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Clinical manifestations and treatment of syphilis in nonpregnant adults

Clinical manifestations and treatment of syphilis in nonpregnant adults
  Clinical manifestations* Treatment Monitoring after treatmentΔ
Early syphilis

Primary syphilis:
Typically consists of a single painless chancre at the site of inoculation, accompanied by regional adenopathy.

Secondary syphilis:
A systemic illness that often includes a rash (disseminated and/or involving the palms and soles), fever, malaise, and other symptoms such as pharyngitis, hepatitis, mucous patches, condyloma lata, alopecia.

Early latent:
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:
  • Penicillin G benzathine 2.4 million units IM once

Alternatives (choose one):◊

  • Doxycycline 100 mg orally twice daily for 14 days§
  • Ceftriaxone 1 g daily IM or IV for 10 to 14 days

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:
Patients with late syphilis who have symptomatic manifestations involving the cardiovascular system or gummatous disease (granulomatous disease of the skin and subcutaneous tissues, bones, or viscera).

Late latent 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:
  • Penicillin G benzathine 2.4 million units IM once weekly for three weeks

Alternatives (choose one):

  • Doxycycline 100 mg orally twice daily for four weeks§
  • Ceftriaxone 2 g daily IM or IV for 10 to 14 days
 Clinical exam and serologic testing with a nontreponemal test (eg, RPR) at 6, 12, and 24 months.
Neurosyphilis

Neurosyphilis:
Can occur at any time during the course of infection.

Early neurosyphilis:
Patients with early neurosyphilis may have asymptomatic meningitis, symptomatic meningitis, or less commonly meningovascular disease (ie, meningitis or stroke). Vision or hearing loss with or without concomitant meningitis may also be present, and ocular/otologic syphilis is treated as neurosyphilis.

Late neurosyphilis:
The most common forms involve the brain and spinal cord (dementia [general paresis] and tabes dorsalis).		 Preferred:
  • Aqueous penicillin G 3 to 4 million units IV every four hours (or 18 to 24 million units continuous IV infusion) for 10 to 14 days
  • For patients with late neurosyphilis, some experts give an additional dose of penicillin G benzathine (2.4 million units IM once) after completing IV therapy.¥
  • If possible, patients allergic to penicillin should be desensitized and treated with IV penicillin

Alternative:‡

  • Ceftriaxone 2 g IV daily for 10 to 14 days

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.
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