by Jeffrey T. Kirchner, DO, AAHIVS, AAHIVM Chief Medical Officer

March 17, 2020

Featured Literature:

Ghanem, KG et al. The Modern Epidemic of Syphilis.
N Engl J Med 2020; 382:845-854. DOI: 10.1056/NEJMra190159

With the continued increase in STIs seen in the U.S. over the past few years, I have decided to cite an excellent review article on Syphilis and have included- several key points below.

  • There continues to be an increase in rates of 1° and 2° syphilis in the U.S. with men accounting for 86% of cases. More than > 50% are in MSM of whom 42% are HIV infected. Rates of 1° and 2° syphilis among women doubled between 2014 and 2018.
  • Treponema pallidum disseminates within days after infection to distant tissues, including the CNS. Primary syphilis is manifested as a solitary ulcerative chancre. Findings with 2° syphilis include a nonpruritic rash, often on the palms and soles. Many cases of early latent syphilis (< 1-year cutoff) often go unnoticed or are misdiagnosed.
  • Syphilis cases are diagnosed by serologic testing. Two algorithms are used and require two-stage testing. Standard screening is with a non-treponemal test (RPR or VDRL), and reactivity is confirmed with specific treponemal test. Some labs use a reverse screening algorithm with a treponemal test done initially and reactive samples are reflex-tested with the non-treponemal test. The non-treponemal test provides a titer needed for clinical management.
  • Routine CSF examination for persons with early syphilis even with HIV-infection in not recommended unless neurologic signs are present. Risk factors for neurosyphilis in HIV-infected patients include an RPR titer of > 1:32, a CD4 count of 350 cells or lower, and absence of ART.
  • Penicillin is the drug of choice for all stages of syphilis and resistance has not been observed. A single IM dose of 2.4 million units of penicillin G benzathine is recommended and sustains drug levels for 7 to 10 days. Late-latent syphilis should be treated with 3 doses of PCN given weekly. Ceftriaxone has similar efficacy to PCN but data are restricted to observational studies.
  • Goal of treatment for syphilis is clinical and serologic cure. Serologic cure is a decline in RPR titer by a factor of 4 or more by 6 to 12 months for early syphilis and 12 to 24 months after therapy for late syphilis.
  • A vaccine for prevention of syphilis is likely years away. Recent data from two small studies provided preliminary evidence that a biomedical approach to prevention may be possible. Doxycycline given prophylactically (100 mg qd) reduced combined odds of syphilis, gonorrhea, and chlamydia infection by 73% in a small study HIV-infected MSM. An open-label study in 116 MSM found PEP with doxycycline (200 mg 24 hours after a sexual encounter) produced a 73% reduction in the risk of syphilis over a mean follow-up about 9 months.

Author’s Commentary:

I would strongly encourage review of the full content of the cited article. Syphilis screening at least annually is recommended for the majority of our HIV-infected patients as well as those on PrEP. Fortunately, PCN remains highly effective as primary treatment. There remains nuances regarding follow-up titers including a discussion regarding the need for CSF analysis via LP, “sero-fast” status and what constitutes treatment failure (this is rare). 

The author has no conflicts of interest to disclose.

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