Neurosyphilis, Ocular Syphilis, and Otosyphilis

Neurosyphilis

Neurosyphilis is a result of invasion of the central nervous system by Treponema pallidum, which can occur at any stage of syphilis. It is unknown whether certain T. pallidum strains are neurotropic.

Early neurologic clinical manifestations (e.g., cranial nerve dysfunction, meningitis, meningovascular syphilis, stroke, and altered mental status) are usually present within the first few months or years of infection. Late neurologic manifestations (e.g., tabes dorsalis and general paresis) occur 10–30 years after infection but can occur earlier in people who are immunocompromised.

Invasion of cerebrospinal fluid (CSF) by T. pallidum can occur during any stage of syphilis and CSF laboratory abnormalities are common among people with early syphilis regardless of neurologic signs or symptoms. No evidence supports variation from the CDC-recommended treatment regimen for syphilis at any stage for people without clinical neurologic findings. If clinical signs or symptoms of neurologic involvement are present (e.g., cranial nerve dysfunction, meningitis, stroke, acute or chronic altered mental status, or motor or sensory deficits), CSF examination should be performed.

Infection of the visual system (ocular syphilis) or auditory system (otosyphilis) can also occur at any stage of syphilis.

Ocular Syphilis

Ocular syphilis can occur at any stage of syphilis, with variable clinical presentations, including isolated ocular abnormalities or with neurologic manifestations. Ocular syphilis can involve almost any eye structure, but posterior uveitis and panuveitis are the most common clinical manifestations. Additional ocular manifestations may include anterior uveitis, optic neuropathy, retinal vasculitis, and interstitial keratitis. Ocular syphilis may lead to decreased visual acuity with subsequent permanent blindness.

Ocular syphilis may be the initial presentation of syphilis in a patient. Screening for syphilis should be considered in new onset vision changes.

Otosyphilis

Otosyphilis is caused by an infection of the cochleovestibular system with T. pallidum and typically presents with sensorineural hearing loss, tinnitus, or vertigo. Hearing loss can be unilateral or bilateral, have a sudden onset, and progress rapidly. Otosyphilis can result in permanent hearing loss.

Otosyphilis may be the initial presentation of syphilis in a patient. Screening for syphilis should be considered in new onset sensorineural hearing loss, tinnitus, and vertigo.

Patients who present with otosyphilis may also have manifestations of ocular and neurosyphilis (especially involving cranial nerve VIII) and should be evaluated accordingly.

Evaluation and Treatment

Patients who receive a diagnosis of syphilis and have neurologic, ocular, and/or otologic symptoms should be evaluated for neurosyphilis, ocular syphilis, or otosyphilis according to their clinical presentation.

Patients who have syphilis and symptoms or signs suggestive of neurologic disease (e.g., cranial nerve dysfunction, meningitis, stroke, acute or chronic altered mental status, or motor or sensory deficits) should have an evaluation that includes CSF analysis before treatment. Patients with syphilis who have symptoms or signs of ocular syphilis (e.g., uveitis, iritis, neuroretinitis, or optic neuritis) should have a full ocular slit-lamp and ophthalmologic examination, including a thorough cranial nerve evaluation; if cranial nerve dysfunction is present, CSF examination is indicated.

Patients with syphilis, isolated ocular symptoms (no cranial nerve dysfunction or other neurologic abnormalities), and confirmed ocular abnormalities on examination, CSF analysis is not necessary before treatment. CSF examination may be helpful in evaluating patients with syphilis who have ocular symptoms and do not have abnormalities on ocular examination.

Patients with syphilis, isolated auditory symptoms, and normal neurologic examination, CSF examination is not recommended before treatment since it is usually normal. If there are signs and symptoms of otosyphilis, then otologic examination is needed.

All patients with syphilis should receive an HIV test if status is unknown or previously HIV-negative.

Treatment

Treatment for neurosyphilis should be managed according to the STI Treatment Guidelines, 2021 – Neurosyphilis, Ocular Syphilis, and Otosyphilis.

Ocular syphilis should be managed in collaboration with an ophthalmologist; immediate referral to an ophthalmologist is critical if ocular syphilis is suspected. Patients diagnosed with ocular syphilis should be managed according to the STI Treatment Guidelines, 2021 – Neurosyphilis, Ocular Syphilis, and Otosyphilis.

Otosyphilis should be managed in collaboration with an otolaryngologist. Treatment for otosyphilis should follow the STI Treatment Guidelines, 2021 – Neurosyphilis, Ocular Syphilis, and Otosyphilis.

Follow-up

Repeat CSF examinations are not necessary for patients without HIV infection or among patients with HIV infection who are on antiretroviral therapy and who exhibit serologic and clinical responses after treatment.

Reporting

In 2018, the Council of State and Territorial Epidemiologists revised the syphilis case definition to include neurosyphilis related variables: neurologic, ocular, and otic manifestations.  Cases should be reported according to stage of infection and the clinical manifestations should be reported with the case report data. Healthcare providers should follow state or local health department’s guidance for reporting clinical manifestations of cases of syphilis.

Laboratory

CDC is conducting a study on ocular syphilis to determine whether specific molecular strain types of T. pallidum are associated with this type of syphilis. Healthcare providers with patients suspected of ocular syphilis can collect clinical specimens for molecular typing. Pre-antibiotic residual clinical samples (whole blood in EDTA tubes, exudate or tissue from primary and secondary lesions, CSF or ocular fluid) collected as part of routine clinical testing should be saved and stored at -80°C immediately upon collection for molecular typing.

For assistance with the collection procedure or shipment of samples, please contact Dr. Allan Pillay at 404-639-2140 or stdlaboratoryspecim@cdc.gov. Submitters should notify CDC and their respective state and local public laboratory prior to sending specimens.

For additional laboratory considerations, see the Sexually Transmitted Infections Treatment Guidelines, 2021.

For More Information

Healthcare providers needing CDC advice on the clinical management of neurosyphilis, ocular syphilis, or otosyphilis can contact:

CDC-INFO
1-800-CDC-INFO (800-232-4636)
TTY: 1-888-232-6348
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