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Serologic Testing for syphilis - Letter from Matt Golden, MD. Director of PHSKC STD Control Program [12/09] - UW Net ID required

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General observations on HIV-infected patients with syphilis:

  • Case reports suggest that the unusual clinical manifestations of syphilis may be more common (e.g. overlap of primary & secondary manifestations) and the course more rapid in patients with HIV infection.
  • Though above not corroborated in prospective studies, case reports have largely driven the hypotheses that among patients coinfected with HIV and T pallidum:
    • Mucocutaneous lesions may be more severe or numerous,
    • Symptomatic neurosyphilis may be more likely to develop,
    • Latency period before the development of meningovascular syphilis may be shorter,
    • Efficacy of standard therapy for early syphilis may be reduced.
  • HIV-infected patients can have atypical serologic responses. More typical is higher-than-expected RPR titers (e.g. 1:128). More rare: false negative and delayed onset of seroreactivity. Biologic false positives can occur (treponemal test negative), esp. if polyclonal gammopathy present.
    • The “serofast” state is not uncommon among HIV-infected persons. It is the persistence of a reactive nontreponemal syphilis test, usually 1:16 or less, with variation no greater than 1 to 2 dilutions over time, despite adequate therapy and no evidence of reexposure.
    • NOTE: Reinfection may be difficult to rule out in some patients, and reactivation or relapse of a previously treated infection is also possible in a person with HIV infection.

General treatment principles – areas of consensus [ CDC STD 2010 Guidelines]

  • Long-acting penicillin G is treatment of choice:
    • Benzathine penicillin G (Bicillin LA) 2.4 million U intrasmuscularly x 1 should be used in all cases for incubating, primary, secondary or early latent syphilis with no evidence of neurologic involvement.
    • For late latent or syphilis of unknown duration:
      • For late latent or syphilis of unknown duration without neurologic symptoms and/or negative CSF examination, then benzathine PCN G should be given as 7.2 million IU IM as 3 doses of 2.4 million IU in successive weeks.
      • If CSF without evidence of neurosyphilis (CSF WBC>20/μL or reactive CSF VDRL), then benzathine PCN G should be given as 7.4 million IU IM as 3 doses of 2.4 million IU in successive weeks.
    • Neurosyphilis (or syphilitic eye or auditory disease):

      • Aqueous crystalline penicillin G 18-24 million U IV per day, dosed as continuous infusion or q4h, x 14 days 

      • Procaine penicillin 2.4 million U per day IM + Probenecid 500 mg PO QID x 14 days
  • Doxycycline is an oral alternative and reserved only for patients who are truly penicillin-allergic – oral agents should never be used for neurosyphilis or pregnant patients with syphilis.
  • Azithromycin, though it has shown promise in early syphilis, should not be used because of reported resistance.
  • Confirmation of post-treatment serologic response:
    • NOTE: Nontreponemal test antibody titers (RPR or VDRL) usually correlate with disease activity. Sequential serologic tests should be performed by same testing method (RPR or VDRL) & preferably by same lab.
    • Follow-up of RPR or VDRL titer recommended at 3, 6, 9, 12 and 24 months after therapy.
    • Appropriate response to treatment = 4-fold decrease in titer (2 dilutions) in 6 months.
  • When do you perform a lumbar puncture to examine CSF?

    • Any patient with syphilis who has neurologic complaints (includes ophthalmic or otologic complaints as well as cranial nerve palsy, meningitis, stroke, altered mental status or loss of vibratory sensation).
    • Evidence of active tertiary syphilis (e.g., aortitis and gumma);
    • All patients with treatment failure defined as:
      • Recurrence or persistence of symptoms
      • Lack of a 4-fold decrease in RPR titers after 12 months in early syphilis, 24 months in late syphilis
      • 4-fold increase in RPR titers at any time after treatment
    • More controversial: any asymptomatic HIV+ patient with RPR titer >1:32 or CD4 count <350.
    • If you think your patient needs an LP, contact Trudy Jones, ARNP who can perform the LP and enroll patient in Christina Marra’s syphilis study [link]. Need UW ID to log in.


Zetola , NM and Klausner JD. Syphilis and HIV infection: an update. Clin Infect Dis 2007; 44:1222-8.

Workowski KA, Berman SM. Sexually transmitted diseases treatment guidelines, 2006. MMWR Recomm Rep 2006; 55:1–94.


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