Clinical manifestations* | Treatment¶ | Monitoring after treatmentΔ | |
Early syphilis | Primary syphilis: Secondary syphilis: Refers to the period when a patient is infected with Treponema pallidum as demonstrated by serologic testing but has no symptoms. Early latent syphilis occurs within the first year of initial infection. | Preferred:
Alternatives (choose one):◊
| Clinical exam and serologic testing with a nontreponemal test (eg, RPR) at 6 and 12 months. Titers should be checked more frequently if the patient is HIV infected, follow-up is uncertain, or reinfection is a concern. |
Late syphilis | Tertiary syphilis: The period when a patient is infected with T. pallidum as demonstrated by serologic testing but has no symptoms. Late latent syphilis by definition is present more than one year after initial infection. If the timing of an infection is not known, late latent syphilis is presumed. | Preferred:
Alternatives (choose one):
| Clinical exam and serologic testing with a nontreponemal test (eg, RPR) at 6, 12, and 24 months. |
Neurosyphilis | Neurosyphilis: Early neurosyphilis: The most common forms involve the brain and spinal cord (dementia [general paresis] and tabes dorsalis). | Preferred:
Alternative:‡
| Clinical and serologic monitoring with nontreponemal tests (eg, RPR). The frequency depends upon the stage of disease (eg, early or late). CSF monitoring may be warranted.† |
CSF: cerebrospinal fluid; IM: intramuscular; IV: intravenous; RPR: rapid plasma reagin.
* Refer to the UpToDate topics that discuss the clinical manifestations of syphilis and neurosyphilis for more detailed information.
¶ For the treatment of pregnant women and children, refer to the UpToDate topics that discuss syphilis and pregnancy and congenital syphilis.
Δ Patients infected with HIV are typically monitored more frequently. Refer to the UpToDate topic that discusses the treatment of syphilis in patients with HIV infection.
◊ Amoxicillin 3 g plus probenecid 500 mg, both given orally twice daily for 14 days, is another alternative but is rarely used given the complexity of the regimen. Azithromycin, previously an alternative regimen for syphilis, is no longer considered an appropriate treatment option in the United States and Canada due to widespread macrolide resistance. Outside of North America, the decision to use a macrolide should be made in accordance with local guidelines.
§ Tetracycline 500 mg orally four times daily is also an alternative but is harder to take.
¥ For patients with clinical manifestations of late neurosyphilis (eg, general paresis or tabes dorsalis), we suggest an additional single dose of IM penicillin G benzathine after the IV course. Without this IM dose, the duration of treatment for neurosyphilis is shorter than the regimens used for other forms of late syphilis and may be insufficient. However, data supporting this approach are lacking, and it is reasonable for a patient or provider to defer this additional dose.
‡ Limited clinical experience suggests that doxycycline (200 mg orally twice daily) for 21 to 28 days may be effective as an alternative regimen. However, this regimen should be reserved for exceptional circumstances.
† Refer to the UpToDate topic on neurosyphilis for a more detailed discussion of monitoring after treatment.