobe T2 hyperintense lesion with overlying pachymeningeal enhancement, initially interpreted as a new lesion potentially related to her MS. She was started on levetiracetam with seizure control and instructed to follow up with her neurologist. Unfortunately, this was delayed for several months due to lack of transportation options, limited healthcare coverage, and low health literacy. Eventually, a repeat MRI brain revealed interval enlargement of the left frontal lesion with significant vasogenic edema. Ultimately, a brain biopsy was performed and demonstrated findings consistent with cerebral syphilitic gumma and meningovascular neurosyphilis. She was treated for neurosyphilis, and Rituximab was discontinued.

The immunosuppressive effects of anti-CD20 therapy in patients with MS and related conditions increases the risk for atypical infections, such as cerebral syphilitic gumma. Our case also highlights the importance of addressing social determinates of health in management of patients with chronic medical conditions and the need for recurrent infectious screening in high-risk populations.