Syphilis (Lues)


First-line therapy: The first-line therapy for syphilis depends on the duration of infection and the immune competence of the host. Patients’ contacts should be traced and evaluated for possible syphilis infection. All documented cases of syphilis should be reported. All patients require clinical and serologic monitoring until seronegative.

First steps

Table 2. Syphilis and Treatment Options

First-line treatment Alternative treatment Treatment options for penicillin-allergic patients Treatment options for pregnant individuals Monitoring
Primary, secondary, or early syphilis Intramuscular benzathine penicillin G 2.4 x 106 U as a single dose A single 2 g dose of azithromycin may be considered as a second choice treatment; azithromycin-resistant strains are common. Azithromycin should not be used in men who have sex with men or in pregnant women. IM Ceftriaxone 1 g daily for 10 days Doxycycline 100 mg b.i.d. for 14 days If penicillin allergic: strongly consider penicillin desensitization or consider oral erythromycin 500 mg q.i.d. for 15 days; erythromycin may not adequately treat the fetus.Give additional penicillin therapy as for congenital syphilis (see below) to the baby at birth. 3, 6, 9, 12 and 24 months
Indeterminate length, > 1 year duration Intramuscular benzathine penicillin G 2.4 x 106 U weekly for 3 successive weeks Azithromycin 2 g single dose, doxycycline 100 mg b.i.d. for 28 days, IM Ceftriaxone 1 g daily for 10 days Doxycycline 100 mg b.i.d. for 28 days If penicillin-allergic: oral erythromycin 500 mg q.i.d. for 30 days 6, 12 and 24 months
Neurosyphilis Intravenous aqueous penicillin G 4 x 106 U q4 hours or continuous infusion for 10-14 days Procaine penicillin G 2.4 X 106 U daily with oral probenecid 500 mg q.i.d. for 10-14 days. Another option is ceftriaxone 2 g IM or IV daily for 10-14 days Doxycycline 200 mg b.i.d. for 28 days or Oral erythromycin 500 mg q.i.d. for 30 days
Congenital A positive CSF VDRL in the asymptomatic infant requires treatment for possible CNS involvement(a) Infants with normal CSF: Intramuscular benzathine penicillin G 50,000 U/kg in a single dose.(b) Infants with abnormal CSF and those in whom CNS involvement cannot be ruled out: Intramuscular aqueous procaine penicillin G 50,000 U/kg/day for 10 days(c) For older children the dosage of penicillin is as noted above, but should not exceed that recommended for adults with syphilis of more than 1 year’s duration 3, 6, 9, 12 and 24 months
Syphilis in HIV-infected individual Intramuscular benzathine penicillin G 2.4 x 106 U as a single dose Efficacy of alternative regimens is not well established


  • Compliance with long courses of oral antibiotics is a concern. Parenteral treatment is preferred. If oral therapy is given, compliance must be stressed, and careful follow-up is essential to document cure.
  • Tetracycline is contraindicated in the second and third trimesters of pregnancy and in children less than 8 years of age.
  • A Jarisch-Herxheimer reaction may occur in the first 24 hours after treating any patient, resulting from inflammatory cytokines triggered by antigens elaborated by dying spirochetes. Patients should be warned before therapy. Anti-inflammatory treatment, including aspirin (and prednisone in rare cases), is helpful. Patients may need additional monitoring for hemodynamic instability.

When to refer to a dermatologist

  • If the diagnosis is not clear.
  • If a skin or mucosal biopsy is needed.
  • For co-management of cutaneous manifestations of the disease.