Syphilis can present in three stages: primary, secondary, and tertiary. This is dened based on the time from infection as well as clinical presentation. In primary syphilis, an ulcer may present at the site of inoculation 1–21days after infec­tion; although lesions are commonly painless, extragenital ulcers are more likely to have signicant pain. Ulcers often resolve within 3–6weeks regardless of treatment, and thus only a small portion of patients are diagnosed during this stage. In HIV-positive patients, primary disease is more likely to be asymptomatic; therefore, this cohort more commonly presents in the secondary stage [44]. Secondary disease usually occurs weeks to months after the initial inoc­ulation and can present with more systemic symptoms such as fever, malaise, arthralgias, diffuse lymphadenopathy, a rectal mass, and a rash. The rash, which signies hematoge­nous spread, is often characterized by a diffuse maculopapu­lar lesion that can involve the palms of the hands and soles of the feet. A less common presentation includes both nodular and ulcerated lesions. Failure to treat these patients results in progression to a latent asymptomatic stage for a period of 1–30years following initial infection. Progression to tertiary syphilis occurs in a minority of patients and is characterized by cardiac involvement and gummas, non-cancerous growths with a necrotic and ulcerated center that can develop through­out the body. Neurosyphilis can occur at any stage of disease and is characterized by ocular and/or central nervous system (CNS) involvement of the brain, peripheral nerves, or spinal cord. Symptoms of neurosyphilis include meningitis, cranial nerve palsies, paralysis, dementia, and even death. There is an increase prevalence of neurosyphilis in the HIV-positive population, with ndings that support HIV may accelerate the clinical course of neurosyphilis [44].