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Therapeutic Strategies

Syphilis (Lues)

Timothy Berger Bruce Wintroub

Saturday, December 01, 2012

Overview

The treatment of syphilis is based on the duration of infection and the organ systems involved. Five groups can be distinguished: primary, secondary, or early syphilis of less than 1 year's duration; infection of indeterminate length, or more than 1 year's duration; neurosyphilis; congenital syphilis; and syphilis infection in association with HIV infection. In all cases of syphilis, it is important to examine for and treat other sexually transmitted diseases (STDs), and to trace and treat all contacts. Syphilis cases should be reported to the local health department. Infected individuals may resume sexual activity after skin lesions, if present, are healed, or after therapy is complete. The treatment of early, late, HIV-associated, and neurosyphilis will be discussed below. Readers are referred to the CDC website (www.cdc.gov) for the management of neonatal syphilis.

First Steps

Primary, secondary, or early syphilis

  1. Intramuscular benzathine penicillin G 2.4 X 106 units as a single dose. Some experts feel that a second 2.4 X 106 unit dose 1 week later leads to enhanced clinical and serologic cures.
  2. Penicillin-allergic patients: Doxycycline 100 mg twice daily or tetracycline HCl 500 mg 4 times daily for 14 days.
  3. For possibly noncompliant penicillin-allergic patients and pregnant patients with penicillin allergy: Refer to an allergist for skin testing and desensitization if required to allow for penicillin treatment.

Infection of indeterminate length, or more that 1 year's duration

  1. Intramuscular benzathine penicillin G 2.4 X 106 units/week for 3 successive weeks.
  2. Penicillin-allergic patients: Doxycycline 100 mg twice daily or tetracycline HCl 500 mg 4 times daily for 28 days.
  3. For possibly noncompliant penicillin-allergic patients and pregnant patients with penicillin allergy: Refer to an allergist for skin testing and desensitization if required to allow for penicillin treatment.

Neurosyphilis

Neurosyphilis may occur at any time during syphilitic infection. Diagnosis requires a reactive cerebrospinal fluid (CSF) with increased cell count, increased protein content, and a positive CSF Venereal Disease Research Laboratory (VDRL) test. The serum FTA-Abs or MHA-TP is positive in all cases. Neurologically normal patients with early syphilis do not require CSF examination. CSF examination is required in neurosyphilis during and after treatments as an index of cure.

First Steps

Intravenous aqueous penicillin G 4 X 106 units every 4 hours. for 14 days.

Alternative Steps

  1. Intramuscular procaine penicillin G 2.4 X 106 units/day with oral probenecid 500 mg 4 times daily for 14 days.
  2. For penicillin-allergic patients: Ceftriaxone 2 g IV or IM daily for 10-14 days.
  3. For possibly noncompliant penicillin-allergic patients and pregnant patients with penicillin allergy: Refer to an allergist for skin testing and desensitization if required to allow for penicillin treatment.

Syphilis in the HIV-infected individual

HIV infection may alter the natural history of syphilis in two ways: A negative VDRL or rapid plasma reagin (RPR) can occur with active secondary syphilis; and early CNS relapse can happen after apparently adequate therapy has been observed on multiple occasions.

First Steps

  1. The current CDC guidelines recommend no change in therapy for early syphilis in the HIV-infected individual (see above). It may be prudent to treat all HIV-infected individuals with early syphilis with 3 consecutive, weekly, intramuscular injections of benzathine penicillin 2.4 X 106 units. Therapeutic failures with oral erythromycin and azithromycin have been reported.
  2. A CSF examination should precede and guide treatment of HIV-infected individuals with latent syphilis or syphilis present for 1 year or more or of unknown duration. If CSF examination is not possible, treat for presumed neurosyphilis.
  3. Do not use benzathine penicillin to treat neurosyphilis in the HIV-infected individual. (See treatment regimen 3, above.)
  4. HIV-positive persons with CNS findings should be evaluated for possible neurosyphilis.
  5. Notify state epidemiologists of any HIV-infected patient with neurosyphilis or seronegative-documented secondary syphilis.

Alternative Steps

Use only the standard regimens noted above. Efficacy of other regimens is not established.

Subsequent Steps

  1. All patients require repeat serum VDRL determinations: For those with early syphilis at 3, 6, and 12 months; for those with syphilis of more than 1 year's duration at 12 and 24 months; for pregnant patients, monthly until delivery; for HIV-infected individuals at 1, 2, and 3 months, and at 3-month intervals until a two-dilution or greater decrease in VDRL titer occurs. Thereafter repeat every 6 months until seronegative.
  2. For all patients with neurosyphilis, and infants with possible neurosyphilis, in addition, a CSF examination must be repeated 6 months following treatment. Adequate therapy is determined by a normal CSF cell count and a falling protein content. The VDRL may not return to negative. CSF examination in documented neurosyphilis (with abnormal CSF findings) is continued at 6-month intervals for 2 years. A normal CSF at 1 year is evidence of cure.

Pitfalls

  1. 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.
  2. Tetracycline and doxycycline are contraindicated in pregnancy and in children under 8 years of age.
  3. A Jarisch-Herxheimer reaction may occur in the first 24 hours after treating any patient. Patients should be warned before therapy. The treatment is bed rest and aspirin. Do not discontinue therapy.

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