Because syphilis and its psychiatric effects are relatively uncommon (Box 1), many psychiatrists do not consider neurosyphilis in high-risk patients who present with depression, dementia, or psychosis (Box 2).
HOW SYPHILIS BECOMES NEUROSYPHILIS
Primary syphilis incubates for 10 to 90 days following infection. After this period, an infectious chancre appears along with regional adenopathy. If untreated, the chancre will disappear but the infection will progress.
Secondary syphilis is characterized by skin manifestations and occasionally affects the joints, eyes, bones, kidneys, liver, and CNS. Common effects include condylomata—highly infectious warty lesions—and a diffuse maculopapular rash on the palms and soles. These lesions disappear if left untreated, but most patients then either enter syphilis’ latent stage or experience a potentially fatal relapse of secondary syphilis.5
Latent syphilis usually remains latent or resolves, but about one-third of patients with latent syphilis slowly progress to tertiary syphilis. Neurosyphilis, one of the main forms of tertiary syphilis, can surface 5 to 35 years after an untreated primary infection.7
There are four categories of neurosyphilis:
- General paresis results in dementia, changes in personality, transient hemiparesis, depression, and psychosis.
- Tabes dorsalis degenerates the posterior columns and dorsal root ganglia of the spinal cord. This results in ataxia, parasthesias, decreased proprioception and vibratory sense, Argyll Robertson pupil (an optical disorder in which the pupil does not react normally to light), neurogenic bladder, and sharp shooting pains throughout the body.
- Meningovascular neurosyphilis can result in cranial nerve abnormalities, symptoms of meningitis, and cerebral infarctions.
- Asymptomatic but with CSF positive for syphilis.
Neurosyphilis is fatal if untreated, and treatment usually does not eliminate symptoms but prevents further progression. Approximately 8% of patients with untreated primary syphilis develop neurosyphilis.5,7
Standard nontreponemal tests, such as the VDRL or rapid plasmin reagin, can be used to screen for syphilis. Because these tests often produce false positives, confirm positive results with a syphilis-specific test, such as the fluorescent treponemal antibody absorption (FTA-ABS) test, microhemagglutination assay for antibodies to T pallidum., and the T pallidum. hemagglutination assay.
If neurosyphilis is suspected, CSF testing is strongly recommended. Diagnostic findings include elevated white blood cell and protein counts and a positive VDRL. If the CSF is negative, refer the patient for treatment anyway because false negatives are common. Patients with consistent neurologic symptoms, positive VDRL and/or FTA-ABS, and negative CSF are diagnosed with neurosyphilis and warrant treatment.7
How would you manage Mr. S’ psychiatric symptoms concomitant with medical treatment of late-stage syphilis?
Dr. Greenberg’s and Tampi’s observations
Although no specific guidelines exist for treating psychosis secondary to neurosyphilis, atypical antipsychotics remain the first-line treatment. Atypicals do not interact significantly with penicillin and can be given safely with syphilis treatment. Atypicals also are better tolerated than typical antipsychotics and produce fewer extrapyramidal symptoms, which are common among older patients and those with neurologic diseases.
Screening for syphilis. Every patient with a history of high-risk sexual behavior who presents with new-onset dementia or psychosis should be screened for syphilis. Sexual history can be difficult to obtain from some patients and family members, so communication between providers becomes crucial. Obtain lab test results from other care team members to monitor compliance, and coordinate patient education with other doctors on safe sexual practices.
TREATMENT: Taking his medicine
Mr. S refused further testing and emergency conservatorship was sought. Citalopram was discontinued and risperidone was gradually increased to 6 mg at bedtime. He remained paranoid and delusional.
A brain MRI showed chronic ischemic small-vessel disease. HIV testing was negative, and serum FTA-ABS was reactive. CSF showed elevated protein and white blood cell count with a nonreactive VDRL and a reactive FTA-ABS. A diagnosis of neurosyphilis was made, and treatment was initiated with aqueous crystalline penicillin G, 4 million units every 4 hours for 2 weeks.
Mr. S was discharged back to the nursing home where his penicillin injections were continued. His paranoia diminished slightly but he remained ataxic, incontinent, and confused. He was discharged from the nursing home but needed confirmative HIV screening and repeated CSF testing to determine if syphilis treatment was effective.
Six months after treatment, Mr. S’ niece reports that his paranoia has decreased. He has not needed additional psychiatric hospitalizations.
Related resources
- Merck Manual. www.merck.com. Search: “syphilis”
- U.S. Centers for Disease Control and Prevention—Syphilis elimination: History in the making. www.cdc.gov. Click on “Health Topics A-Z,” then click on “S” and find “syphilis.”
- National Institute of Allergy and Infectious Disease. www.niaid.nih.gov. Search: “syphilis”
Drug brand names
- Citalopram • Celexa
- Risperidone • Risperdal
Disclosure
The authors report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.